An Analysis of Past Surgical Infection Society Award Recipients.

BACKGROUND: The Surgical Infection Society (SIS) through its foundation (FDTN) confers awards to individuals who demonstrate interest in researching infection in the surgical setting. We sought to characterize the research output from prior award recipients and determine the impact of these awards on the individual and the SIS. METHODS: The SIS website was queried for the names of all past award recipients. A MEDLINE search of the recipients was performed. Total number of publications and publications in the society's journal, Surgical Infections (SI), were identified. Gender and leadership positions within SIS were determined. Meeting attendance and participation were assessed. Donations by scholarship recipient to the FDTN were evaluated. RESULTS: Between 1984 and 2012, 116 individuals received an SIS award or scholarship. Of these, 72% were male. There were 101 scholarships awarded, totaling nearly $3 million. Of the 19 new Junior Faculty Scholarships awarded, four were to consecutive recipients (CR). There were 11 clinical evaluative award scholarships awarded, three to CR. There were 100 Resident/Fellow scholarships awarded, and of these, 22 were awarded to CR. Past recipients had multiple publications (median total publications = 27; interquartile range (IQR): Nine to 62) and published multiple papers on the topic for which they received an award (median two; IQR: Zero to four). Recipients did not publish in SI (median SI publications = zero; IQR: Zero to one). There was no substantial difference in the number of publications by gender. Multiple awards (MA) were conferred to 26 (22%) individuals. Six (5.1%) assumed an executive position within SIS, two (1.7%) became SIS president. Those who received MA were more likely to serve as an officer than those who only received one award (15% vs. 2%, p = 0.02). CONCLUSIONS: Scholarships have a large benefit for individual recipients; however, the benefit to the society remains harder to quantify.

Efficacy of therapy with recombinant human activated protein C of critically ill surgical patients with infection complicated by septic shock and multiple organ dysfunction syndrome.

BACKGROUND: Septic shock causing or complicating critical surgical illness results in high mortality. Drotrecogin alfa (activated), known also as recombinant human activated protein C (rhAPC) has become controversial as therapy, owing to persisting questions of efficacy and safety. We hypothesized rhAPC to be effective therapy for critically ill surgical patients with septic shock. METHODS: Open-label therapy with rhAPC (by predefined criteria) of 108 critically ill surgical patients. Treated patients were matched individually in prospect for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE)-II and -III scores, site of infection, and organism (0-2 points each, maximum 12 points) with 108 patients from our 15,000-patient surgical intensive care unit database who did not receive rhAPC. No match was accepted if <6 points. Multiple organ dysfunction (MOD) scores and data regarding cortisol concentrations, bleeding complications, and transfusion requirements were collected. The primary endpoint was 28-day mortality, with mortality for hospitalization and resolution of organ dysfunction as secondary endpoints. Statistical analyses included ANOVA, c statistic, binary logistic regression, and Kaplan-Meier time-to-event and Cox proportional hazards analyses; α=0.05. RESULTS: The mean match score was 9.2±0.1 points (range, 6-12 points). Patients were well matched by all criteria, including baseline MOD score (9.5±0.7 vs. 9.8±0.3 points, p=0.66). Mean age was 68.1±1.1 years (p=0.49), Mean APACHE-III score was 99.6±1.5 points (p=0.87). Mean time to rhAPC administration was 25±3 h. Survival at 28 days after rhAPC was 71.3% vs. 49.1% (p=0.001); hospital survival was 57.4% vs. 40.7% (p=0.02). By logistic regression, rhAPC therapy resulted in improved 28-day survival (OR 2.57, 95% CI 1.46-4.52, p=0.001) (model χ2 11.244, p=0.001); and hospital survival (OR 1.96, 95% CI 1.14-3.36, p=0.015) (model χ2 6.03, p=0.014). The MOD score decreased significantly (p=0.012) during rhAPC therapy. CONCLUSION: Therapy with rhAPC appeared to improve survival in surgical ICU patients with life-threatening infection characterized by septic shock and organ dysfunction.

Contemporary predictors of conversion from laparoscopic to open appendectomy.

BACKGROUND: We defined the contemporary conversion rate from laparoscopic appendectomy (LA) to open appendectomy and identified pre-operative factors associated with conversion. METHODS: Retrospective review of 941 consecutive LAs performed for suspected acute appendicitis in a single urban university hospital between 2000 and 2007. Patient characteristics, clinical features, physical examination findings, laboratory values, computed tomography (CT) findings, surgeon identity, operative findings, and pathologic results were assessed. Categorical variables were compared in patients undergoing LA and those in whom conversion was necessary using the Fisher exact test; the Student t-test was used to compare continuous variables. Multivariable analysis was performed with binomial logistic regression. Statistical significance was established at α = 0.05. RESULTS: The overall conversion rate was 4.1% and did not change significantly over the course of the study. By univariable analysis, conversion was significantly associated with older age, male gender, American Society of Anesthesiologists (ASA) score >2 points, longer duration of symptoms, rigidity on physical examination, increased percentage of neutrophils on admission white blood cell differential count, extraluminal air on CT, inexperience of the attending surgeon with LA, retrocecal location of the appendix, gross necrosis or perforation, murky or purulent ascites, and microscopic evidence of perforation. By multivariable analysis, advanced age (hazard ratio [HR] 1.02 per year; 95% confidence interval [CI] 1.01-1.04, p = 0.02), ASA score >2 points (HR 11.2; 95% CI 5.6-24.4; p < 0.001), CT inflammation grade ≥ 4 (HR 4.8; 95% CI 1.9-12.3; p = 0.001), and attending surgeon inexperience (HR 7.4; 95% CI 2.6-20.8; p < 0.001) were independent predictors of conversion. CONCLUSION: The conversion rate during laparoscopic appendectomy has not changed significantly over the past seven years and remains ~4%. Independent pre-operative predictors of conversion are advanced age, ASA score >2 points, attending surgeon inexperience, and extensive inflammation observed on pre-operative CT scan. Proceeding directly with open appendectomy under these circumstances may reduce operative time, expense, and morbidity.

The pathogen of ventilator-associated pneumonia does not influence the mortality rate of surgical intensive care unit patients treated with a rotational antibiotic system.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the leading causes of morbidity in critically ill surgical patients. Certain pathogens (e.g., methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa) have been associated with an excess mortality rate from sepsis in several studies, but not in the surgical setting specifically or when protocol-driven antibiotic therapy is administered. PURPOSE: We sought to determine which factors and, in particular, whether the individual pathogen affected the mortality rate in our surgical intensive care unit (ICU), where a rotational antibiotic system has been employed continuously since 1997. We hypothesized that the type of pathogen and illness severity were the primary influences on the mortality rate of patients with VAP. METHODS: A total of 198 consecutive patients from a university surgical ICU, with clinical signs of VAP confirmed by quantified isolation of significant numbers of a pathogen (> or =10(4) colony-forming units [cfu]/mL) from bronchoalveolar (BAL) fluid obtained by fiberoptic bronchoscopy, were identified prospectively from January 2001 to November 2004. The data collected were age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) III score, multiple organ dysfunction score, unit day of diagnosis, time (h) to antibiotic administration (TTA), appropriateness of initial therapy (AIT), unit and hospital length of stay, and mortality rate. Pathogens were classified as non-lactose-fermenting gram-negative bacilli (NGNB), lactose-fermenting gram-negative bacilli (LGNB), methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, yeast, community-acquired pneumonia (e.g., Streptococcus pneumoniae), or other pathogens. Patients with a polymicrobial isolate were placed in the "other" category. RESULTS: The overall mortality rate was 32.3% vs. 55% as predicted by APACHE III normative data. The overall AIT was 92%. The mortality rate for NGNB infections was 35.6% vs. 29.4% for LGNB infections (p = NS). By logistic regression, neither TTA, AIT, nor pathogen influenced the mortality rate. CONCLUSIONS: The type of pathogen does not influence death in surgical ICU patients with VAP diagnosed rigorously and treated by a rotational antibiotic system. The high proportion of AIT as a result of the rotational antibiotic administration system optimizes bacterial killing and negates the impact of bacterial resistance, contributing to better outcomes.

Multiple organ dysfunction syndrome in critical surgical illness.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is the leading cause of death in surgical patients and in trauma patients who survive the first 24 h. First observed systematically among Vietnam War-era battle casualties who began to survive previously fatal injuries owing to improved evacuation, triage, and resuscitation, only to develop catastrophic manifestations of organ failure never before seen, the syndrome was recognized formally in 1975 as "multiple organ failure." Ensuing observations and investigations, undertaken in large part by surgeon-scientists, have refined our current understanding of MODS, yielding better outcomes. METHODS: Review and synthesis of pertinent literature with personal observations and recollections of the senior investigator. RESULTS: The MODS is now recognized as a continuum of physiologic derangements, rather than an all-or-nothing phenomenon. The most common precipitant appears to be ischemia-reperfusion injury, although severe sepsis also is commonplace. Descriptive biology has enhanced the understanding of the pathogenesis and outcomes of MODS, although the therapy is largely supportive, making prevention of paramount importance. Measures such as drotrecogin alfa (activated), intensive insulin therapy, corticosteroids, and low tidal volume ventilation may be effective. CONCLUSIONS: Although current treatment of MODS remains primarily supportive, the mortality rate appears to be decreasing. Appreciation of the interrelations between the inflammatory and coagulation systems provides hope in the battle against this frequent, elusive, deadly, and costly syndrome.

Implementation of tight glucose control for critically ill surgical patients: a process improvement analysis.

BACKGROUND: Tight glucose control has been advocated as a method to improve outcomes of surgical critical care. However, continuous infusion of insulin has potential morbidity (e.g., neurologic consequences of hypoglycemia), and it remains unclear to what degree the glucose concentration must be controlled. We examined our performance in instituting a protocol for tight glucose control in our surgical intensive care unit (ICU). METHODS: Prospective study of 220 consecutive patients (February, 2003-March, 2006) who received an infusion of insulin for glucose control for >24 h by protocol. Data collected included age, acuity (Acute Physiology and Chronic Health Evaluation [APACHE] III) score, sex, history of diabetes mellitus, organ dysfunction (Marshall), and death or survival. Infusion-related data included initial glucose concentration, time to glucose <120 mg/dL, h/day of glucose <110 mg/dL and <140 mg/dL, duration of infusion (days), insulin units/day, year of therapy, and complications. Analysis was performed by chi(2), analysis of variance, and logistic regression, with p < 0.05 considered significant. RESULTS: Insulin drips were required by 10.2% of patients (287/2,804); 29 of these (10.1%) had diabetes mellitus. The mean APACHE III score for the treated patients was 77 +/- 2 (standard deviation), and the mortality rate was 24%. Hypoglycemia (<60 mg/dL) occurred in 4.2% of patients. The trigger insulin concentration decreased over time (2003 vs. 2005) from 249 +/- 14 to 160 +/- 5 mg/dL, and the h/day of glucose <140 increased from 11 +/- 1 to 16 +/- 1. However, age, acuity, APACHE III, days of insulin, time to achieve glucose <120, h/day of glucose <110, and mortality rate were unchanged. By logistic regression, only the year of treatment (odds ratio [OR] 1.871; 95% confidence interval [CI] 1.177, 2.972; p = 0.008] predicted success in controlling the blood glucose concentration to <140 mg/dL; age, illness severity, diabetes history, and trigger glucose concentration [OR 0.996; 95% CI 0.992, 1.001; p = 0.11] did not. CONCLUSIONS: Success in implementing tight glucose control was modest, albeit improving, despite a specific protocol for administration. No medical reason could be identified for inability to achieve tight glucose control; therefore, successful implementation must be volitional. Education, particularly regarding hypoglycemia, and possible refinement of our protocol may improve our ability to control blood glucose in our ICU.

Does de-escalation of antibiotic therapy for ventilator-associated pneumonia affect the likelihood of recurrent pneumonia or mortality in critically ill surgical patients?

BACKGROUND: Ventilator-associated pneumonia (VAP) is a leading cause of mortality in critically ill patients. Although previous studies have shown that de-escalation therapy (DT) of antibiotics may decrease costs and the development of resistant pathogens, minimal data have shown its effect in surgical patients or in any patients with septic shock. We hypothesized that DT for VAP was not associated with an increased rate of recurrent pneumonia (RP) or mortality in a high acuity cohort of critically ill surgical patients. METHODS: All surgical intensive care unit (SICU) patients from January 2005 to May 2007 with VAP diagnosed by quantitative bronchoalveolar lavage with a positive threshold of 10,000 CFU/mL were identified. Data collected included age, gender, Acute Physiologic and Chronic Health Evaluation Score III (A3), type of bacterial or other pathogen, antibiotics used for initial and final therapy, mortality, RP, and appropriateness of initial therapy (AIT). Patients were designated as receiving AIT, DT, or escalation of antibiotic therapy based on microbiology for their VAP. RESULTS: One hundred thirty-eight of 1,596 SICU patients developed VAP during the study period (8.7%). For VAP patients, the mean Acute Physiologic and Chronic Health Evaluation III score was 82.7 points with a mean age of 63.8 years. The RP rate was 30% and did not differ between patients receiving DT (27.3%) and those who did not receive DT (35.1%). Overall mortality was 37% (55% predicted by A3 norms) and did not differ between those receiving DT (33.8%) or not (42.1%). The most common pathogens for primary VAP were methicillin-resistant Staphylococcus aureus (14%), Escherichia coli (11%), and Pseudomonas aeruginosa (9%) whereas P. aeruginosa was the most common pathogen in RP. The AIT for all VAP was 93%. De-escalation of therapy occurred in 55% of patients with AIT whereas 8% of VAP patients required escalation of antibiotic therapy. The most commonly used initial antibiotic choice was vancomycin/piperacillin-tazobactam (16%) and the final choice was piperacillin-tazobactam (20%). Logistic regression demonstrated no specific parameter correlated with development of RP. Higher A3 (Odds ratio, 1.03; 95% confidence interval, 1.01-1.05) was associated with mortality whereas lack of RP (odds ratio, 0.31; 95% confidence interval, 0.12-0.80), and AIT reduced mortality (odds ratio, 0.024; 95% confidence interval, 0.007-0.221). Age, gender, individual pathogen, individual antibiotic regimen, and the use of DT had no effect on mortality. CONCLUSION: De-escalation therapy did not lead to RP or increased mortality in critically ill surgical patients with VAP. De-escalation therapy was also shown to be safe in patients with septic shock. Because of its acknowledged benefits and lack of demonstrable risks, de-escalation therapy should be used whenever possible in critically ill patients with VAP.

Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness.

BACKGROUND: Critical illness is characterized by hypoferremia, iron-deficient erythropoiesis (IDE), and anemia. The relative risks and benefits of iron supplementation in this setting are unknown. METHODS: Anemic, critically ill surgical patients with an expected intensive care unit length of stay (ULOS) >or= 5 days were randomized to either enteral iron supplementation (ferrous sulfate 325 mg three times daily) or placebo until hospital discharge. Outcomes included hematocrit, iron markers (i.e., serum concentrations of iron, ferritin, and erythrocyte zinc protoporphyrin [eZPP]), red blood cell (RBC) transfusion, transfusion rate (mL RBC/study day), nosocomial infection, antibiotic days, study length of stay (LOS), ULOS, and death. Iron-deficient erythropoiesis was defined as an elevated eZPP concentration. RESULTS: Two hundred patients were randomized; 97 received iron, and 103 received placebo. Socio-demographics, baseline acuity, hematocrit, and iron markers were similar in the two groups. No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days. However, patients treated with iron were significantly less likely to receive an RBC transfusion (29.9% vs. 44.7%, respectively; p = 0.03) and had a significantly lower transfusion rate (22.0 mL/day vs. 29.9 mL/day; p = 0.03). Subgroup analysis revealed that these differences were observed in patients with baseline IDE only. Iron and placebo groups did not differ with respect to incidence of infection (46.8% vs. 48.9%; p = 0.98), antibiotic days (14 vs. 16; p = 0.45), LOS (14 vs. 16 days; p = 0.24), ULOS (12 vs. 14 days; p = 0.69), or mortality rate (9.4% vs. 9.9%; p = 0.62). CONCLUSIONS: Enteral iron supplementation of anemic, critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion. A trial comparing enteral and parenteral iron supplementation in this setting is warranted (ClinicalTrials.gov number, NCT00450177).

Decreasing magnitude of multiple organ dysfunction syndrome despite increasingly severe critical surgical illness: a 17-year longitudinal study.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) remains prevalent and the leading cause of mortality in the surgical intensive care unit (ICU). Improvements in ICU care in the last 10 years (e.g., tight glycemic control, activated protein C, fewer transfusions causing fewer nosocomial infections) may have decreased the incidence, magnitude, and mortality of MODS, as hypothesized in this study. METHODS: Longitudinal 17-year prospective study of 11,314 ICU patients (academic/tertiary unit, Level I trauma center), 5,157 (45.5%) of whom developed any degree of MODS (Marshall score, cumulative). Data collected included Admission Acute Physiology and Chronic Health Evaluation (APACHE)-II and APACHE-III scores, MOD score (MODsc), hospital mortality, and the incidence and magnitude of MODS. The ratio of MODsc: APACHE III was calculated. Analyses (X +/- SEM, chi2, repeated-measures ANOVA, linear and polynomial regression, c-statistic) were performed for calendar-year intervals beginning in 1990 through 2006. RESULTS: Among MODS patients, the mean MODsc was 6.3 +/- 0.1 points, and the mortality rate was 22%. The APACHE III score increased significantly (p < 0.0001) over time, but the mortality rate was unchanged (r2 = 0.02). Adjusted for illness severity (MODsc:A3), the magnitude of MODS decreased significantly (p < 0.0001) during the time period. CONCLUSIONS: Despite significant increases in admission APACHE III score over 17 years, the adjusted magnitude of MODS (MODsc:A3) decreased. Given the strong association between MODS and mortality for critically ill surgical patients, it is likely that the unchanged risk-adjusted mortality observed over time is due to the reduced magnitude of MODS.

Prospective analysis of life-sustaining therapy discussions in the surgical intensive care unit: a housestaff perspective.

BACKGROUND: Prospective data addressing end-of-life care in the surgical ICU are lacking. We determined factors surrounding life-sustaining therapy discussions (LSTDs) in our surgical ICU as experienced by housestaff. STUDY DESIGN: Housestaff were interviewed daily about the occurrence of an LSTD between themselves and either a patient or surrogate. Patients for whom at least one LSTD occurred were compared with patients for whom an LSTD never occurred. Housestaff also completed a standardized questionnaire that captured events surrounding each LSTD. RESULTS: Eighty LSTDs occurred among 50 patients. Lack of decision-making capacity (p = 0.04), age (p = 0.02), and acuity (p = 0.01) predicted independently the occurrence of an LSTD. Housestaff were significantly more likely to both report recent clinical deterioration (p < 0.01) and to assign a worse prognosis (p < 0.01) to patients for whom an LSTD occurred. Housestaff initiated the majority of LSTDs (70.0%) and usually did so because of clinical deterioration (60.7%); patient surrogates were most commonly believed to initiate LSTDs because of lack of improvement (60.1%). In no instance did a patient initiate an LSTD. For 39 of 50 patients (78.0%), changes in end-of-life care plans were eventually enacted as proposed originally. Housestaff reported that the likelihood of enactment depended on both the preexisting end-of-life care plan and the proposed change in end-of-life care plan. CONCLUSIONS: Age, acuity, and lack of decision-making capacity were the most important factors involved in the initiation of an LSTD. Housestaff reported that they initiated LSTDs for different reasons and proposed different end-of-life care plans relative to both patients and their surrogates. These disparities can contribute to failed enactment of proposed changes in end-of-life care plans.

Treatment of severe sepsis secondary to mycobacterium avium-intracellulare with recombinant human activated protein C.

BACKGROUND: Mycobacterium avium-intracellulare (MAI) is a well-described pathogen in patients with acquired immune deficiency syndrome (AIDS). However, peritonitis and severe sepsis as a complication of disseminated MAI is rare. We report a case that represents the first successful use of recombinant human activated protein C (rhAPC) in the treatment of severe sepsis secondary to mycobacterial infection and only the second reported case of MAI peritonitis with no known predisposing factor other than AIDS. METHODS: Case report and review of the pertinent literature. RESULTS: A 36-year-old man with AIDS presented to the emergency department with acute-onset right-sided abdominal pain, fever, and chills. Abdominal computed tomography revealed multiple rim-enhancing fluid collections. Despite immediate surgical drainage and debridement and appropriate antimicrobial therapy targeting the non-tuberculous acid-fast bacilli found in intraperitoneal fluid, the patient developed severe sepsis and septic shock. Clinical improvement occurred after infusion of recombinant human activated protein C (rhAPC) and specific antimicrobial chemotherapy directed against MAI. CONCLUSIONS: Treatment with rhAPC decreases the mortality rate of bacterial sepsis of abdominal origin and may confer a similar benefit in the treatment of abdominal mycobacterial sepsis.

Use of long-term anticoagulation is associated with traumatic intracranial hemorrhage and subsequent mortality in elderly patients hospitalized after falls: analysis of the New York State Administrative Database.

BACKGROUND: Previous studies addressing the relationship between anticoagulation and risk of traumatic intracranial hemorrhage (ICH) have provided conflicting results, and have examined infrequently elderly patients after falls. We used a statewide hospital discharge database to test the hypothesis that long-term anticoagulation (LTA) increases the likelihood of traumatic ICH and subsequent mortality in this patient population. METHODS: Patients aged 65 years or older and hospitalized as the result of a fall were extracted from the New York State Statewide Planning and Cooperative Systems Database for the year 2004. LTA, ICH, and additional injuries including skull fracture, vertebral fracture, rib fracture, lower extremity fracture, thoracic visceral injury, and abdominal visceral injury were defined using corresponding International Classification for Disease, Ninth Edition coding. Covariates included age, gender, and comorbidity. Additional outcomes included length of stay and mortality. Multivariable logistic regression was used to identify independent predictors of traumatic ICH and subsequent mortality. RESULTS: A total of 47,717 patients met the inclusion criteria. Falls were associated with a traumatic ICH in 2,517 patients (5.1%), and the mortality rate of patients with a fall-related, traumatic ICH was 15.5% (n = 394). A total of 1,511 (3.2%) patients hospitalized after a fall used LTA. Based on univariate analysis, ICH was the only injury that occurred more commonly in patients who used LTA, when compared with those who did not (8.0% vs. 5.3%, respectively, p < 0.0001). Furthermore, although overall mortality did not differ by use of LTA, mortality after ICH was significantly higher in patients who used LTA when compared with those who did not (21.9% vs. 15.2%, respectively, p = 0.04). Controlling for age, gender, and comorbidity, patients on LTA were 50% more likely to sustain a traumatic ICH after a fall (odds ratio = 1.50; 95% confidence interval, 1.23-1.81; p < 0.0001). Furthermore, among patients who sustained an ICH, mortality was 1.57-fold greater in patients on LTA (odds ratio = 1.57; 95% confidence interval, 1.02-2.45; p = 0.04). CONCLUSIONS: These data indicate that use of LTA is independently associated with traumatic ICH and subsequent mortality in elderly patients hospitalized after a fall.

Degree of anticoagulation, but not warfarin use itself, predicts adverse outcomes after traumatic brain injury in elderly trauma patients.

BACKGROUND: The relationship between preinjury warfarin use and outcomes after traumatic brain injury in elderly trauma patients remains controversial. We hypothesized that, among elderly warfarin users, the degree of anticoagulation, rather than warfarin therapy itself, would predict the severity of traumatic brain injury. METHODS: Retrospective study (2004-2006) of all elderly trauma patients (age >/=65 years) who were evaluated by the trauma service at a Level I trauma center and underwent computed tomography of the head for suspicion of an intracranial injury was performed. Three cohorts were grouped: (1) warfarin users with an admission International Normalized Ratio >/=2 (therapeutic group), (2) warfarin users with an admission International Normalized Ratio <2 (nontherapeutic group), and (3) warfarin nonusers. Main outcome variables were presenting with a Glasgow Coma Scale (GCS) score

Acute renal failure in critically ill surgical patients: persistent lethality despite new modes of renal replacement therapy.

OBJECTIVE: Despite improved resuscitation and sepsis care, acute renal failure (ARF) remains common in critically ill surgical patients. New methods of renal replacement therapy (RRT) are being used in surgical intensive care units (SICUs), including high-flux hemodialysis (HD) and continuous RRT (CRRT). RRT is being used increasingly early in the course of ARF, but data are scant to suggest that mortality is improved. Consequently, we determined whether outcomes were improved with CRRT in SICU patients, and hypothesized that CRRT lowers mortality for patients with ARF. METHODS: Patients who developed ARF (acute increase in serum creatinine concentration >or=2.4 mg/dL) in the SICU from 1993 to 2004 were identified. Data collected prospectively included year of admission, age, gender, Acute Physiology and Chronic Health Evaluation (APACHE) III score, cumulative multiple organ dysfunction score and its individual components, cumulative nonrenal organ dysfunction score, and need for RRT. Patients were stratified January 1994 to January 2001 (pre-CRRT) and February 2001 to December 2004 (post-CRRT). The primary endpoint was mortality. RESULTS: Among 8,505 SICU patients, 530 (6.2%) developed ARF. Three hundred and eleven patients were treated pre-CRRT and 219 thereafter. Female patients comprised 35% of ARF patients. The mean age was 69 years +/- 2 years, and the mean APACHE III score was 81 +/- 1 point for ARF patients. HD was performed in 15.6% of ARF patients before 2001 and 5.5% of ARF patients in 2001 and thereafter. CRRT was performed in 20.1% of ARF patients in 2001 and thereafter. Overall mortality for ARF patients was 45% (APACHE III normative predicted mortality: 55%) with no difference over time (pre-CRRT = 46.3%, post-CRRT = 45.2%, p = 0.86). Patients who required RRT had a mean APACHE III score of 91 +/- 1 point, with 61% mortality (predicted mortality: 67%), with no difference over time. Independent predictors of mortality overall and for ARF patients included age and the magnitude of renal, cardiovascular, hepatic, and neurologic dysfunction. In comparison with CRRT, HD was associated with a decreased risk of death. CONCLUSIONS: Despite more frequent RRT and the use of CRRT, the mortality of ARF in critically ill surgical patients remains high because of nonrenal organ dysfunction. Considering that ARF-related mortality was decreased by intermittent HD, and that intermittent RRT is less costly, patients who need RRT should be treated preferentially with HD.

Outcomes of acute respiratory distress syndrome (ARDS) in elderly patients.

BACKGROUND: Elderly patients have become an increasingly prevalent proportion of the intensive care unit population. Outcomes of patients with acute respiratory distress syndrome (ARDS) have been improving in recent years, but studies of ARDS rarely include substantial numbers of elderly patients. Historically, the mortality rate for ARDS has been 69% to 80% among elderly patients. We reviewed our experience with ARDS to determine whether outcomes were improving over time, and in particular whether outcomes were equally favorable among our elderly patients aged 65 years or older. METHODS: Patients who developed ARDS in a university surgical intensive care unit from 1993 to 2003 were identified and their data were collected prospectively. Data collected included age, gender, cause of ARDS, Acute Physiology and Chronic Health Evaluation (APACHE) III score (AIII), initial Pao2:FIO2, lung injury score (LIS), maximum positive end-expiratory pressure, multiple organ dysfunction pulmonary and nonpulmonary organ dysfunction scores (MODnp), vasopressor dependence, and development of ventilator-associated pneumonia. Outcomes of patients >65 years old with ARDS were compared with those of patients <65 years old. RESULTS: In the study period, 343 patients developed ARDS, 210 of whom were >65 years old. Overall, age was 65.2 +/- 0.2 years, with a mean APACHE III score of 83.4 +/- 2.0 points. Sixty-six percent were men. The initial Pao2:FIO2 for the entire group was 104.3 +/- 4.1, and was less in younger patients. Maximum positive end-expiratory pressure was 15.6 +/- 0.5 cm H2O, and mean LIS was 3.3 +/- 0.6 points; these values did not differ between cohorts. Elderly patients had a mortality of 51.9% when compared with 41.7% for younger patients (p = not significant). By logistic regression analysis, factors predicting mortality included APACHE III score (each point, odds ratio [OR], 1.022; 95% confidence interval [CI], 1.008-1.035; p < 0.01) and nonpulmonary multiple organ dysfunction score (each point, OR, 1.366; 95% CI, 1.223-1.526; p < 0.0001), but neither age (p = 0.37), LIS (p = 0.49), multiple organ dysfunction pulmonary (p = 0.90), nor year of treatment (p = 0.74) had any effect on mortality. CONCLUSIONS: The mortality rate for elderly patients with ARDS is lower in our experience when compared with historical series, even though illness severity may be higher, and comparable to that of other patients. Careful hemodynamic monitoring and resuscitation combined with other strategies to ameliorate nonpulmonary organ dysfunction achieved good outcomes in high-risk patients and could contribute in the future to further improved outcomes of elderly patients with ARDS.

Efficacy and safety of drotrecogin alfa (activated) for the therapy of surgical patients with severe sepsis.

BACKGROUND: The efficacy of therapy with drotrecogin alfa (activated) (DrotAA) (recombinant human activated protein C) for surgical patients with severe sepsis has been questioned, and there is concern that patients who have undergone surgery recently may be at increased risk of bleeding complications from the drug. This review was performed to analyze recent data and clinical trends in the management of surgical patients with severe sepsis with respect to the efficacy and safety of therapy with DrotAA. METHODS: Review and synthesis of the pertinent English-language literature. RESULTS: Source control is the mainstay of therapy for surgical infections, including intraabdominal infections, whereas antibiotics, fluid resuscitation, and support of visceral organ function are necessary adjuncts. Therapy with DrotAA can be given to surgical patients, albeit with some delay (most protocols specify a 12-h wait after major surgery to mitigate the perceived increased risk of bleeding), but efficacy as well as safety have been questioned. In the pivotal PROWESS clinical trial, DrotAA therapy did not appear to be efficacious for surgical sepsis, but rigorous scrutiny of surgical indications and adequacy of source control by blinded reappraisal of the PROWESS database suggested that DrotAA therapy may be effective for surgical patients at high risk of death (Acute Physiology and Chronic Health Evaluation [APACHE] II score>or=25 points). Several comparable studies have now been aggregated in the INDEPTH database, which shows a significant reduction in mortality (OR 0.66; 95% CI 0.45-0.97) for therapy with DrotAA of surgical patients with severe sepsis and a high risk of death. The risk of bleeding is higher in surgical patients compared with DrotAA-treated non-surgical patients, but there is a substantial improvement in survival with DrotAA treatment. In contrast, surgical patients at a lower risk of death do not benefit from therapy with DrotAA but are placed at risk for bleeding. CONCLUSION: Accumulating experience indicates that surgical patients with severe sepsis and a high risk of death (APACHE II>or=25 points) have a significantly lower mortality rate if treated with DrotAA. The increased risk of bleeding associated with therapy is acceptable given the clear improvement in survival. Surgical patients with sepsis who are at lower risk of death do not appear to benefit from therapy with DrotAA, which should be withheld in most circumstances because of the increased risk of bleeding.

Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection.

BACKGROUND: Conceptually, appropriateness of antibiotic therapy includes choice of agent relative to susceptibility of pathogens as well as dosing, timing of onset, and duration of therapy, but is most commonly considered in terms of choice of antibiotic. It has been suggested that inappropriate antibiotic selection can result in increased mortality. This study was performed to elucidate the role of scheduled, rotating antibiotic therapy in defining mortality among febrile, infected surgical ICU patients. METHODS: Prospective inception-cohort study of 356 patients during their initial episode of fever (temperature > 38.2 degrees C), caused by infection diagnosed by positive cultures or direct inspection (some cases of peritonitis). Collected data included age, gender, admission APACHE III score, peak temperature, microbial isolates and susceptibility, source of infection, multiple organ dysfunction score, mortality, and several time intervals (time that cultures were collected, time from collection to antibiotic prescription, time from collection to antibiotic administration, duration of therapy). RESULTS: The mean age was 63 +/- 1 years, the mean APACHE III score was 74 +/- 2 points, the mean multiple organ dysfunction score was 8 +/- 1 points, and overall mortality was 31%. Neither the source of infection nor the specific isolate influenced mortality. Antibiotic therapy was appropriate (covered the isolates) in 94% of cases, and did not influence mortality. Duration of therapy was identical between groups (5.1 +/- 0.3 vs. 5.4 +/- 0.3 days, p = 0.61). By logistic regression (dependent variable = mortality), APACHE III score OR 1.025, 95% C.I. 1.021-1.04) and delayed antibiotic administration (30-min intervals, OR 1.021, 95% C.I. 1.003-1.038) were independent predictors of mortality. CONCLUSIONS: The use of scheduled monthly antibiotic cycling in the surgical ICU is associated with a high rate of "appropriate" antibiotic therapy, and appears to maintain or improve resistance patterns. Because antibiotic therapy was mostly appropriate for isolates, initial inappropriate therapy could not be identified as a risk factor for mortality. However, in the setting of appropriate antibiotic choice, the prompt initial administration of antibiotics appears to be crucial for survival, but neither site of infection nor specific pathogen are influential.

The role of laparoscopy in penetrating abdominal stab wounds.

The role of diagnostic laparoscopy (DL) in abdominal stab wounds (ASWs) is not clearly defined. We hypothesized that peritoneal penetration (PP) during DL was a valid indication to convert to an exploratory laparotomy (EL). Retrospective review of hemodynamically stable ASWs requiring operation. A total of 161 patients with ASWs were identified, with 36 of 92 patients (39.1%) undergoing DL converted to EL. All 36 patients had PP; 20 of 36 (55.6%) ELs were therapeutic (TL). The number of nontherapeutic laparotomies (NTLs) prevented was 56 (60.9%). Five of 92 patients had PP on DL but did not undergo EL. Twenty-four of 69 patients who underwent initial EL had an NTL (34.8%). If this group had undergone an initial DL, and PP was used to determine need for EL, the number of NTLs would have been reduced to 10 (14.5%), a 58.3% reduction. Evidence of PP during DL is a reasonable indicator to determine the need for EL and reduce the number of NTLs.

Causes and consequences of fever complicating critical surgical illness.

BACKGROUND: Fever may have malign consequences in the postoperative period. This study was performed to determine the causes and consequences of fever in critically ill surgical patients. The specific hypothesis tested is that postoperative fever is associated with adverse clinical outcomes, including increased organ dysfunction and risk of death. METHODS: Inception-cohort study of critically ill surgical patients who manifested a core temperature of >/=38.2 degrees C for the first time. The episode of fever was monitored until resolution, which was defined as a core temperature of <38.2 degrees C for at least 72 consecutive h. Demographic data collected included age, gender, admission diagnosis, admission status (elective/emergency), severity of illness (APACHE III), the systemic inflammatory response syndrome (SIRS) score, the cumulative multiple organ dysfunction score, cause of fever (infectious/non-infectious), ICU and hospital length of stay, and mortality. The day of onset of fever in the ICU, peak temperature, ICU day of peak temperature, and duration of fever episode were recorded. All diagnostic and therapeutic interventions were recorded, including the type and duration of antibiotic therapy. Univariate results of possible significance (alpha < 0.15) were tested in logistic regression models for independence of effect upon mortality after auto-correlation was excluded by matrix correlations and the Durbin-Watson statistic. Cases where both non-infectious and infectious causes of fever were present were analyzed as part of the infectious group, whereas the cumulative MOD score was dichotomized (< 5, >/=5 points) at a value known to be associated with increased mortality. RESULTS: Among 2,419 screened patients, 626 patients (26%) developed fever. Febrile patients were older, sicker, more likely to have undergone emergency surgery, more likely to develop organ dysfunction, and more likely to die (all, p < 0.0001). The mean day of onset of fever was day 1 and the mean peak temperature for the episode was 39.1 +/- 0.1 degrees C. For most patients, it was their only episode of fever, with a mean of 1.4 +/- 0.1 episodes/patient. Forty-six percent of febrile patients were found to have an infectious cause of fever. Nearly all patients had SIRS, and nearly all developed organ dysfunction to some degree. By logistic regression, the presence of SIRS (as opposed to fever in isolation), emergency status, higher APACHE III score and the peak temperature were associated with increased mortality, with peak temperature being the most powerful predictor in the model (OR 2.20, 95% Cl 1.57-3.19). Gender had no bearing on outcome, and there was a trend toward a protective effect from an infectious etiology of fever. CONCLUSIONS: Postoperative fever is deleterious to critically ill patients. The magnitude of fever is a determinant of mortality, whereas an infectious etiology of fever may not be. The impacts of nosocomial infection and suppression of fever on critically surgical patients deserve further study.