Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus.
...In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90.
A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval CI, 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group.
In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).
Lumbar puncture is among the investigations used to identify various neurological conditions, including some that can cause cardiac arrest (CA). However, CA per se may alter cerebrospinal fluid (CSF) ...characteristics. Few studies have investigated CSF findings after CA. In this descriptive work, we assessed the frequency and risk factors of abnormal CSF findings after CA and the contribution of CSF analysis to the etiological diagnosis. We retrospectively studied data from prospectively established databases of consecutive patients who were admitted to two French ICUs in 2007-2016 with sustained return of spontaneous circulation (ROSC) after CA and who underwent lumbar puncture as an etiological investigation. Of 1984 patients with sustained ROSC, 55 (2.7%) underwent lumbar puncture and were included. Lumbar puncture identified a neurological cause of CA in 2/55 (3.6%) patients. Nonspecific CSF abnormalities were noted in 37/53 (69.8%) patients. By multivariate analysis, postresuscitation shock was positively associated with CSF abnormalities (OR, 6.92; 95% confidence interval 95%CI, 1.62-37.26; P = 0.013). A no-flow time above 6 minutes (OR, 0.19; 95%CI, 0.03-1.11; P = 0.076) and a respiratory cause of CA (OR, 2.91; 95%CI, 0.53-23.15; P = 0.24) were not statistically associated with CSF abnormalities. Nonspecific CSF abnormalities were not significantly associated with poor outcomes (Cerebral Performance Category greater than or equal to3; P = 0.06). Lumbar puncture, although infrequently performed, may contribute to the etiological diagnosis of CA, albeit rarely. Nonspecific CSF abnormalities seem common after CA, notably with postresuscitation shock, and may be related to blood-brain barrier disruption. These findings may help to interpret CSF findings after CA. Further studies are warranted to assess our results.
Background
The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may ...be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP.
Methods
This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for
Streptococcus pneumoniae
. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients.
Results
Among 614 included patients, 274 had a blood culture positive for
S. pneumoniae
at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%,
p
= 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%,
p
= 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (
p
= 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (
p
= 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone.
Conclusion
Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.
The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown.
To determine whether preemptive ...treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation.
A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between February 2, 2014, and February 22, 2018.
Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo.
The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis.
Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median IQR age, 61 50-70 years; 76 32% women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50) for controls (P = .17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P = .06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P = .40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events.
In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting.
ClinicalTrials.gov identifier: NCT02152358.
Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to ...identify subgroups with similar immune profiles and their clinical and outcome correlates. A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. Two hundred and three patients were assessed, of median age 64.5 52.0-77.0 years and SAPS2 score 55 49-61 points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies.
Purpose
This prospective observational study aimed at describing prescription patterns of tigecycline and patient outcomes in 26 French intensive care units (ICU).
Methods
Data of consecutive cases ...of adult patients treated with tigecycline were collected from the initiation until 7 days after the end of treatment. Response to treatment was classified as success, failure or undetermined and analyses were presented according to severity (SOFA score <7 or ≥7). Survival was recorded at 28 days.
Results
A total of 156 patients were included (64 % male, age 60 ± 15 years). At inclusion, 53 % had a SOFA score ≥7; 93 % had received prior anti-infective agents. Tigecycline was given as first-line treatment in 47 % of patients, mostly in combination (67 %), for intra-abdominal (IAI 56 %), skin and soft tissue (SSTI 19 %) or other infections. A total of 76 % of the treated infections were hospital-acquired. Bacteraemia was reported in 12 % of patients. Median treatment duration was 9 days. Tigecycline was prematurely stopped in 42 % patients. The global success rate was 60 % at the end of treatment, and significantly higher with treatment duration more than 9 days (76 vs. 47 %,
P
< 0.001). Success rate was 65 % for patients alive at the end of treatment. Success rates tended to decrease with illness severity, immunosuppression, bacteraemia and obesity. Survival rate at day 28 was 85 % in the whole cohort and significantly higher in the less severely ill patients (
P
< 0.001).
Conclusions
Tigecycline success rates appear comparable to those reported in clinical studies in ICU with severe infections. Tigecycline could be an alternative in ICU patients.
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.
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.
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).
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.
Community-acquired pneumonia (CAP) account for a high proportion of ICU admissions, with Streptococcus pneumoniae being the main pathogen responsible for these infections. However, little is known on ...the clinical features and outcomes of ICU patients with pneumococcal pneumonia. The aims of this study were to provide epidemiological data and to determine risk factors of mortality in patients admitted to ICU for severe S. pneumoniae CAP.
We performed a retrospective review of two prospectively-acquired multicentre ICU databases (2001-2008). Patients admitted for management of severe pneumococcal CAP were enrolled if they met the 2001 American Thoracic Society criteria for severe pneumonia, had life-threatening organ failure and had a positive microbiological sample for S. pneumoniae. Patients with bronchitis, aspiration pneumonia or with non-pulmonary pneumococcal infections were excluded.
Two hundred and twenty two patients were included, with a median SAPS II score reaching 47 36-64. Acute respiratory failure (n = 154) and septic shock (n = 54) were their most frequent causes of ICU admission. Septic shock occurred in 170 patients (77%) and mechanical ventilation was required in 186 patients (84%); renal replacement therapy was initiated in 70 patients (32%). Bacteraemia was diagnosed in 101 patients. The prevalence of S. pneumoniae strains with decreased susceptibility to penicillin was 39.7%. Although antibiotherapy was adequate in 92.3% of cases, hospital mortality reached 28.8%. In multivariate analysis, independent risk factors for mortality were age (OR 1.05 (95% CI: 1.02-1.08)), male sex (OR 2.83 (95% CI: 1.16-6.91)) and renal replacement therapy (OR 3.78 (95% CI: 1.71-8.36)). Co-morbidities, macrolide administration, concomitant bacteremia or penicillin susceptibility did not influence outcome.
In ICU, mortality of pneumococcal CAP remains high despite adequate antimicrobial treatment. Baseline demographic data and renal replacement therapy have a major impact on adverse outcome.
In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to ...rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics.
Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. ...The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d’Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.
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