Stéphane Legriel

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.

Early EEG Monitoring for Detecting Postanoxic Status Epilepticus during Therapeutic Hypothermia: A Pilot Study

ObjectiveTo determine whether routine electroencephalography (EEG) detected electrical status epilepticus (ESE), masked by neuromuscular blockade, in comatose cardiac-arrest survivors receiving therapeutic hypothermia.DesignProspective 3-year studySettingMedical ICUPatientsFifty-one consecutive comatose cardiac-arrest patients treated between May 2005 and May 2008 using a standardized protocol of hypothermia with neuromuscular blockade.InterventionEEG was performed routinely as soon as possible after starting therapeutic hypothermia. EEG recordings were read by an independent neurophysiologist who was blinded to patient data.Measurements and Main ResultsMedian body temperature at EEG recording was 33.0°C (range 32.4–33.8). ESE was found on 5 (10%) of the 51 EEG recordings: three patients had continuous rhythmic generalized spikes and two patients had continuous rhythmic focal spike-waves. Of the 17 (33%) patients who were discharged alive, 8 (8/51, 16%) had a CPC score of 1, 4 (8%) of 2, and 5 (10%) of 3. All patients with ESE died during their ICU stay.ConclusionThese preliminary results indicate that postanoxic status epilepticus can be masked by neuromuscular blockade during our protocol of therapeutic hypothermia. Routine EEG monitoring might be helpful in cardiac-arrest survivors receiving therapeutic hypothermia. Further studies including continuous EEG monitoring are needed to determine whether early diagnosis and treatment of ESE during therapeutic hypothermia improves the outcome.

Prognostic value of electrographic postanoxic status epilepticus in comatose cardiac-arrest survivors in the therapeutic hypothermia era

BACKGROUND The independent prognostic significance of postanoxic status epilepticus (PSE) has not been evaluated prospectively since the introduction of therapeutic hypothermia. We studied 1-year functional outcomes and their determinants in comatose survivors of cardiac arrest (CA), with special attention to PSE. METHODS 106 comatose CA survivors admitted to the intensive care unit in 2005-2010 were included in a prospective observational study. The main outcome measure was a Cerebral Performance Category scale (CPC) of 1 or 2 (favorable outcome) 1 year after CA. RESULTS CA occurred out-of-hospital in 89 (84%) patients and was witnessed from onset in 94 (89%). Median times were 6 min (IQR, 0-11) from CA to first-responder arrival and 23 min (14-40) from collapse to return of spontaneous circulation. PSE was diagnosed in 33 (31%) patients at a median of 39 h (4-49) after CA. PSE was refractory in 24 (22%) cases and malignant in 19 (20%). After 1 year, 31 (29.3%) patients had favorable outcomes including 2 (6.44%) with PSE. Factors independently associated with poor outcome (CPC ≥ 3) were PSE (odds ratio [OR], 14.28; 95% confidence interval [95% CI], 2.77-50.0; P=0.001), time to restoration of spontaneous circulation (OR, 1.04/min; 95% CI, 1-1.07; P=0.035), and LOD score on day 1 (OR, 1.28/point; 95% CI, 1.08-1.54; P=0.003). CONCLUSION PSE strongly and independently predicts a poor outcome in comatose CA survivors receiving therapeutic hypothermia, but some patients with PSE survive with good functional outcomes. PSE alone is not sufficient to predict failure to awaken after CA in the era of therapeutic hypothermia.

Determinants of recovery from severe posterior reversible encephalopathy syndrome.

Objective Few outcome data are available about posterior reversible encephalopathy syndrome (PRES). We studied 90-day functional outcomes and their determinants in patients with severe PRES. Design 70 patients with severe PRES admitted to 24 ICUs in 2001–2010 were included in a retrospective cohort study. The main outcome measure was a Glasgow Outcome Scale (GOS) of 5 (good recovery) on day 90. Main Results Consciousness impairment was the most common clinical sign, occurring in 66 (94%) patients. Clinical seizures occurred in 57 (81%) patients. Median mean arterial pressure was 122 (105–143) mmHg on scene. Cerebral imaging abnormalities were bilateral (93%) and predominated in the parietal (93%) and occipital (86%) white matter. Median number of brain areas involved was 4 (3–5). Imaging abnormalities resolved in 43 (88%) patients. Ischaemic and/or haemorrhagic complications occurred in 7 (14%) patients. The most common causes were drug toxicity (44%) and hypertensive encephalopathy (41%). On day 90, 11 (16%) patients had died, 26 (37%) had marked functional impairments (GOS, 2 to 4), and 33 (56%) had a good recovery (GOS, 5). Factors independently associated with GOS<5 were highest glycaemia on day 1 (OR, 1.22; 95%CI, 1.02–1.45, p = 0.03) and time to causative-factor control (OR, 3.3; 95%CI, 1.04–10.46, p = 0.04), whereas GOS = 5 was associated with toxaemia of pregnancy (preeclampsia/eclampsia) (OR, 0.06; 95%CI, 0.01–0.38, p = 0.003). Conclusions By day 90 after admission for severe PRES, 44% of survivors had severe functional impairments. Highest glycaemia on day 1 and time to causative-factor control were strong early predictors of outcomes, suggesting areas for improvement.

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.

Survival trends in critically ill HIV-infected patients in the highly active antiretroviral therapy era

IntroductionThe widespread use of highly active antiretroviral therapy (ART) has reduced HIV-related life-threatening infectious complications. Our objective was to assess whether highly active ART was associated with improved survival in critically ill HIV-infected patients.MethodsA retrospective study from 1996 to 2005 was performed in a medical intensive care unit (ICU) in a university hospital specialized in the management of immunocompromised patients. A total of 284 critically ill HIV-infected patients were included. Differences were sought across four time periods. Risk factors for death were identified by multivariable logistic regression.ResultsAmong the 233 (82%) patients with known HIV infection before ICU admission, 64% were on highly active ART. Annual admissions increased over time, with no differences in reasons for admission: proportions of patients with newly diagnosed HIV, previous opportunistic infection, CD4 counts, viral load, or acute disease severity. ICU and 90-day mortality rates decreased steadily: 25% and 37.5% in 1996 to 1997, 17.1% and 17.1% in 1998 to 2000, 13.2% and 13.2% in 2001 to 2003, and 8.6% in 2004 to 2005. Five factors were independently associated with increased ICU mortality: delayed ICU admission (odds ratio (OR), 3.04; 95% confidence interval (CI), 1.29 to 7.17), acute renal failure (OR, 4.21; 95% CI, 1.63 to 10.92), hepatic cirrhosis (OR, 3.78; 95% CI, 1.21 to 11.84), ICU admission for coma (OR, 2.73; 95% CI, 1.16 to 6.46), and severe sepsis (OR, 3.67; 95% CI, 1.53 to 8.80). Admission to the ICU in the most recent period was independently associated with increased survival: admission from 2001 to 2003 (OR, 0.28; 95% CI, 0.08 to 0.99), and between 2004 and 2005 (OR, 0.13; 95% CI, 0.03 to 0.53).ConclusionsICU survival increased significantly in the highly active ART era, although disease severity remained unchanged. Co-morbidities and organ dysfunctions, but not HIV-related variables, were associated with death. Earlier ICU admission from the hospital ward might improve survival.

Important questions asked by family members of intensive care unit patients.

Objectives: Relatives often lack important information about intensive care unit patients. High-quality information is crucial to help relatives overcome the often considerable situational stress and to acquire the ability to participate in the decision-making process, most notably regarding the appropriate level of care. We aimed to develop a list of questions important for relatives of patients in the intensive care unit. Design, Setting, and Participants: This was a multicenter study. Questions asked by relatives of intensive care unit patients were collected from five different sources (literature, panel of 28 intensive care unit nurses and physicians, 1-wk survey of nurses and 1-wk survey of physicians in 14 intensive care units, and in-depth interviews with 14 families). After a qualitative analysis (framework approach and thematic analysis), questions were rated by 22 relatives and 14 intensive care unit physicians, and the ratings were analyzed using principal component analysis and hierarchical clustering. Results: The five sources produced 2,135 questions. Removal of duplicates and redundancies left 443 questions, which were distributed among nine predefined domains using a framework approach (“diagnosis,” “treatment,” “prognosis,” “comfort,” “interaction,” “communication,” “family,” “end of life,” and “postintensive care unit management”). Thematic analysis in each domain led to the identification of 46 themes, which were reworded as 46 different questions. Ratings by relatives and physicians showed that 21 of these questions were particularly important for relatives of intensive care unit patients. Conclusion: This study increases knowledge about the informational needs of relatives of intensive care unit patients. This list of questions may prove valuable for both relatives and intensive care unit physicians as a tool for improving communication in the intensive care unit.

Recurrent Takotsubo Cardiomyopathy Triggered by Convulsive Status Epilepticus

IntroductionTakotsubo cardiomyopathy can complicate several conditions including neurological emergencies. A few recurrent cases associated with seizures have been reported, but none of the patients had status epilepticus. The pathophysiology of takotsubo syndrome, although debated, may involve stunning of the myocardium by a catecholamine storm triggered by stress. Patients with epilepsy may be at increased risk for takotsubo syndrome, which may occur repeatedly.MethodsWe report on a postmenopausal woman with symptomatic epilepsy who experienced recurrent takotsubo cardiomyopathy triggered by convulsive status epilepticus. Brief seizures were not associated with takotsubo syndrome. The relevant literature was reviewed.ResultsOver a 1-year period, she experienced two episodes of convulsive status epilepticus with complete neurological recovery after treatment. Echocardiography showed latero-septo-apical hypokinesia and apical ballooning. The cardiac abnormalities resolved fully and she recovered her baseline level of self-sufficiency. During the same period, she experienced several brief seizures, with no cardiac manifestations.ConclusionThe occurrence of takotsubo cardiomyopathy in association with convulsive status epilepticus, but not with brief seizures, supports neurogenically mediated myocardial stunning related to direct toxicity of endogenous catecholamines. Neuro-intensivists must be aware of this potentially fatal but fully reversible cardiac complication, which may be among the causes of death in patients with status epilepticus.

Complicated grief after death of a relative in the intensive care unit

An increased proportion of deaths occur in the intensive care unit (ICU). We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months. Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives). End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements. End-of-life care and communication in the ICU are associated with the prevalence of complicated grief http://ow.ly/DCqjB

Out-of-hospital cardiac arrest from brain cause: epidemiology, clinical features, and outcome in a multicenter cohort*.

Objectives:Although sudden cardiac death has been broadly studied, little is known on cerebrovascular events revealed by out-of-hospital cardiac arrest. We aimed to describe clinical features and prognosis of these patients and identify characteristics that could suggest a cerebrovascular etiology of the out-of-hospital cardiac arrest. Design:Retrospective review (1999–2012) of databases of three regional referral ICU centers for out-of-hospital cardiac arrest. Setting:Patients admitted to ICU for management of successfully resuscitated out-of-hospital cardiac arrest. Patients:Patients were included when subarachnoid hemorrhage, intracranial hemorrhage, ischemic stroke, sub/epidural hematoma, or cerebral thrombophlebitis was identified as the primary cause of out-of-hospital cardiac arrest. Traumatic or infectious causes were excluded. Patients were compared with a group of out-of-hospital cardiac arrest of nonneurological origin. Interventions:All medical records of the three prospective ICU databases, registered according to the Utstein style, were reviewed. Measurements and Main Results:Among 3,710 patients admitted for out-of-hospital cardiac arrest, 86 were included (mainly subarachnoid hemorrhage, n = 73). Prodromes were mostly neurological but falsely evoked a cardiac origin in six patients. Electrocardiogram displayed abnormalities in 64% of patients, with 23% of pseudoischemic pattern (ST-segment elevation or left bundle branch block). Mortality rate was 100%, with brain death as the leading cause. In comparison with the nonneurological out-of-hospital cardiac arrest group, female gender, onset of neurological prodromes, lack of other prodromes, initial nonshockable rhythm, and unspecific electrocardiogram repolarization abnormalities were independent predictive factors of a primary cerebrovascular etiology. When present, the combination of these elements displayed an area under the receiver operating characteristic curve of 0.86 (95% CI, 0.81–0.91). Conclusions:Presentation of cerebrovascular event complicated with out-of-hospital cardiac arrest may mimic coronary etiology, but several clinical elements may help to identify brain causes. Even if survival is null, the high proportion of brain deaths provides opportunity for organ donation.