François G. Brivet

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.

Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest A Randomized, Controlled Study

Background— Targeted temperature management is recommended after out-of-hospital cardiac arrest. Whether advanced internal cooling is superior to basic external cooling remains unknown. The aim of this multicenter, controlled trial was to evaluate the benefit of endovascular versus basic surface cooling. Methods and Results— Inclusion criteria were the following: age of 18 to 79 years, out-of-hospital cardiac arrest related to a presumed cardiac cause, time to return of spontaneous circulation <60 minutes, delay between return of spontaneous circulation and inclusion <240 minutes, and unconscious patient after return of spontaneous circulation and before the start of cooling. Exclusion criteria were terminal disease, pregnancy, known coagulopathy, uncontrolled bleeding, temperature on admission <30°C, in-hospital cardiac arrest, immediate need for extracorporeal life support or hemodialysis. Patients were randomized between 2 cooling strategies: endovascular femoral devices (Icy catheter, Coolgard, Zoll, formerly Alsius; n=203) or basic external cooling using fans, a homemade tent, and ice packs (n=197). The primary end point, that is, favorable outcome evaluated by survival without major neurological damage (Cerebral Performance Categories 1–2) at day 28, was not significantly different between groups (odds ratio, 1.41; 95% confidence interval, 0.93–2.16; P=0.107). Improvement in favorable outcome at day 90 in favor of the endovascular group did not reach significance (odds ratio, 1.51; 95% confidence interval, 0.96–2.35; P=0.07). Time to target temperature (33°C) was significantly shorter and target hypothermia was more strictly maintained in the endovascular than in the surface group (P<0.001). Minor side effects directly related to the cooling method were observed more frequently in the endovascular group (P=0.009). Conclusion— Despite better hypothermia induction and maintenance, endovascular cooling was not significantly superior to basic external cooling in terms of favorable outcome. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00392639.

Pentamidine and Pancreatitis

Excerpt To the editor: Among the adverse effects of pentamidine, fatal acute pancreatitis has never been reported. We have seen this complication in two patients with the acquired immunodeficiency ...

Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis

ObjectiveSepsis and systemic inflammatory response syndrome (SIRS) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation. This study was designed to compare cerebrospinal fluid (CSF) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood–CSF barrier or from local production.DesignProspective observational study.SettingUniversity hospital medical intensive care unit.PatientsNineteen patients with meningitis and 41 patients with sepsis or SIRS without cerebrospinal infection consecutively admitted to the critical care unit over an 18-month period.InterventionsSoluble forms of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (interleukin (IL)-1β and TNF−α) were measured in paired CSF and blood samples.ResultsSerum concentrations of soluble adhesion molecules and cytokines were increased in the two groups, without significant differences. The CSF concentrations were elevated in both cases, whereas patients with meningitis demonstrated significantly higher CSF concentrations of soluble ICAM-1, VCAM-1, E-selectin, and TNF-α (p<0.001), with higher corresponding CSF/serum ratios. Correlations between CSF and serum concentrations were found only in meningitis. These correlations were strong for soluble ICAM-1 (r2=0.7, p<0.001) and E-selectin (r2=0.9, p<0.001), but weaker for VCAM-1. VCAM-1 CSF/serum ratios were increased, in comparison with ICAM-1 and E-selectin CSF/serum ratios, despite similar molecular weights. Serum and CSF levels of cytokines and adhesion molecules were not predictive of death for the whole population, except concentrations of ICAM-1 significantly increased in non-surviving patients (p<0.05).ConclusionsThe CSF soluble adhesion molecules are increased in sepsis, SIRS and meningitis. In meningitis, the correlation between CSF and serum concentrations of adhesion molecules and the presence of a discrepancy of CSF/serum ratios for molecules of the same molecular weight may suggest intrathecal shedding in addition to diffusion through blood–CSF barrier.

Usefulness of abdominal CT scan in severe peritoneal sepsis linked to primary peritonitis

We report 2 cases of primary group A streptococcal peritonitis in which emergency abdominal CT scan ruled out a hollow viscus perforation, or necrosis, avoiding unnecessary laparotomy. These cases highlight the usefulness of abdominal CT scan and suggest that blind surgical exploration has no advantages.

Acute Pancreatitis Caused by Severe Legionella pneumophila Infection

SummaryWe report three cases of severe community-acquired Legionella pneumophila with acute pancreatitis. Pancreas involvement is unusual. The clinical presentations consisted of painless pancreatitis with only elevation of serum pancreatic enzymes (case 1), tender abdomen with edematous pancreas on computed tomography scan (case 2) and necrosis (case 3). We discuss the possible mechanisms of L. pneumophila associated acute pancreatitis for which the pathophysiology is still undertermined: infection, toxin release or cytokine secretion.

Streptococcus salivarius acute meningitis with latent petromastoiditis.

A 48-y-old woman, with a previous history of neurosurgical intervention for a trigeminal neurinoma, presented with acute meningitis due to Streptococcus salivarius. There were significant changes in the petrous region, as revealed by MRI, leading to the diagnosis of associated latent subacute mastoiditis.A 48-y-old woman, with a previous history of neurosurgical intervention for a trigeminal neurinoma, presented with acute meningitis due to Streptococcus salivarius. There were significant changes in the petrous region, as revealed by MRI, leading to the diagnosis of associated latent subacute mastoiditis.

Renal Replacement Therapy in Patients with Severe Precapillary Pulmonary Hypertension with Acute Right Heart Failure

Background: Renal replacement therapy has been suggested as a therapeutic option in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension. However, there are few data supporting this strategy. Objectives: To describe the clinical course and the prognosis of pulmonary hypertensive patients undergoing renal replacement therapy in the setting of acute right heart failure. Methods: This was a single-center retrospective study over an 11-year period. Data were collected from all patients with chronic precapillary pulmonary hypertension requiring catecholamine infusions for clinical worsening and acute kidney injury that necessitated renal replacement therapy. Results: Fourteen patients were included. At admission, patients had a blood urea of 28.2 mmol/l (22.3-41.2), a creatinine level of 496 µmol/l (304-590), and a mean urine output in the 24 h preceding hospitalization of 200 ml (0-650). Sixty-eight renal replacement therapy sessions were performed, 36 of which were continuous and 32 of which were intermittent. Systemic hypotension occurred in 16/32 intermittent and 16/36 continuous sessions (p = 0.9). Two patients died during a continuous session. The intensive care unit-related, 1-, and 3-month mortality was 46.7, 66.7, and 73.3%, respectively. Conclusion: Renal replacement therapy is feasible in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension but is associated with a poor prognosis. The best modality and timing in this population remain to be defined.

Bronchoalveolar lavage cytological alveolar damage in patients with severe pneumonia

IntroductionHistological examination of lung specimens from patients with pneumonia shows the presence of desquamated pneumocytes and erythrophages. We hypothesized that these modifications should also be present in bronchoalveolar lavage fluid (BAL) from patients with hospital-acquired pneumonia.MethodsWe conducted a prospective study in mechanically ventilated patients with clinical suspicion of pneumonia. Patients were classified as having hospital-acquired pneumonia or not, in accordance with the quantitative microbiological cultures of respiratory tract specimens. A group of severe community-acquired pneumonias requiring mechanical ventilation during the same period was used for comparison. A specimen of BAL (20 ml) was taken for cytological analysis. A semiquantitative analysis of the dominant leukocyte population, the presence of erythrophages/siderophages and desquamated type II pneumocytes was performed.ResultsIn patients with confirmed hospital-acquired pneumonia, we found that 13 out of 39 patients (33.3%) had erythrophages/siderophages in BAL, 18 (46.2%) had desquamated pneumocytes and 8 (20.5%) fulfilled both criteria. Among the patients with community-acquired pneumonia, 7 out of 15 (46.7%) had erythrophages/siderophages and 6 (40%) had desquamated pneumocytes on BAL cytology. Only four (26.7%) fulfilled both criteria. No patient without hospital-acquired pneumonia had erythrophages/siderophages and only 3 out of 18 (16.7%) had desquamated pneumocytes on BAL cytology.ConclusionCytological analysis of BAL from patients with pneumonia (either community-acquired or hospital-acquired) shows elements of cytological alveolar damage as hemorrhage and desquamated type II pneumocytes much more frequently than in BAL from patients without pneumonia. These elements had a high specificity for an infectious cause of pulmonary infiltrates but low specificity. These lesions could serve as an adjunct to diagnosis in patients suspected of having ventilator-associated pneumonia.

Response to Letter Regarding Article, "Endovascular Versus External Targeted Temperature Management for Patients With Out-of-Hospital Cardiac Arrest: A Randomized, Controlled Study".

We thank Dr Yan Kang and colleagues for their comments assuming that endovascular cooling may theoretically present more advantages than surface cooling. We agree with this assertion as we consider that automated devices control like endovascular cooling allow significant shortening in time-to-target temperature, better controlled maintenance and rewarming phases, and improvement in intensive care unit nurses’ workload as described in our trial.1 However, as reported in several studies, it is not clear whether reaching the targeted temperature more quickly may result in a better prognosis in post–cardiac arrest patients. Although demonstrated by most of animal studies,2 several clinical studies failed to prove any relationship between time-to-target temperature and final outcome.3 In contrast, studies even observed that the lower the time-to-target temperature, the worse the prognosis could be, suggesting that the more the brain is damaged, the more the thermoregulation is impaired leading to lower core temperature on admission.4 This …