The impact of obesity in cirrhotic patients with septic shock: A retrospective cohort study.

BACKGROUND & AIMS: The prevalence of obesity in cirrhosis is rising. The impact of obesity in critically ill cirrhotic patients with sepsis/septic shock has not been evaluated. This study aimed to examine the relationship between obesity and mortality in cirrhotic patients admitted to the intensive care unit with septic shock. METHODS: A retrospective cohort study of all cirrhotic patients with septic shock (n = 362) and a recorded body mass index (BMI) from an international, multicentre (CATSS) database (1996-2015) was performed. Patients were classified by BMI as per WHO categories. Primary outcome was in-hospital mortality. Multivariate logistic regression analyses were carried out to determine independent associations with outcome. RESULTS: In this analysis, mean age was 56.4 years, and 62% were male. Median BMI was 26.3%, and 57.7% were overweight/obese. In-hospital mortality was 71%. Obese patients were more likely to have comorbidities of cardiac disease, lung disease and diabetes. Compared to survivors (n = 105), non-survivors (n = 257) had significantly higher MELD and APACHEII scores and higher requirements for renal replacement therapy and mechanical ventilation (P < .03 for all). Using multivariable logistic regression, increase in BMI (OR 1.07, P = .034), time delay to appropriate antimicrobials (OR 1.16 per hour, P = .003), APACHEII (OR 1.12 per unit, P = .008) and peak lactate (OR 1.15, P = .028) were independently associated with in-hospital mortality. CONCLUSIONS: Septic shock in cirrhosis carries a high mortality. Increased BMI is common in critically ill cirrhotic patients and independently associated with increased in-hospital mortality.

Patient and Organizational Factors Associated With Delays in Antimicrobial Therapy for Septic Shock.

OBJECTIVES: To identify clinical and organizational factors associated with delays in antimicrobial therapy for septic shock. DESIGN: In a retrospective cohort of critically ill patients with septic shock. SETTING: Twenty-four ICUs. PATIENTS: A total of 6,720 patients with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p < 0.0001); older age (+16 min per 10 yr; p < 0.0001); presence of comorbidities (+35 min; p < 0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p < 0.0001), between 3 and 7 days (+121 min; p < 0.0001), and longer than 7 days (+130 min; p < 0.0001); and a diagnosis of pneumonia (+45 min; p < 0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (-53 min; p < 0.001) and higher temperature (-15 min per 1°C; p < 0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p< 0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p < 0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, -47 min; p< 0.001) had shorter times to antimicrobial therapy. CONCLUSIONS: We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study.

INTRODUCTION: Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients. METHODS: We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality. RESULTS: Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese). CONCLUSIONS: The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.

BACKGROUND: Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern. OBJECTIVE: To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock. DESIGN: Retrospective, propensity matched, multicenter, cohort study. SETTING: Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007. SUBJECTS: A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated. MEASUREMENTS AND MAIN RESULTS: The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with beta-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days. CONCLUSION: Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.

Early reversible acute kidney injury is associated with improved survival in septic shock.

INTRODUCTION: The fact that acute kidney injury (AKI) is associated with worse clinical outcomes forms the basis of most AKI prognostic scoring systems. However, early reversibility of renal dysfunction in acute illness is not considered in such systems. We sought to determine whether early (≤24 hours after shock documentation) reversibility of AKI was independently associated with in-hospital mortality in septic shock. METHODS: Patient information was derived from an international database of septic shock cases from 28 different institutions in Canada, the United States and Saudi Arabia. Data from a final cohort of 5443 patients admitted with septic shock between Jan 1996 and Dec 2009 was analyzed. The following 4 definitions were used in regards to AKI status: (1) reversible AKI = AKI of any RIFLE severity prevalent at shock diagnosis or incident at 6 hours post-diagnosis that reverses by 24 hours, (2) persistent AKI = AKI prevalent at shock diagnosis and persisting during the entire 24 hours post-shock diagnosis, (3) new AKI = AKI incident between 6 and 24 hours post-shock diagnosis, and (4) improved AKI = AKI prevalent at shock diagnosis or incident at 6 hours post followed by improvement of AKI severity across at least one RIFLE category over the first 24 hours. Cox proportional hazards were used to determine the association between AKI status and in-hospital mortality. RESULTS: During the first 24 hours, reversible AKI occurred in 13.0%, persistent AKI in 54.9%, new AKI in 11.7%, and no AKI in 22.4%. In adjusted analyses, reversible AKI was associated with improved survival (HR, 0.64; 95% CI, 0.53-0.77) compared to no AKI (referent), persistent AKI (HR, 0.99; 95% CI, 0.88-1.11), and new AKI (HR, 1.41; 95% CI, 1.22-1.62). Improved AKI occurred in 19.1% with improvement across any RIFLE category associated with a significant decrease in mortality (HR, 0.53; 95% CI, 0.45-0.63). More rapid antimicrobial administration, lower Acute Physiology and Chronic Health Evaluation II score, lower age, and a smaller number of failed organs (excluding renal) on the day of shock as well as community-acquired infection were independently associated with reversible AKI. CONCLUSION: In septic shock, reversible AKI within the first 24 hours of admission confers a survival benefit compared to no, new, or persistent AKI. Prognostic AKI classification schemes should consider integration of early AKI reversibility into the scoring system.