Epidermal Necrolyis: A Skin Disease to Take Your Breath Away* Thomas V. Brogan, MD Division of Critical Care Medicine Seattle Children's Hospital; and Department of Pediatrics University of Washington School of Medicine Seattle, WA
I
n this issue of Critical Care Medicine, de Prost et al (1) report their sobering experience with patients who present to their national referral center in Erance with StevensJohnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and SJS/TEN overlap. In their study, the authors reviewed the records of 221 patients of whom 66 (30%) were admitted to the ICU and 56 (25%) received mechanical ventilation. Patients receiving mechanical ventilation were demonstrably sicker than patients who did not receive mechanical ventilation. They had larger total body surface area (BSA) skin lesions at presentation as well as maximal skin involvement and they were plagued by more medical complications including shock, acute kidney injury, hemodialysis, and infections (e.g., pneumonia and bloodstream infections [BSIs]). It is worth noting that more than 90% of ventilated patients suffered shock. The severity of their illness was reflected in the sobering mortality of 57% of mechanically ventilated patients. Unfortunately, beyond the details of routine bronchoscopy for ventilated patients within the first 24 hours of intubation, the authors do not describe their strategy for mechanical ventilation. The readers are left to guess whether the early and aggressive application of therapies (e.g., low tidal volume and early prone positioning) shown to improve outcome in the acute respiratory distress syndrome (ARDS) (2, 3) may amehorate the high mortality rate in this group of patients. Of the patients who received mechanical ventilation, the authors documented bronchial epithelial lesions in nearly 40%. Bronchial lesions appear to be more common in patients with greater skin involvement and resulted in earlier application of mechanical ventilation (4). Patients with bronchial lesions were more likely to receive antibiotic therapy. Intriguingly, no differences in course, complications, or mortality were reported for the two groups although those with bronchial lesions received significantly earlier institution of mechanical ventilation. Thus, the precise meaning of these lesions remains unclear. *Seealso p. 118. Key Words: acute respiratory failure; bronchial epithelial lesions; SCORTEN; Stevens-Johnson syndrome; toxic epidermal necrolysis The author has disclosed that he does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI:10.1097/CCM.0b013e3182a51f06
210
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The authors evaluated a number of variables to assess their association with receipt of mechanical ventilation: anemia (serum hemoglobin, < 8g/dL), leukocytosis (WBC, > 12,000/ mm^), and a higher the toxic epidermal necrolysis-specific severity of illness score (SCORTEN) value. The SCORTEN is a prognostic scoring system for patients with epidermal necrolysis (5) and includes the following variables: age more than 40 years, heart rate more than 120 beats/min, malignancy, BSA involved more than 10%, serum urea more than lOmM, serum bicarbonate less than 20 mM, and serum glucose more than 14 mM. Importantly, the SCORTEN scale does not include a variable for respiratory involvement that may make the scale less sensitive to impending respiratory decompensation. When the elements of the SCORTEN were added to the model individually, six variables remained significant: greater skin involvement, low serum bicarbonate level, elevated serum urea, leukocytosis, anemia, and extension of pulmonary infiltrates. Adjuvant therapies (cyclosporine and IV gamma globulin) were not associated with receipt of mechanical ventuation. The mortality of this disease has not changed over the past quarter century (6,7). These results appear all the more disheartening when compared against the progress made in critical care during that time and the improvement in survival of disease such as ARDS (2, 3). But sepsis has been identified as the leading risk factor for mortality in prior studies of SJS/TEN. Creater skin involvement appears to be associated with infection (6,7). In the current study by de Prost et al ( 1 ), nearly half of the patients who were ventilated had 30% or greater total BSA involvement, extensive involvement indeed. Because of mucosal involvement of the gastrointestinal tract and lungs, patients are at risk for BSI not only from common skin pathogens but also from enteric organisms. Unfortunately, skin cultures are not sensitive at predicting these organisms (7). However, these studies point out that therapy needs to address the multiple organ nature of this disease. Previous studies have shown that the only factors that have been correlated with better outcomes are the rapid removal of the suspected causative agent(s) and transfer to a referral center, a point underscored by the authors (8, 9). This study and others studies clearly show that patients with lesser area of skin involvement receive less mechanical ventilation and have lower rates of BSI and lower mortality. These findings suggest that patients would probably benefit from education about early signs of this debihtating illness and the need for consultation especially when receiving one of the dozen or so high-risk medications that have been identified with SJS/TEN. Half of the patients who received mechanical ventilation were admitted directly to the ICU, supporting the notion that the disease had progressed to an advanced stage before patients sought care or were transferred to the regional center. Also, genetic markers associated with SJS/TEN have been identified (10-12) and may present an important preventative strategy moving forward. January 2014 • Volume 42 • Number 1
Editorials
Although the authors have done an admirable job of assembling a large cohort to study, their findings emphasize the need for multi-institutional, multinational collaboration to study this uncommon disease process in order to better understand risk factors, pathophysiology, and possible therapies that the high mortality demands. Fortunately, a start in this direction has already occurred with the European Registry of Severe Cutaneous Adverse Drug Reactions (severe cutaneous adverse drug reaction) Project, a multinational database. Thus, de Prost et al have identified the complex nature of epidermal necrolysis; it is a challenge to us now to improve care.
REFERENCES 1. de Prost N, Mekontso-Dessap A, Valeryie-Allanore L, et al: Acute Respiratory Failure in Patients With Toxic Epidermal Necrolysis: Clinical Features and Factors Associated With Mechanical Ventilation. Crit Care Med 2014; 42:118-1 28 2. The Acute Respiratory Distress Syndrome Network: Ventilation wifh lower tidal volumes for acute lung injury and fhe acute respiratory distress syndrome. N EngI J Med 2000; 342:1301 -1308 3. Guérin C, Reignier J, Richard JC, et al; PROSEVA Study Group: Prone positioning in severe acute respiratory distress syndrome. N EngI J Med 2013; 368:2159-21 68
4. Lebargy F, Wolkensfein P, Gisselbrecht M, et al: Pulmonary complications in toxic epidermal necrolysis: A prospective clinical study. Intensive Care Med 1997; 23:1 237-1 244 5. Bastuji-Garin S, Fouchard N, Bertocchi M, et al: SCORTEN: A severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115:149-153 6. Revuz J, Penso D, Rcujeau JC, et al: Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients. Arch Dermatol 1987; 123:1160-1165 7 de Prest N, Ingen-Housz-Oro S, Duong TA, et al: Bacteremia in StevensJohnson syndrome and toxic epidermal necrolysis: Epidemiology, risk factors, and predictive value of skin cultures. Medicine (Baltimore) 2010; 89:28-36 8. Garcia-Doval I, LeCleach L, Bocquet H, et al: Toxic epidermal necrolysis and Stevens-Johnson syndrome: Dees early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 2000; 136:323-327 9. Palmieri TL, Greenhaigh DG, Saffle JR, et al: A multicenter review of toxic epidermal necrclysis treated in U.S. burn centers at the end of the twentieth century. J Burn Care Rehabil 2002; 23:87-96 10. Chung WH, Hung SI, Hong HS, et al: Medical genetics: A marker for Stevens-Johnson syndrome. Nature 2004; 428:486 11. Hung SI, Chung WH, Liou LB, et al: HLA-B*5801 alíele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Nati Acad Sei USA 2005; 102:4134-4139 12. Chung WH, Hung SI, Chen YT: Genetic predisposition of life-threatening antiepileptic-induced skin reactions. Expert Opin Drug Saf 2010; 9:15-21
Are We Offtrack Using Propofol for Sedation After Traumatic Brain Injury?* MarkCoburn, MD Department of Anesthesiology University Hospital RWTH Aachen Aachen, Germany Pratik P. Pandharipande, MD, MSCI, FCCM Department of Anesthesiology Division of Critical Care Vanderbilt University Medical Center Nashville, TN
'See also p. 129. Key Words: mortality; neurogenesis; propofol; sedatives; traumatic brain injury Dr. Coburn consulted for Air Liquide Sante International, his institution received grant support from Deutsche Forschungsgemeinschaff and Air Liquide Sante International. Dr. Pandharipande's institution received grant support from Hospira (cosuppcrt with the National Institutes of Health). Dr. Sanders consulted for Air Liquide (consultancy on the development of medical gases) and lectured for Orion. Dr. Sanders and his institution received grant support from Orion (unrestricted grant for electroencephalography/functionai MRI study of dexmedefomidine in healthy volunteers). Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097CCM.0000000000000009
Critical Care Medicine
Robert D. Sanders, BSc, MBBS, PhD, FRCA Department of Anaesthesia and Surgical Outcomes Research Centre University College London Hospital; and Wellcome Department of Imaging Neuroscience University College London London, United Kingdom
P
ropofol is widely used for sedation in ICU patients, including sedation after traumatic brain injury. The gamma-aminobutyric acid type A (CABA^) receptor has been identified as a molecular target for propofol underlying general anesthesia and sedation (1). Interestingly, the neurotransmitter, GABA, serves as a key mediator in adult neurogenesis (2). Neurogenesis occurs throughout life in mammals, including humans (3,4), and plays a restorative role after brain injury. Despite overlapping receptor targets, limited data exist on the inñuence of propofol on endogenous neurogenesis after traumatic brain injury, hence the importance of the work carried out by Thai et al (5). In this issue of Critical Care Medicine, Thai et al (5) assessed, in a well-established adult rat model of traumatic brain injury, the effects of propofol on mortality rate, neurological function, and neurogenesis. A mechanical vwvw.ccr-njournal.org
211
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
I
n this issue of Critical Care Medicine, de Prost et al (1) report their sobering experience with patients who present to their national referral center in Erance with StevensJohnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and SJS/TEN overlap. In their study, the authors reviewed the records of 221 patients of whom 66 (30%) were admitted to the ICU and 56 (25%) received mechanical ventilation. Patients receiving mechanical ventilation were demonstrably sicker than patients who did not receive mechanical ventilation. They had larger total body surface area (BSA) skin lesions at presentation as well as maximal skin involvement and they were plagued by more medical complications including shock, acute kidney injury, hemodialysis, and infections (e.g., pneumonia and bloodstream infections [BSIs]). It is worth noting that more than 90% of ventilated patients suffered shock. The severity of their illness was reflected in the sobering mortality of 57% of mechanically ventilated patients. Unfortunately, beyond the details of routine bronchoscopy for ventilated patients within the first 24 hours of intubation, the authors do not describe their strategy for mechanical ventilation. The readers are left to guess whether the early and aggressive application of therapies (e.g., low tidal volume and early prone positioning) shown to improve outcome in the acute respiratory distress syndrome (ARDS) (2, 3) may amehorate the high mortality rate in this group of patients. Of the patients who received mechanical ventilation, the authors documented bronchial epithelial lesions in nearly 40%. Bronchial lesions appear to be more common in patients with greater skin involvement and resulted in earlier application of mechanical ventilation (4). Patients with bronchial lesions were more likely to receive antibiotic therapy. Intriguingly, no differences in course, complications, or mortality were reported for the two groups although those with bronchial lesions received significantly earlier institution of mechanical ventilation. Thus, the precise meaning of these lesions remains unclear. *Seealso p. 118. Key Words: acute respiratory failure; bronchial epithelial lesions; SCORTEN; Stevens-Johnson syndrome; toxic epidermal necrolysis The author has disclosed that he does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI:10.1097/CCM.0b013e3182a51f06
210
vwvw.ccnnjournal.org
The authors evaluated a number of variables to assess their association with receipt of mechanical ventilation: anemia (serum hemoglobin, < 8g/dL), leukocytosis (WBC, > 12,000/ mm^), and a higher the toxic epidermal necrolysis-specific severity of illness score (SCORTEN) value. The SCORTEN is a prognostic scoring system for patients with epidermal necrolysis (5) and includes the following variables: age more than 40 years, heart rate more than 120 beats/min, malignancy, BSA involved more than 10%, serum urea more than lOmM, serum bicarbonate less than 20 mM, and serum glucose more than 14 mM. Importantly, the SCORTEN scale does not include a variable for respiratory involvement that may make the scale less sensitive to impending respiratory decompensation. When the elements of the SCORTEN were added to the model individually, six variables remained significant: greater skin involvement, low serum bicarbonate level, elevated serum urea, leukocytosis, anemia, and extension of pulmonary infiltrates. Adjuvant therapies (cyclosporine and IV gamma globulin) were not associated with receipt of mechanical ventuation. The mortality of this disease has not changed over the past quarter century (6,7). These results appear all the more disheartening when compared against the progress made in critical care during that time and the improvement in survival of disease such as ARDS (2, 3). But sepsis has been identified as the leading risk factor for mortality in prior studies of SJS/TEN. Creater skin involvement appears to be associated with infection (6,7). In the current study by de Prost et al ( 1 ), nearly half of the patients who were ventilated had 30% or greater total BSA involvement, extensive involvement indeed. Because of mucosal involvement of the gastrointestinal tract and lungs, patients are at risk for BSI not only from common skin pathogens but also from enteric organisms. Unfortunately, skin cultures are not sensitive at predicting these organisms (7). However, these studies point out that therapy needs to address the multiple organ nature of this disease. Previous studies have shown that the only factors that have been correlated with better outcomes are the rapid removal of the suspected causative agent(s) and transfer to a referral center, a point underscored by the authors (8, 9). This study and others studies clearly show that patients with lesser area of skin involvement receive less mechanical ventilation and have lower rates of BSI and lower mortality. These findings suggest that patients would probably benefit from education about early signs of this debihtating illness and the need for consultation especially when receiving one of the dozen or so high-risk medications that have been identified with SJS/TEN. Half of the patients who received mechanical ventilation were admitted directly to the ICU, supporting the notion that the disease had progressed to an advanced stage before patients sought care or were transferred to the regional center. Also, genetic markers associated with SJS/TEN have been identified (10-12) and may present an important preventative strategy moving forward. January 2014 • Volume 42 • Number 1
Editorials
Although the authors have done an admirable job of assembling a large cohort to study, their findings emphasize the need for multi-institutional, multinational collaboration to study this uncommon disease process in order to better understand risk factors, pathophysiology, and possible therapies that the high mortality demands. Fortunately, a start in this direction has already occurred with the European Registry of Severe Cutaneous Adverse Drug Reactions (severe cutaneous adverse drug reaction) Project, a multinational database. Thus, de Prost et al have identified the complex nature of epidermal necrolysis; it is a challenge to us now to improve care.
REFERENCES 1. de Prost N, Mekontso-Dessap A, Valeryie-Allanore L, et al: Acute Respiratory Failure in Patients With Toxic Epidermal Necrolysis: Clinical Features and Factors Associated With Mechanical Ventilation. Crit Care Med 2014; 42:118-1 28 2. The Acute Respiratory Distress Syndrome Network: Ventilation wifh lower tidal volumes for acute lung injury and fhe acute respiratory distress syndrome. N EngI J Med 2000; 342:1301 -1308 3. Guérin C, Reignier J, Richard JC, et al; PROSEVA Study Group: Prone positioning in severe acute respiratory distress syndrome. N EngI J Med 2013; 368:2159-21 68
4. Lebargy F, Wolkensfein P, Gisselbrecht M, et al: Pulmonary complications in toxic epidermal necrolysis: A prospective clinical study. Intensive Care Med 1997; 23:1 237-1 244 5. Bastuji-Garin S, Fouchard N, Bertocchi M, et al: SCORTEN: A severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000; 115:149-153 6. Revuz J, Penso D, Rcujeau JC, et al: Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients. Arch Dermatol 1987; 123:1160-1165 7 de Prest N, Ingen-Housz-Oro S, Duong TA, et al: Bacteremia in StevensJohnson syndrome and toxic epidermal necrolysis: Epidemiology, risk factors, and predictive value of skin cultures. Medicine (Baltimore) 2010; 89:28-36 8. Garcia-Doval I, LeCleach L, Bocquet H, et al: Toxic epidermal necrolysis and Stevens-Johnson syndrome: Dees early withdrawal of causative drugs decrease the risk of death? Arch Dermatol 2000; 136:323-327 9. Palmieri TL, Greenhaigh DG, Saffle JR, et al: A multicenter review of toxic epidermal necrclysis treated in U.S. burn centers at the end of the twentieth century. J Burn Care Rehabil 2002; 23:87-96 10. Chung WH, Hung SI, Hong HS, et al: Medical genetics: A marker for Stevens-Johnson syndrome. Nature 2004; 428:486 11. Hung SI, Chung WH, Liou LB, et al: HLA-B*5801 alíele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Nati Acad Sei USA 2005; 102:4134-4139 12. Chung WH, Hung SI, Chen YT: Genetic predisposition of life-threatening antiepileptic-induced skin reactions. Expert Opin Drug Saf 2010; 9:15-21
Are We Offtrack Using Propofol for Sedation After Traumatic Brain Injury?* MarkCoburn, MD Department of Anesthesiology University Hospital RWTH Aachen Aachen, Germany Pratik P. Pandharipande, MD, MSCI, FCCM Department of Anesthesiology Division of Critical Care Vanderbilt University Medical Center Nashville, TN
'See also p. 129. Key Words: mortality; neurogenesis; propofol; sedatives; traumatic brain injury Dr. Coburn consulted for Air Liquide Sante International, his institution received grant support from Deutsche Forschungsgemeinschaff and Air Liquide Sante International. Dr. Pandharipande's institution received grant support from Hospira (cosuppcrt with the National Institutes of Health). Dr. Sanders consulted for Air Liquide (consultancy on the development of medical gases) and lectured for Orion. Dr. Sanders and his institution received grant support from Orion (unrestricted grant for electroencephalography/functionai MRI study of dexmedefomidine in healthy volunteers). Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097CCM.0000000000000009
Critical Care Medicine
Robert D. Sanders, BSc, MBBS, PhD, FRCA Department of Anaesthesia and Surgical Outcomes Research Centre University College London Hospital; and Wellcome Department of Imaging Neuroscience University College London London, United Kingdom
P
ropofol is widely used for sedation in ICU patients, including sedation after traumatic brain injury. The gamma-aminobutyric acid type A (CABA^) receptor has been identified as a molecular target for propofol underlying general anesthesia and sedation (1). Interestingly, the neurotransmitter, GABA, serves as a key mediator in adult neurogenesis (2). Neurogenesis occurs throughout life in mammals, including humans (3,4), and plays a restorative role after brain injury. Despite overlapping receptor targets, limited data exist on the inñuence of propofol on endogenous neurogenesis after traumatic brain injury, hence the importance of the work carried out by Thai et al (5). In this issue of Critical Care Medicine, Thai et al (5) assessed, in a well-established adult rat model of traumatic brain injury, the effects of propofol on mortality rate, neurological function, and neurogenesis. A mechanical vwvw.ccr-njournal.org
211
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
