Kevin K. Chung

Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis

LEARNING OBJECTIVES:On completion of the article, the reader should be able to: Define the benefits of prophylactic fluconazole administration. Identify the population benefiting from the use of fluconazole. Use this information in a clinical setting. Dr. Kollef has disclosed that was previously the recipient of direct grant/research funding from Intrabiotics and is currently the recipient of direct grant/research funding from Pfizer, Merck Bard, and Elan. Dr. Kollef has also disclosed that he is on the speakers bureau of Pfizer and Merck. All of the remaining authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objective:To evaluate the impact of fluconazole prophylaxis on the incidence of fungal infections and on mortality among critically ill surgical patients. Design:Meta-analysis of randomized, placebo-controlled trials of fluconazole prophylaxis. Patients:Subjects participating in the clinical trials in this area. Measurements and Main Results:We identified four randomized studies comparing fluconazole to placebo for prevention of fungal infections in the surgical intensive care unit (SICU). The studies enrolled 626 patients and used differing dosing regimens of fluconazole. All trials were double-blind and two were multicenter studies. Fluconazole administration significantly reduced the incidence of fungal infections (pooled odds ratio, 0.44; 95% confidence interval, 0.27–0.72; p < .001). However, fluconazole prophylaxis was not associated with a survival advantage (pooled OR for mortality, 0.87; 95% confidence interval, 0.59–1.28; p = NS). Fluconazole did not statistically alter the rate of candidemia, as this was low across the studies and developed in only 2.2% of all participants. Performing a sensitivity analysis and including two additional studies that indirectly examined fluconazole prophylaxis in the critically ill did not change our observations. Data from the reports reviewed were insufficient to allow comment on the impact of fluconazole prophylaxis on resource utilization, the distribution of nonalbicans species of Candida, and the emergence of antifungal resistance. Generally, fluconazole appeared to be safe for SICU patients. Conclusions:Prophylactic fluconazole administration for prevention of mycoses in SICU patients appears to successfully decrease the rate of these infections, but this strategy does not improve survival. The absence of a survival advantage may reflect the few studies in this area and the possibility that this issue has not been adequately studied. Because of the potential for both resistance and emergence of nonalbicans isolates, clinicians must consider these issues when evaluating fluconazole prophylaxis in the SICU. Future trials should focus on more precisely identifying patients at high risk for fungal infections and on determining if broader use of fluconazole alters the distribution of candidal species seen in the SICU and impacts measures of resource utilization such as length of stay and duration of mechanical ventilation.

Prevalence of multidrug-resistant organisms recovered at a military burn center §

Infections caused by multidrug-resistant (MDR) pathogens are associated with significant morbidity and mortality in patients with burn injuries. We performed a 6-year antibiotic susceptibility records review from January 2003 to December 2008 to assess the prevalence of MDR isolates by pathogen at the US Army Institute of Surgical Research Burn Center. During the study period Acinetobacter baumannii (780 isolates [22%]) was the most prevalent organism recovered, followed by Pseudomonas aeruginosa (703 isolates [20%]), Klebsiella pneumoniae (695 isolates [20%]), and Staphylococcus aureus (469 isolates [13%]). MDR prevalence rates among these isolates were A. baumannii 53%, methicillin-resistant S. aureus (MRSA) 34%, K. pneumoniae 17% and P. aeruginosa 15%. Two isolates, 1 A. baumannii and 1 P. aeruginosa, were identified as resistant to all 4 classes of antibiotics tested plus colistin. A. baumannii isolates recovered from patients with burns greater than 30% of total body surface area (TBSA) were more likely to be MDR (61%) with no significant difference for P. aeruginosa and K. pneumoniae. A higher proportion of MDR P. aeruginosa isolates were recovered from respiratory specimens compared to blood specimens (24% vs. 9%) while the opposite was true for MRSA (35% vs. 54%). A comparison of A. baumannii recovered during hospitalization days 1-5 and 15-30 revealed higher MDR levels as length of stay increased (48% vs. 75%) while no significant trends were observed for P. aeruginosa and K. pneumoniae. A similar pattern was observed for MDR A. baumannii levels for the facility between 2003 and 2005 and 2006-2008 (39% vs. 70%), with no significant increase in MDR P. aeruginosa and MDR K. pneumoniae. Increasing antibiotic resistance patterns of the most prevalent isolates recovered during extended hospitalization, impact of % TBSA and other clinical parameters may affect empirical antimicrobial therapy and patient management decisions during treatment.

Prevention of infections associated with combat-related extremity injuries

During combat operations, extremities continue to be the most common sites of injury with associated high rates of infectious complications. Overall, ∼ 15% of patients with extremity injuries develop osteomyelitis, and ∼ 17% of those infections relapse or recur. The bacteria infecting these wounds have included multidrug-resistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Klebsiella species and Escherichia coli, and methicillin-resistant Staphylococcus aureus. The goals of extremity injury care are to prevent infection, promote fracture healing, and restore function. In this review, we use a systematic assessment of military and civilian extremity trauma data to provide evidence-based recommendations for the varying management strategies to care for combat-related extremity injuries to decrease infection rates. We emphasize postinjury antimicrobial therapy, debridement and irrigation, and surgical wound management including addressing ongoing areas of controversy and needed research. In addition, we address adjuvants that are increasingly being examined, including local antimicrobial therapy, flap closure, oxygen therapy, negative pressure wound therapy, and wound effluent characterization. This evidence-based medicine review was produced to support the Guidelines for the Prevention of Infections Associated With Combat-Related Injuries: 2011 Update contained in this supplement of Journal of Trauma.

Fungal Wound Infection (Not Colonization) Is Independently Associated With Mortality in Burn Patients

Objective:To analyze the occurrence of fungal wound infection (FWI) after thermal injury and its relationship to mortality. Background:FWI is an uncommon but potentially lethal complication of severe thermal injury. Methods:The records of patients with thermal burns admitted to a single burn center (1991–2002) were reviewed. Analyses accounted for total burn size (TBS, percentage body surface area), full-thickness burn size (FTBS, percentage body surface area), age, inhalation injury, sex, and fungal-status category. Fungal colonization and infection were determined histopathologically. Results:Criteria for inclusion were met by 2651 patients. Each patient’s fungal-status category was defined according to the deepest level of fungal involvement observed during the hospital course: no fungus (2476 patients), fungal wound colonization (FWC, 121 patients), or fungal wound infection (FWI, 54 patients). Median TBS (9%, 47%, 64%, respectively) and mortality (5%, 27%, 76%, respectively) varied significantly among fungal-status groups. Logistic regression was used to detect significant independent associations. FWI was associated with higher TBS. Mortality was associated with TBS, FTBS, inhalation injury, FWI, and age. Unlike FWI, FWC was not independently related to mortality, the greater observed mortality in FWC being explained by other variables such as TBS. The odds ratio for FWI (8.16) suggested about the same mortality impact as augmenting TBS by 33%. A midrange TBS of 30% to 60% was required for most of the detectable association of FWI with mortality. Conclusions:FWI accompanies larger burns and is associated with mortality in burn patients, particularly in those with TBS 30% to 60%. This association is independent of burn size, inhalation injury, and age.

Guidelines for the prevention of infections associated with combat-related injuries: 2011 update endorsed by the infectious diseases society of America and the surgical infection society

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications, and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.

High-frequency percussive ventilation and low tidal volume ventilation in burns: a randomized controlled trial.

Objectives:In select burn intensive care units, high-frequency percussive ventilation is preferentially used to provide mechanical ventilation in support of patients with acute lung injury, acute respiratory distress syndrome, and inhalation injury. However, we found an absence of prospective studies comparing high-frequency percussive ventilation with contemporary low-tidal volume ventilation strategies. The purpose of this study was to prospectively compare the two ventilator modalities in a burn intensive care unit setting. Design:Single-center, prospective, randomized, controlled clinical trial, comparing high-frequency percussive ventilation with low-tidal volume ventilation in patients admitted to our burn intensive care unit with respiratory failure. Setting:A 16-bed burn intensive care unit at a tertiary military teaching hospital. Patients:Adult patients ≥18 yrs of age requiring prolonged (>24 hrs) mechanical ventilation were admitted to the burn intensive care unit. The study was conducted over a 3-yr period between April 2006 and May 2009. This trial was registered with ClinicalTrials.gov as NCT00351741. Interventions:Subjects were randomly assigned to receive mechanical ventilation through a high-frequency percussive ventilation-based strategy (n = 31) or a low-tidal volume ventilation-based strategy (n = 31). Measurements and Main Results:At baseline, both the high-frequency percussive ventilation group and the low-tidal volume ventilation group had similar demographics to include median age (interquartile range) (28 yrs [23–45] vs. 33 yrs [24–46], p = nonsignificant), percentage of total body surface area burn (34 [20–52] vs. 34 [23–50], p = nonsignificant), and clinical diagnosis of inhalation injury (39% vs. 35%, p = nonsignificant). The primary outcome was ventilator-free days in the first 28 days after randomization. Intent-to-treat analysis revealed no significant difference between the high-frequency percussive ventilation and the low-tidal volume ventilation groups in mean (± sd) ventilator-free days (12 ± 9 vs. 11 ± 9, p = nonsignificant). No significant difference was detected between groups for any of the secondary outcome measures to include mortality except the need for “rescue” mode application (p = .02). Nine (29%) in the low-tidal volume ventilation arm did not meet predetermined oxygenation or ventilation goals and required transition to a rescue mode. By contrast, two in the high-frequency percussive ventilation arm (6%) required rescue. Conclusions:A high-frequency percussive ventilation-based strategy resulted in similar clinical outcomes when compared with a low-tidal volume ventilation-based strategy in burn patients with respiratory failure. However, the low-tidal volume ventilation strategy failed to achieve ventilation and oxygenation goals in a higher percentage necessitating rescue ventilation.

Incidence and bacteriology of burn infections at a military burn center

Considerable advancements in shock resuscitation and wound management have extended the survival of burned patients, increasing the risk of serious infection. We performed a 6-year review of bacteria identification and antibiotic susceptibility records at the US Army Institute of Surgical Research Burn Center between January 2003 and December 2008. The primary goal was to identify the bacteria recovered from patients with severe burns and determine how the bacteriology changes during extended hospitalization as influenced by population and burn severity. A total of 460 patients were admitted to the burn ICU with 3507 bacteria recovered from 13,727 bacteriology cultures performed. The most prevalent organisms recovered were Acinetobacter baumannii (780), Pseudomonas aeruginosa (703), Klebsiella pneumoniae (695) and Staphylococcus aureus (469). A. baumannii was most often recovered from combat-injured (58%) and S. aureus the most frequent isolate from local (46%) burn patients. Culture recovery rate of A. baumannii and S. aureus was highest during the first 15 hospital days (73% and 71%); while a majority of P. aeruginosa and K. pneumoniae were recovered after day 15 (63% and 53%). All 4 pathogens were recovered throughout the course of hospitalization. A. baumannii was the most prevalent pathogen recovered from patients with total body surface area (TBSA) burns less than 30% (203) and 30-60% (338) while P. aeruginosa was most prevalent in patients with burns greater than 60% TBSA (292). Shifting epidemiology of bacteria recovered during extended hospitalization, bacteriology differences between combat-injured and local burn patients, and impact of % TBSA may affect patient management decisions during the course of therapy.

Joint Theater Trauma System implementation of burn resuscitation guidelines improves outcomes in severely burned military casualties.

BACKGROUND Between March 2003 and June 2007, our burn center received 594 casualties from the conflicts in Iraq and Afghanistan. Ongoing acute burn resuscitation as severely burned casualties are evacuated over continents is very challenging. To help standardize care, burn resuscitation guidelines (BRG) were devised along with a burn flow sheet (BFS) and disseminated via the new operational Joint Theater Trauma System to assist deployed providers. METHODS After the BRG was implemented in January 2006, BRF data were prospectively collected in consecutive military casualties with >30% total body surface area (TBSA) burns (BRG Group). Baseline demographic data and fluid requirements for the first 24 hours of the burn resuscitation were collected from the BFS. Percentage full thickness TBSA burns, presence of inhalation injury, injury severity score, resuscitation-related abdominal compartment syndrome, and mortality were collected from our database. Individual charts were reviewed to determine the presence of extremity fasciotomies and myonecrosis. These results were compared with consecutive military casualties admitted during the 2-year- period before the system-wide implementation of the BRG (control group). RESULTS One hundred eighteen military casualties with burns >30% TBSA were admitted between January 2003 and June 2007, with n = 56 in the BRG group and n = 62 in the control group. The groups were different in age, but similar in %TBSA, %full thickness, presence of inhalation injury, and injury severity score. There was no difference in the rate of extremity fasciotomies or the incidence of myonecrosis between groups. CONCLUSIONS The composite endpoint of abdominal compartment syndrome and mortality was significantly lower in the BRG group compared with the control group (p = 0.03). Implementation of the BRG and system-wide standardization of burn resuscitation improved outcomes in severely burned patients. Utilization of the joint theater trauma system to implement system-wide guidelines is effective and can help improve outcomes.

Evolution of burn resuscitation in operation Iraqi freedom.

Abstract : Burns are common in all military conflicts, comprising approximately 10% of all casualties. Of these, nearly 20% are categorized as severe, or involving greater than 20% TBSA, and require significant intravenous resuscitation. A unique set of challenges have emerged during the present conflict associated with global evacuation of burned soldiers, adding a new dimension to the already complex and often-controversial topic of the burn resuscitation. Critical advances in air evacuation of the war wounded, thorough prewar planning, and sustained burn care education of deployed personnel have proven vital in the optimal care of our injured soldiers. During the Vietnam conflict, burned soldiers were evacuated to an Army Hospital in Japan (Camp Zama) and were treated for up to 6 months before they were evacuated to the United States. Since that time, the transfer of the patient to the burn center for definitive care has been expedited by the Army Burn Flight Teams ability to transport the most severely burned patients within the first several days after injury. With the emergence of the U.S. Air Force Critical Care Air Transport Team (CCATT) program in the 1990s, global air evacuation of burn patients became even more rapid, maximizing available U.S. Air Force aircraft for patient evacuation. The doctrine has shifted from aeromedical transport of the stable to aeromedical transport of the stabilized. In burn patients, evacuation presents a unique problem because it usually takes place while resuscitation in the first 24 to 48 hours after burn injury is ongoing. In addition to the innate complexity involved in global evacuation, war burn patients often exhibit multisystem traumatic injuries further complicating and augmenting resuscitation fluid needs above and beyond standard burn resuscitation formulas. The presence of smoke inhalation injury, occurring in 5% to 15% of patients with severe burns, also increases fluid requirements.

Computerized decision support system improves fluid resuscitation following severe burns: An original study

Objective:Several formulas have been developed to guide resuscitation in severely burned patients during the initial 48 hrs after injury. These approaches require manual titration of fluid that may result in human error during this process and lead to suboptimal outcomes. The goal of this study was to analyze the efficacy of a computerized open-loop decision support system for burn resuscitation compared to historical controls. Design:Fluid infusion rates and urinary output from 39 severely burned patients with >20% total body surface area burns were recorded upon admission (Model group). A fluid-response model based on these data was developed and incorporated into a computerized open-loop algorithm and computer decision support system. The computer decision support system was used to resuscitate 32 subsequent patients with severe burns (computer decision support system group) and compared with the Model group. Setting:Burn intensive care unit of a metropolitan Level 1 Trauma center. Patients:Acute burn patients with >20% total body surface area requiring active fluid resuscitation during the initial 24 to 48 hours after burn. Measurements and Main Results:We found no significant difference between the Model and computer decision support system groups in age, total body surface area, or injury mechanism. Total crystalloid volume during the first 48 hrs post burn, total crystalloid intensive care unit volume, and initial 24-hr crystalloid intensive care unit volume were all lower in the computer decision support system group. Infused volume per kilogram body weight (mL/kg) and per percentage burn (mL/kg/total body surface area) were also lower for the computer decision support system group. The number of patients who met hourly urinary output goals was higher in the computer decision support system group. Conclusions:Implementation of a computer decision support system for burn resuscitation in the intensive care unit resulted in improved fluid management of severely burned patients. All measures of crystalloid fluid volume were reduced while patients were maintained within urinary output targets a higher percentage of the time. The addition of computer decision support system technology improved patient care.