Induced hypothermia in severe bacterial meningitis: a randomized clinical trial.

IMPORTANCE: Despite advances in care, mortality and morbidity remain high in adults with acute bacterial meningitis, particularly when due to Streptococcus pneumoniae. Induced hypothermia is beneficial in other conditions with global cerebral hypoxia. OBJECTIVE: To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis. DESIGN, SETTING, AND PATIENTS: An open-label, multicenter, randomized clinical trial in 49 intensive care units in France, February 2009-November 2011. In total, 130 patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale [GCS] score of ≤8 for <12 hours) with community-acquired bacterial meningitis were randomized. INTERVENTIONS: Hypothermia group received a loading dose of 4°C cold saline and were cooled to 32°C to 34°C for 48 hours. The rewarming phase was passive. Controls received standard care. MAIN OUTCOMES AND MEASURES: Primary outcome measure was the Glasgow Outcome Scale score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4 [unfavorable outcome]). All patients received appropriate antimicrobial therapy and vital support. Analyses were performed on an intention-to-treat basis. The data and safety monitoring board (DSMB) reviewed severe adverse events and mortality rate every 50 enrolled patients. RESULTS: After inclusion of 98 comatose patients, the trial was stopped early at the request of the DSMB because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99; 95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3°C (0.9°C) and 37.0°C (0.9°C) in the hypothermia and control group, respectively. At 3 months, 86% in the hypothermia group compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78-6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the presence of septic shock at inclusion, mortality remained higher, although not significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar results. Post hoc analysis showed a low probability to reach statistically significant difference in favor of hypothermia at the end of the 3 planned sequential analyses (probability to conclude in favor of futility, 0.977). CONCLUSIONS AND RELEVANCE: Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Careful evaluation of safety issues in future trials on hypothermia are needed and may have important implications in patients presenting with septic shock or stroke. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00774631.

A communication strategy and brochure for relatives of patients dying in the ICU.

BACKGROUND: There is a need for close communication with relatives of patients dying in the intensive care unit (ICU). We evaluated a format that included a proactive end-of-life conference and a brochure to see whether it could lessen the effects of bereavement. METHODS: Family members of 126 patients dying in 22 ICUs in France were randomly assigned to the intervention format or to the customary end-of-life conference. Participants were interviewed by telephone 90 days after the death with the use of the Impact of Event Scale (IES; scores range from 0, indicating no symptoms, to 75, indicating severe symptoms related to post-traumatic stress disorder [PTSD]) and the Hospital Anxiety and Depression Scale (HADS; subscale scores range from 0, indicating no distress, to 21, indicating maximum distress). RESULTS: Participants in the intervention group had longer conferences than those in the control group (median, 30 minutes [interquartile range, 19 to 45] vs. 20 minutes [interquartile range, 15 to 30]; P<0.001) and spent more of the time talking (median, 14 minutes [interquartile range, 8 to 20] vs. 5 minutes [interquartile range, 5 to 10]). On day 90, the 56 participants in the intervention group who responded to the telephone interview had a significantly lower median IES score than the 52 participants in the control group (27 vs. 39, P=0.02) and a lower prevalence of PTSD-related symptoms (45% vs. 69%, P=0.01). The median HADS score was also lower in the intervention group (11, vs. 17 in the control group; P=0.004), and symptoms of both anxiety and depression were less prevalent (anxiety, 45% vs. 67%; P=0.02; depression, 29% vs. 56%; P=0.003). CONCLUSIONS: Providing relatives of patients who are dying in the ICU with a brochure on bereavement and using a proactive communication strategy that includes longer conferences and more time for family members to talk may lessen the burden of bereavement. (ClinicalTrials.gov number, NCT00331877.)

Functional outcome after convulsive status epilepticus.

OBJECTIVES: Few outcome data are available about convulsive status epilepticus managed in the intensive care unit. We studied 90-day functional outcomes and their determinants in patients with convulsive status epilepticus. DESIGN: Two hundred forty-eight convulsive status epilepticus patients admitted to 18 intensive care units in 2005-2007 were included in a prospective observational cohort study. The main outcome measure was a Glasgow Outcome Scale score of 5 (good recovery) on day 90. MAIN RESULTS: Convulsive status epilepticus occurred out of hospital in 177 (67%) patients, and all but 15 patients were still seizing at medical team arrival. The median time from convulsive status epilepticus onset to anticonvulsant drug initiation was 40 mins (interquartile range, 5-80). Total seizure duration was 85 mins (interquartile range, 46.5-180). Convulsive status epilepticus was refractory in 49 (20%) patients. The most common causes of convulsive status epilepticus were anticonvulsive agent withdrawal (36.4%) in patients with previous epilepsy and stroke (27.7%) in inaugural convulsive status epilepticus. Mechanical ventilation was needed in 210 (85%) patients. On day 90, 42 (18.8%) patients were dead, 87 (38.8%) had marked functional impairments (Glasgow Outcome Scale score, 2-4), and 95 (42.4%) had a good recovery (Glasgow Outcome Scale score, 5). Factors showing independent positive associations with poor outcome (Glasgow Outcome Scale score, <5) were older age (odds ratio, 1.04/year; 95% confidence interval, 1.02-1.05; p=.0005), cerebral insult (odds ratio, 2.70; 95% confidence interval, 1.37-5.26; p=.007), longer seizure duration (odds ratio, 1.72/120 min; 95% confidence interval, 1.05-2.86; p=.03), on-scene focal neurologic signs (odds ratio, 2.08; 95% confidence interval, 1.03-4.16; p=.04), and refractory convulsive status epilepticus (odds ratio, 2.70; 95% confidence interval, 1.02-7.14; p=.045). CONCLUSIONS: Ninety days after intensive care unit admission for convulsive status epilepticus, half the survivors had severe functional impairments. Longer seizure duration, cerebral insult, and refractory convulsive status epilepticus were strongly associated with poor outcomes, suggesting a role for early neuroprotective strategies.

Ability of family members to predict patient's consent to critical care research.

OBJECTIVE: A European Union Directive provides for the designation of a surrogate who can consent to or refuse inclusion of an incapacitated patient in research studies. The accuracy with which surrogates consent to research on behalf of patients has not been evaluated in the intensive care unit (ICU). METHODS: A prospective multicenter study was conducted in ten ICUs of the French Famirea study group between July and October 2004. Two hypothetical studies were simultaneously submitted to the patient, surrogate, and physician at the time that the patient was discharged to a ward. One study involved minimal risk and the other greater-than-minimal risk to the patients. RESULTS: With the minimal risk study there was patient-surrogate discrepancy in 32% of cases and patient-physician discrepancy in 25%. Corresponding figures with the greater-than-minimal risk study were 42% and 46%. None of the collected variables differed significantly between cases with and without patient-surrogate discrepancy. CONCLUSIONS: Family members designated to serve as surrogate decision makers may fail to accurately consent to research for critically ill patients in one-third to nearly one-half of cases.

Prognosis of patients presenting extreme acidosis (pH <7) on admission to intensive care unit.

PURPOSE: The purpose was to determine prognosis of patients presenting extreme acidosis (pH <7) on admission to the intensive care unit (ICU) and to identify mortality risk factors. MATERIALS AND METHODS: We retrospectively analyzed all patients who presented with extreme acidosis within 24 hours of admission to a polyvalent ICU in a university hospital between January 2011 and July 2013. Multivariate analysis and survival analysis were used. RESULTS: Among the 2156 patients admitted, 77 patients (3.6%) presented extreme acidosis. Thirty (39%) patients suffered cardiac arrest before admission. Although the mortality rate predicted by severity score was 93.6%, death occurred in 52 cases (67.5%) in a median delay of 13 (5-27) hours. Mortality rate depended on reason for admission, varying between 22% for cases linked to diabetes mellitus and 100% for cases of mesenteric infarction (P = .002), cardiac arrest before admission (P < .001), type of lactic acidosis (P = .007), high Simplified Acute Physiology Score II (P = .008), and low serum creatinine (P = .012). CONCLUSIONS: Patients with extreme acidosis on admission to ICU have a less severe than expected prognosis. Whereas mortality is almost 100% in cases of cardiac arrest before admission, mortality is much lower in the absence of cardiac arrest before admission, which justifies aggressive ICU therapies.

Impact of a high loading dose of amikacin in patients with severe sepsis or septic shock.

BACKGROUND: The therapeutic effect of aminoglycosides is highest and optimal when the peak plasma concentration (C max)/minimal inhibitory concentration (MIC) ratio is between 8 and 10. The French guidelines recommend to use high doses of aminoglycosides for empiric antibiotic therapy in patients suffering from severe sepsis or septic shock. In clinical practice, the recommended target is an amikacin C max between 60 and 80 mg/L, which corresponds to approximately 8 times the MIC breakpoint, as defined by the European Committee on Antimicrobial Susceptibility Testing. The aim of this study was to assess the incidence and impact on mortality of an amikacin concentration between 60 and 80 mg/L in patients suffering from severe sepsis or septic shock. METHODS: This was a prospective observational cohort study conducted in two intensive care units (ICU). Patients receiving amikacin at a loading dose of 30 mg/kg for severe sepsis or septic shock were enrolled in the cohort. The target C max for amikacin was between 60 and 80 mg/L, as recommended by French guidelines (i.e. C max/MIC breakpoint = 8-10). RESULTS: Over the study period, the amikacin C max was <60 mg/L, between 60 and 80 mg/L, and >80 mg/L in 20 (18.2%), 46 (41.8%) and 44 (40%) of the 110 selected patients, respectively. Mortality rate was 40, 28.3 and 56.8% in the groups of patients with C max < 60 mg/L, 60 mg/L < C max < 80 mg/L and C max > 80 mg/L, respectively. Following multivariate analysis, mortality rate was significantly lower in the group of patients with amikacin C max between 60 and 80 mg/L than in the group of patients with amikacin C max > 80 mg/L (P = 0.004). The multivariate analysis also revealed that the factors independently associated with a higher in-ICU mortality rate were age (P = 0.02) and norepinephrine dose (P = 0.0001). CONCLUSIONS: With a loading dose of 30 mg/kg of amikacin, concentration was potentially suboptimal (C max < 60 mg/L) in only 18.2% of patients. The pharmacodynamic target (60 mg/L < C max < 80 mg/L) recommended by French guidelines was reached in 41.8% of patients and was associated with reduced in-ICU mortality. But amikacin overexposure (i.e. C max > 80 mg/L) was frequent and potentially associated with increased mortality.

Clinically documented pleural effusions in medical ICU patients: how useful is routine thoracentesis?

STUDY OBJECTIVES: To assess the impact of routine thoracentesis on diagnostic assessment and therapeutic measures in patients with clinically documented pleural effusions. DESIGN AND SETTING: Prospective, 1-year, three-center study in medical ICU (MICU) patients with physical and radiographic evidence of pleural effusion. PATIENTS: Of 1,351 patients admitted to three MICUs during the study period, 113 patients had physical and radiographic evidence of pleural effusion, yielding an annual incidence of 8.4%. INTERVENTION: Routine thoracentesis in 82 patients without contraindications to thoracentesis. MEASUREMENTS AND RESULTS: Twenty patients (24.4%) had a transudate, 35 patients (42.7%) had an infectious exudate (parapneumonic, n = 21; empyema, n = 14), and 27 patients (32.9%) had a noninfectious exudate. Laboratory parameters including the leukocyte count, the neutrophil percentage in pleural fluid, and the fluid/serum protein and lactate dehydrogenase ratios differed significantly among the three groups. Thoracentesis yielded improvements in the diagnosis and/or treatment in 46 patients (56%): the presumptive (prethoracentesis) diagnosis was changed in 37 patients (32 patients with certain benefit and 5 patients with probable benefit from thoracentesis), of whom 27 patients received a change in treatment based on the new diagnosis; 9 other patients received a change in treatment although the diagnosis remained the same. The only complications were pneumothorax in six patients (7%), all with a favorable outcome after drainage. CONCLUSION: Infection was the main cause of pleural effusions detected based on physical and radiographic findings in our MICU population. Routine thoracentesis proved a simple and safe means of improving the diagnosis and treatment.

Family participation in care to the critically ill: opinions of families and staff.

BACKGROUND: Allowing family members to participate in the care of patients in intensive care units (ICUs) may improve the quality of their experience. No previous study has investigated opinions about family participation in ICUs. METHODS: Prospective multicenter survey in 78 ICUs (1,184 beds) in France involving 2,754 ICU caregivers and 544 family members of 357 consecutive patients. We determined opinions and experience about family participation in care; comprehension (of diagnosis, prognosis, and treatment) and satisfaction (Critical Care Family Needs Inventory) scores to assess the effectiveness of information to families and the Hospital Anxiety and Depression score for family members. RESULTS: Among caregivers 88.2% felt that participation in care should be offered to families. Only 33.4% of family members wanted to participate in care. Independent predictors of this desire fell into three groups: patient-related (SAPS II at ICU admission, OR 0.984); ICU stay length, OR 1.021), family-related (family member age, OR 0.97/year); family not of European descent, OR 0.294); previous ICU experience in the family, OR 1.59), and those related to emotional burden and effectiveness of information provided to family members (symptoms of depression in family members, OR 1.58); more time wanted for information, OR 1.06). CONCLUSIONS: Most ICU caregivers are willing to invite family members to participate in patient care, but most family members would decline.

Health-related quality of life in family members of intensive care unit patients.

OBJECTIVE: The intensive care unit (ICU) experience has been reported to cause adverse health effects in families during and after the ICU stay. The objective of this study was to evaluate health-related quality of life (HRQOL) in relatives of patients 90 days after ICU discharge or death. DESIGN: Multicenter observational study. SETTING: Twenty-one ICUs in France. PARTICIPANTS: Among 459 eligible relatives of ICU patients, 284 (62%) were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a telephone interview, the SF-36 was completed to assess HRQOL 90 days after ICU discharge or death. The physical component summary score of the SF-36 was normal (89/100 [66-94]) but the mental component summary score showed substantial impairments (emotional role, 67 [50-80]; social functioning, 70 [60-90]; vitality, 60 [45-70]; and mental health, 60 [48-2]). Moreover, 35.9% of relatives were taking anxiolytic or antidepressant drugs, and 8.4% were taking psychotropic agents prescribed since the discharge or death of the patient. Among factors independently associated with a worse mental score, 2 were patient-related (admission for shock or implementation of end-of-life decision), 6 were family-related (older age, female gender, child of the patient, low income, chronic disease, and newly prescribed psychotropic medications), and 1 was related to the ICU experience (perceived conflicts between ICU staff and relatives). CONCLUSIONS: The SF-36 showed evidence of impaired mental health in relatives of ICU patients 90 days after discharge. Better end-of-life care, psychiatric support after the ICU experience, and better conflict prevention and resolution are potential targets for improvement.

Risk of post-traumatic stress symptoms in family members of intensive care unit patients.

RATIONALE: Intensive care unit (ICU) admission of a relative is a stressful event that may cause symptoms of post-traumatic stress disorder (PTSD). OBJECTIVES: Factors associated with these symptoms need to be identified. METHODS: For patients admitted to 21 ICUs between March and November 2003, we studied the family member with the main potential decision-making role. MEASUREMENTS: Ninety days after ICU discharge or death, family members completed the Impact of Event Scale (which evaluates the severity of post-traumatic stress reactions), Hospital Anxiety and Depression Scale, and 36-item Short-Form General Health Survey during a telephone interview. Linear regression was used to identify factors associated with the risk of post-traumatic stress symptoms. MAIN RESULTS: Interviews were obtained for family members of 284 (62%) of the 459 eligible patients. Post-traumatic stress symptoms consistent with a moderate to major risk of PTSD were found in 94 (33.1%) family members. Higher rates were noted among family members who felt information was incomplete in the ICU (48.4%), who shared in decision making (47.8%), whose relative died in the ICU (50%), whose relative died after end-of-life decisions (60%), and who shared in end-of-life decisions (81.8%). Severe post-traumatic stress reaction was associated with increased rates of anxiety and depression and decreased quality of life. CONCLUSION: Post-traumatic stress reaction consistent with a high risk of PTSD is common in family members of ICU patients and is the rule among those who share in end-of-life decisions. Research is needed to investigate PTSD rates and to devise preventive and early-detection strategies.