Alexis Tabah

Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

CONTEXT Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. OBJECTIVES To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. DESIGN, SETTING, AND PATIENTS A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. INTERVENTIONS Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). CONCLUSIONS Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00320099.

Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case-Control Study to Assess Risks for Disease and Outcome

BACKGROUND Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

Perceptions of a 24-hour visiting policy in the intensive care unit.

Objective:To examine perceptions by intensive care unit (ICU) workers of unrestricted visitation, to measure visiting times, and to determine prevalence of symptoms of anxiety and depression in family members. Design:Observational, prospective, single-center cohort. Setting:Medical-surgical ICU in a 460-bed tertiary-care hospital. Patients:Two hundred nine consecutive patients hospitalized >3 days were studied over the first 5 ICU days. Interventions:None. Measurements and Main Results:Characteristics of patients (n = 209), families (n = 149), and ICU workers (n = 43) were collected. ICU workers reported their perceptions of unrestricted visitation, and family members completed the Hospital Anxiety and Depression Scale. Daily severity scores (Simplified Acute Physiology Score II and Logistic Organ Failure) and a workload score (Nine Equivalents of Nursing Manpower) were computed. Maximum median visit length was 120 mins per patient per day and occurred on days 4 and 5. No correlations were found among severity of illness, workload, and visit length. For 115 patients, both nurse and physician questionnaires were available; although several differences were noted, neither nurses nor physicians perceived open visitation as disrupting patient care. The median rating for delay in organizing care was “never” for physicians and “occasionally” for nurses. Nurses perceived more disorganization of care than physicians (p = .008). Compared with nurses, the physicians reported greater family trust (p = .0023), more family stress (p = .047), and greater unease when examining the patient (p = .02). The Hospital Anxiety and Depression Scale indicated symptoms of anxiety in 73 (49%) family members and depression in 44 (29.5%). Conclusions:The 24-hr visitation policy was perceived favorably by families. It induced only moderate discomfort among ICU workers, due to the potential for care interruption, in particular for nurses.

Selected medical errors in the intensive care unit: results of the IATROREF study: parts I and II.

RATIONALE Although intensive care units (ICUs) were created for patients with life-threatening illnesses, the ICU environment generates a high risk of iatrogenic events. Identifying medical errors (MEs) that serve as indicators for iatrogenic risk is crucial for purposes of reporting and prevention. OBJECTIVES We describe the selection of indicator MEs, the incidence of such MEs, and their relationship with mortality. METHODS We selected indicator MEs using Delphi techniques. An observational prospective multicenter cohort study of these MEs was conducted from March 27 to April 3, 2006, in 70 ICUs; 16 (23%) centers were audited. Harm from MEs was collected using specific scales. MEASUREMENTS AND MAIN RESULTS Fourteen types of MEs were selected as indicators; 1,192 MEs were reported for 1,369 patients, and 367 (26.8%) patients experienced at least 1 ME (2.1/1,000 patient-days). The most common MEs were insulin administration errors (185.9/1,000 d of insulin treatment). Of the 1,192 medical errors, 183 (15.4%) in 128 (9.3%) patients were adverse events that were followed by one or more clinical consequences (n = 163) or that required one or more procedures or treatments (n = 58). By multivariable analysis, having two or more adverse events was an independent risk factor for ICU mortality (odds ratio, 3.09; 95% confidence interval, 1.30-7.36; P = 0.039). CONCLUSIONS The impact of medical errors on mortality indicates an urgent need to develop prevention programs. We have planned a study to assess a program based on our results.

Neurologic complications and outcomes of infective endocarditis in critically ill patients: The ENDOcardite en REAnimation prospective multicenter study

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.

Quality of life in patients aged 80 or over after ICU discharge

IntroductionOur objective was to describe self-sufficiency and quality of life one year after intensive care unit (ICU) discharge of patients aged 80 years or over.MethodsWe performed a prospective observational study in a medical-surgical ICU in a tertiary non-university hospital. We included patients aged 80 or over at ICU admission in 2005 or 2006 and we recorded age, admission diagnosis, intensity of care, and severity of acute and chronic illnesses, as well as ICU, hospital, and one-year mortality rates. Self-sufficiency (Katz Index of Activities of Daily Living) was assessed at ICU admission and one year after ICU discharge. Quality of life (WHO-QOL OLD and WHO-QOL BREF) was assessed one year after ICU discharge.ResultsOf the 115 consecutive patients aged 80 or over (18.2% of admitted patients), 106 were included. Mean age was 84 ± 3 years (range, 80 to 92). Mortality was 40/106 (37%) at ICU discharge, 48/106 (45.2%) at hospital discharge, and 73/106 (68.9%) one year after ICU discharge. In the 23 patients evaluated after one year, self-sufficiency was unchanged compared to the pre-admission status. Quality of life evaluations after one year showed that physical health, sensory abilities, self-sufficiency, and social participation had slightly worse ratings than the other domains, whereas social relationships, environment, and fear of death and dying had the best ratings. Compared to an age- and sex-matched sample of the general population, our cohort had better ratings for psychological health, social relationships, and environment, less fear of death and dying, better expectations about past, present, and future activities and better intimacy (friendship and love).ConclusionsAmong patients aged 80 or over who were selected at ICU admission, 80% were self-sufficient for activities of daily living one year after ICU discharge, 31% were alive, with no change in self-sufficiency and with similar quality of life to that of the general population matched on age and sex. However, these results must be interpreted cautiously due to the small sample of survivors.

Systemic antifungal therapy in critically ill patients without invasive fungal infection

Objective:To determine the number of adult or pediatric intensive care unit patients without documented invasive fungal infection who receive systemic antifungal therapy. Design:A 1-day cross-sectional cohort study. Setting:One hundred sixty-nine intensive care units in France and Belgium. Patients:All patients staying in the participating intensive care units. Intervention:None. Measurement and Main Results:A hierarchical mixed model was used to identify center-based and patient-based determinants of systemic antifungal therapy use. Day 28 mortality was compared in patients with and without systemic antifungal therapy. Two thousand forty-seven patients were recruited. Systemic antifungal therapy was used in 154 (7.5%) patients, including 100 without and 54 with a proven invasive fungal infection. Overall, systemic antifungal therapy consisted of monotherapy of fluconazole (60%), caspofungin (24%), voriconazole (8%), or liposomal amphotericin B (5%). Independent predictors of systemic antifungal therapy included patient-related factors (severity, emergency surgery, malignancy, Candida colonization, and severe sepsis) and center-related factors (hospital with <800 beds, solid organ transplantation activity, higher annual incidence of candidemia, uncontrolled use of fluoroquinolones, and routine systemic antifungal therapy in patients with unresolved documented or undocumented sepsis). The group given systemic antifungal therapy had greater disease severity and higher rates of sepsis and organ failures. Nevertheless, crude 28-day mortality in the systemic antifungal therapy group was not significantly higher than in the group not given systemic antifungal therapy (20% vs. 19.2%; hazard ratio, 0.97 [0.61–1.52]; p = .88). Conclusions:Systemic antifungal therapy was used in 7.5% of intensive care unit patients. Two-thirds of patients given systemic antifungal therapy had no documented invasive fungal infection. Our results warrant a trial of systemic antifungal therapy in severely ill intensive care unit septic patients without documented invasive fungal infection based on their severity of illness and the presence of Candida colonization.

Opinions of families, staff, and patients about family participation in care in intensive care units

PURPOSE The aims of the study were to assess opinions of caregivers, families, and patients about involvement of families in the care of intensive care unit (ICU) patients; to evaluate the prevalence of symptoms of anxiety and depression in family members; and to measure family satisfaction with care. MATERIALS AND METHODS Between days 3 and 5, perceptions by families and ICU staff of family involvement in care were collected prospectively at a single center. Family members completed the Hospital Anxiety and Depression Scale (HADS) and a satisfaction scale (Critical Care Family Needs Inventory). Nurses recorded care provided spontaneously by families. Characteristics of patient-relative pairs (n = 101) and ICU staff (n = 45) were collected. Patients described their perceptions of family participation in care during a telephone interview, 206 ± 147 days after hospital discharge. RESULTS The numbers of patient-relative pairs for whom ICU staff reported favorable perceptions were 101 (100%) of 101 for physicians, 91 (90%) for nurses, and 95 (94%) for nursing assistants. Only 4 (3.9%) of 101 families refused participation in care. Only 14 (13.8%) of 101 families provided care spontaneously. The HADS score showed symptoms of anxiety in 58 (58.5%) of 99 and of depression in 26 (26.2%) of 99 family members. The satisfaction score was high (11.0 ± 1.25). Among patients, 34 (77.2%) of 44 had a favorable perception of family participation in care. CONCLUSIONS Families and ICU staff were very supportive of family participation in care. Most patients were also favorable to care by family members.

Pulmonary zygomycosis in solid organ transplant recipients in the current era.

Fifty‐eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra‐pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2–11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.

A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance.