SURGICAL INFECTIONS Volume 15, Number 6, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/sur.2014.052
Mycobacterium abscessus Infection in a Burn Intensive Care Unit Patient Tanaz Vaghaiwalla, Shevonne S. Satahoo, Rolla Zarifa, Marc Dauer, James S. Davis, Doreann Dearmas, Nicholas Namias, Louis R. Pizano, and Carl I. Schulman
Abstract
Background: Infection is the leading cause of death in burn patients. Historically, this was due to burn wound sepsis but pneumonia has now emerged as the most common source. In light of the increasing incidence of multi-drug-resistant organisms, the description of rare infections is paramount in continuing the fight against deadly pathogens. We aim to describe the second case of non-tuberculous mycobacterium (NTM) reported in a burn patient. Difficulties in diagnosis and management will also be highlighted. Methods: A 70-y-old Caucasian female, with a past medical history for type 2 diabetes mellitus, was transferred to our facility after a house fire. She had sustained a 28% total body surface area (TBSA) flame burn to her neck, torso, and all four extremities. She underwent excision and grafting on hospital day five with multiple subsequent attempts at excision and grafting due to graft loss. On hospital day 14, a tracheostomy was performed. Her hospital course was complicated by ongoing respiratory failure, renal injury, and sepsis. Results: Mycobacterium abscessus was found on blood cultures from central venous catheters and arterial line catheters as well as on tracheal aspirate and bronchoalveolar lavage (BAL) on hospital day 86. Imaging then revealed multiple pulmonary nodular densities with patchy ground-glass opacities. After multiple adjustments to the antibiotic regimen, tigecycline, clarithromycin, and cefoxitin therapy was started. She remained on this regimen for almost 4 wks. Her other infections included Acinetobacter baumanii treated with tobramycin and colistin, as well as Candida albicans for which she received fluconazole. Ultimately, her clinical state worsened leading to withdrawal of care. Conclusions: Sepsis NTM is rare in burn patients with only one other case described in the English-language literature. Both cases reflect differences in diagnosis and management. This highlights the need to discuss rare infections in an attempt to broaden the clinician’s awareness of such pathogens, as well as to collaborate to form a consensus about their management.
I
nfection is the leading cause of death in burn patients after recovery from the initial burn injury [1,2]. It is estimated that there are 3,400 deaths from thermal burns per year [3]. Historically, these deaths were secondary to burn wound infection, but with current therapies, pneumonia is now the primary reason [1]. Primary pathogenic agents are Staphylococcus aureus and Pseudomonas aeruginosa [1,2]. Nevertheless, in the age of multi-drug-resistant organisms, documenting rare infections is crucial to expand clinician awareness of potential infectious pathogens and double as a barometer of infectious disease evolution in the burn population.
We present a case of non-tuberculous Mycobacterium (NTM) infection in a burn patient. Mycobacteria are grampositive and acid-fast bacilli (AFB) ubiquitous in the natural environment [2,4]. Non-tuberculous mycobacterium refers to a subset of mycobacterium that excludes M. tuberculosis complex and M. leprae [5]. Non-tuberculous Mycobacterium infections have been associated with human disease since the 1930s [5]. There are approximately 50 mycobacterial species believed to be responsible for human disease states [5]. With the advent of immunosuppressant diseases and medications, the incidence of NTM infections has increased [5], although this case is only the second such report in the burn population [2].
Division of Trauma and Critical Care, Jackson Memorial Hospital/University of Miami Burn Center, University of Miami Miller School of Medicine, Miami, Florida.
847
848 Case Report
A 70-y-old Caucasian female suffered a 28% total body surface area (TBSA) flame burn after her house caught fire secondary to an unknown mechanism. The patient suffered second- and third-degree burns to regions of the neck, chest, back, and bilateral upper and lower extremities. She was intubated and stabilized initially at an outside hospital prior to transfer to our facility’s burn center for further management. Pertinent past medical history included type 2 diabetes mellitus and no prior surgical history. The patient was extubated on hospital day two in the burn intensive care unit (ICU). On hospital day five, the patient underwent initial excision and debridement with grafting using cadaveric skin of full-thickness wounds to the torso, right arm, right breast, and abdomen, which constituted approximately 25% TBSA. The patient remained intubated on transfer back to the burn ICU after experiencing several episodes of hypotension despite fluid resuscitation. She had a tracheostomy on hospital day 14. Throughout her stay, she underwent multiple additional excision and grafting procedures, complicated by graft loss and poor donor site healing. Burn wound care included 1% silver sulfodiazene, silver silicone foam dressing, and sulfamylon soaks. The patient’s hospital stay was complicated by continued respiratory failure, acute-one-chronic kidney injury frequently requiring dialysis, and sepsis. Positive blood cultures included methicillin-resistant S. aureus on hospital day 10, Candida albicans on hospital day 34, and Acinetobacter baumannii complex on hospital days 100 and 118. On hospital days 41, 46, and 69, M. abscessus was cultured from central venous catheters and arterial catheters. Multiple tracheal aspirates and bronchoalveolar lavage (BAL) testing grew various bacteria, including M. abscessus on hospital day 86 on tracheal aspirate via culture and staining for acid-fast bacteria. With infectious disease consultation, on hospital day 86 the patient was treated with intravenous azithromycin, linezolid, and imipenem-cilastatin while initially awaiting antibiotic sensitivities. On hospital day 95, azithromycin was discontinued and the patient was started on clarithromycin. On hospital day 101, the patient was started on colistin. Biochemical and mycolic acid tests were sent, and ultimately confirmed the initial M. abscessus blood cultures. Culture susceptibilities returned on hospital day 105, demonstrating susceptibility to amikacin, kanamycin, tobramycin, cefoxitin, tigecycline, clarithromycin, and azithromycin, tentative susceptibility to clofazimine and intermediate susceptibility to imipenem-cilastatin. Resistance was noted to ciprofloxacin, moxifloxacin, doxycycline, amoxicillin-clavulanaic acid, trimethoprim-sulfamethoxazole, and linezolid. On hospital day 105, the patient began receiving cefoxitin, clarithromycin, and amikacin once antibiotic susceptibilities became available, while colistin was discontinued. Amikacin was discontinued on hospital day 107 due to concern for further nephrotoxicity in the setting of the patient’s oliguric renal failure. As of hospital day 103, culture of the sputum revealed no further isolates. Biochemical and mycolic acid testing of blood cultures were performed at National Jewish Health Medical Center (Denver, CO). Antimicrobial susceptibility testing of the isolate in the patient showed M. abscessus. The patient’s central lines were changed every three days or sooner when suspicious for infection.
VAGHAIWALLA ET AL.
On hospital day 100, computed tomography (CT) of the chest with contrast showed multiple calcified and non-calcified pulmonary nodular densities. The largest non-calcified nodule measured up to 5 mm. Other pertinent findings on CT included patchy ground-glass opacities in the bilateral lower lobes, as well as tree in bud densities consistent with multiple focal infection or inflammation and peripheral endobronchial spread of infection. Additional workup was negative, including transthoracic echocardiography (hospital day 108). On hospital day 111, the patient was started on tigecycline and remained on a triple regimen that also included clarithromycin and cefoxitin. The patient’s blood cultures and tracheal aspirates remained free of NTM isolates. On hospital days 100 and 118, the patient’s blood cultures grew A. baumannii, at which point tobramycin, and ultimately colistin was added to her antibiotic regimen. Candida albicans was also found in her urine on hospital days 116 and 130, for which she received fluconazole. Ultimately, the patient’s clinical course worsened. She became increasingly acidotic and hypotensive requiring multiple vasopressors for support. After extended conversations, the family chose to withdraw care, and the patient died on hospital day 137. Discussion
Mycobacteria are gram-positive and acid-fast bacteria [2]. Non-tuberculous mycobacteria are free-living bacteria that are ubiquitous throughout the environment with reservoirs that include water, soil, rarely animals, and dairy products [4,5]. Non-tuberculous Mycobacterium can colonize medical equipment such as endoscopes and surgical solutions [2,4]. There are numerous species of mycobacteria that can cause differing disease states [5]. Potential disease states include pulmonary disease, lymphadenitis, skin and soft tissue infection, skeletal infection (bone, joint or tendon), foreign body and catheter-related infections, and widely disseminated disease [4,5]. Similar to M. tuberculosis, NTM have an increased risk in patients with pre-existing lung disease [1]. Individuals with acquired immunodeficiency such as human immunodeficiency virus infection, diabetes mellitus, leukemia, and other immunosuppressed states are at increased risk of developing an NTM infection [1]. Patients with burns may be more susceptible to NTM infections because they are immunosuppressed and potentially have inhalation injuries [2]. Severely burned patients lack the protective barrier of the skin due to the inherent nature of burns [2]. In addition these patients may have prolonged ICU stays with extended use of venous catheters, which may also leave them more susceptible to infection with NTM [2]. Sepsis remains the primary cause of mortality in burn patients after recovery from the initial thermal injury [1,2]. Burn patients are more susceptible to infections for multiple reasons including immunosuppressive state, impaired skin integrity, and multiple prolonged central verous and arterial catheterizations [2]. These factors also increase the risk of contracting insidious infections such as NTM. Nevertheless, NTM sepsis remains rare among burn patients, and only one other case has been documented in the English-language literature [2]. Boyer et al. [2] reported a 52-y-old male patient with 65% TBSA burn from an explosive device in Iraq where
MYCOBACTERIUM ABSCESSUS IN BURNS
he was intubated emergently and transferred to Landstuhl Regional Medical Center in Germany for initial stabilization. Subsequently the patient was transferred to U.S. Army Institute of Surgical Research Burn Intensive Care Unit at Brooke Army Medical Center (San Antonio, TX) for further care. The patient received initial excision and debridement with grafting, with approximately 10% TBSA remaining open. This patient’s hospital course was reportedly complicated by episodes of sepsis with several bacterial organisms including Pseudomonas aeruginosa and Enterobacter cloacae treated with broad-spectrum antibiotics. The patient’s blood cultures on hospital days 72 and 79 showed acid-fast bacteria. The patient’s BAL and tracheal aspirates were negative, which is unlike our patient who also produced positive BAL. The patient was treated empirically with imipenem, tobramycin, and azithromycin, although our patient was treated initially with cefoxitin, clarithromycin, and amikacin. According to the American Thoracic Society, patients with suspected NTM-related pulmonary disease should receive a chest radiograph (or high-resolution CT in the absence of cavitations) and three or more sputum specimens for testing [4,6]. Mycobacterium tuberculosis infection must be excluded [4,6]. Two positive sputum samples or one positive BAL sample are sufficient to diagnose pulmonary disease [4]. Our patient’s microbiologic workup was consistent with pulmonary NTM. Given the rarity of NTM, data on antibiotic course remain limited [1]. This report documents an exceedingly rare case of M. abscessus infection in a burn patient. In this era of multidrug-resistant organisms, thorough documentation can help broaden the clinician’s awareness of potential infectious pathogens. Moreover, such information is vital for determining optimal antimicrobial duration and course. At this time it is unclear whether the patient’s M. abscessus infection resulted from endovascular source of infection or pulmonary disease with CT findings concerning for mycobacterial infection and positive BAL. There were no obvious abscesses
849
or cellulitic changes to suggest primary infection of the skin or soft tissue, however, biopsies were not performed. The patient underwent withdrawal of intensive care and died shortly after. Author Disclosure Statement
No competing financial interests exist. References
1. Mayhall CG. The epidemiology of burn wound infections: Then and now. Clin Infect Dis 2003;37:543–550. 2. Boyer JM, Blatz PJ, Akers KS, et al. Nontuberculous mycobacterium infection in a burn ICU patient. Burns 2010; 36:e136–e139. 3. Burn incidence and treatment in the United States: 2012 fact sheet. www.ameriburn.org/resources_factsheet.php (Last accessed January 14, 2014). 4. Brown-Elliott BA, Wallace RJ Jr. Infections caused by nontuberculous mycobacteria. In: Mandell GL, Bennett JE, Dolin R (eds): Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease, Volume 2, 6th ed. Philadelphia. Elsevier, 2005: 2909–2916. 5. Wagner D, Young LS. Nontuberculous mycobacterial infections: A clinical review. Infection 2004;32:257–270. 6. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367–416.
Address correspondence to: Dr. Carl I. Schulman Ryder Trauma Center PO Box 016960 (D-40) Miami, FL 33136 E-mail: [email protected]
Mycobacterium abscessus Infection in a Burn Intensive Care Unit Patient Tanaz Vaghaiwalla, Shevonne S. Satahoo, Rolla Zarifa, Marc Dauer, James S. Davis, Doreann Dearmas, Nicholas Namias, Louis R. Pizano, and Carl I. Schulman
Abstract
Background: Infection is the leading cause of death in burn patients. Historically, this was due to burn wound sepsis but pneumonia has now emerged as the most common source. In light of the increasing incidence of multi-drug-resistant organisms, the description of rare infections is paramount in continuing the fight against deadly pathogens. We aim to describe the second case of non-tuberculous mycobacterium (NTM) reported in a burn patient. Difficulties in diagnosis and management will also be highlighted. Methods: A 70-y-old Caucasian female, with a past medical history for type 2 diabetes mellitus, was transferred to our facility after a house fire. She had sustained a 28% total body surface area (TBSA) flame burn to her neck, torso, and all four extremities. She underwent excision and grafting on hospital day five with multiple subsequent attempts at excision and grafting due to graft loss. On hospital day 14, a tracheostomy was performed. Her hospital course was complicated by ongoing respiratory failure, renal injury, and sepsis. Results: Mycobacterium abscessus was found on blood cultures from central venous catheters and arterial line catheters as well as on tracheal aspirate and bronchoalveolar lavage (BAL) on hospital day 86. Imaging then revealed multiple pulmonary nodular densities with patchy ground-glass opacities. After multiple adjustments to the antibiotic regimen, tigecycline, clarithromycin, and cefoxitin therapy was started. She remained on this regimen for almost 4 wks. Her other infections included Acinetobacter baumanii treated with tobramycin and colistin, as well as Candida albicans for which she received fluconazole. Ultimately, her clinical state worsened leading to withdrawal of care. Conclusions: Sepsis NTM is rare in burn patients with only one other case described in the English-language literature. Both cases reflect differences in diagnosis and management. This highlights the need to discuss rare infections in an attempt to broaden the clinician’s awareness of such pathogens, as well as to collaborate to form a consensus about their management.
I
nfection is the leading cause of death in burn patients after recovery from the initial burn injury [1,2]. It is estimated that there are 3,400 deaths from thermal burns per year [3]. Historically, these deaths were secondary to burn wound infection, but with current therapies, pneumonia is now the primary reason [1]. Primary pathogenic agents are Staphylococcus aureus and Pseudomonas aeruginosa [1,2]. Nevertheless, in the age of multi-drug-resistant organisms, documenting rare infections is crucial to expand clinician awareness of potential infectious pathogens and double as a barometer of infectious disease evolution in the burn population.
We present a case of non-tuberculous Mycobacterium (NTM) infection in a burn patient. Mycobacteria are grampositive and acid-fast bacilli (AFB) ubiquitous in the natural environment [2,4]. Non-tuberculous mycobacterium refers to a subset of mycobacterium that excludes M. tuberculosis complex and M. leprae [5]. Non-tuberculous Mycobacterium infections have been associated with human disease since the 1930s [5]. There are approximately 50 mycobacterial species believed to be responsible for human disease states [5]. With the advent of immunosuppressant diseases and medications, the incidence of NTM infections has increased [5], although this case is only the second such report in the burn population [2].
Division of Trauma and Critical Care, Jackson Memorial Hospital/University of Miami Burn Center, University of Miami Miller School of Medicine, Miami, Florida.
847
848 Case Report
A 70-y-old Caucasian female suffered a 28% total body surface area (TBSA) flame burn after her house caught fire secondary to an unknown mechanism. The patient suffered second- and third-degree burns to regions of the neck, chest, back, and bilateral upper and lower extremities. She was intubated and stabilized initially at an outside hospital prior to transfer to our facility’s burn center for further management. Pertinent past medical history included type 2 diabetes mellitus and no prior surgical history. The patient was extubated on hospital day two in the burn intensive care unit (ICU). On hospital day five, the patient underwent initial excision and debridement with grafting using cadaveric skin of full-thickness wounds to the torso, right arm, right breast, and abdomen, which constituted approximately 25% TBSA. The patient remained intubated on transfer back to the burn ICU after experiencing several episodes of hypotension despite fluid resuscitation. She had a tracheostomy on hospital day 14. Throughout her stay, she underwent multiple additional excision and grafting procedures, complicated by graft loss and poor donor site healing. Burn wound care included 1% silver sulfodiazene, silver silicone foam dressing, and sulfamylon soaks. The patient’s hospital stay was complicated by continued respiratory failure, acute-one-chronic kidney injury frequently requiring dialysis, and sepsis. Positive blood cultures included methicillin-resistant S. aureus on hospital day 10, Candida albicans on hospital day 34, and Acinetobacter baumannii complex on hospital days 100 and 118. On hospital days 41, 46, and 69, M. abscessus was cultured from central venous catheters and arterial catheters. Multiple tracheal aspirates and bronchoalveolar lavage (BAL) testing grew various bacteria, including M. abscessus on hospital day 86 on tracheal aspirate via culture and staining for acid-fast bacteria. With infectious disease consultation, on hospital day 86 the patient was treated with intravenous azithromycin, linezolid, and imipenem-cilastatin while initially awaiting antibiotic sensitivities. On hospital day 95, azithromycin was discontinued and the patient was started on clarithromycin. On hospital day 101, the patient was started on colistin. Biochemical and mycolic acid tests were sent, and ultimately confirmed the initial M. abscessus blood cultures. Culture susceptibilities returned on hospital day 105, demonstrating susceptibility to amikacin, kanamycin, tobramycin, cefoxitin, tigecycline, clarithromycin, and azithromycin, tentative susceptibility to clofazimine and intermediate susceptibility to imipenem-cilastatin. Resistance was noted to ciprofloxacin, moxifloxacin, doxycycline, amoxicillin-clavulanaic acid, trimethoprim-sulfamethoxazole, and linezolid. On hospital day 105, the patient began receiving cefoxitin, clarithromycin, and amikacin once antibiotic susceptibilities became available, while colistin was discontinued. Amikacin was discontinued on hospital day 107 due to concern for further nephrotoxicity in the setting of the patient’s oliguric renal failure. As of hospital day 103, culture of the sputum revealed no further isolates. Biochemical and mycolic acid testing of blood cultures were performed at National Jewish Health Medical Center (Denver, CO). Antimicrobial susceptibility testing of the isolate in the patient showed M. abscessus. The patient’s central lines were changed every three days or sooner when suspicious for infection.
VAGHAIWALLA ET AL.
On hospital day 100, computed tomography (CT) of the chest with contrast showed multiple calcified and non-calcified pulmonary nodular densities. The largest non-calcified nodule measured up to 5 mm. Other pertinent findings on CT included patchy ground-glass opacities in the bilateral lower lobes, as well as tree in bud densities consistent with multiple focal infection or inflammation and peripheral endobronchial spread of infection. Additional workup was negative, including transthoracic echocardiography (hospital day 108). On hospital day 111, the patient was started on tigecycline and remained on a triple regimen that also included clarithromycin and cefoxitin. The patient’s blood cultures and tracheal aspirates remained free of NTM isolates. On hospital days 100 and 118, the patient’s blood cultures grew A. baumannii, at which point tobramycin, and ultimately colistin was added to her antibiotic regimen. Candida albicans was also found in her urine on hospital days 116 and 130, for which she received fluconazole. Ultimately, the patient’s clinical course worsened. She became increasingly acidotic and hypotensive requiring multiple vasopressors for support. After extended conversations, the family chose to withdraw care, and the patient died on hospital day 137. Discussion
Mycobacteria are gram-positive and acid-fast bacteria [2]. Non-tuberculous mycobacteria are free-living bacteria that are ubiquitous throughout the environment with reservoirs that include water, soil, rarely animals, and dairy products [4,5]. Non-tuberculous Mycobacterium can colonize medical equipment such as endoscopes and surgical solutions [2,4]. There are numerous species of mycobacteria that can cause differing disease states [5]. Potential disease states include pulmonary disease, lymphadenitis, skin and soft tissue infection, skeletal infection (bone, joint or tendon), foreign body and catheter-related infections, and widely disseminated disease [4,5]. Similar to M. tuberculosis, NTM have an increased risk in patients with pre-existing lung disease [1]. Individuals with acquired immunodeficiency such as human immunodeficiency virus infection, diabetes mellitus, leukemia, and other immunosuppressed states are at increased risk of developing an NTM infection [1]. Patients with burns may be more susceptible to NTM infections because they are immunosuppressed and potentially have inhalation injuries [2]. Severely burned patients lack the protective barrier of the skin due to the inherent nature of burns [2]. In addition these patients may have prolonged ICU stays with extended use of venous catheters, which may also leave them more susceptible to infection with NTM [2]. Sepsis remains the primary cause of mortality in burn patients after recovery from the initial thermal injury [1,2]. Burn patients are more susceptible to infections for multiple reasons including immunosuppressive state, impaired skin integrity, and multiple prolonged central verous and arterial catheterizations [2]. These factors also increase the risk of contracting insidious infections such as NTM. Nevertheless, NTM sepsis remains rare among burn patients, and only one other case has been documented in the English-language literature [2]. Boyer et al. [2] reported a 52-y-old male patient with 65% TBSA burn from an explosive device in Iraq where
MYCOBACTERIUM ABSCESSUS IN BURNS
he was intubated emergently and transferred to Landstuhl Regional Medical Center in Germany for initial stabilization. Subsequently the patient was transferred to U.S. Army Institute of Surgical Research Burn Intensive Care Unit at Brooke Army Medical Center (San Antonio, TX) for further care. The patient received initial excision and debridement with grafting, with approximately 10% TBSA remaining open. This patient’s hospital course was reportedly complicated by episodes of sepsis with several bacterial organisms including Pseudomonas aeruginosa and Enterobacter cloacae treated with broad-spectrum antibiotics. The patient’s blood cultures on hospital days 72 and 79 showed acid-fast bacteria. The patient’s BAL and tracheal aspirates were negative, which is unlike our patient who also produced positive BAL. The patient was treated empirically with imipenem, tobramycin, and azithromycin, although our patient was treated initially with cefoxitin, clarithromycin, and amikacin. According to the American Thoracic Society, patients with suspected NTM-related pulmonary disease should receive a chest radiograph (or high-resolution CT in the absence of cavitations) and three or more sputum specimens for testing [4,6]. Mycobacterium tuberculosis infection must be excluded [4,6]. Two positive sputum samples or one positive BAL sample are sufficient to diagnose pulmonary disease [4]. Our patient’s microbiologic workup was consistent with pulmonary NTM. Given the rarity of NTM, data on antibiotic course remain limited [1]. This report documents an exceedingly rare case of M. abscessus infection in a burn patient. In this era of multidrug-resistant organisms, thorough documentation can help broaden the clinician’s awareness of potential infectious pathogens. Moreover, such information is vital for determining optimal antimicrobial duration and course. At this time it is unclear whether the patient’s M. abscessus infection resulted from endovascular source of infection or pulmonary disease with CT findings concerning for mycobacterial infection and positive BAL. There were no obvious abscesses
849
or cellulitic changes to suggest primary infection of the skin or soft tissue, however, biopsies were not performed. The patient underwent withdrawal of intensive care and died shortly after. Author Disclosure Statement
No competing financial interests exist. References
1. Mayhall CG. The epidemiology of burn wound infections: Then and now. Clin Infect Dis 2003;37:543–550. 2. Boyer JM, Blatz PJ, Akers KS, et al. Nontuberculous mycobacterium infection in a burn ICU patient. Burns 2010; 36:e136–e139. 3. Burn incidence and treatment in the United States: 2012 fact sheet. www.ameriburn.org/resources_factsheet.php (Last accessed January 14, 2014). 4. Brown-Elliott BA, Wallace RJ Jr. Infections caused by nontuberculous mycobacteria. In: Mandell GL, Bennett JE, Dolin R (eds): Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Disease, Volume 2, 6th ed. Philadelphia. Elsevier, 2005: 2909–2916. 5. Wagner D, Young LS. Nontuberculous mycobacterial infections: A clinical review. Infection 2004;32:257–270. 6. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367–416.
Address correspondence to: Dr. Carl I. Schulman Ryder Trauma Center PO Box 016960 (D-40) Miami, FL 33136 E-mail: [email protected]
