Evolution and Impact of Thrombocytopenia in Septic Shock: A Retrospective Cohort Study.

OBJECTIVES: To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets < 100 × 10/L) in septic shock and to investigate the independent association of thrombocytopenia on clinical outcomes. DESIGN: Retrospective, propensity-matched, cohort study. SETTING: Two academic ICUs in Winnipeg, Canada. PATIENTS: Nine-hundred eighty adult patients diagnosed with septic shock between 2007 and 2012. INTERVENTIONS: Propensity-matched cohort analysis and Cox proportional hazard model evaluating thrombocytopenia over time. MEASUREMENTS AND MAIN RESULTS: Of 980 adults, 165 patients (16.8%) had thrombocytopenia at ICU admission (prevalent), whereas 271 (27.7%) developed thrombocytopenia during ICU admission (incident). Among patients with incident thrombocytopenia, the median time from ICU admission to thrombocytopenia was 2 days (interquartile range, 1-3 d). Among survivors, the median time from incident thrombocytopenia to platelet recovery was 6 days (interquartile range, 4-8 d). The median time from liberation of vasopressors to recovery of platelets concentration (≥ 100 × 10/L) was 2 days (interquartile range, 0-4 d). In a propensity-matched analysis, thrombocytopenia was associated with increased durations of ICU length of stay (9 vs 6 d; p < 0.01), mechanical ventilation (7 vs 4 d; p < 0.01), and vasopressor use (4 vs 3 d; p < 0.01), as well as increased major bleeding events (41% vs 18%; p < 0.01). In an adjusted Cox proportional hazards model, thrombocytopenia was significantly associated with both increased ICU mortality (hazard ratio, 1.99; 95% CI, 1.51-2.63) and hospital mortality (hazard ratio, 1.93; 95% CI, 1.48-2.51). CONCLUSIONS: Both the prevalence and incidence of thrombocytopenia are high in septic shock. Incident thrombocytopenia occurs early in septic shock, and platelet recovery lags behind clinical recovery. In septic shock, thrombocytopenia is associated with increased length of stay, longer duration of organ support, major bleeding events, and mortality.

Low-dose corticosteroid treatment in septic shock: a propensity-matching study.

OBJECTIVE: Given conflicting data and current guidelines, low-dose corticosteroids are often used in the treatment of septic shock. To evaluate the therapeutic benefit of early low-dose corticosteroid in patients with septic shock. DESIGN: Retrospective, multicenter, propensity-matched cohort study. SETTING: ICUs of 28 academic and community hospitals in three countries between 1996 and 2007. SUBJECTS: Six thousand six hundred sixty-three eligible patients with septic shock of whom 1,838 received IV low-dose corticosteroid treatment within 48 hours of the diagnosis of septic shock and were matched to a comparable group who did not receive low-dose corticosteroid. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 30-day mortality. Mortality analyses were stratified by severity of illness (Acute Physiology and Chronic Health Evaluation II quartile). Using a Cox proportional hazards model, corticosteroid therapy was associated with similar 30-day mortality when compared with the matched control cohort (652/1,838 [35.5%] vs 641/1,838 [34.9%]; hazard ratio, 0.98; 95% CI, 0.88-1.10; p = 0.77). In the subgroup of patients with the Acute Physiology and Chronic Health Evaluation II score quartile more than or equal to 30, low-dose corticosteroid was associated with lower mortality (232/461 [50.6%] vs 251/450 [55.8%]; hazard ratio, 0.81; 95% CI, 0.68-0.97; p = 0.02). In logistic regression models, corticosteroid therapy was not associated with reductions in ICU (556/1,838 [30.3%] vs 558/1,838 [30.4%]; odds ratio, 0.99; 95% CI, 0.86-1.15; p = 0.94) or hospital mortality (797/1,838 [43.4%] vs 773/1,838 [42.1%]; odds ratio, 1.05; 95% CI, 0.93-1.20; p = 0.42). Similarly, there were no significant differences in ventilator- (median and interquartile range, 13 [0-25] vs 15 [0-25]; p = 0.8) and pressor/inotrope-free days (median and interquartile range, 25 [3-27] vs 24 [2-28]; p = 0.63) up to 30 days between groups. CONCLUSION: Early administration of low-dose corticosteroid is not associated with decreased mortality when it is administered to unselected patients with septic shock. A beneficial effect of low-dose corticosteroid on mortality may exist in patients with the highest severity of illness. Future trials of low-dose corticosteroid in septic shock should consider restricting the study population to this cohort.

Early intravenous unfractionated heparin and mortality in septic shock.

BACKGROUND: Sepsis and septic shock represent a systemic inflammatory state with substantial pro-coagulant elements. Unfractionated heparin is a known anticoagulant, which also possesses anti-inflammatory properties. Unfractionated heparin has been shown to increase survival in experimental models of septic shock. OBJECTIVE: To evaluate the impact of intravenous therapeutic dose unfractionated heparin in a cohort of patients diagnosed with septic shock. DESIGN: Retrospective, propensity matched, multicenter, cohort study. SETTING: Regional intensive care units in Winnipeg, Canada between 1989 and 2005. PATIENTS: Two thousand three hundred fifty-six patients diagnosed with septic shock, of which 722 received intravenous therapeutic dose heparin. MEASUREMENTS AND MAIN RESULTS: The primary outcome of study was 28-day mortality, and mortality stratified by severity of illness (Acute Physiologic and Chronic Health Evaluation II quartile). Safety was assessed by comparing rates of gastrointestinal hemorrhage, intracranial hemorrhage, and the need for transfusion. By using a Cox proportional hazards model, systemic heparin therapy was associated with decreased 28-day mortality (307 of 695 [44.2%] vs. 279 of 695 [40.1%]; hazard ratio 0.85 [confidence interval (CI) 95% 0.73-1.00]; p = 0.05). In the highest quartile of severity of illness (Acute Physiologic and Chronic Health Evaluation II score 29-53), heparin administration was associated with a clinically and statistically significant reduction in 28-day mortality [127 of 184 (69.0%) vs. 94 of 168 (56.0%); hazard ratio 0.70 (CI 95% 0.54-0.92); p = 0.01]. The use of intravenous unfractionated heparin was associated with successful liberation from mechanical ventilation [odds ratio of 1.42 (CI 95% 1.13-1.80); p = 0.003], and successful discontinuation of vasopressor/inotropic support [odds ratio of 1.34 (CI 95% 1.06-1.71); p = 0.01]. No significant differences in the rates of major hemorrhage or need for transfusion were identified. CONCLUSION: Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock, especially in patients with higher severity of illness. Prospective randomized trials are needed to further define the role of this agent in sepsis and septic shock.

Incidence of cutaneous malignant melanoma in the Ottawa region: 1996 to 2006.

BACKGROUND: The incidence rates of invasive primary cutaneous malignant melanoma in Canada have shown a gradual tapering in recent years, after decades of increases. This trend suggests that the incidence of melanoma in Canada is stabilizing; however, knowledge of the recent trend for both in situ and invasive tumors was lacking. OBJECTIVE: The purpose of this study was to examine the temporal trend of both in situ and invasive melanoma within the Ottawa region over a 10-year period. METHODS: The histopathology of cutaneous melanomas diagnosed in the Ottawa region was obtained for the years 1996, 2001, and 2006 from the main diagnostic centers servicing the area; however, not all melanomas have been accounted for. All rates are expressed per 100,000 population per year. RESULTS: Melanoma incidence decreased between 1996 and 2001 (-3.83) and increased between 2001 and 2006 (+7.46; p < or = .05). This increase is mainly attributable to in situ melanoma (+5.49; p < or = .05). There has been no statistically significant change in invasive melanoma. CONCLUSIONS: Invasive melanoma incidence in the Ottawa region remained stable, whereas in situ melanoma incidence increased.

Factor XIII Val34Leu variant and the risk of myocardial infarction: a meta-analysis.

Genetic factors are thought to contribute to the pathogenesis of acute myocardial infarction (AMI). A common variant of factor XIII (FXIII), FXIII Val34Leu, may be protective against developing an AMI, but various studies show conflicting results. We performed a meta-analysis to determine whether the FXIII Val34Leu variant is associated with a decreased risk of AMI. One hundred ninety-five articles were reviewed and 12 case-control studies were selected. We included studies involving patients with objectively diagnosed AMIs (WHO criteria), provided that FXIII Val34Leu genotyping data were available. Inclusion decisions, quality assessment, and data extraction were conducted by two reviewers. Hypothesizing that the Leu allele was protective, we performed three analyses with the Val/Val genotype as the reference group. Pooled odds ratios (OR) and their 95% confidence intervals (95% CI) were determined. Prior to pooling, heterogeneity testing was performed using the I(2) statistic. These studies included a total of 8,743 patients, of which 3,663 were AMI patients and 5,080 were healthy controls. Using the random effects methods, protective effects were seen with the Leu/Val genotype alone (OR 0.79, 95% CI 0.68-0.93) and with Leu/Val and Leu/Leu genotypes combined (OR 0.79, 95% CI 0.66-0.93). There was also a protective effect with the Leu/Leu genotype alone, (not statistically significant: OR 0.83, 95% CI 0.61-1.12), likely due to the low frequency of this genotype. These results suggest that there is an association between the factor XIII Leu allele and a modest protective effect against AMI and may provide useful information in profiling susceptibility to myocardial infarction.