Prospective derivation and validation of a NECROtizing Soft tissue InfectionS (NECROSIS) score: An EAST multicenter trial.

BACKGROUND: Although several risk indices have been developed to aid in the diagnosis of NSTIs, these instruments suffer from varying levels of reproducibility and failure to incorporate key clinical variables in model development. The objective of this study was to derive and validate a clinical risk index score - NECROSIS - for identifying NSTIs in emergency general surgery (EGS) patients being evaluated for severe skin and soft tissue infections. METHODS: We performed a prospective study across 16 sites in the US of adult EGS patients with suspected NSTIs over a 30-month period. Variables analyzed included demographics, admission vitals and labs, physical exam, radiographic, and operative findings. The main outcome measure was the presence of NSTI diagnosed clinically at the time of surgery. Multivariate analysis was performed to identify independent predictors for the presence of NSTI using the Hosmer-Lemeshow test and the Akaike information criteria. RESULTS: Of 362 patients, 297 (82%) were diagnosed with a NSTI. Overall mortality was 12.3%. Multivariate analysis identified 3 independent predictors for NSTI: systolic blood pressure ≤ 120 mmHg, violaceous skin, and WBC ≥15 (x103/uL). Multivariate modelling demonstrated Hosmer-Lemeshow goodness of fit (p = 0.9) with a c-statistic for the prediction curve of 0.75. Test characteristics of the NECROSIS score were similar between the derivation and validation cohorts. CONCLUSION: NECROSIS is a simple and potentially useful clinical index score for identifying at-risk EGS patients with NSTIs. Future validation studies are warranted. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria, Level III.

Short Courses of Antibiotics Are Safe in Necrotizing Soft Tissue Infections.

INTRODUCTION: Necrotizing soft tissue infections (NSTIs) carry high morbidity and mortality. While early aggressive surgical debridement is well-accepted treatment for NSTIs, the optimum duration of adjunct antibiotic therapy is unclear. An increasing focus on safety and evidence-based antimicrobial stewardship suggests a value in addressing this knowledge gap. OBJECTIVE: To determine whether shorter antibiotic courses have similar outcomes compared to longer courses in patients with NSTI following adequate source control. POPULATION: 142 consecutive patients with surgically managed NSTI were identified on retrospective chart review between December 2014 and December 2018 at two academic medical centers. RESULTS: Patients were predominately male (74%) with a median age of 52 and similar baseline characteristics. The median number of debridements to definitive source control was 2 (IQR 1-3) with the short course group undergoing a greater number of debridements control 2.57 ± 1.8 vs 1.9 ± 1.2, (P = .01). Of 142 patients, 34.5% received a short course and the remaining 65.5% received a longer course of antibiotics. There was no significant difference in the incidence of bacteremia or wound culture positivity between groups. There was also no significant difference in in-hospital mortality, 8% vs 6% (P = .74), incidence of C. difficile infection, median length of stay, or 30-day readmission. CONCLUSION: Provided adequate surgical debridement, similar outcomes in morbidity and mortality suggest antibiotic courses of 7 days or less are equally safe compared to longer courses.

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis.

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

Investigating the effect of discordant clinical and pathological diagnoses of complicated appendicitis on clinical outcomes.

BACKGROUND: Following appendectomy, management is often guided by surgeon determination of whether the appendicitis is uncomplicated or complicated. Our objectives were to determine the incidence of discordance between intraoperative and pathological findings and determine effect on outcomes. METHODS: We performed a retrospective five-year cohort analysis of adults who underwent appendectomy for acute appendicitis. Outcomes examined were length of stay (LOS), return to ED, and 30-day readmission. We reported p-values from logistic regression. RESULTS: Of 1479 cases, 36.4% were labeled complicated appendicitis, among which, 58.2% were discordant. When intraoperative findings underestimated pathological findings, there was a decreased LOS (p < 0.001) compared to concordant diagnoses. There was no significant difference for readmission (p = 0.592) or ED (p = 0.857). CONCLUSION: Operative underestimation of appendicitis severity was associated with a shorter LOS. Discordance did not adversely affect hospital readmission or rate of return to ED. These findings suggest reliance on intraoperative findings is sufficient in guiding management. SUMMARY: We wanted determine the incidence of discordance between operative and pathological findings and determine effect on outcomes. Operative underestimation of appendicitis severity was associated with a shorter LOS. Discordance did not adversely affect hospital readmission or rate of return to ED. These findings suggest reliance on intraoperative findings is sufficient in guiding management.

Methods of conservative antibiotic treatment of acute uncomplicated appendicitis: A systematic review.

BACKGROUND: Meta-analyses and a recent guideline acknowledge that conservative management of uncomplicated appendicitis with antibiotics can be successful for patients who wish to avoid surgery. However, guidance as to specific management does not exist. METHODS: PUBMED and EMBASE search of trials describing methods of conservative treatment was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. RESULTS: Thirty-four studies involving 2,944 antibiotic-treated participants were identified. The greatest experience with conservative treatment is in persons 5 to 50 years of age. In most trials, imaging was used to confirm localized appendicitis without evidence of abscess, phlegmon, or tumor. Antibiotics regimens were generally consistent with intra-abdominal infection treatment guidelines and used for a total of 7 to 10 days. Approaches ranged from 3-day hospitalization on parenteral agents to same-day hospital or ED discharge of stable patients with outpatient oral antibiotics. Minimum time allowed before response was evaluated varied from 8 to 72 hours. Although pain was a common criterion for nonresponse and appendectomy, analgesic regimens were poorly described. Trials differed in use of other response indicators, that is, white blood cell count, C-reactive protein, and reimaging. Diet ranged from restriction for 48 hours to as tolerated. Initial response rates were generally greater than 90% and most participants improved by 24 to 48 hours, with no related severe sepsis or deaths. In most studies, appendectomy was recommended for recurrence; however, in several, patients had antibiotic retreatment with success. CONCLUSION: While further investigation of conservative treatment is ongoing, patients considering this approach should be advised and managed according to study methods and related guidelines to promote informed shared decision-making and optimize their chance of similar outcomes as described in published trials. Future studies that address biases associated with enrollment and response evaluation, employ best-practice pain control and antibiotic selection, better define cancer risk, and explore longer time thresholds for response, minimized diet restriction and hospital stays, and antibiotic re-treatment will further our understanding of the potential effectiveness of conservative management. LEVEL OF EVIDENCE: Systematic review, level II.

Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

INTRODUCTION: Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy. OBJECTIVES: The Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy. METHODS/ANALYSIS: CODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4 weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm. ETHICS AND DISSEMINATION: This trial was approved by the University of Washington's Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02800785.

Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management.

STUDY OBJECTIVE: Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy. METHODS: Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate. RESULTS: Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/µL (range 6,200 to 23,100/µL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group. CONCLUSION: A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.

Routine intraoperative cholangiography is unnecessary in patients with mild gallstone pancreatitis and normalizing bilirubin levels.

BACKGROUND: The benefit of intraoperative cholangiography (IOC) is controversial in patients with gallstone pancreatitis whose bilirubin levels are normalizing. IOC with subsequent endoscopic retrograde cholangiopancreatography may lengthen duration of surgery and length of stay, whereas failure to clear the common bile duct may result in recurrent pancreatitis. METHODS: We performed a 6-year retrospective cohort analysis of consecutive adult patients with mild gallstone pancreatitis undergoing same-admission cholecystectomy at 2 university-affiliated medical centers. Institution A routinely performed IOC, whereas institution B did not. The primary outcome was readmission within 30 days for recurrent pancreatitis. RESULTS: Of 520 patients evaluated, 246 (47%) were managed at institution A (routine IOC) and 274 (53%) were managed at institution B (restricted IOC). Patients at institution B had a shorter duration of surgery (1.0 vs 1.6 hours, P < .001), shorter length of stay (4 vs 5 days, P < .001), and fewer postoperative endoscopic retrograde cholangiopancreatographies performed (1.8% vs 21%, P < .001), without a difference in readmissions (1.5% vs 0%, P = .12). CONCLUSIONS: Routine IOC is not necessary in the setting of mild gallstone pancreatitis with normalizing bilirubin values.

Association of Admission Laboratory Values and the Timing of Endoscopic Retrograde Cholangiopancreatography With Clinical Outcomes in Acute Cholangitis.

Importance: Acute cholangitis (AC), particularly severe AC, has historically required urgent endoscopic decompression, although the timing of decompression is controversial. We previously identified 2 admission risk factors for adverse outcomes in AC: total bilirubin level greater than 10 mg/dL and white blood cell count greater than 20 000 cells/µL. Objectives: To validate previously identified prognostic factors in AC, evaluate the effect of timing of endoscopic retrograde cholangiopancreatography on clinical outcomes, and compare recent experience with AC vs an historical cohort. Design, Setting, and Participants: A retrospective analysis (2008-2015) of patients with AC (validation cohort, n = 196) was conducted at 2 academic medical centers to validate predictors of adverse outcome. Timing of endoscopic retrograde cholangiopancreatography and outcome were stratified by severity using the Tokyo Guidelines for acute cholangitis diagnosis. Outcomes for the validation cohort were compared with the derivation cohort (1995-2005; n = 114). Data analysis was conducted from July 1, 2015, to September 9, 2015. Main Outcomes and Measures: Death and a composite outcome of death or organ failure. Results: The median age of patients in the derivation cohort was 54 years (interquartile range, 40-65 years) and in the validation cohort was 59 years (45-67 years). Multivariate logistic regression analysis of the validation cohort confirmed white blood cell count of more than 20 000 cells/µL (odds ratio, 3.4; 95% CI, 1.2-9.5; P = .02) and total bilirubin level of more than 10 mg/dL (odds ratio, 5.4; 95% CI, 1.8-16.4; P = .003) as independent risk factors for poor outcomes. In the validation cohort, timing of endoscopic retrograde cholangiopancreatography was not significantly different between those with and without an adverse outcome, even when stratified by AC severity (moderate: median, 0.6 hours [interquartile range (IQR), 0.5-0.9] vs 1.7 hours [IQR, 0.7-18.0] and severe: median, 10.6 hours [IQR, 1.2-35.1] vs 25.5 hours [IQR, 15.5-58.5] for those with and without adverse events, respectively). Patients in the validation cohort had a shorter hospital length of stay (median, 7 days [IQR, 4-10 days] vs 9 days [IQR, 5-16 days]) and lower rate of intensive care unit admission (26% vs 82%), despite a higher rate of severe cholangitis (n = 131 [67%] vs n = 29 [25%]). There were no significant differences in the composite outcome between the validation and derivation cohorts (22 [18.6%] vs 44 [22.4%]; P = .47). Adjusted analysis demonstrated decreased mortality in the validation cohort (odds ratio, 0.3; 95% CI, 0.1-0.7; P = .01). Conclusions and Relevance: White blood cell count greater than 20 000 cells/µL and total bilirubin level greater than 10 mg/dL are independent prognostic factors for adverse outcomes in AC. Consideration should be given to include these criteria in the Tokyo Guidelines severity assessment. Timing of endoscopic retrograde cholangiopancreatography does not appear to affect clinical outcomes in these patients. Management of AC has improved with time, with an overall shorter hospital length of stay, lower rate of intensive care unit admission, and a decreased adjusted mortality, demonstrating improvements in care efficiency and delivery.

Postoperative antibiotics are not associated with decreased wound complications among patients undergoing appendectomy for complicated appendicitis.

BACKGROUND: The objective of this study was to determine the role of postoperative antibiotics in reducing complications in patients undergoing appendectomy for complicated appendicitis. METHODS: We performed a 5-year retrospective cohort study of adult patients who underwent appendectomy for acute appendicitis. Patients with complicated appendicitis (perforated or gangrenous) were analyzed on the basis of whether they received postoperative antibiotics. Main outcome measures were wound complications, length of stay (LOS), and readmission to hospital. RESULTS: Of 410 patients with complicated appendicitis, postoperative antibiotics were administered to 274 patients (66.8%). On univariate and multivariate analyses, postoperative antibiotics were not associated with decreased wound complications or readmission, but independently predicted an increased LOS (P = .01). CONCLUSIONS: Among patients with complicated appendicitis, postoperative antibiotics were not associated with a decrease in wound complications but did result in an increased hospital LOS.

Can it wait until morning? A comparison of nighttime versus daytime cholecystectomy for acute cholecystitis.

BACKGROUND: The urgency of laparoscopic cholecystectomy for acute cholecystitis is under debate. We hypothesized that nighttime cholecystectomy is associated with decreased length of stay. METHODS: Retrospective review of 1,140 patients at 2 large urban referral centers with acute cholecystitis who underwent daytime (7 am to 7 pm) versus nighttime (7 pm to 7 am) cholecystectomy was conducted. RESULTS: Nighttime cholecystectomy did not affect the overall length of stay (3.7 vs 3.8 days, P = .08) or complication rate (5% vs 7%, P = .5) versus daytime cholecystectomy. Nighttime cholecystectomy was associated with a higher conversion rate to open cholecystectomy (11% vs 6%, P = .008). On multivariable analysis, independent predictors of conversion to open surgery were nighttime cholecystectomy, age, and gangrenous cholecystitis (P = .01). The only predictor of complications was gangrenous cholecystitis (P = .02). CONCLUSIONS: Nighttime cholecystectomy is associated with an increased conversion to open surgery without decrease in length of stay or complications. These findings suggest that laparoscopic cholecystectomy for acute cholecystitis should be delayed until normal working hours.

Predictors of mortality and limb loss in necrotizing soft tissue infections.

Necrotizing soft tissue infections (NSTIs) require prompt diagnosis and treatment. Early identification of patients at greatest risk of limb amputation and death may help in targeting aggressive medical and surgical management. The aim of this study was to assess predictors of limb loss and mortality in patients with NSTI based on admission variables. We performed a retrospective review of two hospitals that care for a large volume of patients with NSTI. Univariate and multivariable analyses were used to determine the association of admission biochemical markers to limb loss and mortality. Of 174 patients with NSTI, there were 19 deaths (10.9%) and 42 required amputations (24.1%). Multivariable logistic regression analysis revealed that only arterial lactate was predictive for both mortality (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; P = 0.009) and limb loss (OR, 1.3; 95% CI, 1.0 to 1.7; P = 0.02). In patients with a suspected NSTI, an arterial lactate should be ordered early on to guide aggressive therapeutic interventions and to provide information with regard to long-term outcomes of amputation and death that is needed for early discussion with the patient and family.

Microvascular changes following four-hour single arteriole occlusion.

BACKGROUND: Free tissue transplantations are lengthy procedures that result in prolong tissue ischemia. Restoral of blood flow is essential for free flap recovery; however, upon reperfusion tissue that is viable may continue to be nonperfused. To further elucidate this pathophysiology skeletal muscle microcirculation was investigated during reperfusion following 4-hour single arteriole occlusion. MATERIALS AND METHODS: A blunt micropipette probe was use to compress a single arteriole in the unanesthetized hamster (N = 20) dorsal skinfold chamber. Arteriole (n = 20), capillary (n = 97), and postcapillary venule (n = 16) diameters and blood flow were analyzed at 0, 30, 60, 120, 240 min and 24 hours of reperfusion after 4 hour occlusion. RESULTS: Feeding arcade arterioles exhibited a brief (<10 min) vasoconstriction [0.31 ± 0.26 (mean ± SE) of baseline] upon reperfusion followed by a maximum vasodilation at 120 min (1.3 ± 0.10: P < 0.05). Vasodilation was observed in transverse arterioles (A3) (1.8 ± 0.20: P < 0.05). Correspondingly, all arteriole and venule flow was increased by 120 min (P < 0.05) of reperfusion. There was a transient decrease in the number of flowing capillaries at 0 and 30 min reperfusion (0.73 ± 0.09 and 0.84 ± 0.06: P < 0.05, respectively). CONCLUSIONS: At the onset of reperfusion heterogeneous arteriole flow and transient decrease in flowing capillaries was observed; however, return of flow in all capillaries and an eventual hyperemic response in all arterioles suggests the reversible nature of this response. Single arteriole occlusion may allow for a more controlled and detailed microcirculatory analysis during ischemia-reperfusion.

Early laparoscopic cholecystectomy for mild gallstone pancreatitis: time for a paradigm shift.

HYPOTHESIS Patients with mild gallstone pancreatitis may undergo an early laparoscopic cholecystectomy (LC) within 48 hours of hospital admission without awaiting the normalization of pancreatic and liver enzyme levels. This may decrease the hospital stay without increasing morbidity or mortality and may minimize the unnecessary use of endoscopic retrograde cholangiopancreatography. DESIGN A retrospective review. SETTING Two university-affiliated urban medical centers. PATIENTS A total of 303 patients with mild gallstone pancreatitis, of whom 117 underwent an early LC and 186 underwent a delayed LC. MAIN OUTCOME MEASURES Hospital length of stay, morbidity and mortality rates, and the use of endoscopic retrograde cholangiopancreatography. RESULTS Similar hospital admission variables were observed in the early and delayed LC groups, although the delayed group was older (P = .006). The median hospital length of stay was significantly less for the early group than for the delayed group (3 vs 6 days; P < .001). There were no patients who died, and the complication rates were similar for both groups. However, the patients who underwent an early LC were less likely than patients who underwent a delayed LC to undergo endoscopic retrograde cholangiopancreatography (P = .02). CONCLUSIONS An early LC may be safely performed for patients with mild gallstone pancreatitis, without concern for increased morbidity and mortality, resulting in shortened hospital stays and a decrease in the use of endoscopic retrograde cholangiopancreatography. The practice of delaying an LC until normalization of laboratory values appears to be unnecessary.

Analysis of exhaled volatile compounds following acute superior mesenteric artery occlusion in a pilot rat study.

BACKGROUND: Prompt diagnosis and treatment of acute mesenteric ischemia (AMI) requires a high index of suspicion for timely management. Poor clinical outcomes and delays in surgical treatment are demonstrated even in modern clinical series. Recognition of exhaled volatile organic compounds (VOCs) specific to AMI may facilitate early detection and diagnosis and improve patient outcomes. METHODS: Adult Wistar rats (n = 5) were intubated and anesthetized, and control tracheostomy breath samples were collected using Tedlar gas sample bags. Intestinal ischemia was induced by placing an occlusive clip across the superior mesenteric artery, and breath samples were collected after 1 hour of intestinal ischemia and after 15 minutes of intestinal reperfusion. Gas chromatography was used to identify and measure levels of VOCs obtained, and measured retention indices were compared with known values in the Kovats retention index database. RESULTS: Multiple retention indices (n = 41) were noted on gas chromatography, representing a variety of VOCs detected. Z,Z-farnesol (C15H26O), an isoprenoid, was the only compound detected that was undetectable during the control phase (median = 0 cts/sec) but which significantly elevated during the ischemic (median = 34 cts/sec, range = 25-37) and reperfusion (median = 148 cts/sec, range = 42-246) phases. Three other isoprenoid compounds (E,E-alpha-farnesene, germacrene A, and Z,Z-4,6,8-megastigmatriene) were also detected in all five animals, but their levels did not differ significantly between control, ischemic, and reperfusion phases. CONCLUSIONS: This pilot study demonstrates the feasibility of analyzing exhaled VOCs using a novel rat model for AMI. These findings may be useful for the development and identification of similar assays for the rapid diagnosis of AMI.