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We recently published a comparison of two hydrocortisone dosage regimens in patients with septic shock. We compare the results conferred by the two regimens as a function of the response to cosyntropin stimulation test (CST). Patients with septic shock were treated by one of two hydrocortisone regimens: either a 50-mg intravenous bolus every 6 h during 7 days (200 mg group; n = 49), or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300 mg group; n = 50). Nonresponders was defined as a CST response of 9 μg/dL or less. Nonresponders had more severe septic shock, greater fluid resuscitation needs, and greater vasopressor dependence than responders. When analyzed only as a function of CST results, there was no difference in survival between responders and nonresponders. However, analyses crossing CST results and the treatment regimens showed that patients who were responders and in the 300 mg group had significantly less intensive care unit mortality compared with responders in the 200 mg group (respective mortality of 24% vs. 55% [relative risk 0.43, 95% confidence interval, 0.20 to 0.94, P = 0.018]). Multivariate analysis identified baseline blood cortisol as an independent prognostic factor for 28-day mortality in all groups (hazard ratio 1.002, 95% confidence interval, 1.001 to 1.002, P ≤ 0.0001). The results suggest that in patients who respond to CST, hydrocortisone can provide a dose-dependent benefit. In contrast, nonresponse may indicate corticosteroid resistance. This heterogeneity of response to hydrocortisone may explain the difficulties encountered when trying to demonstrate its benefit in septic shock.

Background: Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts., Methods: An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest)., Results: A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths., Conclusions: In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.

Purpose: The Surviving Sepsis Campaign guidelines recommend hydrocortisone in septic shock only when fluid resuscitation and vasopressors fail to restore hemodynamic stability. Hydrocortisone administration modalities are supported only by low-grade recommendations. Our main objective here was to determine differences in 28-day mortality between two low-dose hydrocortisone regimens for the treatment of septic shock., Methods: We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every 6 h during 7 days (200-mg group; n = 59) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300-mg group; n = 63). Hydrocortisone was stopped abruptly at the end of treatment., Results: There were no significant differences between the 200-mg and 300-mg groups as concerns 28-day mortality (respectively 52.5% vs. 44.4% [RR 0.84, 95% CI, 0.58-1.22, P = 0.47]), refractory shock incidence or delay from shock to vasopressor cessation. There were also no differences in adverse events between the groups. Shock relapse after hydrocortisone cessation was independent of hydrocortisone regimens, but it was associated with the persistence of infection and the use of etomidate. The resumption of hydrocortisone due to shock relapse was significantly more frequent in the 300-mg group., Conclusion: We found no differences in mortality or adverse events between the two hydrocortisone administration regimens. Shock relapse was significantly associated with the persistence of infection and the use of etomidate.

Objective: To describe the clinical spectrum of infective endocarditis in critically ill patients and assess the impact of neurologic complications on outcomes., Design: Prospective multicenter observational study conducted from April 2007 to October 2008., Setting: Thirty-three intensive care units in 23 university-affiliated and 10 general French hospitals., Patients: Two hundred twenty-five patients with definite IE were studied. Factors associated with neurologic complications and predictors of 3-month mortality were identified by logistic regression analysis. Functional outcomes of patients with neurologic complications were evaluated with the modified Rankin Scale., Interventions: None., Measurements and Main Results: Among 198 patients with definite left-sided infective endocarditis, 108 (55%) experienced at least one neurologic complication. These complications were ischemic stroke (n = 79), cerebral hemorrhage (n = 53), meningitis or meningeal reaction (n = 41), brain abscess (n = 14), and mycotic aneurysm (n = 10). Factors independently associated with neurologic complications were (subhazard ratio [95% confidence interval]): Staphylococcus aureus infective endocarditis (1.45 [1.02-2.05]), mitral valve infective endocarditis (1.54 [1.07-2.21]), and nonneurologic embolic events (1.51 [1.09-2.09]). In contrast, health care-associated infective endocarditis had a protective effect (0.46 [0.27-0.77]). Multivariate analysis identified three variables associated with 3-month mortality (odds ratio [95% confidence interval]): neurologic failure, as defined as a Glasgow Coma Scale <10 (7.41 [2.89-18.96]), S. aureus infective endocarditis (3.26 [1.53-6.94]), and severe comorbidities before admission as defined as a Charlson score >2 (3.16 [1.47-6.77]). Among the 106 patients with neurologic complications assessed at follow-up (3.9 [3-8.5] months), 31 (29%) had a modified Rankin Scale score ≤3 (ability to walk without assistance), nine (9%) a modified Rankin Scale score of 4 or 5 (severe disability), and 66 (62%) a modified Rankin Scale score of 6 (death)., Conclusions: Neurologic events are the most frequent complications in infective endocarditis patients requiring intensive care unit admission. They contribute to a severe prognosis, leaving less than one-third of patients alive with functional independence. Neurologic failure at intensive care unit admission represents a major determinant of mortality regardless of the underlying neurologic complication.