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Can you work out the cause of this DVT?

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End-o-bed-o-gram – case 2.

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Spot diagnosis #1, the nejm critical care challenge: case 11 (end of life care), nejm critical care challenge case 10 (sdh) answer, the nejm critical care challenge: case 10 (acute sdh), icu-acquired weakness: nejm critical care challenge case 9 (question and answer).

Nutrition: NEJM Critical Care Challenge Case 8 Answer

End-o-bed-o-gram 1, the nejm critical care challenge: case 8, coagulopathy: nejm critical care challenge case 7 answer, coagulopathy: nejm critical care challenge case 7, icu sedation: nejm critical care challenge case 6 answer, icu sedation: nejm critical care challenge case 6, acute liver failure: nejm critical care challenge case 5 answer, acute liver failure: nejm critical care challenge case 5, ventilation: nejm critical care challenge case 4 answer.

Haemodynamic Monitoring: NEJM Critical Care Challenge Case 3 ANSWER

Haemodynamic monitoring: the nejm critical care challenge case 3, resuscitation fluid: nejm critical care challenge case 2 answer.

The NEJM Critical Care Challenge: Case 2

Septic shock: nejm critical care challenge case 1 answer, septic shock: nejm critical care challenge case 1.

The NEJM Critical Care Challenge: Case 1

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The nejm critical care challenge: case 4.

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September Case of the month

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Burn injuries in the ICU

A case scenario approach part 2.

Simko, Lynn Coletta PhD, RN, CCRN; Culleiton, Alicia L. DNP, RN, CNE

Lynn Coletta Simko is a clinical associate professor at the Duquesne University School of Nursing, Pittsburgh, Pa.

Alicia L. Culleiton is a practicing educator and clinician in Pittsburgh, Pa.

The authors have disclosed that they have no financial relationships related to this article.

This article is the second part of a case study about Abe, a young Amish patient with severe burn injuries. In Part 1, various types of burns were described, as well as initial resuscitative care for patients with severe burn injuries. In Part 2, the authors detail Abe's unfolding case scenario and conclusion, cultural concerns in nursing care for an Amish patient, and the treatment modalities necessary to manage patients with burn injuries in the ICU.

Part 1 of this two-part series ( Burn injuries in the ICU: A case scenario approach , March 2017) reviewed the various types of burn injuries and what critical care nurses need to know to provide initial resuscitative care for patients with severe burn injuries using the case study of a young Amish boy, Abe. This article is based on Abe's unfolding case scenario and conclusion and describes various treatment modalities necessary to manage the extended care of patients with burn injuries in the ICU. The article also outlines system-based nursing considerations and important cultural aspects of care for members of the Amish community.

Abe's story

Abe is a 14-year-old Amish boy who stoked a fire in a wood-burning stove and was hurt by a subsequent explosion. He was transported by helicopter to the local burn ICU (BICU). He sustained an 82% total body surface area (TBSA) thermal burn (calculated using the Lund-Browder chart). Abe's burns included bilateral full-thickness circumferential burns to his legs and feet, arms and hands, genitalia, and deep partial-thickness burns to his head, neck, and anterior trunk.

Before Abe's arrival to the BICU, the flight team stabilized Abe by initiating cervical spine precautions, endotracheally intubating him, and providing fluid resuscitation and sedation and analgesia with I.V. propofol and morphine via two large-bore peripheral venous catheters.

Once Abe was admitted to the BICU, a right brachial arterial line was placed along with a right internal jugular central venous catheter. Initial I.V. fluid resuscitation was calculated based on Abe's weight of 79 lb (36 kg), a urinary catheter was placed, and a tetanus injection was administered. The morphine drip was discontinued, an I.V. ketamine drip was started, and wound care began.

Upon reassessment, the nursing staff noted that Abe's pedal and radial pulses were absent bilaterally, and emergent bilateral upper and lower extremity escharotomies were performed. At this point of care, Abe's clinical status was critical but stable.

The road to recovery

Once the escharotomies were completed and Abe was stable, an enteral nasogastric tube was placed in the left nares and feedings began. Abe received standard wound dressings with silver sulfadiazine until his burn wounds were grafted (with the exception of his genital burns).

Abe experienced a slow recovery. Within 72 hours of his admission to the BICU, the first surgical excision and grafting on Abe's hands, feet, head, and neck were completed. His anterior trunk also required surgical excision and grafting at this time. Nurses explained to Abe's parents that further excisions and grafting procedures would be performed until all of Abe's burn wounds were closed. The excisions and grafting on Abe's arms and legs were completed over the next month.

A conservative approach was employed to treat Abe's genital burn. Initially, all obvious retained material (loose debridement) and contaminated remnants of Abe's clothing were removed. Next, the BICU nurses completed a prolonged cooling-down procedure with water. During the duration of Abe's admission, topical antibiotic ointments such as mupirocin were impregnated into gauze and applied over the perineal area and changed after every bowel movement. Scheduled and p.r.n. cleansing was accomplished using 4% chlorhexidine skin wash. This approach led to the successful healing of Abe's genital burns.

Abe was weaned from the ventilator on the third attempt during his second week in the BICU, and solid foods were introduced gradually. The following sections expand on Abe's care and address the cardiovascular, respiratory, integumentary, infection, nutrition, mobility, and pain management considerations Abe's nurses had to take into account during his stay in the BICU.

Cardiovascular management

The priority nursing diagnoses for cardiovascular management are decreased cardiac output (CO) related to increased capillary permeability, fluid volume deficit related to loss of plasma from the vascular space, and an alteration in tissue perfusion related to decreased CO and edema.

Fluid resuscitation for Abe was addressed in Part 1 and is based on the TBSA burned as well as his weight and age. Fluids may be titrated to keep the adult patient's urine output at 0.5 mL/kg/h, which is recommended by the American Burn Association. 1,2 Patients with electrical burns and/or inhalation injury may need increased fluid resuscitation. 3

The critical care nurse should monitor the patient's hemodynamic status: urine output, central venous pressure, CO, and mean arterial pressure. 4 Lactated Ringer solution is the crystalloid of choice for the first 24 hours because it contains electrolytes, and lactate may reduce hyperchloremic acidosis, which can occur with the very large volumes of 0.9% sodium chloride solution administered to patients with severe burns. 5 Hypertonic dextrose solutions and colloids may be administered when capillary permeability is restored. After the first 24 hours, colloid-containing solutions can help reduce edema and third-space fluid shifts by increasing oncotic pressure in the intravascular space and pulling fluid from the interstitial space. 3,5

Patients may be placed on digoxin to address myocardial dysfunction and decreased myocardial contractility after a burn injury. 2 Cardiac dysfunction occurs secondary to activation of the complement system, which generates anaphylatoxins. 2 Vasopressors, such as dopamine, also may be needed to help increase the patient's CO. 5 Monitor the patient's cardiac rate and rhythm. Remember that age-related alterations and reduced physiologic reserve put older adults at an increased risk for developing atrial fibrillation after a burn injury. 5

Patients with burn injuries also are at risk for venous thromboembolism (VTE, the umbrella term for deep vein thrombosis [DVT] and pulmonary embolism [PE]), due to endothelial injury, hypercoagulability, and venous stasis. DVT occurs in 1% to 23% of patients with burn injuries. 2

Abe developed a right lower extremity DVT in the BICU even though he was prescribed SQ heparin twice daily. Given the extent of his injuries and the amount of grafting remaining, the burn surgeon decided to insert a retrievable inferior vena cava filter. 6 This was done to help prevent Abe from suffering a PE. The filter was removed prior to discharge.

Administer VTE prophylaxis as prescribed; intermittent pneumatic compression and low-molecular-weight heparin are typically used. If the patients' legs are edematous from a burn injury, assessing leg edema from DVT is difficult. Further, pain can mask the patient's discomfort from a DVT, so look for signs and symptoms of a PE, including dyspnea and sudden shortness of breath. 2

If the patient has circumferential burns of the chest, abdomen, or extremities, like Abe, an emergency decompressive escharotomy may be needed to accommodate tissue edema or relieve mechanical constriction interfering with respiration. The eschar in a circumferential burn can compress the blood vessels in an extremity, decreasing distal perfusion. If the abdomen or thorax is involved, an abdominal compartment syndrome can develop along with decreased lung expansion. The escharotomy is done at the bedside and does not require analgesia because this dead tissue has no nerve endings. 5 In addition, eschar is avascular, so blood loss is minimal. In some patients, a fasciotomy (incision down to the muscle fascia) may be needed. 2 Postponing necessary escharotomies can result in limb loss and respiratory arrest. 4

Respiratory management

A priority nursing diagnosis involving the respiratory system is ineffective breathing pattern related to inhalation injury and airway obstruction. As discussed in Part 1, the signs and symptoms of inhalation injury include facial burns, hoarseness, soot in the nose or mouth, carbon in the sputum, lip edema, and singed eyebrows or nasal hair. 2

Fiberoptic bronchoscopy is a simple, accurate, and safe method of diagnosing acute inhalation injury. 2,7 It also allows for oxygen delivery, deep suctioning, and removal of necrotic tissue. The endotracheal tube should be secured without putting pressure on the ears or other burned areas. The head of the bed should be elevated to decrease airway and facial edema from fluid resuscitation, unless medically contraindicated. 2

When patients with burn injuries are admitted to the ED or the ICU, plan to obtain a chest X-ray and sputum culture and sensitivity. Typically, patients with an inhalation injury are intubated and placed on mechanical ventilation. Aim to maintain a PaO 2 over 90 mm Hg and an SaO 2 over 95%. 2 Because these patients' carboxyhemoglobin (COHb) levels typically are elevated due to the inhalation of carbon monoxide, they will receive 100% oxygen until their COHb level is 5% to 10% or lower. 2

Hyperbaric oxygen therapy (HBOT) may be indicated for some patients; this treatment displaces carbon monoxide from intracellular stores and may improve mitochondrial function. 8 HBOT should be considered in patients with COHb levels greater than 40%, who are unresponsive, have other neurologic deficits, or have severe metabolic acidosis (pH less than 7.1). 8

Patients with inhalation injury also are treated for cyanide poisoning because of the number of household synthetics (such as upholstered furniture, window coverings, plastics, vinyl flooring) that, when combusted, produce cyanide. Cyanide, one of the toxins released when these products burn, inhibits intracellular respiration and oxygen utilization. Cyanide binds with cytochrome oxidase, which is in high concentrations in the mitochondria. This decreases cell metabolism and adenosine triphosphate, which then causes a shift from aerobic to anaerobic metabolism. Anaerobic metabolism leads to lactic acidosis and cell death. 2 The liver detoxifies cyanide to thiocyanate, which is excreted by the kidneys. Although it will not reverse cyanide poisoning, 100% oxygen is an important intervention for all patients involved in enclosed-space fires. Antidotes for cyanide poisoning such as hydroxocobalamin should be given by I.V. infusion. 2 Patients with acute kidney injury may need hemodialysis.

Patients who were taking corticosteroids before the injury may experience adrenal insufficiency and should receive stress doses of corticosteroids. Bronchodilators may also be used to reverse bronchospasms. 5,9

Patients with severe inhalation injury may need extracorporeal membrane oxygenation (ECMO), in which blood is oxygenated via machine before being returned to the body. By taking over lung function, ECMO lets the lungs heal. (See Extracorporeal membrane oxygenation: A review in our July 2017 issue.) Patients who develop acute respiratory distress syndrome may need a neuromuscular blocking drug such as cisatracurium to allow uninterrupted ventilation and better gas exchange. 2,5,7

Although most pulmonary damage is self-limited and resolves in 2 to 3 days, patients with inhalation injuries may need a tracheostomy with prolonged mechanical ventilation or at the surgeon's discretion. 3,5 In the past, tracheostomy was discouraged because of potential pulmonary contamination with burn wound bacterial flora. But advances in burn care have decreased the risk of pneumonia associated with tracheostomy in patients with burn injury. 2,10

Nursing care includes meticulous pulmonary hygiene to decrease the patient's risk of ventilator-associated pneumonia (VAP). Interventions to decrease VAP risk include regular oral care, eliminating cross-contamination when suctioning, glove use, elevating the head of the bed 30 to 45 degrees unless medically contraindicated, and use of a secretion evacuation port on the endotracheal tube or tracheostomy. Also assess the patient's breath sounds, and monitor for tachypnea, fever, leukocytosis, pulmonary infiltrates, and purulent secretions. 2 Turn and reposition the patient at least every 2 hours, perform chest physical therapy, and encourage ambulation.

Abe experienced an inhalation injury and was intubated on a ventilator for 2 weeks. He also had difficulty with extubation, and to help decrease the complications of immobility he was ambulated to a bedside chair while intubated on mechanical ventilation.

Integumentary management

Integumentary management includes restoring skin integrity and preventing skin loss. Once successfully resuscitated, patients with larger burns begin a period of chronic inflammation, hypermetabolism, and lean body mass wasting, all of which can prolong and impair wound healing. 11

Debridement . A major focus of burn wound management is debridement, which removes eschar and other cellular debris from the wound to promote skin restoration by natural wound healing or grafts. Debridement methods include mechanical, enzymatic, surgical, and autolytic methods.

When Abe initially presented to the BICU, mechanical debridement was completed on all of his burn wounds. Mechanical debridement is often done via hydrotherapy, which is defined as application of water for therapy. 2,5 Shower trolleys are used to let water flow over the burn wound and immediately drain away, or alternatively, wounds are cleansed at the bedside with water. It is no longer recommended that patients be immersed in a tube or whirlpool as this increases the risk of infection. 5 Hydrotherapy allows for visualization and cleansing of the burn wound. During this therapy, previously applied topical agents, exudate, necrotic tissue, and fibrous debris are removed from the wound to expose healthy tissue.

Other methods of mechanical debridement include wet-to-dry dressings. Because mechanical debridement may damage newly formed viable tissue, this method is most often effective for large areas of unhealthy tissue when used with discretion. 12

Enzymatic debridement can occur naturally by autolysis or by applying topical proteolytic enzyme ointments that digest necrotic tissue. Enzymatic debridement is usually performed on deep partial- or full-thickness burns that cover a small area. 2,5

Surgical debridement is done early in the burn rehabilitation process, typically 1 to 3 days postinjury. Performed in the OR, surgical debridement involves excising necrotic tissue until brisk punctate bleeding occurs, indicating a wound that is ready to be grafted. 13

Surgical debridement can cause a great deal of blood loss, yet the literature discourages aggressive transfusions. 13 Current recommendations for a patient with a burn injury not at considerable risk for acute coronary syndrome (ACS) include transfusion of two units of packed red blood cells only if the hemoglobin falls below 8 g/dL. In contrast, for patients at risk for ACS, use a transfusion threshold of 10 g/dL. 13

Autolytic debridement is a process in which the body uses its own wound fluids to digest necrotic tissues. The process promotes the application of a moisture-retentive dressing, which is left in place for several days. The wound fluid trapped beneath the dressing softens and liquefies the necrotic tissue, while growth factors and inflammatory cells within the wound encourage and hasten the early phases of wound healing. 2,5

Prior to any type of wound cleansing and/or debridement, explain the procedure to the patient and family. The room temperature should be maintained between 85° F and 90° F (29.4° C and 32.2° C) to prevent excessive body heat loss and chilling. Analgesia and/or anxiolytics must be administered prior to the procedure per healthcare provider order or hospital protocol. In addition, techniques such as hypnosis, massage, relaxation, distraction, music therapy, and guided imagery may be useful adjuncts for reducing anxiety and enhancing pain relief. Any hair noted around the wound should be shaved, with careful attention not to shave the eyebrows. 2,5

Dressings . Various dressings may be used after the wound is cleansed, such as standard wound dressings and biologic, biosynthetic, and synthetic dressings.

The standard wound dressing involves applying a thin layer of a topical antimicrobial agent to the area, covering the wound with a fine, nonadherent mesh gauze, and holding the gauze in place with either a tubular net bandage or gauze wraps. Common topical antimicrobial agents include, but are not limited to, silver sulfadiazine, mafenide acetate, and silver nitrate. 5 Silver sulfadiazine use is contraindicated in patients with a sulfa allergy. Following the application of silver sulfadiazine, the patient is at risk for the development of leukopenia. 2,5 Therefore, the nurse should monitor the patient's white blood cell count.

Burn wounds may be left open to air after an antimicrobial agent is applied (open method) or covered with a gauze dressing immediately after the agent is applied (closed method). Another variation of the closed method is the application of gauze dressing soaked with a topical antimicrobial agent.

Biologic dressings protect granulation tissue in patients with healing partial-thickness burns, and granulating, clean, eschar-free full-thickness wounds. They also are used as a temporary skin cover to decrease infection, heat loss, and pain. These dressings are skin or membranes collected from human tissue donors (homografts) or animals (heterografts; see the section on grafting, below).

Biosynthetic dressings (a combination of biologic and synthetic materials) are commonly used to cover superficial burns and partial-thickness burn areas. They are made up of nylon fabric that is partially embedded into a silicone film. Collagen is incorporated into both components, and when the nylon is applied to the wound surface it adheres and promotes epithelialization.

Synthetic dressings are made up of solid silicone and plastic membranes and are used to cover donor sites. This type of dressing is applied to a prepared wound and remains intact until it falls off or is removed.

Grafting . As previously discussed, the depth of the burn injury will determine whether skin grafting is required. Full-thickness and deep partial-thickness burns require grafting. Skin grafting is the process of placing skin on a healthy, well-vascularized burn wound bed. Prior to grafting, the necrotic tissue of the burn wound is surgically removed. Grafts are usually secured to the burn wound by surgical staples, dressed, and the affected area kept immobile for 3 to 5 days. Several types of skin can be used for grafting: homografts, heterografts, or autografts. 2,5

Homografts , also called allografts, are obtained from cadavers via skin banks. Disadvantages associated with homografts include their high cost and the potential to transmit infection. In contrast, heterografts , or xenografts, are most commonly obtained from an animal such as a pig.

Autografts are the only permanent type of skin grafting. They are transplanted skin from unburned areas on the patient's body used as wound coverings. The unburned areas where the skin is removed are referred to as donor sites, which can be reharvested once they have healed. 2,5

Common nursing care for all graft sites includes immobilizing and/or splinting the grafted site and elevating grafted extremities. Initial and subsequent graft dressing changes are completed per the healthcare provider orders. Once the dressings are removed, the nurse should apply basic wound care knowledge and principles to evaluate and care for the wound. All graft sites should be monitored for nonvascularization, nonadherence, infection, and graft necrosis. 2,5

Abe underwent many surgical excisions and grafting procedures. Initially, autografts were applied to Abe's hands, feet, head, and neck. Skin was harvested from Abe's back (donor site) and heterografts were applied until his donor site could heal. As the weeks went by, Abe returned multiple times to the OR to have the burns on his arms and legs grafted.

Following surgery, the graft sites were dressed with bulky cotton dressings and left in place for 5 days to permit vascularization of the newly grafted skin. Abe's limbs were immobilized/splinted to prevent movement and shearing, and to promote graft adherence. Abe's extremities were elevated to prevent pooling of blood and edema formation that could lead to increased pressure and graft loss.

After the dressings were removed, Abe's graft sites were inspected for pockets of serous/serosanguineous fluid that could compromise graft adherence. His left foot graft was found to contain fluid, which was evacuated by needle aspiration and rolling a cotton tip applicator over the graft toward the skin edges. Following these interventions, the graft remained viable.

Abe's donor site offered unique challenges for the nursing staff. When grafting procedures are completed on the posterior of the body, or the donor sites involve the posterior body, the patient must remain immobilized for 7 to 10 days in a prone or side-lying position. After 2 days in the side-lying position being repositioned every 2 hours, the nursing staff placed Abe on an air-fluidized and low air loss bed to reduce donor-site ischemia and prevent skin breakdown and pressure injuries. 14

Infection management

The primary risk for infection is related to altered skin integrity and immunosuppression. Patients with severe burns are at a high risk for infection, especially drug-resistant infection. 15 Drug-resistant infection can lead to longer hospital admission stays, delayed wound healing, higher costs, and higher mortality. 16

Assess burns frequently for signs of infection and dysfunctional wound healing. Patients with extensive burns are considered immunosuppressed because the burn destroys the skin barrier to pathogens, and cytokine and neutrophil activity are altered. Pathogens can colonize burn eschar and enter the tissues, causing secondary bacteremia. 5 Localized signs and symptoms of burn wound infection include conversion of a partial-thickness injury to a full-thickness wound, eschar separation, worsening cellulitis of surrounding normal tissue, and tissue necrosis. 17

Infection often leads to a pronounced immune response, accompanied by sepsis or septic shock. Resultant hypotension and impaired perfusion of the end organs, including the skin, prolong wound healing. The leading causes of death following a severe burn are multiorgan failure and sepsis. 18

Sources of infection are invasive monitoring, peripheral and central venous catheters, urinary catheters, endotracheal tubes, and treatments such as debridement. These interventions may be a necessary adjunct to the patient's medical regimen. Maintain sterile technique during invasive and wound care procedures to decrease the risk of infection. (See Fighting infection .)

To avoid encouraging antibiotic resistance, healthcare providers rarely prescribe prophylactic antibiotics for patients with burn injuries. Systemic antibiotics are prescribed and administered only for patients with documented wound infection or other positive culture. 19

Nutrition management

The priority nursing diagnosis for nutrition management is nutrition imbalance related to increased metabolic demands from stress and the physiologic demands of wound healing. 2,5 The patient's resting energy expenditure can be double its normal level because of heat loss from the burn wound, pain, infection, and an increase in beta-adrenergic activity. 5 Some patients may need 4,000 to 6,000 kcal per day. The patient's daily estimated caloric needs should be regularly calculated by a dietitian and readjusted as the patient's condition warrants. The goals of care are to provide optimal nutrition, maintain skeletal muscle, prevent weight loss, promote wound healing and graft adherence, prevent sepsis, and achieve an anabolic state and positive nitrogen balance.

Patients with burn injuries have hyperdynamic circulatory, physiologic, catabolic, and immune system responses. Muscle wasting, increased body temperature, increased infection risk, and peripheral insulin resistance are some characteristics of this hypermetabolic state, which begins within 5 days of a major burn injury and can last as long as 3 years. Persistent elevations of stress mediators such as serum cytokines, catecholamines, and basal energy requirements, as well as impaired glucose metabolism and insulin sensitivity, also may persist for up to 3 years after a severe burn injury. 2,5

Nutrition (enteral, parenteral, or a combination) generally is initiated immediately or 24 to 72 hours postinjury. For enteral feedings, a nasointestinal feeding tube is placed under fluoroscopy into the duodenum or jejunum; the tip of the tube should extend past the pyloric sphincter to prevent reflux and aspiration. Enteral feedings are contraindicated if the patient has a Curling ulcer, bowel obstruction, septic ileus, pancreatitis, intra-abdominal hypertension, or a feeding intolerance. 2,5

Parenteral nutrition is only started when the enteral route cannot be used. Specific indications for parenteral nutrition include inadequate enteral intake because of clinical status, weight loss greater than 10% of normal body weight, prolonged wound exposure, or debilitated condition before injury. 4 When the patient can tolerate an oral diet, a high-calorie, high-protein diet with vitamin and mineral supplements should be prescribed.

Monitor the patient for evidence of enteral feeding intolerance such as diarrhea, constipation, emesis, excessive gastric residual, increased abdominal pressure, and/or abdominal distension. Weigh the patient daily, and monitor serum protein, iron, glucose, and albumin levels. Subtherapeutic values indicate inadequate nutritional intake. 11 Among nonnutrition treatments, research findings support the use of propranolol, a beta blocker, to spare muscle tissue and reduce the patient's heart rate, and it is considered standard of care for patients with burns. 20

Abe was given enteral nasogastric tube feedings upon admission to the BICU. On day 2 he was taken to interventional radiology and a nasoduodenal tube was inserted into his duodenum and secured by a nasal bridle clip. Once extubated he was started on an oral high-calorie, high-protein diet with vitamin and mineral supplements along with enteral tube feedings.

Mobility management

Patients with burns may experience impaired physical mobility and an inability to perform self-care related to contractures, splinting, or immobilization after skin grafts. As burn wounds heal, contractures can develop and significantly limit mobility, especially if a joint is involved. 2,5 Patients with burns also may experience permanent physical changes that can affect their psychosocial status (see Understanding body image issues ). Patient-care goals are to avoid permanent joint dysfunction and return patients to their normal routine with no or few adjustments.

Physical therapy should begin at the early stages of treatment, with ambulation and a planned exercise regimen starting as soon as the patient's condition stabilizes. Exercises should help patients to regain their strength and endurance, and balance needed for activities such as standing, getting into a chair, and early ambulation after the wounds are closed. Intervene to prevent contracture development and implement measures to decrease edema such as elevating burned extremities. Nurses can also facilitate mobility by optimizing pain management (see the next section). 2,5,21

Occupational therapists can help prevent deformities and contractures with the use of passive and active range of motion (ROM) exercises, elevation of the limbs, use of wedges and splints to prevent edema, scar management, and assisting the patient to perform activities of daily living (ADL). 21

There is debate as to which treatment(s)—pressure treatment garments, 3D-printed transparent facemasks, and/or use of fractional CO 2 laser treatment for mature burn scars, and so on—are the best therapy to help decrease scarring. More randomized trials need to be conducted to inform evidence-based practice. 22-24

Nursing interventions associated with mobility include performing active and passive ROM exercises on all joints, maintaining limbs in functional alignment, early ambulation, and applying splints as directed while monitoring the splinted area for vascular compromise, nerve compression, and skin breakdown.

Other interventions used to combat the complications of immobility include deep-breathing exercises, use of an incentive spirometer, turning, and proper positioning to prevent atelectasis and pneumonia. 25

Abe experienced difficulty with extremity movement and his ADL. For the first 4 to 6 weeks he could not feed himself because of his hand grafts and the splints placed on his hands and fingers. Once the splints were removed and he had complete ROM in his wrists and hands, he began to participate in his ADL with the help of an occupational therapist.

Pain management

Patients may have acute pain related to burn injury and treatments, and related to the exposed nerve endings in damaged dermis. Assess the patient's need for and response to pain medication, with the ultimate goal of the patient reporting pain relief and satisfaction with the level of pain control. Pain can be: 5

• background: pain that is present while the patient is in a resting state, and is of lower intensity and longer duration than acute pain.
• procedural: an intense, short-lived pain produced by wound care, activities, or therapies.
• breakthrough: pain that breaks through the ongoing treatment for persistent pain.

General nursing interventions associated with each type, phase, or stage include using a reliable pain intensity rating tool, administering analgesics before performing painful procedures, administering I.V. analgesics as prescribed, explaining all procedures and the expected associated level of discomfort beforehand, using nonpharmacologic methods of pain management such as guided imagery, music therapy, and meditation in combination with analgesics and/or anxiolytics, and encouraging patients to verbalize their pain experience.

I.V. analgesia is recommended during the acute postburn period because shock or paralytic ileus can impair gastrointestinal function. 5 Avoid I.M. injections because the medication often is not absorbed adequately in burned or edematous areas, and can pool in the tissues. When fluid mobilization begins, the patient may be inadvertently over- or undermedicated from the interstitial accumulation of previously received I.M. injections. 2,5

A variety of analgesics are used for patients with burn injuries; however, I.V. morphine is the drug of choice. 2 Remember that depending on the severity and extent of the injury, these patients may require much higher doses compared with other patients. 13 In the case of central nervous system depression from a morphine overdose, administer naloxone, an opioid-receptor antagonist. 26

Continuous I.V. infusions of morphine are reserved for patients with severe burns who need mechanical ventilation. Morphine may be delivered via a patient-controlled analgesia (PCA) pump for severe background pain. The PCA pump is ideal for patients who are neurologically intact and can actively participate in their pain management. Mild-to-moderate background pain can be treated with oral oxycodone and acetaminophen in patients who are hemodynamically stable and without an ileus.

Because patients with burns usually receive higher-than-normal morphine dosages, closely monitor their vital signs, level of consciousness, respiratory rate and rhythm, end-tidal carbon dioxide levels, and oxygen saturation. 26 Be alert for signs and symptoms of opioid-induced sedation, respiratory depression, and hypotension, and have emergency equipment readily available. Morphine-induced hypotension may occur in patients who have hypovolemia secondary to burn shock or sepsis.

Abe did not respond well to the standard doses of morphine; it did not provide him with adequate analgesia. His healthcare provider ordered a low-dose ketamine infusion in combination with an I.V. infusion of propofol. Ketamine, a nonbarbiturate general anesthetic agent, can be used to provide adequate levels of analgesia for burn wound care. 27 It can also be successfully used for bedside sedation procedures. The literature shows that a combination of ketamine and propofol can provide better relief than morphine for some patients, and is a worthy treatment choice for pain during burn dressing changes as noted in Abe's care. 28

Cultural considerations

Many cultural considerations came into play throughout Abe's hospitalization. For example, education ends at the eighth grade in the Amish community (age 14 years). Amish children then enter the workforce, which is mostly farming. Thus, when interacting with the Amish patient, nurses should use age-appropriate language and educational material. 29

The Amish devote their entire life to God. As in the case of Abe's family, most Amish avoid modern conveniences such as telephones, electricity, hot water lines, or bathtubs, and their most common mode of transportation is a horse and buggy. These restrictions affected Abe's family as they related to communication with the healthcare team, and the parents' ability to stay with Abe throughout his hospitalization. After much back-and-forth with the hospital social worker and the leaders of Abe's community, it was decided Abe's family could be provided with a hospital track phone and stay in provided hospital housing. This was necessary for them to actively participate in Abe's extended plan of care. 29

The Amish do not have health insurance. They feel that it is a worldly product and purchasing it shows a lack of faith in God. The Amish prefer to use folk medicine (faith healing, herbal treatments, and vitamins). However, each Amish family contributes a predetermined amount of money to a community fund on a regular basis for community needs such as healthcare expenses. The church elders in Abe's community agreed to pay for Abe's hospital costs. Costs were mitigated by a discount offered by hospital representatives after negotiations with Abe's community leaders. 29

These examples only scratch the surface of cultural considerations when caring for an Amish community member. Given the extended hospitalization of a burn injury patient, it is the healthcare team's responsibility to take a holistic approach that ensures a hospital course that meets each individual patient's specific needs.

Throughout Abe's hospitalization, he had a very positive outlook and relied on his Amish upbringing for his spiritual strength. During the 18 weeks of his hospitalization his father, mother, aunts, and community members were either visiting, in the waiting room of the BICU, or in hospital housing nearby.

By the 18th week of his hospitalization, Abe's grafting procedures were complete, and he was discharged from the hospital. The interdisciplinary team, in tandem with the hospital's social worker, developed a rehabilitation plan for Abe to receive physical and occupational therapy at home, as well as twice-weekly visits by a home healthcare nurse.

Abe left the hospital with the ability to walk and perform all of his ADL. Abe was fitted with compression garments and completed all the physical and occupational activities as prescribed.

Fighting infection 2,5,15

• Monitor the burn wound daily for general signs and symptoms of infection. Remove all topical medications and wound exudate so the entire wound can be visualized.
• Culture all body secretions and wounds as indicated.
• Administer antimicrobial therapies as prescribed, based on culture and sensitivity results.
• Monitor blood culture results for possible bacteremia.
• Assure that the patient is up-to-date with tetanus immunization; patients with severe burns are at risk for anaerobic infection caused by Clostridium tetani .
• Monitor white blood cell counts and report leukocytosis, which may indicate infection.
• Monitor vital signs as prescribed, remembering that fever in the absence of other signs and symptoms of infection does not indicate infection. Patients with burn injuries have a hypermetabolic response that automatically increases their core temperature (often to 101.3° F [38.5 °C]).
• Monitor for signs and symptoms of pneumonia. Wean patients from the ventilator as soon as possible.
• Maintain appropriate nutritional support.
• Maintain an aseptic environment at all times, and use standard precautions and sterile technique for procedures when indicated.
• Avoid cross-contamination during wound care. Wear a cap, mask, protective eye wear, gown, and gloves; perform hand hygiene before and after contact; expose, clean, and rewrap uninfected areas first.
• Be aware that cross-contamination can occur from the air, healthcare providers, and visitors. Visitors who are ill should not be permitted to see the patient.
• Avoid autocontamination from the oropharynx, fecal flora, and unburned skin.

Understanding body image issues

Patients with burn injuries can suffer profound losses. These may include an inability to work, loss of personal property, loved ones, and their home. 28 As a result, nurses should continually assess the patient's psychosocial status. Consider asking the following questions:

• What are your concerns or fears?
• Are you afraid of pain or changes in physical appearance?
• Do you feel powerless?
• Are you afraid of being rejected by family and loved ones?
• Do you have concerns or fears concerning sexual function?

An important goal of care is for patients to adapt to their altered body. Assess patient response to changes based on their ability to verbalize feelings related to changes in physical appearance, interest in resources that may improve function and appearance (such as wigs, cosmetics, and prostheses), and readiness to socialize with family and usual social groups. Being aware of patient anxieties and fears will better prepare nurses to provide support and request referrals specific to patient needs.

Amish; burn ICU; critical care; cultural competency; severe burn injuries; thermal burns; trauma; wound care

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Problems in care and avoidability of death after discharge from intensive care: a multi-centre retrospective case record review study

• Sarah Vollam   ORCID: orcid.org/0000-0003-2835-6271 1 , 2 ,
• Owen Gustafson 2 , 3 ,
• J. Duncan Young 1 ,
• Benjamin Attwood 4 ,
• Liza Keating 5 &
• Peter Watkinson 1 , 2  

Critical Care volume  25 , Article number:  10 ( 2021 ) Cite this article

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Over 138,000 patients are discharged to hospital wards from intensive care units (ICUs) in England, Wales and Northern Ireland annually. More than 8000 die before leaving hospital. In hospital-wide populations, 6.7–18% of deaths have some degree of avoidability. For patients discharged from ICU, neither the proportion of avoidable deaths nor the reasons underlying avoidability have been determined. We undertook a retrospective case record review within the REFLECT study, examining how post-ICU ward care might be improved.

A multi-centre retrospective case record review of 300 consecutive post-ICU in-hospital deaths, between January 2015 and March 2018, in 3 English hospitals. Trained multi-professional researchers assessed the degree to which each death was avoidable and determined care problems using the established Structured Judgement Review method.

Agreement between reviewers was good (weighted Kappa 0.77, 95% CI 0.64–0.88). Discharge from an ICU for end-of-life care occurred in 50/300 patients. Of the remaining 250 patients, death was probably avoidable in 20 (8%, 95% CI 5.0–12.1) and had some degree of avoidability in 65 (26%, 95% CI 20.7–31.9). Common problems included out-of-hours discharge from ICU (168/250, 67.2%), suboptimal rehabilitation (167/241, 69.3%), absent nutritional planning (76/185, 41.1%) and incomplete sepsis management (50/150, 33.3%).

Conclusions

The proportion of deaths in hospital with some degree of avoidability is higher in patients discharged from an ICU than reported in hospital-wide populations. Extrapolating our findings suggests around 550 probably avoidable deaths occur annually in hospital following ICU discharge in England, Wales and Northern Ireland. This avoidability occurs in an elderly frail population with complex needs that current strategies struggle to meet. Problems in post-ICU care are rectifiable but multi-disciplinary.

Trial Registration : ISRCTN14658054.

For patients discharged alive from an intensive care unit (ICU), the subsequent in-hospital days are high risk. Post-ICU in-hospital mortality rates are 4–13% worldwide [ 1 , 2 , 3 ] and 6.6% in England and Wales [ 4 ]. Around a third of in-hospital mortality in those treated on an ICU occurs between ICU and hospital discharge.

Risk factors for post-ICU in-hospital mortality identifiable whilst in ICU have been investigated using ICU databases [ 1 , 2 , 3 , 5 , 6 ]. These studies show older, sicker patients are more at risk. However, there is little work identifying either what proportion of these deaths are avoidable or how post-ICU care could be changed to decrease mortality. Recent studies attempting to improve mobility or nutrition post-ICU have not changed outcomes [ 7 , 8 ] emphasising the need to better understand where successful interventions could be directed.

Hogan et al. used retrospective case record review (RCRR) to investigate preventability of deaths in English hospitals [ 9 ]. This work established the RCRR methodology for mortality review, since refined into the Structured Judgement Review method (SJR) [ 10 ]. The SJR approach standardises critical assessment of care delivery, splitting a hospital stay into defined care periods. The SJR has been used internationally [ 11 ] and implemented throughout NHS hospitals in England [ 12 ]. It is advocated as the mortality review method for all UK NHS ICUs [ 13 ]. However, to the best of our knowledge this approach has not previously been used to examine deaths following ICU discharge.

This work is part of the REFLECT project, with the overall aim of developing a multi-component intervention to reduce post-ICU in-hospital mortality [ 14 ]. The primary aim of this study was to quantify the avoidability of deaths in patients on hospital wards following an ICU admission, using RCRR methodology. We also report care areas that could be changed to improve outcomes in this vulnerable patient group.

We report our study according to the STROBE statement [ 15 ]. We obtained ethical approval (Wales REC 4 reference: 17/WA/0139) and Confidentiality Advisory Group support (reference: 17/CAG/0063). We published the protocol [ 14 ] and registered the study (ISRCTN14658054).

We conducted SJRs in three UK hospitals in separate NHS trusts, in adjoining regions: a large tertiary referral centre, a large university-affiliated district general hospital and a small district general hospital. We selected sites representing different clinical settings both within and outside the ICUs (Additional file 1 : Table S1). All sites had nurse-led ICU outreach/follow-up services who visit patients discharged from ICU to the ward.

Sampling strategy

Non-survivors.

We pre-specified a sample size of 300 consecutive patients who had died post-ICU in hospital prior to April 2018 in our published protocol [ 14 ] based on a previous audit. From this we anticipated around 10% of deaths reviewed would be avoidable and that 300 patients would be available from participating hospitals within approximately three preceding years, allowing us to represent recent practice. We excluded patients with missing medical notes or who were transferred away from study hospitals.

We selected cases using electronic hospital records in reverse chronological order from March 2018 until 300 eligible cases were identified across the three sites. We excluded cases where medical notes were unavailable (e.g. missing) or the record was incomplete (e.g. key documents such as observations charts or sections of medical documentation were missing from the record of care). We reviewed ward care following the first discharge from an ICU.

A convenience sample of cases was selected from participants interviewed as part of the REFLECT study. Details of the approach are included in the published protocol [ 14 ]. We reviewed an equal number of survivor cases as ‘probably avoidable’ deaths to offer a comparison of care.

We collected summary data on all patients discharged from each ICU during the study period including age, sex and Clinical Frailty Scale (CFS) prior to hospital admission [ 16 ], type of admission (surgical/medical and elective/emergency), Acute Physiology and Chronic Health Evaluation (APACHE II) score on ICU admission [ 17 ], ICU length of stay (LOS) and post-ICU ward.

Detailed data on deaths following discharge from ICU were collected using the SJR methodology [ 18 ]. The SJR form [ 12 ] categorises care into distinct periods: initial management; ongoing management; care during a procedure; end-of-life care; and overall care. For each period, a short narrative account of care is written, including ‘judgement statements’. A quality of care score is assigned to each period on a scale from 1 (very poor care) to 5 (excellent care). Scores for each care period contribute to a final overall score of quality of care, derived from and supported by the judgement statements. Following review of care, an ‘avoidability of death’ judgement score is assigned, considering any problems in care identified as contributing to the outcome. This is a 6-point scale from 6: definitely not avoidable to 1: definitely avoidable.

We piloted the published SJR Case Report Form [ 12 ] resulting in minor adjustments to fit the post-ICU cohort. We changed the focus of the ‘initial management’ section from ‘first 24 h in hospital’ to ‘first 24 h following ICU discharge’; added more detailed demographic data; and included focused data capture of pre-identified care issue areas obtained from literature review [ 3 , 19 , 20 ] and a previous local audit. These included discharge from an ICU out-of-hours; mobility and rehabilitation; nutrition; and management of atrial fibrillation (AF) or sepsis. We also collected information on the provision of ICU outreach/follow-up care for each patient.

We recorded when patients were discharged for end-of-life care (EOLC) following ICU discharge and whether death occurred from progression of a chronic disease. We collected additional data on the pre-identified care issues. We recorded problems in care where they were judged to result in harm to a patient. The pre-identified care issues were not defined as a ‘problem in care’ unless they were judged to have resulted in harm to the patient. Data sources and rules (where interpretation was required) were defined for each variable (Additional file 1 : Tables S2 and S3).

In line with previous work we defined ‘avoidable deaths’ as those classified ‘probably avoidable’ or greater levels of avoidability (score 1–3). We also calculated a wider ‘relaxed’ definition of preventable deaths (including ‘possibly preventable but not very likely’, score 1–4) [ 9 , 11 ]. We classified all deaths other than those that were ‘definitely not avoidable’ (score 6) as having some degree of avoidability.

Data extraction

We extracted summary data for all discharged patients from electronic records. Sources of data included nursing and medical notes, laboratory results, vital signs documentation, therapy documentation, and drug, food and fluid charts. We defined data sources and rules (where interpretation was required) for each variable collected (Additional file 1 : Table S3). We extracted data onto paper case report forms. These were then transcribed into a pre-piloted spreadsheet (Microsoft Excel version 16, Microsoft Corporation, Redmond, USA).

We accessed anonymised population descriptive data for patients discharged from an ICU in England, Wales and Northern Ireland over the study period (excluding the study sites) from the Intensive Care National Audit and Research Centre (ICNARC—the national audit covering all general ICUs) case mix programme, to assess the comparability of our sample.

Three reviewers (two nurses and a physiotherapist) with clinical experience of both ICU and general wards completed the reviews. All three reviewers attended SJR training, run by the Clinical Governance team in the lead hospital. Reviewers also studied published SJR guidance [ 21 ]. To improve agreement, 10 initial cases were dual reviewed and discussed by two reviewers (SV and OG) to develop extraction approaches. Uncertainties and complex cases were discussed and scores agreed. Where uncertainty remained, cases were discussed with an ICU consultant (PW). To assess inter-rator reliability, 15 undiscussed cases were dual reviewed and scores for each care period, overall quality of care and avoidability judgments compared.

Statistical analyses

The primary outcome measure was the proportion of in-hospital deaths following ICU discharge that were probably avoidable. Secondary outcomes included the proportion of in-hospital deaths following ICU discharge with lesser degrees of avoidability, characteristics of post-ICU non-survivors and survivors, quality of care scores for deaths by avoidability and data on pre-identified care issues and delivery of outreach/follow-up services. Data are presented as mean (95% CIs), median (inter-quartile range) or proportion (%, 95% CI), as appropriate. Confidence intervals of proportions were calculated using the Clopper–Pearson method. Agreement between reviewers was assessed using linear-weighted Cohen’s Kappa with confidence intervals calculated using bootstrapping (10,000 samples). Comparisons of proportion were undertaken using Fisher’s exact test. Analyses were undertaken in R [ 22 ].

Participants

Between January 2015 and March 2018, 352 of 7434 (4.7%) patients consecutively discharged from the study ICUs died during the same hospital admission. We excluded 52 incomplete (16 records) or unavailable records (36 records). Of the 300 eligible cases, 50 patients were discharged for end-of-life care (Additional file 1 : Fig. S1). We reviewed the care of 20 patients who survived to hospital discharge, matching the number of avoidable deaths.

Descriptive data

Baseline characteristics for study patients were similar to national findings (Table  1 ). However, the APACHE II scores appeared higher in the study population, suggesting the overall severity of illness and probability of in-hospital death were greater in the study hospitals.

Patients discharged from ICU for end-of-life care who died before leaving hospital were numerically more likely to be male medical patients and tended to be older, frailer and with higher APACHE II scores than survivors (Table  1 ). By the 9th day following discharge 50% of deaths occurred (Additional file 1 : Fig. S2).

Avoidability of death and quality of care

Overall agreement between reviewers was good (weighted Kappa 0.77, 95% CI 0.64–0.88 for all scores combined) (Additional file 1 : Table S4). During review of the 300 cases, only two were discussed with a third party (PW), where uncertainties could not be resolved between two reviewers. Death had some degree of avoidability (scoring one to five) in 65/250 (26%, 95% CI 20.7–31.9) of cases (Table  2 ). For 20 patients (8%, 95% CI 5.0–12.1) death was probably avoidable (more than a 50:50 chance of avoidability). For the more relaxed definition of avoidability, 44 (17.6%, 95% CI 13.1–22.9) patients qualified. Two case vignettes are presented below, illustrating examples of deaths judged to be probably avoidable and possibly avoidable.

Vignette 1. Probably avoidable (more than 50:50) and poor care.

Vignette 2. Possibly avoidable but not likely with poor care.

We judged 185 deaths to have no avoidability: for 51/185 (27.6%) death was caused by progression of a chronic disease (such as liver failure, chronic respiratory disease or cancer); 14/185 (7.6%) were transitioned to end-of-life care within 24 h of ICU discharge and 5/185 (2.7%) died suddenly within 48 h of ICU discharge without ward-based problems in care. Of the remaining 115 patients: in 64/185 (34.6%) death was considered unavoidable despite having problems in care and 51/185 (27.6%) had no problems in care delivery (Additional file 1 : Table S5). A case vignette is presented below, illustrating an example of a death judged to be probably unavoidable.

Vignette 3: Slight evidence of avoidability and poor care.

Patients received poor or very poor overall care in 46/65 (70.8%, 95% CI 58.2–81.4) cases where death had some degree of avoidability, in comparison with 16/185 (8.65%, 95% CI 5.02–13.7) cases for patients with no problems in care contributing to death ( p  < 0.001). All cases judged to be probably avoidable were judged to have received poor or very poor care. Care was judged poor or very poor overall in 8/20 (40%, 95% CI 19.1–63.9) cases for survivors (Table  3 ).

Problems in care

The occurrence of problems in care by care period is shown (Table  4 ). The frequency of problems in a 24-h period was greatest during the first 24-h following discharge, although problems in care occurred most frequently during the ‘ongoing care’ period, as this period was often long (median between 8 and 14.5 days across the groups).

Pre-identified care issues were common in post-ICU non-survivors (excluding those discharged for end-of-life care) (Table  5 ). ICU discharge occurred out-of-hours (after 4 p.m.) for 168/250 (67.2%) patients. In 155/250 (62%) cases, patients were unable to stand and step from bed to chair. Of 241 discharges where bed to chair mobilisation was appropriate, mobilisation did not occur in 167/241 (69.3%) on every day this was deemed possible. A new episode of confirmed or suspected sepsis was documented in 150/250 (60%), of whom 50/150 (33.3%) received the full ‘Sepsis 6′ care bundle [ 23 ]. A nutrition plan was not documented in 76/185 (41.1%) patients requiring nutritional support. Pre-identified care issues also occurred frequently in survivors after ICU discharge. Follow-up practitioners reviewed 207/250 (82.8%) patients, 66/207 (31.9%) of whom were discharged from the follow-up service on the first post-ICU day.

Worldwide, post-ICU in-hospital mortality rates are high, ranging from 4 to 13% [ 1 , 2 , 3 ]. Most of these patients are discharged with curative intent [ 1 ]. The reasons why these patients die are poorly described. To the best of our knowledge, this is the first study using the SJR method to describe the patient population who die in hospital following ICU discharge.

Around 1/6th of post-ICU in-hospital deaths were discharged to the ward with an end-of-life care plan. In over a quarter of the remaining cases, death had some degree of avoidability. Death was probably avoidable in around 8% of discharges, when those discharged for end-of-life care were excluded (6.7% of all the post-ICU in-hospital deaths) rising to around 18% (or 14.7% of all post-ICU in-hospital deaths) using the more relaxed definition. In 2017–2018, the national case-mix programme reported 8272 deaths in hospital following discharge from adult general critical care units [ 4 ]. Our figures suggest 551 (95% CI 346–827) of these deaths were probably avoidable, rising to 1213 (95% CI 903–1578) cases using the more relaxed definition.

In total, 155/250 deaths were judged to be unavoidable despite the presence of problems in post-ICU ward care. Although not the focus of the study, this finding suggests there may be a problem with ICU triage. For some patients for whom survival was highly unlikely, an ICU admission may have prolonged suffering. Nearly half the (small number of) survivors studied were judged to have received poor care, suggesting substantial problems exist with providing good post-ICU care, regardless of the patient outcome.

Problems in care occurred disproportionately in the first 24 h following discharge from an ICU, suggesting focusing on improving safety in this period is important. Effective handover of care requirements between ICU and the ward requires identification of a clear plan for how these requirements will be met [ 24 , 25 ]. The RCRR classifications of poor or very poor care occurred commonly in avoidable deaths, reflecting the complexity of care required. Importantly, all three organisations studied had average or above performance in the ICNARC Case Mix Programme during the period under study. Our findings therefore do not represent poor-performing institutions and so are likely to be generalisable.

Comparison with previous work

Unlike previous work in entire hospital populations, we found no cases where death was definitely or strongly likely to have been avoidable. Conversely, 18% of deaths qualified for the more relaxed definition of avoidable, in comparison with 8.5% in general hospital populations [ 9 ]. Similarly, 26% of cases had some degree of avoidability, more than the 6.7% reported in general hospital populations [ 11 ]. Hogan et al. [ 9 ] classified 5.2% (95% CI 3.8–6.6) of deaths in the general hospital population they studied as avoidable, similar to Rogne et al. at 4.2% [ 11 ]. Although the numerical proportion in our post-ICU cohort was higher at 8% (95% CI 5.0–12.1), with a higher lower confidence limit, it remains possible that overall rates are similar.

It is possible the differences we found are explained by the population in our study. Inherent in having been to intensive care may be the understanding that there has been a risk of not surviving, making classifying subsequent death as entirely avoidable difficult. However, the complex care required by this post-ICU population may mean there are more aspects of care to be missed. We cannot exclude the possibility that the differences result from other differences between the studies.

Our study investigated the post-ICU care period. As problems in care may occur prior to ICU discharge, our findings may underestimate the overall in-hospital avoidability of death in this patient group. Further work is also required to investigate whether problems in care whilst in ICU contribute to adverse outcomes after ICU discharge.

Less than adequate care occurred rarely in patients where death was judged not avoidable, in common with previous work [ 9 ]. In contrast, less than adequate care occurred in over 70% of those with a problem contributing to mortality—double the rate seen in Hogan et al.’s previous study [ 9 ]. Whilst again this may suggest differences in the study rather than the population, it seems possible that our findings may reflect the difficulties presented to general wards in caring for the complex post-ICU population. In this cohort, non-survivors were considerably frailer at ICU admission than survivors (Table  1 ). Frail patients are known to be at higher risk of adverse events in hospital [ 26 ].

Out-of-hours discharge is highly associated with in-hospital post-ICU mortality and readmission [ 1 , 2 , 19 ]. In part this has been suggested to result from a higher proportion of patients with an end-of-life care plan in place being discharged at night [ 1 ]. However, we found discharge out-of-hours to be very common in patients who were not discharged for end-of-life care.

In this study, physical dependence at ICU discharge was high. Our findings are in line with a previous small study of patients who had spent 48 h or more on an ICU [ 27 ]. Perhaps because of the severity of dependency, delivering daily rehabilitation for this cohort occurred rarely on the ward, despite being essential to maximise physical recovery from critical illness [ 28 , 29 ].

Both ongoing nutritional support needs and new episodes of sepsis were common post-ICU, with problems with ongoing management frequently identified. Previous studies have also demonstrated poor delivery of nutrition in post-ICU patients [ 30 , 31 ] which has been linked to poor physical rehabilitation in the medium and long term [ 32 , 33 ]. Sepsis is known to impair nutritional status and therefore may impact ongoing rehabilitation [ 34 , 35 ]. In addition, new onset AF, also identified in this study as poorly managed, is a common complication of critical illness [ 36 ] where onset is known to be associated with sepsis and may be triggered by systemic inflammation [ 37 ].

Previous studies have suggested follow-up visits from specialist ICU outreach nurses may improve post-ICU survival and reduce adverse events [ 38 , 39 , 40 ]. However, in this study patients were frequently discharged from this service in the first 1–2 days following ICU discharge. There was no difference in the proportion of patients experiencing early discharge between possibly avoidable and unavoidable deaths, suggesting future opportunities to focus this service on those patients who would benefit the most from such visits.

Patients frequently had more than one problem in care [for example, over half the patients studied had severe mobilisation difficulties and over half developed sepsis, demonstrating that problems frequently overlapped (Table  5 )]. Future interventions will need to address multiple needs to impact outcomes for these vulnerable patients.

Strengths and limitations

Our study has several strengths. Data collection was undertaken by a small multi-disciplinary team. This provided a wider insight into care delivery than in other studies where reviewing teams consisted solely of medical staff. Reviewers also worked collaboratively, were able to communicate freely and discuss uncertainties in cases. We piloted our data collection forms and defined each of the variables collected in standard operating procedures. As a result, in undiscussed cases, our inter-rater reliability was at least as good as previous studies [ 9 , 41 , 42 ]. Our multi-centre design, with population descriptors mainly comparable to national data, suggests our findings should be generalisable, at least within the UK. Additionally, undertaking the same process on a small number of survivors helps place our findings in context.

However, several weaknesses should be acknowledged. RCRR relies on documentation from a variety of sources, which risks missing information due to omissions or inconsistencies in documentation. During the review process this was acknowledged. Care was taken to ensure all potential sources of documentation were carefully reviewed to assess actions in care delivery. In addition, 52/352 cases were excluded due to unavailable or incomplete records. This was likely inevitable due to the reliance on paper documents but may have introduced a degree of selection bias. It is also possible that documents in the included cases may have been missing but not detected where they did not form a clear part of the chronological record. As with all retrospective case record reviews, a problem of hindsight bias must be acknowledged [ 21 , 43 ]. Knowledge of outcome severity has been shown to affect assessment of the quality of (anaesthetic) care [ 43 ]. However, it is not realistic to blind the reviewer from the (likely) outcome without removing key information for the analysis, and this has not been attempted in major studies in the field [ 9 , 11 ].

Our sample size was larger than in similar studies of specific patient cohorts [ 44 , 45 , 46 ] but smaller than in previous work focused on general hospital populations, where a smaller proportion of deaths were anticipated to be modifiable [ 9 , 11 ]. As a result, our estimates of the rates of avoidable deaths have relatively wide confidence intervals. However, we chose instead to record greater detail on specific pre-identified care issues to inform both clinicians and future work on how such deaths could be prevented. Our sample of 20 hospital survivors is small, as this was not a key focus of the overall REFLECT study. Importantly, it shows that problems in care are common post-ICU, regardless of outcome, but further work is needed to allow comparisons with other groups to be made.

Specific pre-identified care issues were chosen following literature review and findings from a previous audit. There may have been other problematic aspects of care, for which we did not collect quantitative data. We focused  our investigation on patients who did not survive, so cannot determine whether similar problems in care occur in those who survive to hospital discharge. As part of the overall REFLECT project, we will undertake in-depth analysis of the care received in those deaths judged to be avoidable in comparison with an equal number of patients who survived to address this issue.

There is significant avoidability associated with death on the ward following ICU discharge. This avoidability occurs in an elderly frail population with complex needs that current strategies struggle to meet. Our work highlights opportunities to address common problems in care delivery which could improve both patient outcome and quality of care. Problems in care occurred disproportionately in the first 24 h following discharge from an ICU, suggesting interventions to improve safety should concentrate on this period. Recognition and management of sepsis, mobilisation and provision of nutrition were frequently sub-optimal and could be improved. Targeted CCOT input may assist in delivering these improvements but would require regular ward review beyond the first discharge day.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Abbreviations

Atrial fibrillation

Critical care outreach team

Clinical Frailty Score

End-of-life care

Intensive Care National Audit and Research Centre

Intensive care unit

Retrospective case record review

Structured Judgement Review

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Acknowledgements

The authors wish to gratefully acknowledge Melanie Gager and Sophie Mason for their support with data collection. We also thank Oliver Redfern and Stephen Gerry for statistical advice and Robert Hatch for help with statistical analysis. In addition, we are grateful to Prof Charles Vincent for advice on an early draft of this manuscript.

This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0215-36149). This research was also supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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Owen Gustafson

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SV, PW and JDY conceived the project. SV and OG collected the data. SV wrote the first draft of the manuscript. All authors contributed to and revised the final manuscript. All authors read and approved the final manuscript.

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Ethical approval was granted by Wales REC 4 (reference: 17/WA/0139). Surviving patients consented to their involvement in the study. Details of the approach are included in the published protocol [ 14 ]. Confidentiality Advisory Group support was sought to access the records of deceased patients (reference: 17/CAG/0063).

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Peter Watkinson co-developed the System for Electronic Notification and Documentation (SEND), for which Sensyne Health has purchased a sole licence. The company has a research agreement with the University of Oxford and royalty agreements with Oxford University Hospitals NHS Trust and the University of Oxford. Sensyne Health may in the future pay Peter Watkinson personal fees. Peter Watkinson was Chief Medical Officer for Sensyne Health.

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Vollam, S., Gustafson, O., Young, J.D. et al. Problems in care and avoidability of death after discharge from intensive care: a multi-centre retrospective case record review study. Crit Care 25 , 10 (2021). https://doi.org/10.1186/s13054-020-03420-5

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Care of the critically ill patient

The care of critically ill patient within the intensive care unit requires a multidisciplinary approach. An understanding of the main principles of intensive care medicine is essential for surgeons, both for participating in the management of their own critically ill patients and also because surgical complications of critical care are well recognized. This article describes the main principles of intensive care medicine within the context of the COVID-19 pandemic, giving an overview of a systematic approach to assessment and treatment of organ dysfunction, and highlights some of the complex ethical and organizational challenges.

Principles of critical care

Critical care is the process of looking after patients who either suffer from life-threatening conditions or are at risk of developing them. The intensive care unit (ICU) is a distinct geographical entity in which high staffing ratios, advanced monitoring and organ support can be offered to improve patient morbidity and mortality. However, effective intensive care demands an integrated approach that stretches beyond the boundaries of the ICU. It requires prevention, early warning and response systems, a multidisciplinary approach before and during an ICU stay, as well as comprehensive follow-up or good quality palliative care.

The cornerstones of intensive care management are the optimization of a patient's physiology, the provision of advanced organ support, and the identification and treatment of underlying pathological processes. This is best achieved through a multidisciplinary team approach, with shared responsibility between the admitting ‘parent’ team and a specialized critical care team coordinated by a critical care physician.

The surgeon on ICU

The role of the surgeon within the critical care team is crucial for advice on individual aspects of the patient care such as specific management of the surgical condition, wound care, nutrition and management of anticoagulation in the immediate postoperative period. Moreover, strategic decisions on the overall care of surgical patients, and a duty to communicate these to patients and relatives, rest jointly on both the surgeon and critical care physician. Difficult decisions regarding the need for treatment limitations and the recognition of failing treatments and burdensome treatments should be explored between both teams, the patient and family.

Organization of critical care services

Prevention and ‘critical care without walls’.

Early recognition of acutely ill patients in hospitals is a challenging task but can potentially improve outcomes. The use of early warning scores and ‘track and trigger' systems has now been widely implemented in many countries. Rapid optimization of care on the ward and early senior involvement are essential to minimize any deterioration and reduce the need for subsequent critical care admission. Medical emergency and critical care outreach teams may play an important role in facilitating early aggressive ward care as well as helping with education and development of skilled ward staff.

Referral and admission to the ICU

The decision to admit an acutely deteriorating patient to the ICU is complex and warrants senior involvement, both from the parent specialty and a critical care physician. The primary question is whether an ICU admission and escalation of care is in the patient's best interest. While considerable effort has been spent to predict outcomes with scoring systems – based on disease process, physiological parameters prior to admission, age and comorbidities – these do not necessarily apply to individual patients and may not be relevant in the acute setting. An increasingly referenced concept is that of patient frailty, as this may be an important determinant of outcome in ICU. The assessment of frailty may add important information to the decision making process in the perioperative period.

Frailty can be quantified quickly using tools such as the Clinical Frailty Scale (CFS), which gives a numerical score between 1 and 9 equating to the patient's pre-morbid activity and dependence levels. A higher score has been associated with increased mortality in surgical patients. 1 It should be noted that the CFS is not validated in patients under the age of 65 and so should be used with caution in this age group. The CFS is not designed for use in those with stable long term disability or those with a learning disability.

For each emergency referral the following issues need to be considered:

• • Is there a reversible pathological process?
• • Does the patient have the physiological reserve to withstand the insults of their illness and the necessary treatment?
• • Is there a reasonable chance of recovery with the prospect of return to an acceptable quality of life, as viewed by the patient?
• • Has the patient expressed any wishes regarding their care? Do they have an advanced directive?

For any admission, a balance must be reached between the available technical ICU interventions and the potential to cause considerable distress to the patient, with both physical and psychological impact during and beyond their ICU stay. The inherent ethical conflicts of beneficence (chance of good outcome), non-maleficence (ICU often involves distressing/painful interventions), autonomy (patients often do not have the capacity to express their wishes) and justice (responsibility with resource allocation) need to be carefully considered. These factors are complex and need individual, careful, and experienced consideration for each patient.

Broadly speaking, two types of critical care admissions are recognized:

• • Planned admissions: patients requiring optimization and monitoring of their physiological condition before or usually after an intervention, e.g. the postoperative care of the high-risk major general surgical patient to monitor for complications of the surgical procedure, anaesthetic or exacerbation of known comorbidities.
• • Emergency admissions: patients with potential or established organ failure needing monitoring and support of one or more vital organ functions, e.g. a patient with septic shock secondary to four quadrant peritonitis requiring invasive ventilation and haemodynamic support post operatively.

Overall, surgical patients requiring critical care appear to have lower acute hospital mortality than medical patients. Recent UK data estimated this at 2.4% for planned and 13.6% for emergency surgery, with 27% for non-surgical patients. 2

Levels of care

Modern critical care medicine offers a large variety of advanced monitoring and organ support capabilities ( Table 1 ). These depend on the design and scope of individual units. Below, two levels of critical care are described:

Overview of some critical care organ support and monitoring options

High-dependency unit (HDU) or ‘level 2’: Admission for single-organ support (not including invasive ventilation) and should not require a dedicated critical care nurse for each patient. Provides an environment for close monitoring of patients with or at risk of developing organ failure:

• • respiratory: non-invasive ventilation, arterial blood gases
• • cardiovascular: low dose vasopressors, invasive arterial pressure monitoring
• • renal: close fluid balance control, certain renal replacement therapies.

Intensive care unit (ICU) or ‘level 3’: Admission for multi-organ support or delivery of advanced monitoring techniques requiring at least one dedicated critical care nurse for each patient:

• • respiratory: invasive and non-invasive ventilation, extra-corporeal membrane oxygenation (ECMO) or carbon dioxide removal (ECCO 2 R) in selected centres
• • cardiovascular: vasopressor and inotropic support, advanced cardiac output monitoring, intra-aortic balloon pump, ventricular assist devices, ECMO
• • renal: renal replacement therapies
• • neurological: intracranial pressure monitoring, EEG, advanced neurological monitoring.

Post critical care

Discharge from ICU does not terminate the involvement of the critical care team and many units are developing processes to ensure high-quality in-patient follow-up with some hospitals having established RaCI (Recovery after critical illness) clinics. These may help to understand, alleviate and prevent the detrimental long-term effects of critical illness. With more patients surviving to hospital discharge it is only recently that the long-term burden and reduction in quality of life post-critical illness is being understood. 3

Sepsis is a major cause of morbidity and mortality around the world, and affects a large proportion of ICU patients either at the point of admission or as a complication during their ICU stay. Sepsis is defined as ‘life-threatening organ dysfunction caused by a dysregulated host response to infection ( Table 2 ). 3 Septic shock is sepsis complicated by hypotension despite volume resuscitation and raised serum lactate >2 mmol/L. It is worth noting that sepsis is no longer defined in terms of the systemic inflammatory response syndrome (SIRS) as this may in fact represent an appropriate response to inflammation, infection or a combination of the two. 4

Common definitions in relation to Sepsis-3 3

Over the past decade there has been a significant improvement in survival from sepsis in the developed world. This has been attributed to the fact that the basic principles of sepsis have become widely accepted, in part by global initiatives such as the Surviving Sepsis Campaign. 5

The main principles of progressive sepsis care are:

• • early recognition of sepsis
• • appropriate balanced resuscitation
• • rapid identification of the source of infection
• • timely source control
• • early and effective antimicrobial therapy
• • haemodynamic support, consideration of adjunctive therapies and high-quality supportive care.

Critical care organ support

Comprehensive care for critically ill patients usually requires a systems-based approach and integration of complex information. To provide a consistently high standard of care, some interventions have been grouped into ‘care bundles’, which have been shown to improve outcome when implemented together.

Airway and respiratory support

A significant proportion of critically ill patients will need some form of advanced respiratory support during their admission. The decision to commence mechanical ventilation must not be taken lightly as it may be associated with significant patient morbidity. On the other hand, it should not be delayed unnecessarily until the patient is in extremis. However, technical interventions do not replace good quality basic respiratory therapy, which often features input from a variety of specialties, most crucially the physiotherapist.

High flow oxygen therapy: is now widely used perioperatively, for single system ward-based support in medical and surgical patients, and in the ICU. An air–oxygen blender is used to deliver very high flows of warmed humidified oxygen at a set oxygen fraction to patients via a nasal or facial interface. The high flows of up to 60 litres/min are thought to reduce work of breathing and improve respiratory mechanics by providing a small amount of positive end expiratory pressure (PEEP) and washing out dead space gases. This combination with humidification acts to prevent drying of the mucous membranes, aids tolerability and promotes secretion clearance. High flow nasal cannula (HFNC) has been shown to be beneficial in the management of patients with severe acute hypoxic respiratory failure in comparison to non-invasive ventilation or face mask oxygen. 6

Non-invasive ventilation (NIV): is a form of respiratory support that obviates the need for endotracheal intubation. It is most commonly delivered by application of positive airway pressure via a facial interface utilizing either continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP).

CPAP refers to maintaining a constant positive pressure throughout the respiratory cycle. This is similar to PEEP in invasively ventilated patients. The benefits include a reduction in the work of breathing, reversal of hypoxia through alveolar recruitment and correction of pulmonary shunt as well as a reduction in cardiac afterload (via reduced left ventricular transmural pressure). CPAP is delivered either via a tight-fitting facemask or via a dedicated CPAP hood or helmet. Great care must be taken to avoid pressure damage, particularly to the nasal bridge.

Bi-level positive airway pressure (BiPAP) allows separate settings for positive airway pressure during the inspiratory (IPAP) and expiratory (EPAP) phase of the respiratory cycle. It maintains the benefits of CPAP but has the added benefits of augmenting the patient's tidal volume and overcoming respiratory muscle insufficiency. NIV BiPAP is most commonly provided through tight-fitting facemasks.

Successful delivery of NIV depends on many factors including patient co-operation and the absence of contraindications such as: an unprotected airway; the inability to clear secretions; marked haemodynamic instability; or the presence of an untreated pneumothorax.

NIV is well established in the treatment of respiratory failure secondary to cardiogenic pulmonary oedema and COPD. However, it is now also being used successfully in asthma, pneumonia (particularly in the immuno-compromised patient), other forms of acute lung injury, in postoperative respiratory failure and as a tool to assist weaning from mechanical ventilation.

Surgical opinion may be requested when commencing NIV in patients who have had recent upper GI or head and neck surgery, or those who have pathology in these areas due to the risk of surgical emphysema associated with delivery of positive pressure. In these cases balancing the risks of respiratory or surgical complications must be carefully considered.

Invasive ventilation: mandates tracheal intubation in one form or another. Securing the airway in critically ill patients poses significant additional challenges compared with the controlled environment of an elective theatre list. This may be due to profound physiological derangement (often paired with a rapid decline), the presence of anatomical difficulties (e.g. airway burns), external factors (e.g. cervical in-line stabilization in trauma), significant time pressures, suboptimal positioning, unfamiliar environments, and limited availability of equipment and help. Thus, thorough preparation and excellent communication of airway plans are paramount for patient safety. Some indications for tracheal intubation are outlined in Table 3 .

Indications for tracheal intubation

The mechanical ventilators used in most UK intensive care units are increasingly sophisticated and allow a wide variety of different modes that can be selected based on the patients underlying physiology and acute pathology. The more advanced machines can monitor the patient's respiratory mechanics and automatically adjust to optimize ventilation.

Broadly speaking, when intubated, a patient may be fully ventilated by the machine, may trigger breaths spontaneously, or a combination of the two. The process of reducing the support given by the ventilator to allow the patient to be safely extubated is known as weaning. When reviewing a patient who is intubated it is worth noting the amount of oxygen they require (the FiO 2 ), whether the patient is breathing spontaneously, and basic setting such as the level of PEEP they require.

Advanced techniques of respiratory support include prone ventilation (may confer mortality benefit in severe acute respiratory distress syndrome (ARDS)), extra-corporeal carbon dioxide removal (ECCO 2 R) and ECMO.

Mechanical ventilation can itself induce lung injury, presumably through barotrauma and volutrauma, but also through repeat inflation and deflation of collapsed lung areas (atelectotrauma) and through triggering the release of inflammatory mediators (biotrauma). A lung-protective ventilation strategy has been extrapolated from ventilatory management in ARDS 7 and has now been widely adopted in clinical practice. It includes the following ventilator goals:

• • Aim for tidal volumes of 6–8 ml/kg (of ideal body weight).
• • Limit plateau pressures to ≤30 cmH 2 O.
• • Apply PEEP ≥5 cmH 2 O to avoid alveolar collapse.

Complications of mechanical ventilation can be divided into those related to tracheal intubation such as damaged lips and teeth, and vocal cord injury; those resulting from equipment problems, for example ventilator malfunction or contamination; those from mechanical ventilation itself such as cardiovascular instability, ventilator-associated lung injury or pneumonia, and oxygen toxicity; and complications stemming from prolonged immobilization and sedative use in the critically ill, for example pressure sores, peripheral and respiratory muscle weakness, deep vein thrombosis, delirium, gastrointestinal tract erosions with bleeding, and so on. To reduce the likelihood and severity of these complications a ‘ventilator care bundle’ has been established featuring the following components:

• • Elevation of the head of the bed to between 30° and 45°.
• • Daily sedative interruption or reduction and assessment for readiness to extubate.
• • Peptic ulcer disease prophylaxis.
• • Thromboembolic disease prophylaxis.

Respiratory support is usually guided by clinical and laboratory findings, supplemented by chest radiographs and computer tomography. Lung ultrasound is now widely used as a non-invasive bedside diagnostic tool for the assessment of pleural effusions, pneumothoraces and lung pathology (consolidation, pulmonary oedema etc.), without using radiation or transferring the patient from the safety of the ICU.

Cardiovascular support

Haemodynamic management of critically ill patients aims to optimize tissue perfusion and oxygen delivery to the various organ systems. The cornerstones of this approach are appropriate fluid management and use of vasoactive drugs based on frequent assessment of cardiovascular changes.

Haemodynamic monitoring: Haemodynamic derangements in critical illness are complex and their assessment is notoriously difficult. Clinicians must consider pathophysiological insults to both macrocirculation and microcirculation, and to integrate complex information from various sources. These include history, physical examination, clinical observations and various monitoring modalities. The latter often assess either pressures (such as arterial or central venous pressure monitors) or blood flow (such as cardiac output monitors). Invasive cardiac output monitoring devices such as the pulmonary artery flotation catheters have drifted out of favour (outside specialized cardiac ICUs) due to their associated significant risks in the absence of improved clinical outcomes. However, several less invasive techniques, such as arterial pulse contour analysis (i.e. LiDCO™) or oesophageal Doppler devices have been developed. As most values are derived rather than measured, they are best used in a dynamic fashion, for example to assess response to a fluid challenge. Specialized investigations such as echocardiography are finding an increasing role in the haemodynamic assessment at the bedside and many intensive care physicians are now trained to perform focussed echocardiography exams.

Fluid management: the goal of fluid management is restoration of an adequate circulating volume to support tissue perfusion. However, endothelial damage and capillary leakage can lead to significant tissue oedema, which can in turn adversely affect diffusion of oxygen and nutrients. The presence of a cumulative positive fluid balance during a patients admission to ICU has been associated with worse clinical outcomes. 8 Fluid management is therefore a delicate balance of potentially conflicting requirements and the importance of monitoring fluid balance cannot be overstated.

There is ongoing controversy over the optimal type of intravenous fluid, crystalloid or colloid, used for resuscitation and maintenance during critical illness. Balanced crystalloid solutions are most commonly used in sepsis, blood products in severe trauma and, should a colloid be chosen, albumin is an accepted safe alternative in sepsis and liver disease. 9 Starch solutions are avoided due to potential nephrotoxic side effects and possible increased mortality, 10 and gelatins lack evidence of benefit or harm.

Blood transfusion in all patients, including the general critical care population, is not recommended until the haemoglobin is less than 70 g/L and then optimally should be administered in single unit aliquots. 11 A higher threshold may however be considered in the presence or anticipation of bleeding, or in patients with previous myocardial infarction or unstable angina.

Vasoactive drugs and principles of use: Vasopressor and inotropic agents are short-term to medium-acting drugs that are used to enhance vascular tone or cardiac output in a variety of critical illness conditions. They are used as a temporary measure until sufficient cardiovascular function returns on resolution of the pathological process.

Vasopressors trigger smooth muscle contraction in peripheral blood vessels, leading to increased systemic vascular resistance as well as vasoconstriction in venous capacitance vessels. The observed net effect is often an increase in blood pressure. Frequently used vasopressors include norepinephrine, epinephrine, metaraminol, phenylephrine, dopamine (via α-adrenoceptor effect) and vasopressin (via vasopressin V 1 receptors).

Inotropes increase the contractility of the myocardium, thereby leading to a rise in cardiac output. Examples of commonly used inotropes are epinephrine, dobutamine, dopamine (via β-adrenoceptor effects) and milrinone (a phosphodiasterase inhibitor). Levosimendan is a newer type of inotrope which works by increasing myocardial sensitivity to calcium.

Septic patients often require escalating haemodynamic support. Aggressive fluid resuscitation is followed by increasing doses of vasopressors (e.g. norepinephrine followed by the addition of vasopressin). Hydrocortisone may be added to reduce the dose and duration of vasopressor support. If sepsis-induced myocardial dysfunction is suspected, temporary inotropic support (e.g. with dobutamine or epinephrine) may be required.

Central nervous system

Admission to ICU may be triggered by an altered sensorium, most commonly a reduced level of consciousness and often reported using the Glasgow Coma Scale (GCS). ICU care is required as the patient may be at risk of airway compromise and need higher nursing input.

Neuroprotective management is essential for patients with intracranial or spinal pathology (e.g. traumatic brain injury, ischaemic strokes, intracranial bleeds, spinal cord ischaemia). It requires a multisystem approach with critical importance of meticulous ventilatory and haemodynamic support. Advanced imaging and monitoring techniques such as intracranial pressure or neurological function monitoring are now available to inform treatment decisions. In addition, extracranial disease processes pose a risk of causing secondary brain injury, which may be preventable. An example is targeted temperature management and prevention of hyperthermia, potentially leading to improved neurological outcome in patients surviving out of hospital cardiac arrest. 12

Renal support

Acute kidney injury (AKI) is a major complication of critical illness occurring in up to 67% in the general ICU population and represents a significant therapeutic challenge for the intensive care team as the mortality of critically ill patients with AKI remains high (40–50%). The KDIGO definition of AKI classifies severity based on serum creatinine and urine output to give a stage between 1 and 3.

Pre-renal causes (hypotension, sepsis, low cardiac output) are commonly the initial precipitant of AKI in critical illness. However, renal dysfunction often becomes multifactorial during the ICU stay, for example through parenchymal damage from nephrotoxic drugs. Post-renal causes are rare in the critically ill but need to be excluded.

Treatment of AKI relies on timely diagnosis, adequate fluid management, haemodynamic support and elimination of the underlying and contributing causes. When AKI is severe, renal replacement therapy (RRT) may be necessary to maintain homeostasis of fluid, electrolytes and metabolic waste products. Indications for RRT in critical illness include:

• • oliguria/anuria
• • urea >35 mmol/L or uraemic complications (pericarditis, encephalopathy)
• • creatinine >400 μmol/L
• • K + > 6.5 mmol/L or rapidly rising
• • pulmonary oedema
• • uncompensated metabolic acidosis (pH < 7.1)
• • severe hyperthermia (>40°C)
• • overdose with dialysable toxins

RRT relies on removal of unwanted solutes and water through a semi-permeable membrane. The techniques of intermittent haemodialysis (IHD; relying on diffusion) and continuous veno–veno haemofiltration (CVVH; based on convection; can be combined with dialysis) are widespread. CVVH modes are preferred in the UK for cardiovascular stability but there is lack of strong evidence comparing different modalities. The optimal dose of CVVH is controversial and currently 25–30 mL/kg/h are recommended unless dictated by specialized circumstances. Both IHD and CVVH require insertion of a large-bore double lumen venous catheter into a large central vein and some form of anticoagulation is required. The anticoagulant of choice is changing from a heparin-based to a citrate-based regime to further improve circuit lifespan and reduce bleeding risk.

Gastrointestinal support and nutrition

Many patients are malnourished on admission to the ICU. This has a profound impact on their ability to withstand the physiological stresses of critical illness. Moreover, critical illness can directly affect gut function and contribute to an impaired nutritional balance. Malnutrition may lead to an increased risk of infection, poor wound healing and loss of muscle bulk. A thorough nutritional assessment on admission to identify high-risk patients and timely institution of nutritional support are therefore crucial to improve patient outcome. The surgeon has a key role in decision making regarding the initiation of feeding in the post-surgical patient. The decision of whether to start early enteral feeding, to delay feeding or to start parenteral nutrition is not straightforward.

The preferred route of nutritional support has been an area of great controversy. Enteral feeding often involves nasogastric or nasojejunal feeding tubes, frequently facilitated using prokinetics (metoclopramide and erythromycin). Parenteral nutrition is usually administered through a central vein and provides an alternative route in persistent gut failure. Both modalities are associated with a significant number of complications. At present, early enteral nutrition is the favoured approach as early parenteral nutrition does not confer clear patient benefits and has additional risks. 13 The role of nutritional supplements and immunonutrients such as glutamine and arginine remains controversial. Glycaemic control is now a cornerstone of good critical care practice. However, blood sugar targets have been relaxed (aim ≤10 mmol/L) due to the significant risk of hypoglycaemia with the previously advocated intensive insulin therapy. 14

Neuromuscular considerations

A significant proportion of critically ill patients suffer from profound muscle weakness. In addition to distinct disease entities that may precipitate critical care admission (i.e. Guillain-Barré syndrome, myasthenia gravis), many patients acquire neuropathies, myopathies or a combination of both. These are often collectively described as intensive care unit-acquired weakness (ICUAW). Several factors play a contributing role, including muscle disuse atrophy, sepsis, multiple organ dysfunction syndrome, exposure to certain drugs (i.e. corticosteroids, neuromuscular blocking agents) and malnutrition. This is a common finding in patients who have survived a significant complication of surgery such as an anastomotic leak, these patient have often required multiple trips to theatre and received significant organ support. ICUAW may lead to significant delays in weaning from mechanical ventilation and discharge from ICU. Furthermore, patients are prone to developing muscle contractures. The role of early mobilization and regular and intensive physiotherapy is crucial in ameliorating the consequences of critical illness weakness.

Sleep and delirium

Critical illness is often associated with profound disturbance in the patient's natural sleep–wake cycle. The ideal situation of daytime wakefulness and night time rest is difficult to achieve on the ICU. Contributing factors are the underlying disease process, medication side effects, frequent interventions, pain, mechanical organ support, and high noise and lighting levels. Efforts to minimize the detrimental effects of sleep disturbance therefore focus on minimizing the above risk factors and promoting sleep hygiene by re-establishing a normal circadian rhythm. Furthermore, pharmacological efforts including sedation breaks, analgesia-based sedation regimes and melatonin are being used in some units. Awareness of psychological aspects of critical illness and recovery can improve the patient and relative experience, and the return to function after discharge.

Delirium is an acute and fluctuating confusional state, with features of inattention and disorganized thinking. It affects up to 69% of ventilated patients, is frequently under-recognized (especially hypoactive delirium), and is an independent predictor of mortality. Consequently, daily delirium-screening assessments such as the CAM-ICU are now advocated.

Risk factors for postoperative delirium include age, existing cognitive impairment, depression, sensory impairment, medical co-morbidity and psychotropic drug use. Precipitating factors for postoperative delirium include surgery, critical care admission, polypharmacy (including sedatives, benzodiazepines and opiates), infection, hypoxia, dehydration, poor nutritional status, metabolic derangement, pain, constipation and sleep deprivation. 15 The development of delirium in the post-surgical patient requires careful assessment as this may be the first sign of a complication of surgery such as an anastomotic leak or the development of a postoperative pneumonia. A high index of suspicion is required in patients with a hypoactive delirium as the presentation is more subtle than the hyperactive delirium patient with agitation. Management depends on the type (hyperactive, hypoactive or mixed) and comprises treatment of the underlying cause, avoidance of precipitants, reassurance for the patient as well as judicious and targeted pharmacological intervention to ensure the patient and staff remain safe.

Further critical care considerations

Critical care is a multidisciplinary endeavour. In addition to the resident critical care staff, there is invaluable input from many specialties including physiotherapy, pharmacy, nutrition, microbiology, radiology, psychology, and speech and language teams.

Infection control

Critically ill patients are at increased risk of acquiring infections with multi-resistant organisms. The prevalence of these ‘super bugs’ is often specific to the country, hospital or individual critical care unit. Antimicrobial stewardship is a major part of day-to-day management of the critically ill patient. In surgical patients it is important to ensure that appropriate prophylaxis is given intraoperatively but also that postoperative antibiotics are only prescribed in accordance with the principles of good antibiotic stewardship based on the best available evidence.

Effective infection control needs to focus on prevention, screening and avoidance of cross-contamination. As a visiting team to the intensive care unit, it is important to follow the local protocols such as appropriate personal protective equipment (PPE) when examining patients. Most measures are similar to other hospital wards but specific measures on critical care units include:

• • selective gut decontamination in ventilated patients
• • isolation of contagious patients
• • frequent microbiology input to rationalize antibiotic use
• • meticulous attention to asepsis on insertion and handling of invasive lines.

The Matching Michigan initiative aims to reduce central venous line infection rates and is founded on strong evidence that strict asepsis can lead to a significant reduction in mortality. 16

End-of-life care

Inevitably, a proportion of patients will die on the ICU from their underlying illness. Recent UK figures suggest a critical care unit mortality of around 13% in general ICUs but this will vary depending on case mix. 2 Prognostication is imperfect; therefore, the intended benefits of continued treatment need to be balanced against the potential burden for the patient. Once it becomes apparent that escalation or continuation of treatment is not in the patient's best interest, decisions on limitation or withholding of life-sustaining therapy are required. Often, patients are not able to directly express their wishes. Therefore, this decision rests on the critical care and parent specialty team. Respectful discussions with the patient, when possible, and family are essential in this process. If withdrawal of ongoing active treatment is deemed appropriate, the main focus becomes palliative, addressing symptom relief, comfort and dignity at the end of life.

Organ donation

An international shortage of organ donors necessitates consideration of organ donation in all dying critical care patients. Two different pathways are recognized in the UK: donation after circulatory death (DCD) and donation after brain death (DBD). The latter requires a process of formal brain-stem death testing for diagnosis. Some countries routinely supplement this with ancillary testing (imaging of cerebral blood flow or electro-encephalographic response to external stimuli). Early physiological stabilization and donor optimization improves transplant outcomes after DBD. Dedicated organ donation teams can facilitate this process, help to support the donor's family and coordinate retrieval of organs by the receiving teams.

Critical care in 2020: COVID-19

It is hard to understate the impact of the COVID-19 pandemic on intensive care medicine.

Ventilatory support is the most common indication for critical care admission in COVID-19 with approximately 75% of admitted patients requiring advanced respiratory support which may be prolonged. 17 Patients receiving critical care with a diagnosis of COVID-19 in England, Wales and Northern Ireland have an approximately 39% mortality. 17

Current practice is best supportive care with basic and advanced ventilatory support as required; treatment of any co-existing bacterial infection; strict fluid management to avoid lung injury; thromboprophylaxis; and adherence to infection control. To date, only dexamethasone has been shown to reduce mortality in patients with severe respiratory complications of COVID-19. 18

The associated pro-coagulant state found in COVID-19 makes complications such as venous thromboembolism and ischaemic stroke more common in this patient group and may be the reason for intensive care admission.

Elective surgical patients who develop symptomatic COVID-19 are at increased mortality risk and have higher rates of pulmonary complications. 19

Practice points

• • Intensive care medicine is the provision of advanced organ support and monitoring to patients who are critically ill or at high risk of deterioration
• • Surgeons should be aware of the principles of intensive care medicine to understand the progress of their own patients, but also as they may be asked to assist in the management of surgical complications of critical illness
• • A multidisciplinary approach is essential, from admission through to rehabilitation following discharge
• • Morbidity from critical illness is high, so when considering intensive care admission careful thought must be given to the best interests of the patient

10 September 2024: Due to technical disruption, we are experiencing some delays to publication. We are working to restore services and apologise for the inconvenience. For further updates please visit our website: https://www.cambridge.org/universitypress/about-us/news-and-blogs/cambridge-university-press-publishing-update-following-technical-disruption

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• Case Studies in Adult Intensive Care Medicine

Case Studies in Adult Intensive Care Medicine

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• Edited by Daniele Bryden , Sheffield Teaching Hospitals NHS Trust , Andrew Temple , Sheffield Teaching Hospitals NHS Trust
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Book description

Guiding FFICM and EDIC exam candidates through the intensive care medicine curriculum, this book provides 48 case studies mapped to eight key areas of study in the UK and European syllabuses. Cases include clinical vignettes, explanations and a list of key learning points, while also being formatted along the structure of FICM case reports. Key clinical management points are identified and linked to appropriate scientific or evidence-based research and case studies chosen reflect a general population relevant to a worldwide readership. Conditions covered are significant to large areas of clinical practice as well as more discrete specialist knowledge, making this an essential study guide for trainees preparing for exams in intensive care medicine and also a useful learning tool for candidates in related disciplines such as anaesthesia (FRCA), emergency medicine (MCEM) and surgery (MRCS).

'This book is a good collection of relevant and interesting case studies, pragmatic discussions, and appropriate references for further education. The cases described may be familiar or unfamiliar to the reader, allowing both learning of new material and consolidation of previously reviewed topics … I enjoyed reading this book and found it a useful reference. I would recommend it not only to individuals preparing for ICM examinations, but also as an educational source for all professionals looking after critically ill patients, and as a refresher for experienced intensive care physicians.'

Mika Hamilton Source: Canadian Journal of Anesthesia

'In conclusion, Case Studies in Adult Intensive Care Medicine provides a concise and accurate description of key topics relevant to intensive care medicine. This book is recommended for students who are preparing for exams in intensive care medicine and physicians who seek a clinically oriented approach to the diagnosis and management of critical illnesses.'

Houssein A. Youness and Jean I. Keddissi Source: Anestheisa & Analgesia

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Case Studies in Adult Intensive Care Medicine pp i-ii

• Get access Check if you have access via personal or institutional login Log in Register

Case Studies in Adult Intensive Care Medicine - Title page pp iii-iii

Copyright page pp iv-iv, contents pp v-vi, contributors pp vii-x, preface pp xi-xi, levels of evidence pp xii-xii, abbreviations referred to in case discussions pp xiii-xviii, chapter 1 - cardiac arrest: post resuscitation management pp 1-8.

• By Richard Porter , Andrew Temple

Chapter 2 - Initial Management of the Polytrauma Patient pp 9-16

• By Nicola Pawley , Paul Whiting

Chapter 3 - Management of Major Burns on the Intensive Care Unit pp 17-24

• By Tushar Mahambrey , Emma England , Will Loh

Chapter 4 - Management of Sepsis pp 25-32

• By Chris Thorpe

Chapter 5 - Rhabdomyolysis pp 33-39

• By Ingi Elsayed , Ajay H Raithatha

Chapter 6 - Management of Acute Liver Failure pp 40-47

• By Elizabeth Wilson , Philip Docherty

Chapter 7 - Status Epilepticus pp 48-56

• By Graeme Nimmo

Chapter 8 - Acute Ischaemic Stroke pp 57-64

• By Samir Matloob , Martin Smith

Chapter 9 - Subarachnoid Haemorrhage pp 65-73

• By Alex Trotman , Peter Andrews

Chapter 10 - Management of Traumatic Brain Injury pp 74-83

• By Matthew Wiles

Chapter 11 - Variceal Haemorrhage pp 84-90

• By Gregor McNeill

Chapter 12 - Surgical Management of Pancreatitis pp 91-97

• By Qaiser Jalal , Ahmed Al-Mukhtar

Chapter 13 - Intra-abdominal Hypertension and Abdominal Compartment Syndrome pp 98-106

• By Helen Ellis , Stephen Webber

Chapter 14 - Management of the Ventilated Asthmatic Patient pp 107-114

• By Jochen Seidel

Chapter 15 - Pneumonia pp 115-123

• By Gerry Lynch

Chapter 16 - Interstitial Lung Disease pp 124-130

• By Zhe Hui Hui , Omar Pirzada

Chapter 17 - Chronic Pulmonary Hypertension pp 131-140

• What Does Critical Care Have to Offer?
• By Bevan Vickery , Andrew Klein

Chapter 18 - Acute Lung Injury pp 141-146

• By Gary H Mills

Chapter 19 - The Role of Noninvasive Ventilation Following Extubation of Intensive Care Patients pp 147-151

• By Alastair J Glossop

Chapter 20 - Valvular Heart Disease and Endocarditis: Critical Care Management pp 152-157

• By Jonathan H. Rosser , Nick Morgan-Hughes

Chapter 21 - Cardiac Failure Management and Mechanical Assist Devices pp 158-165

• By Miguel Garcia , Julian Barker

Chapter 22 - Management of Common Overdoses pp 166-171

• A Severe Case of Amitriptyline Overdose
• By Ascanio Tridente

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A 60-year-old man presented to the emergency department complaining of persistent right-sided chest pain and cough. The chest pain was pleuritic in nature and had been present for the last month. The associated cough was productive of yellow sputum without hemoptysis. He had unintentionally lost approximately 30 pounds over the last 6 months and had nightly sweats. He had denied fevers, chills, myalgias or vomiting. He also denied sick contacts or a recent travel history. He recalled childhood exposures to persons afflicted with tuberculosis. 

The patient smoked one pack of cigarettes daily for the past 50 years and denied recreational drug use. He reported ingesting twelve beers daily and had had delirium tremens, remote right-sided rib fractures and a wrist fracture as a result of alcohol consumption. He had worked in the steel mills but had discontinued a few years previously. He collected coins and cleaned them with mercury. 

The patient’s past medical history was remarkable for chronic “shakes” of the upper extremities for which he had not sought medical attention. Other than daily multivitamin tablets, he took no regular medications. 

Hospital course  He was initially admitted to the general medical floor for treatment of community-acquired pneumonia (see Figure 1) and for the prevention of delirium tremens. He was initiated on ceftriaxone, azithromycin, thiamine and folic acid. Diazepam was initiated and titrated using the Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWAS-Ar), a measure of withdrawal severity (1).  By hospital day 5, his respiratory status continued to worsen, requiring transfer to the intensive care unit (ICU) for hypoxemic respiratory failure. His neurologic status had also significantly deteriorated with worsening confusion, memory loss, drowsiness, visual hallucinations (patient started seeing worms) and worsening upper extremity tremors without generalized tremulousness despite receiving increased doses of benzodiazepines.

Physical Exam

White blood cell count was 11,000/mm 3 with 38% neutrophils, 8% lymphocytes, 18 % monocytes and 35% bands

Hematocrit 33%

Platelet count was 187,000/mm 3

Serum sodium was 125 mmol/L, potassium 3 mmol/L, chloride 91 mmol/L, bicarbonate 21 mmol/L, blood urea nitrogen 14 mg /dl, serum creatinine  0.6 mg/dl and anion gap of 14.

Urine sodium <10 mmol/L, urine osmolality 630 mosm/kg

Liver function tests revealed albumin 2.1 with total protein 4.6, normal total bilirubin, aspartate transaminase (AST) 49, Alanine transaminase (ALT) 19 and alkaline phosphatase 47.

Three sputum samples were negative for acid-fast bacilli (AFB).

Bronchoalveolar lavage (BAL) white blood cell count 28 cells/µl, red blood cell count 51 cells/µl, negative for AFB and negative Legionella culture.  BAL gram stain was without organisms or polymorphonuclear leukocytes.

Blood cultures were negative for growth.

Sputum cultures showed moderate growth of Pasteurella multocida.

2D transthoracic ECHO of the heart showed normal valves and an ejection fraction of 65% with a normal left ventricular end-diastolic pressure and normal left atrial size.  No vegetations were noted.

Purified protein derivative (PPD) administered via Mantoux testing was 8 mm in size at 72 hr after placement.

Human immunodeficiency virus (HIV) serology was negative. 

Arterial blood gas (ABG) analysis performed on room air on presentation to the ICU: pH 7.49, PaCO 2 29 mm Hg, PaO 2 49 mm Hg.

After admission to the ICU, the patient was noted to be in acute lung injury (ALI), a subset of acute respiratory distress syndrome (ARDS). The diagnosis of ALI requires all three of the following:  (a) bilateral pulmonary infiltrates, (b) a PaO 2 :FiO 2 ratio of ≤ 300 and (c) echocardiographic evidence of normal left atrial pressure or pulmonary-artery wedge pressure of ≤ 18 mm Hg (2). 

While patients with ALI and ARDS can be maintained with pressure-limited or volume-limited modes of ventilation, only volume assist-control ventilation was utilized in the ARDS Network multicenter randomized controlled trial that demonstrated a mortality benefit.

Noninvasive ventilation has not been demonstrated to be superior to endotracheal intubation in the treatment of ARDS or ALI and is not currently recommended (4).

This is a case of heavy metal poisoning with mercury.  The patient used mercury to clean coins.  Family members who had visited his house while he was hospitalized found several jars of mercury throughout his home.  The Environmental Protection Agency (EPA) was notified and visited the home.  They found aerosolized mercury levels of > 50,000 PPM and had the home immediately demolished. 

Alcoholic hallucinosis is a rare disorder occurring in 0.4 - 0.7% of alcohol-dependent inpatients (5).  Affected persons experience predominantly auditory but occasionally visual hallucinations.  Delusions of persecution may also occur.  However, in contrast to alcohol delirium, other alcohol withdrawal symptoms are not present and the sensorium is generally unaffected.

Delerium tremens (DT) occurs in approximately 5% of patients who withdraw from alcohol and is associated with a 5% mortality rate. DT typically occurs between 48 and 96 hr following the last drink and lasts 1-5 days.  DT is manifested by generalized alteration of the sensorium with vital sign abnormalities.  Death often results from arrhythmias, pneumonia, pancreatitis or failure to identify another underlying problem (6).  While DT certainly could have coexisted in this patient, an important initial step in the management of DT is to identify and treat alternative diagnoses.

Delirium is frequent among older patients in the ICU (7), and may be complicated by pneumonia and sepsis.  However, pneumonia and sepsis as causes for delirium are diagnoses of exclusion and should only be attributed after other possibilities have been ruled out. 

Frontal lobe stroke is unlikely, given the absence of other findings in the history or physical examination present to suggest an acute cerebrovascular event. 

In 1818, Dr. John Pearson coined the term erethism for the characteristic personality changes attributed to mercury poisoning (8).  Erethism is classically the first symptom in chronic mercury poisoning (9).  It is a peculiar form of timidity most evident in the presence of strangers and closely resembles an induced paranoid state.  In the past, when mercury was used in making top hats, the term “mad as a hatter” was used to describe the psychiatric manifestations of mercury intoxication.  Other neurologic manifestations include tremors, especially in patients with a history of alcoholism, memory loss, drowsiness and lethargy.  All of these were present in this patient. 

Acute respiratory failure (ALI/ARDS) can occur following exposure to inhalation of mercury fumes (10). Mercury poisoning has also been associated with acute kidney injury (11). 

Although all of the options mentioned above could possibly contribute to the development of delirium, only mercury poisoning would explain the constellation of findings of confusion, upper extremity tremors, visual hallucinations, somnolence and acute respiratory failure (ALI/ARDS).

Knowledge of the form of mercury absorbed is helpful in the management of such patients, as each has its own distinct characteristics and toxicity. There are three types of mercury: elemental, organic and inorganic. This patient had exposure to elemental mercury from broken thermometers. 

Elemental mercury is one of only two known metals that are liquid at room temperature and has been referred to as quicksilver (12). It is commonly found in thermometers, sphygmomanometers, barometers, electronics, latex paint, light bulbs and batteries (13).  Although exposure can occur transcutaneously or by ingestion, inhalation is the major route of toxicity.  Ingested elemental mercury is poorly absorbed and typically leaves the body unchanged without consequence (bioavailability 0.01% [13]). However, inhaled fumes are rapidly absorbed through the pulmonary circulation allowing distribution throughout the major organ systems.  Clinical manifestations vary based on the chronicity of the exposure (14).  Mercury readily crosses the blood-brain barrier and concentrates in the neuronal lysosomal dense bodies. This interferes with major cell processes such as protein and nucleic acid synthesis, calcium homeostasis and protein phosphorylation.  Acute exposure symptoms manifest within hours as gastrointestinal upset, chills, weakness, cough and dyspnea.

Inorganic mercury salts are earthly-appearing, red ore found historically in cosmetics and skin treatments.  Currently, most exposures in the United States occur from exposure through germicides or pesticides (15).  In contrast to elemental mercury, inorganic mercury is readily absorbed through multiple routes including the gastrointestinal tract.  It is severely corrosive to gastrointestinal mucosa (16).  Signs and symptoms include profuse vomiting and often-bloody diarrhea, followed by hypovolemic shock, oliguric renal failure and possibly death (12).

Organic mercury, of which methylmercury is an example, has garnered significant attention recently following several large outbreaks as a result of environmental contamination in Japan in 1956 (17) and grain contamination in Iraq in 1972 (18).  Organic mercury is well absorbed in the GI tract and collects in the brain, reaching three to six times the blood concentration (19).  Symptoms may manifest up to a month after exposure as bilateral visual field constriction, paresthesias of the extremities and mouth, ataxia, tremor and auditory impairments (12).  Organic mercury is also present in a teratogenic agent leading to development of a syndrome similar to cerebral palsy termed "congenital Minamata disease" (20).

The appropriate test depends upon the type of mercury to which a patient has been exposed.  After exposure to elemental or inorganic mercury, the gold standard test is a 24-hr urine specimen for mercury.  Spot urine samples are unreliable.  Urine concentrations of greater than 50 μg in a 24-hr period are abnormal (21).  This patient’s 24-hr urine level was noted to be 90 μg.  Elemental and inorganic mercury have a very short half-life in the blood.

Exposure to organic mercury requires testing hair or whole blood.  In the blood, 90% of methyl mercury is bound to hemoglobin within the RBCs.  Normal values of whole blood organic mercury are typically < 6 μg/L. This patient’s whole blood level was noted to be 26 μg/L.  This likely reflects the large concentration of elemental mercury the patient inhaled and the substantial amount that subsequently entered the blood.

Mercury levels can be reduced with chelating agents such as succimer, dimercaprol (also known as British anti-Lewisite (BAL)) and D-penicillamine, but their effect on long-term outcomes is unclear (22-25).

• Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353-1357.
• Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818-824.
• The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-1308.
• Agarwal R, Reddy C, Aggarwal AN, et al. Is there a role for noninvasive ventilation in acute respiratory distress syndrome? A meta-analysis. Respir Med 2006;100:2235-2238.
• Soyka M. Prevalence of alcohol-induced psychotic disorders. Eur Arch Psychiatry Clin Neurosci 2008;258:317-318.
• Tavel ME, Davidson W, Batterton TD. A critical analysis of mortality associated with delirium tremens. Review of 39 fatalities in a 9-year period. Am J Med Sci 1961;242:18-29.
• McNicoll L, Pisani MA, Zhang Y, et al. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003;51:591-598.
• Bateman T. Notes of a case of mercurial erethism. Medico-Chirurgical Transactions 1818;9:220-233.
• Buckell M, Hunter D, Milton R, et al. Chronic mercury poisoning. 1946. Br J Ind Med 1993;50:97-106.
• Rowens B, Guerrero-Betancourt D, et al. Respiratory failure and death following acute inhalation of mercury vapor. A clinical and histologic perspective. Chest 1991;99:185-190.
• Aguado S, de Quiros IF, Marin R, et al. Acute mercury vapour intoxication: report of six cases. Nephrol Dial Transplant 1989;4:133-136.
• Ibrahim D, Froberg B, Wolf A, et al. Heavy metal poisoning: clinical presentations and pathophysiology. Clin Lab Med 2006;26:67-97, viii.
• A fact sheet for health professionals - elemental mercury. Available from: http://www.idph.state.il.us/envhealth/factsheets/mercuryhlthprof.htm
• Clarkson TW, Magos L, Myers GJ. The toxicology of mercury - current exposures and clinical manifestations. N Engl J Med 2003;349:1731-1737.
• Boyd AS, Seger D, Vannucci S, et al. Mercury exposure and cutaneous disease. J Am Acad Dermatol 2000;43:81-90.
• Dargan PI, Giles LJ, Wallace CI, et al. Case report: severe mercuric sulphate poisoning treated with 2,3-dimercaptopropane-1-sulphonate and haemodiafiltration. Crit Care 2003;7:R1-6.
• Eto K. Minamata disease. Neuropathology 2000;20:S14-9.
• Bakir F, Damluji SF, Amin-Zaki L, et al. Methylmercury poisoning in Iraq. Science 1973;181:230-241.
• Berlin M, Carlson J, Norseth T. Dose-dependence of methylmercury metabolism. A study of distribution: biotransformation and excretion in the squirrel monkey. Arch Environ Health 1975;30:307-313.
• Harada M. Congenital Minamata disease: intrauterine methylmercury poisoning. Teratology 1978;18:285-288.
• Graeme KA, Pollack CVJ. Heavy metal toxicity Part I: Arsenic and mercury. J Emerg Med 1998;16:45-56.
• Aaseth J, Frieheim EA. Treatment of methylmercury poisoning in mice with 2,3-dimercaptosuccinic acid and other complexing thiols. Acta Pharmacol Toxicol (Copenh) 1978;42:248-252.
• Archbold GP, McGuckin RM, Campbell NA. Dimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals. Ann Clin Biochem 2004;41:233-236.
• Kosnett MJ. Unanswered questions in metal chelation. J Toxicol Clin Toxicol 1992;30:529-547.
• Zimmer LJ, Carter DE. The efficacy of 2,3-dimercaptopropanol and D-penicillamine on methyl mercury induced neurological signs and weight loss. Life Sci 1978;23:1025-1034.

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Kenneth’s Story: A Poignant Example of How Evidence-Based Care Can Improve Patient Outcomes in the Intensive Care Unit

In my haste to convey the horror experienced by so many patients who have been sedated and immobilized in the ICU, the case studies I’ve published have not had particularly happy endings.

So far, the cases I’ve detailed have involved either the patient dying, being traumatized by the delirium they suffered while under sedation, or otherwise having to walk a long, long road to recovery.

That being said, I figured it would be a good idea to start publishing more positive stories of how evidence-based practices have actually helped to improve patient outcomes in the intensive care unit.

I think up until this point, I’ve overlooked how important these happy endings can be for putting things into perspective for people.

They provide additional context, offer an encouraging contrast to offset all the tragedy, and work to illustrate where I would like things to go in terms of how ICU patients are treated.

The case I’m about to describe involves a man whose experience in the ICU offers a poignant example of how evidence-based practices can improve ICU patient outcomes.

If he’d been subjected to the treatment typical of most intensive care units, the outcome of his ICU stay would have been much different, and it probably would have been for the worse.

Luckily for him, things didn’t turn out that way, and the evidence-based care he received has allowed him to resume the quality of life he enjoyed before he was admitted to the ICU.

The man I’m referring to is Dr. Kenneth Hurwitz, and this is his story.

How Evidence-Based Care Ensured Greater Quality of Life for Kenneth

Kenneth was admitted to the high acuity Awake and Walking COVID ICU after being intubated for acute respiratory failure due to COVID-19.

During his first six days on the ventilator, he was able to remain awake and walk around his room. Still, he spent most of his time sitting in a chair, writing on a board, and texting the staff and his wife.

When his status changed and his lungs became worse, he was lightly sedated while proned for two days, and then deeply sedated for another six days because he was unable to oxygenate while being on his back.

After eight days of immobility, including two days of paralysis and four additional days of sedation and delirium, Kenneth returned to a world of weakness and hallucinations.

But as soon as he could be on his back, the nurse gave him a sedation vacation to see if he could oxygenate with movement.

When it was clear that despite his continued high ventilator settings and delirium, he was able to oxygenate while moving his limbs, his nurse recognized there was no longer an indication for sedation. At this point, she discontinued his sedation and called in physical therapy to help with his delirium and agitation. They promptly started to sit him up and began working on getting him back on his feet again.

After being liberated from sedation, he continued to have delusions and hallucinations. But luckily, mobility and engagement within the ICU helped him to cope and emerge from his delirium.

As you can see from the photos below, the ICU team members who treated Kenneth are dedicated to adhering to these kinds of evidence-based practices, and they did whatever they could to help him remain awake and mobile during his time on the ventilator.

The ICU team members who treated Kenneth mourned the loss of the opportunity to walk the halls with their intubated patients.

But as you can see from the image above, they found other ways to keep Kenneth moving, including walking wall-to-wall within the room, as well as arm and hand cycling.

Utilizing this cardiopulmonary challenge from ICU admission to discharge helps to prevent intubation and tracheostomies, and makes patients more likely to walk out of the ICU doors and eventually discharge home from the hospital.

That being said, if Kenneth had received the kind of care practiced in most ICUs, which would have included deep sedation and immediate immobility from the moment he was intubated, he would have spent at least three weeks suffering from delirium and muscular atrophy.

This probably would have caused him to be unable to wean from the ventilator, which could have led to him facing a tracheostomy, spending many more days or weeks being ventilated, and guaranteed, he would have had to be admitted to some sort of nursing facility for extensive rehabilitation.

This would have greatly increased his risks of death, and having to suffer through weeks or months of rehabilitation, at best.

But as a result of the evidence-based care he received, four days after being able to lie on his back again, he was also able to be off the ventilator. Then, ten days after getting off the ventilator, he walked himself to his car, shut the door, and didn’t look back.

He has continued to recover at home, and fortunately, has been able to care for himself and be in the company of his wife.

In addition, he has been able to quickly resume the activities he enjoyed before he was ever struck by COVID.

If you want to hear more about Kenneth’s story, you can check out Episode 44 of my Walking Home From The ICU podcast.

How is Kenneth Doing Now?

Less than six weeks after leaving the hospital, Kenneth was able to do 25 push-ups and 30 sit-ups. He was also able to achieve the goal he set for his 70th birthday and ended up golfing 18 holes.

Two months after discharging home, he was able to walk eight miles on the golf course. And a few months later, he was back to gracefully gliding down the mountains in the Utah snow.

He is still battling pulmonary fibrosis from COVID-19, but the preservation of his physical and mental capacity has enabled him to live a life that many severe COVID-19 survivors could only dream of.

If Kenneth had been subjected to the kind of treatment that’s typical in most ICUs, I have no doubt that things would have been very different, and he wouldn’t have the quality of life he’s able to enjoy today.

In any case, his positive outcomes and long-term quality of life are no accident.

They were realized by the hard work of a team dedicated to following evidence-based practices by avoiding deep sedation and optimizing early ambulation and mobility.

Such outcomes have been the norm for most COVID survivors in this Awake and Walking COVID ICU.

However, the ability to save and preserve lives during critical illness is not exclusively owned by one ICU.

Medicine is a field of evolution and progress, and the practices and outcomes I’ve described in this case study are possible for any ICU team that understands its “why” and works together to find its “how”.

Do you want to know more about how evidence-based practices can reduce ICU complications, and improve patient outcomes in the intensive care unit in your hospital? If your ICU team is ready to improve outcomes, workload, and healthcare costs, we’re ready to help. We can walk you through the entire process, so please don’t hesitate to contact us .

About the Author, Kali Dayton

Kali Dayton, DNP, AGACNP, is a critical care nurse practitioner, host of the Walking Home From The ICU and Walking You Through The ICU podcasts, and critical care outcomes consultant. She is dedicated to creating Awake and Walking ICUs by ensuring ICU sedation and mobility practices are aligned with current research. She works with ICU teams internationally to transform patient outcomes through early mobility and management of delirium in the ICU.

I am a nurse leader responsible for improving practices across the intensive care units of a large health system. As an experienced ICU nurse, I know the culture that most often exists in ICUs is one that promotes and accepts over-sedation that often causes unintended harm. While reviewing the literature to better align our liberation practices with the best evidence, one of our bedside nurses discovered Walking Home From The ICU . The combination of poignant stories from ICU survivors with the expertise of some of ICU Liberation’s leading experts became the impetus for a system-wide evidence-based practice improvement project aimed at changing analgesia and sedation management in our ICUs.

After initially being inspired by Kali’s podcast and the incredible stories it provides, we saw an opportunity for more. We brought Kali in to present a webinar to almost 100 of our critical care team members, including nurses, APPs, physicians, and respiratory therapists. Kali’s presentation struck a needed balance between evidence-based practice information and inspiring stories, highlighting real patients who benefited from a practice that is often very different from what occurs in most ICUs today. The webinar was very well-received by all who attended, and the lessons learned have continued to be referenced by our team members as we strive to create an Awake and Walking ICU culture.

Kali offers a refreshing perspective on critical care, and she supports it with a wealth of knowledge garnered from years as a bedside nurse and advanced practice provider. Kali knows how to speak to clinicians because she is one, and she’s still very connected to the daily lived experiences of those on the frontline of critical care. I believe anyone working in critical care will find inspiration in Walking Home From The ICU to change the harmful culture of sedation in their practice. I would even go so far as to recommend the podcast as required listening for all ICU team members, whether experienced clinicians or new residents and nurses. When additional support is needed, I encourage clinical leaders to utilize Kali’s expertise and experiences to further inspire and motivate their teams. Time spent working with Kali is an investment that will pay dividends in the positive impact it has on the lives of the patients we serve.

Patrick Bradley, MSN, RN, CCRN Virginia, USA

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Open Access

Peer-reviewed

Research Article

Early vs. delayed QTc prolongation in acute poisoning: A prognostic accuracy study—A case series

Roles Data curation, Formal analysis

Affiliation Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

Roles Formal analysis, Methodology, Supervision

Affiliation Department of Emergency Medicine, Kerman University of Medical Sciences, Kerman, Iran

Roles Formal analysis, Methodology

Roles Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliation Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

• Amirhossein Shahpar, 
• Amirhossein Mirafzal, 
• Mitra Movahedi, 
• Nazanin Zeinali Nezhad

• Published: September 10, 2024
• https://doi.org/10.1371/journal.pone.0309940
• Reader Comments

Given the limited capacity of intensive care units in many countries, it is crucial to identify reliable prognostic markers to optimize poisoning patients management and improve outcomes. This study aimed to assess the predictive value of three variables, namely the initial QTc interval (iQTc) measured within two hours of admission, the delayed QTc interval (dQTc) measured between 6 and 12 hours of entry, and the QTc interval trend over time (ΔQTc), for mortality in patients with undifferentiated poisoning. A retrospective case series was conducted on 70 patients with undifferentiated poisoning admitted to the intensive care unit (ICU) of Afzalipour Hospital between March 21, 2021, and March 20, 2023. The results of the multivariate analysis revealed that dQTc, base deficit, and creatinine were independently associated with mortality (P value < 0.001). The dQTc had the highest predictive ability, with an area under the curve (AUC) of 0.84, followed by ΔQTc with an AUC of 0.76, and iQTc with an AUC of 0.67. Additionally, the results of the Generalized Estimating Equation model with repeated measurements revealed a higher odds ratio for dQTc (OR, 6.33; 95% CI, 2.54–15.79) compared to iQTc (OR, 4.92; 95% CI, 1.71–14.17). The study concluded that monitoring the dQTc interval could provide valuable prognostic information in acute poisoning cases.

Citation: Shahpar A, Mirafzal A, Movahedi M, Zeinali Nezhad N (2024) Early vs. delayed QTc prolongation in acute poisoning: A prognostic accuracy study—A case series. PLoS ONE 19(9): e0309940. https://doi.org/10.1371/journal.pone.0309940

Editor: Tomohiko Ai, Juntendo University: Juntendo Daigaku, JAPAN

Received: February 20, 2024; Accepted: August 21, 2024; Published: September 10, 2024

Copyright: © 2024 Shahpar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Poisoning is a critical health problem caused by exposure to harmful substances that affect the body [ 1 ]. Unintentional poisoning is the primary cause of mortality due to accidental injuries in the United States, followed by motor vehicle accidents [ 2 ]. The United States experienced a total of 106,699 fatalities due to drug overdose in 2021. This figure reflects a 14% increase in the age-adjusted mortality rate compared to that in the same period in 2020 [ 3 ]. A wide range of visits to emergency departments (EDs) are related to poisoning. It is estimated that out of 843 million ED visits in the United States between 2003 and 2011, nearly 8 million visits (0.9%) were related to poisoning. This number has shown an increasing trend, from 1.8 million visits in 2003–2004 to 2.9 million visits in 2010–2011 [ 4 ]. Undifferentiated or unknown poisoned patients pose a significant challenge among admissions with suspected poisoning in the ED. Current recommendations for managing poisoned patients needing emergency cardiovascular care are mainly based on expert consensus and consultations with medical toxicologists or poison control centers [ 5 ]. Initial assessments in the ED usually consist of an electrocardiogram (ECG) and laboratory examinations. Healthcare providers must make clinical decisions regarding discharge or hospitalization while considering the medical consequences and potential risks of adverse events [ 6 ].

Adverse cardiovascular events (ACVEs) are a significant cause of morbidity and mortality in patients with drug overdose. These events can manifest as myocardial injury, shock, ventricular dysrhythmia, and cardiac arrest [ 6 ]. Previous research has demonstrated that the presence of ECG abnormalities, particularly prolonged QTc intervals, increases the risk of ACVE by more than tenfold in patients with suspected acute poisoning [ 7 ]. Delayed severe QTc prolongation has been reported in patients receiving opium and selective serotonin reuptake inhibitor (SSRI) overdoses [ 8 , 9 ]. Electrolyte imbalances, delayed drug absorption, toxicokinetics of the drugs, or drug interactions may lead to delayed QTc (dQTc) prolongation [ 10 ].

Even though these cases have been reported, only a few studies have evaluated the potential of initial and delayed QTc (iQTc and dQTc) prolongation and the QTc trend (ΔQTc) as predictors of adverse outcomes in a population of undifferentiated or unknown poisoned patients [ 10 , 11 ]. In this study, we investigated whether iQTc and dQTc prolongation and ΔQTc in the emergency room could be predictive indicators of the outcome of patients with suspected poisoning, regardless of the type of poisoning. We also aimed to compare the predictive value of each indicator.

Study design and time period

This retrospective chart review was conducted to evaluate the predictive value of iQTc and dQTc prolongation and ΔQTc in patients with suspected poisoning admitted to the poisoning intensive care unit (ICU) of Afzalipour Hospital. The study period was from March 21, 2021, to March 20, 2023. The study was granted approval by the Institutional Review Board (IR.KMU.AH.REC.1400.291(. On April 25, 2023, we obtained access to the medical records. Furthermore, throughout the entirety of data access, all information was meticulously anonymized.

Study setting and population

The data were extracted from the medical records of eligible individuals for this investigation. Patients who met the inclusion criteria were those who had at least two 12-lead ECGs—one within two hours of ED admission and another between 6 and 12 hours of access—and had a confirmed poisoning diagnosis based on urine toxicology, blood toxicology, or a combination of history, physical examination, and circumstantial evidence (e.g., presence of a poison bottle or label discovered by relatives). The exclusion criteria included being under 18 years old; having cardiac disease or comorbid illnesses that could affect survival or outcomes; being transferred from another healthcare facility; having missing ECG, laboratory, or vital signs; using medications known to be associated with QTc prolongation; deaths resulting from causes unrelated to ACVEs; and having an alternative diagnosis.

The study included the adult population (aged ≥ 18 years) who were admitted to the ICU of the hospital with a confirmed diagnosis of acute poisoning within the study period. A wide range of patient information was extracted from the medical records, including demographic data; exposure details (such as the time elapsed from exposure to admission, drug type, and route of exposure); initial mental status assessed using the Glasgow Coma Scale (GCS); vital signs; medical history (including previous drug use and preexisting comorbidity); laboratory results; initial ECGs; repeated ECGs; duration of hospitalization; and outcome. Two independent and trained investigators extracted the relevant information from medical records. Each investigator was blinded to the findings of the other investigator. Any discrepancies in chart abstraction were resolved through discussion.

Electrocardiographic evaluation

Two physicians performed independent measurements of the QT interval using a standard 12-lead ECG tracing at a 25 mm/s paper speed and 10 mm/mV amplitude. To determine the QT interval, they calculated the mean value derived from at least 3–5 cardiac cycles. This interval was measured from the beginning of the earliest onset of the QRS complex to the end of the T wave. The measurements were taken in leads II, V5, and V6, and the longest value was used. The tangent method was used to measure the QT interval. In this study, the Bazett formula ( QT / √RR ) was used to adjust the QT interval for heart rate. Interobserver agreement was assessed to evaluate the consistency between the two observers. Any significant discrepancies regarding the QTc value were discussed and resolved through consensus and by rechecking the ECG. Only those discrepancies between the observers that led to categorizing a patient in two different categories (prolonged vs normal QTc) were considered significant. If such a discrepancy could not be resolved, the patient was removed from the study. To evaluate the interrater reliability for continuous data, we calculated the concordance correlation coefficient, which was found to be 0.923, indicating excellent agreement. By definition, the QTc interval was considered prolonged if it was equal to or greater than 450 msec. The QTc value calculated within two hours of admission to the ED was labeled the iQTc, while the QTc value calculated between 6 and 12 hours after admission was labeled the dQTc. The difference between dQTc and iQTc (ΔQTc) was then analyzed for trend.

Exposure and outcome

The primary outcomes in our study were defined as death due to ACVEs. These events were defined as a combination of shock (hypotension requiring vasopressors), myocardial injury (an increase in serum cardiac troponin levels on at least one measurement), ventricular dysrhythmia (ventricular tachycardia or ventricular fibrillation), and cardiac arrest (loss of pulse requiring cardiopulmonary resuscitation). Furthermore, the primary exposure in our study was initial and delayed QTc prolongation. We followed all patients until they were either completely discharged from the hospital units or in-hospital mortality occurred.

Data analysis

The GEE method is a reliable approach that considers the QTc interval as a within-patients variable with repeated measurements at multiple time points, effectively accounting for the correlated structure of the data. Our GEE model evaluated iQTc and dQTc in predicting mortality by treating QTc interval as prolonged or non-prolonged and timing as a within-subject variable.

We also conducted receiver operating characteristic (ROC) curve analysis for continuous variables that were found to be predictive of the outcome to evaluate their potential ability to predict mortality. Data analysis was performed using IBM SPSS Statistics version 27 for Windows (IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp.). The odds ratios (ORs) of each variable were reported with relevant 95% confidence intervals (CIs). P <0.05 was considered to indicate statistical significance.

Basic characteristics

A total of 70 patients were included in the study ( Fig 1 ), 18 (25.7%) were female, and 52 (74.3%) were male. The male-to-female ratio was 2.88. The age range of the whole group of participants was between 18 and 75 years, with a median age of 30.5 years (IQR: 16). The median age of the survivors was 31(IQR:16), and that of the nonsurvivors was 29 (IQR:16). There was no significant difference in age between the survivor and nonsurvivor groups (P value = 0.6). The mortality rate of all patients was 44.3% (31/70), with a male-to-female ratio of 2.44 (22/9). The most common type of drug overdose was benzodiazepines, accounting for 20.0% (14/70) of the total drug use, followed by other drugs. Out of the total number of patients, 26 (37.1%) had a prolonged iQTc, whereas 32 (45.7%) had a prolonged dQTc ( Table 1 ). In our study, it is important to note that all patients were in sinus rhythm upon admission and remained in sinus rhythm during the two ECG recordings for iQTc and dQTc. Table 2 presents the essential characteristics of the quantitative variables. The median duration of hospitalization was three days (IQR: 3). The median time from exposure to admission was 12 hours (IQR: 8.25). The median duration of ICU stay was two days (IQR: 2).

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https://doi.org/10.1371/journal.pone.0309940.t001

https://doi.org/10.1371/journal.pone.0309940.t002

Univariate analysis

Concerning the quantitative variables, several variables, including heart rate (P value = 0.02), base deficit (BD) (P value = 0.01), creatinine (P value <0.001), dQTc interval (P value <0.001), ICU Stay Duration ( P value = 0.005), iQTc interval (P value = 0.03) and ΔQTc (QTc2-QTc1) (P value <0.001), were associated with patient outcome and were significantly greater in the nonsurvival group than in the survival group ( Table 3 ). Nevertheless, due to multiple comparisons, an adjusted analysis was performed to identify variables that had independent associations with the outcome. All variables correlated with outcomes in the univariate analysis were also assessed in the multivariate analysis.

https://doi.org/10.1371/journal.pone.0309940.t003

Multivariate analysis

A multivariable logistic regression model was created using the backward conditional method to identify the most important and independent variables with predictive value for the outcome. The analysis revealed that three variables were independently associated with the outcome. These variables were dQTc (OR, 1.04; 95% CI, 1.01–1.06), BD (OR, 0.91; 95% CI, 0.84–0.99), and creatinine (OR, 6.87; 95% CI, 1.79–26.27) ( Table 4 ).

https://doi.org/10.1371/journal.pone.0309940.t004

Subgroup analysis

To address potential gender-related differences in QTc intervals, we conducted a subgroup analysis focusing solely on male patients (n = 52). This analysis aimed to eliminate the possible confounding effect of gender on our findings. In the male-only univariate analysis, several variables remained associated with patient outcomes in acute poisoning. These included iQTc interval (P value = 0.02), dQTc interval (P value < 0.001), ΔQTc (P value = 0.02), BD (P value < 0.001), and creatinine (P value = 0.002).

Furthermore, we performed a multivariate analysis for the male subgroup. This analysis confirmed that dQTc (OR, 1.03; 95% CI, 1.01–1.06), BD (OR, 0.92; 95% CI, 0.84–1.00), and creatinine (OR, 5.53; 95% CI, 1.36–22.40) continued to be independently associated with the outcome, even after accounting for gender. These results support the robustness of our original findings, suggesting that the prognostic value of QTc interval measurements, particularly dQTc, remains significant even when considering potential gender-related differences in QTc intervals.

It is important to note that our study included only 18 female patients, which represents a relatively small sample size. Due to this limitation, we did not perform a separate subgroup analysis for female patients, as it would likely be underpowered and may not produce reliable or meaningful results.

Repeated measures analysis

The time between poison exposure and hospital admission varies among patients. This variability can potentially affect the comparison of iQTc and dQTc regarding the outcome. To address this issue, we used the GEE longitudinal model with repeated measures to analyze the relationship between QTc prolongation and the outcome. The results of the GEE analysis revealed that dQTc prolongation (OR, 6.33; 95% CI, 2.54–15.79) is more strongly associated with mortality than iQTc prolongation (OR, 4.92; 95% CI, 1.71–14.17) ( Table 5 ).

https://doi.org/10.1371/journal.pone.0309940.t005

To assess the accuracy of these variables in predicting mortality, we used receiver operating characteristic (ROC) curves to determine the optimal cutoff point for each variable that maximized sensitivity and specificity. Table 6 provides the specific details of the ROC curve analysis for the variables independently associated with mortality (dQTc, Cr, and BD) and iQTc and ΔQTc (for comparison with dQTc). Among the variables, dQTc had the highest predictive ability, with an area under the curve (AUC) of 0.84 (95% CI, 0.74–0.95). The optimal cutoff point for dQTc was 445 msec, with a sensitivity of 87% and a specificity of 77%. Cr demonstrated an AUC of 0.76 (0.65–0.87). The optimal cutoff point for Cr was 1.25, with a sensitivity of 71% and a specificity of 74%. The AUC for ΔQTc was 0.76 (0.64 to 0.87), demonstrating moderate predictive ability. The optimal cutoff point for ΔQTc was 10.5 msec, with a sensitivity of 77% and a specificity of 70%. The AUC for BD was 0.78 (0.67–0.89). The optimal cutoff point for BD was -3.3, with a sensitivity of 77% and a specificity of 77%. The AUC for iQTc was 0.67 (0.54–0.80). The optimal cutoff point for iQTc was 441 msec, yielding a sensitivity of 77% and a specificity of 62%. These results indicate that, when comparing the ability of iQTc, dQTc, and ΔQTc to predict outcome, dQTc demonstrated the highest ability, followed by ΔQTc and iQTc ( Fig 2 ).

AUC: area under the curve, iQTc: QTc at presentation, dQTc: QTc 6–12 hours after presentation, ΔQTc: dQTc-iQTc, BD: base deficit, Cr: Creatinine.

https://doi.org/10.1371/journal.pone.0309940.g002

https://doi.org/10.1371/journal.pone.0309940.t006

Poisoning is a primary global health concern, causing an estimated one million yearly morbidities. In some areas, the mortality rate can reach 20%. The World Health Organization predicts that more than 200,000 individuals die annually due to pesticide poisoning alone [ 13 ]. In Iran, a developing country with nearly 80 million residents, poisoning accounts for 15% to 20% of emergency department visits. It is one of the most common causes of hospitalization and the second-leading cause of mortality in the country [ 14 ].

Several examples of drug poisoning associated with QTc prolongation and mortality have been reported in the literature; these include organophosphates [ 15 ], methadone [ 16 ], paraquat [ 17 ], antidepressants [ 18 ], aluminum phosphide [ 19 ], lithium [ 20 ], carbon monoxide [ 21 ], and tramadol [ 22 ]. Researchers have also explored the predictive value of QTc prolongation for outcomes in patients with suspected or unknown poisoning. In a large multicenter cohort study in Sweden and Denmark, a prolonged QTc interval (>450 msec in men and >460 msec in women) was associated with a more than threefold increase in 30-day mortality among adult patients with suspected poisoning [ 11 ]. Another retrospective observational study of 550 patients requiring toxicology consultation revealed that QTc prolongation (>500 msec) was associated with dysrhythmias and cardiac arrest [ 23 ]. A five-year retrospective chart review of patients exposed to substances known to prolong QTc also revealed an association with life-threatening cardiac dysrhythmias [ 24 ]. Additionally, a case‒control study involving the prospective identification of 34 cases of acute cardiovascular events in patients suspected of drug poisoning demonstrated an independent association between QTc prolongation and cardiovascular complications [ 25 ].

Regarding QTc alteration trends in the ED, while numerous studies have shown associations between the QTc interval and mortality in patients with known or unknown poisoning, only a few studies have compared the predictive value of changes in QTc intervals during admission (QTc trend) with a single measurement or assessed the optimal timing for QTc measurement after admission to maximize its predictive accuracy. Several studies have investigated the dynamic nature of the QTc over admission. One study of 104 patients with carbon monoxide poisoning revealed that the QTc interval tended to increase within the first 24 hours of admission and was correlated with carboxyhemoglobin levels [ 26 ]. Additionally, another study has shown increasing changes in QTc intervals over time after administering therapeutic doses of certain drugs that potentially prolong QTc intervals. However, the influence of these alterations on dysrhythmias and mortality was not assessed [ 27 ]. Furthermore, in a study of critically ill patients in a general ICU, the QTc intervals gradually increased. This difference was related to azithromycin administration on the third day and high blood creatinine levels on the fifth day [ 28 ]. Although this study was not conducted in a poisoning setting, it suggested the dynamic nature of the QTc intervals, indicating the potential need for multiple measurements of QTc during admission. In the ED, these measurements can be performed within 6 to 12 hours, during which critically ill patients are typically transferred to an intensive care setting or a less critical hospital unit.

In our study, we observed a higher mortality rate among females than males (50% vs. 42.3%). This finding contrasts with previous reports that suggested female gender, not using an antidepressant as the method for self-poisoning, and a higher initial GCS score were factors that reduced the risk of a severe or fatal course of self-poisoning [ 29 ]. The higher mortality rate in females than males in our study may be attributed to the higher rate of poisoning from cardiotoxic agents, such as Cyclic Antidepressants (CAs), in females (27.7%) compared to males (9.6%). Additionally, the admission GCS in our study was lower among females (mean: 10.05) than males (mean: 11.94). Furthermore, we observed a higher percentage of prolonged QTc intervals (iQTc and dQTc) among females compared to males (iQTc: 50% vs 32.7%, dQTc: 72.2% vs 36.5%).

Interpretation of findings

In an acute setting of unknown, suspected, or multidrug poisoning, it would be practically impossible to determine the effects of probable agents and evaluate the risk for QTc prolongation. However, performing QTc measurements at regular intervals, such as two measurements at 6-hour intervals, can help overcome such limitations, make a more precise prediction of adverse outcomes, and reassess the disposition of patients, even in a busy ED. Our findings suggest that QTc measurements taken 6–12 hours after admission are more accurate predictors of in-hospital mortality than are the initial QTc measurements taken upon admission or QTc trends during the same period. Moreover, the use of QTc measurements after 6–12 hours of admission may be helpful for re-evaluating and confirming (or perhaps altering) the initial predictions. However, developing an outcome prediction model or scoring system within a few hours of admission would be more attractive. Additionally, based on our results, even though a threshold of 450–460 msec is generally recommended for the definition of QTc prolongation and a range of 480–500 msec is mostly considered high risk, considering that a lower cutoff point (440 msec) may be of greater predictive value. However, the heterogeneity of the data on this issue in the literature may confuse practitioners. We also noted that the time lapse between poison exposure and hospital admission varies among patients and may impact the true prognostic significance of QTc when evaluated without taking this time gap into account. While we acknowledge the challenges of accurately determining the exact time of exposure in emergency situations, we strongly recommend further investigations that consider the timing of iQTc or dQTc from the moment of exposure rather than admission to enhance the reliability of the results.

Limitations

Our study has various methodological limitations. First, it was a retrospective chart review with a restricted sample size due to time and human resource limitations. Most of the diagnoses were made based on medical history and qualitative urine dipstick tests, which have high rates of false positive and false negative results. Using the Bazett formula for calculating QTc could also be a source of limitations, as it tends to underestimate QTc at heart rates less than 60 and overestimate it at heart rates greater than 120. The retrospective nature of the data collection limits our ability to perform more frequent measurements and more precise timing of ECGs in the ED. Additionally, the sample size of female patients was relatively small (n = 18), which limited our ability to perform a separate subgroup analysis for females. This imbalance in gender distribution may affect the generalizability of our findings across genders. A prospective study involving more patients is needed to overcome these limitations.

In conclusion, the predictive value of the QTc interval for mortality in acute poisoning patients may be greater when assessing the QTc interval after 6–12 hours of admission than when measuring the QTc at entry or tracking changes in the QTc between these two time points. We suggest that physicians reassess the QTc interval after 6–12 hours of initial evaluation and incorporate this information into risk stratification scores for acute poisoning. Furthermore, setting a lower limit for QTc interval prolongation may be advantageous for identifying patients at high risk of acute poisoning.

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https://doi.org/10.1371/journal.pone.0309940.s001

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Sex differences in the outcome of critically Ill patients with COVID-19 - An international multicenter critical care consortium study

Affiliations.

• 1 Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia; Griffith University School of Medicine, Gold Coast, Australia.
• 2 School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
• 3 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
• 4 Queensland University of Technology, Faculty of Health, Brisbane, Australia.
• 5 Neuroscience Critical Care Division, Departments of Neurology, Neurosurgery, and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
• 6 Cardiac Science Program, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada; University of Manitoba, Canada; Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA.
• 7 IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Surgical Science and Diagnostic Integrated, University of Genoa, Italy.
• 8 Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Queensland, Australia; Nuffield Department of Population Health, University of Oxford, UK; St Andrew's War Memorial Hospital, UnitingCare, Australia.
• 9 Inova Fairfax medical campus, Fairfax, VA, USA.
• 10 Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Queensland, Australia.
• 11 Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia; Queensland University of Technology, Faculty of Health, Brisbane, Australia; Faculty of Medicine, University of Queensland, Queensland, Australia.
• 12 Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia; Queensland University of Technology, Faculty of Health, Brisbane, Australia; Department of Surgical Science and Diagnostic Integrated, University of Genoa, Italy; St Andrew's War Memorial Hospital, UnitingCare, Australia.
• 13 Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA.
• 14 Neuroscience Critical Care Division, Departments of Neurology, Neurosurgery, and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: [email protected].
• PMID: 39260269
• DOI: 10.1016/j.hrtlng.2024.09.001

Background: Sex differences in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility, illness severity, and hospital course are widely acknowledged. The effects of sex on outcomes experienced by patients with severe Coronavirus Disease 2019 (COVID-19) admitted to the intensive care unit (ICU) remains unknown.

Objectives: To determine the effects of sex on ICU mortality in patients with COVID-19 METHODS: This retrospective analysis of an international multi-center prospective observational database included adults admitted to ICU for treatment of acute COVID-19 between 1st January 2020 and 30th June 2022. The primary outcome was ICU mortality. Multivariable Cox regression was used to ascertain the hazard of death (Hazard Ratio=HR) adjusted for pre-selected covariates. The secondary outcome was sex differences in complications of COVID-19 during hospital stay.

Results: Overall, 10,259 patients (3,314 females, 6,945 males) were included with a median age of 60 (interquartile range [IQR]=49-68) and 59 (IQR=49-67) years, respectively. Baseline characteristics were similar between sexes. More females were non-smokers (65% vs. 44 %, p < 0.01) and obese (39% vs. 30 %, p < 0.01), compared to males. Also, males received greater ICU intervention (mechanical ventilation, prone ventilation, vasopressors, and tracheostomy) than females. Males had a greater hazard of death (compared to females, HR=1.14; 95 % CI=1.02-1.26). Adjustment for complications during hospital stay did not alter the hazard of death (HR=1.16; 95 % CI=1.05-1.28). Males had a significantly elevated hazard of death among patients who received ECMO (HR=1.24; 95 % CI=1.01-1.53). Male sex was associated with cardiac arrest (adjusted OR [aOR]=1.37; 95 % CI=1.16-1.62) and PE (aOR=1.28; 95 % CI=1.06-1.55).

Conclusion: Among patients admitted to ICU for severe COVID-19, males experienced higher severity of illness and more frequent intervention than females. Ultimately, the hazard of death was moderately elevated in males compared to females despite greater PE and cardiac arrest.

Keywords: ARDS; COVID-19; ECMO; Mechanical Ventilation; Sex.

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

Declaration of competing interest We, the authors of the manuscript “Sex Differences in The Outcome of Critically Ill COVID-19 Patients - An International Multicentre COVID-19 Critical Care Consortium Study” declare that we have no competing interests in any of the categories listed: employment, consultancies, stock ownership, honoraria, paid expert testimony, patient applications/registrations (as listed on the journal website). Our funding statement as presented in the manuscript is accurate as of the submission date and presents no conflict of interests.

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No difference in 6-month functional outcome between early and late decompressive craniectomies following acute ischaemic stroke in a national neurosurgical centre: a single-centre retrospective case-cohort study

• Original Article
• Published: 10 September 2024

Cite this article

• Adina S. Nesa 1 ,
• Conor Gormley 1 ,
• Christopher Read 1 ,
• Sarah Power 2 ,
• Donncha O’Brien 3 ,
• Darragh Herlihy 2 ,
• Karl Boyle 4 &
• Caroline M. Larkin   ORCID: orcid.org/0000-0001-5373-3978 1  

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Decompressive craniectomies (DCs) are recommended for the treatment of raised intracranial pressure after acute ischaemic stroke. Some studies have demonstrated improved outcomes with early decompressive craniectomy (< 48 h from onset) in patients with malignant cerebral oedema following middle cerebral artery infarction. Limited data is available on suboccipital decompressive craniectomy after cerebellar infarction.

Our primary objective was to determine whether the timing of DCs influenced functional outcomes at 6 months. Our secondary objectives were to analyse whether age, gender, the territory of stroke, or preceding thrombectomy impacts functional outcome post-DC.

We conducted a retrospective study of patients admitted between January 2014 and December 2020 who had DCs post-acute ischaemic stroke. Data was collected from ICU electronic records, individual patient charts, and the stroke database.

Twenty-six patients had early DC (19 anterior/7 posterior) and 21 patients had late DC (17 anterior/4 posterior). There was no difference in the modified Rankin Scale (mRS) score of the two groups at 90 ( p  = 0.318) and 180 ( p  = 0.333) days post early vs late DC. Overall outcomes were poor, with 5 out of 46 patients (10.9%) having a mRS score ≤ 3 at 6 months. There was no difference in mRS scores between the patients who had hemicraniectomies for anterior circulation stroke ( n  = 35) and suboccipital DC for posterior circulation stroke ( n  = 11) ( p  = 0.594).

In this single-centre retrospective study, we found no significant difference in functional outcomes between patients who had early or late DC after ischaemic stroke.

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Outcomes of decompressive craniectomy for large territory cerebral infarction with and without prior reperfusion: a multicentre retrospective review

Surgical timing and indications for decompressive craniectomy in malignant stroke: results from a single-center retrospective analysis

Initial conservative management of severe hemispheric stroke reduces decompressive craniectomy rates, data availability.

The data that support the findings of this study are available on request from the corresponding author, CL. The data are not publicly available because they contain information that could compromise the privacy of research participants.

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Department of Anaesthetics and Intensive Care Medicine, Beaumont Hospital, Dublin, Ireland

Adina S. Nesa, Conor Gormley, Christopher Read & Caroline M. Larkin

Department of Neuroradiology, Beaumont Hospital, Dublin, Ireland

Sarah Power & Darragh Herlihy

Department of Neurosurgery, Beaumont Hospital, Dublin, Ireland

Donncha O’Brien

Department of Geriatric and Stroke Medicine, Beaumont Hospital, Dublin, Ireland

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Contributions

Adina S. Nesa, Caroline M. Larkin, Karl Boyle, Donncha O’Brien, and Sarah Power contributed to the study conception and design. Data collection was performed by Adina S. Nesa, Connor Gormley, Darragh Herlihy, and Christopher Read. Manuscript preparation was performed by Adina S. Nesa, Caroline M. Larkin, Sarah Power, Donncha O’Brien, and Karl Boyle. Data analysis was performed by Adina S. Nesa, Caroline M. Larkin, and Karl Boyle. The first draft of the manuscript was written by Adina S. Nesa, and all authors commented on previous versions of the manuscript. Authorship requirements have been met, and all authors have read and approved the final manuscript.

Corresponding author

Correspondence to Caroline M. Larkin .

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This research study was conducted retrospectively from data obtained for clinical purposes. The clinical audit division of Beaumont Hospital approved this study as a retrospective chart review (CA2021/012) and was exempted from informed consent. This manuscript complies with instructions to the authors.

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Nesa, A.S., Gormley, C., Read, C. et al. No difference in 6-month functional outcome between early and late decompressive craniectomies following acute ischaemic stroke in a national neurosurgical centre: a single-centre retrospective case-cohort study. Ir J Med Sci (2024). https://doi.org/10.1007/s11845-024-03801-7

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Received : 06 June 2024

Accepted : 30 August 2024

Published : 10 September 2024

DOI : https://doi.org/10.1007/s11845-024-03801-7

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