Gwenhael Colin

Recombinant Human Activated Protein C for Adults with Septic Shock. A Randomized Controlled Trial

RATIONALE A decade after drotrecogin alfa (activated) (DAA) was released on the market worldwide, its benefit-to-risk ratio remains a matter of debate. OBJECTIVES The current investigator-led trial was designed to evaluate the efficacy and safety of DAA, in combination with low-dose steroids, in adults with persistent septic shock. METHODS This was a multicenter (24 intensive care units), placebo-controlled, double-blind, 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were randomly assigned to DAA alone (24 μg/kg/h for 96 h), hydrocortisone and fludrocortisone alone, their respective combinations, or their respective placebos. Primary outcome was mortality rate on Day 90. MEASUREMENTS AND MAIN RESULTS On October 25, 2011, the trial was suspended after the withdrawal from the market of DAA. The Scientific Committee decided to continue the trial according to a two parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension. At the time trial was suspended, 411 patients had been recruited, 208 had received DAA, and 203 had received its placebo. There was no significant interaction between DAA and low-dose steroids (P = 0.47). On Day 90, there were 99 deaths (47.6%) among the 208 patients receiving DAA and 94 deaths (46.3%) among the 203 patients receiving placebo (P = 0.79). There was no evidence of a difference between DAA and its placebo for any secondary outcomes or serious adverse events. CONCLUSIONS In adults with established and severe septic shock, DAA showed no evidence of benefit or harm. Clinical trial registered with www.clinicaltrials.gov (NCT00625209).

Video Laryngoscopy vs Direct Laryngoscopy on Successful First-Pass Orotracheal Intubation Among ICU Patients: A Randomized Clinical Trial.

Importance In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopy may decrease this risk by improving glottis visualization. Objective To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients. Design, Setting, and Participants Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up. Interventions Intubation using a video laryngoscope (n = 186) or direct laryngoscopy (n = 185). All patients received general anesthesia. Main Outcomes and Measures The primary outcome was the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications. Results Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7% vs 70.3%; absolute difference, −2.5% [95% CI, −11.9% to 6.9%]; P = .60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n = 290) did not differ between the groups (84.4% with video laryngoscopy vs 83.2% with direct laryngoscopy; absolute difference 1.2% [95% CI, −6.3% to 8.6%]; P = .76). The median time to successful intubation was 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95% CI, 0 to 0]; P = .95). Video laryngoscopy was not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95% CI, −2.7% to 10.4%]; P = .25). In post hoc analysis, video laryngoscopy was associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7% [95% CI, 1.8% to 11.6%]; P = .01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, −2.3% [95% CI, −7.4% to 2.8%]; P = .37). Conclusions and Relevance Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels. Trial Registration clinicaltrials.gov Identifier: NCT02413723

Masseter tissue oxygen saturation predicts normal central venous oxygen saturation during early goal-directed therapy and predicts mortality in patients with severe sepsis.

Objective: This study aimed to investigate, in patients with severe sepsis, the correlation between central venous oxygen saturation and tissue oxygen saturation at different levels. Design: Prospective observational study. Setting: General intensive care unit at an academic medical center in France. Patients: Thirty-eight patients with underresuscitated severe sepsis and septic shock on intensive care unit admission. Interventions: None. Measurements and Main Results: During early resuscitation according to the 6-hr bundles of the Surviving Sepsis Campaign guidelines, tissue oxygen saturation was recorded every other hour at the level of the thenar, masseter, and deltoid muscles along with central hemodynamics, arterial lactate concentrations, and central venous oxygen saturation. Over the 6-hr resuscitation period, thenar tissue oxygen saturation was consistently higher than masseter tissue oxygen saturation (p = .04) and deltoid tissue oxygen saturation (p = .002), and masseter tissue oxygen saturation was consistently higher than deltoid tissue oxygen saturation (p = .04). Receiver operating characteristic curves analyses showed that masseter tissue oxygen saturation was better predictor of central venous oxygen saturation >70% than thenar tissue oxygen saturation (area under the curve, 0.80; 95% confidence interval 0.71−0.89 vs. 0.67; 95% confidence interval 0.56–0.77; p = .02). The crude 28-day mortality was 36.8%. Receiver operating characteristic curve analysis showed that masseter tissue oxygen saturation (area under the curve 0.87; 0.75−0.98) and deltoid tissue oxygen saturation (area under the curve 0.88; 0.77−0.98) but not thenar tissue oxygen saturation (area under the curve 0.66; 0.46–0.86) or central venous oxygen saturation (area under the curve 0.56; 0.38–0.80) were strong predictors of 28-day mortality. Conclusions: This study suggested that in the early 6-hr resuscitation period, masseter tissue oxygen saturation accurately identified patients with severe sepsis and central venous oxygen saturation >70%. Both masseter tissue oxygen saturation and deltoid tissue oxygen saturation but not central venous oxygen saturation or thenar tissue oxygen saturation are strong predictors of 28-day mortality.

Neuromuscular blockade during therapeutic hypothermia after cardiac arrest: Observational study of neurological and infectious outcomes

INTRODUCTION Neuromuscular blockade (NMB) is widely used during therapeutic hypothermia (TH) after cardiac arrest but its effect on patient outcomes is unclear. We compared the effects of NMB on neurological outcomes and frequency of early-onset pneumonia in cardiac-arrest survivors managed with TH. METHODS We retrospectively studied consecutive adult cardiac-arrest survivors managed with TH in a tertiary-level intensive care unit between January 2008 and July 2013. Patients given continuous NMB for persistent shivering were compared to those managed without NMB. Cases of early-onset pneumonia and vital status at ICU discharge were recorded. To avoid bias due to between-group baseline differences, we adjusted the analysis on a propensity score. RESULTS Of 311 cardiac-arrest survivors, 144 received TH, including 117 with continuous NMB and 27 without NMBs. ICU mortality was lower with NMB (hazard ratio [HR], 0.54 [0.32; 0.89], p=0.016) but the difference was not significant after adjustment on the propensity score (HR, 0.70 [0.39; 1.25], p=0.22). The proportion of patients with good neurological outcomes was not significantly different (36% with and 22% without NMB, p=0.16). Early-onset pneumonia was more common with NMB (HR, 2.36 [1.24; 4.50], p=0.009) but the difference was not significant after adjustment on the propensity score (HR, 1.68 [0.90; 3.16], p=0.10). CONCLUSIONS Continuous intravenous NMB during TH after cardiac arrest has potential owns effects on ICU survival with a trend increase in the frequency of early-onset pneumonia. Randomised controlled trials are needed to define the role for NMB among treatments for TH-induced shivering.

Antibiotic Therapy in Comatose Mechanically Ventilated Patients Following Aspiration: Differentiating Pneumonia From Pneumonitis*

Objectives: To determine the proportion of patients with documented bacterial aspiration pneumonia among comatose ICU patients with symptoms suggesting either bacterial aspiration pneumonia or non-bacterial aspiration pneumonitis. Design: Prospective observational study. Setting: University-affiliated 30-bed ICU. Patients: Prospective cohort of 250 patients admitted to the ICU with coma (Glasgow Coma Scale score ⩽ 8) and treated with invasive mechanical ventilation. Interventions: None. Measurements and Main Results: The primary outcome was the proportion of patients with microbiologically documented bacterial aspiration pneumonia. Patients meeting predefined criteria for aspiration syndrome routinely underwent telescopic plugged catheter sampling during bronchoscopy before starting probabilistic antibiotic treatment. When cultures were negative, the antibiotic treatment was stopped. Of 250 included patients, 98 (39.2%) had aspiration syndrome, including 92 before mechanical ventilation discontinuation. Telescopic plugged catheter in these 92 patients showed bacterial aspiration pneumonia in 43 patients (46.7%). Among the remaining 49 patients, 16 continued to receive antibiotics, usually for infections other than pneumonia; of the 33 patients whose antibiotics were discontinued, only two subsequently showed signs of lung infection. In the six patients with aspiration syndrome after mechanical ventilation, and therefore without telescopic plugged catheter, antibiotic treatment was continued for 7 days. Mechanical ventilation duration, ICU length of stay, and mortality did not differ between the 43 patients with bacterial aspiration pneumonia and the 49 patients with non-bacterial aspiration pneumonitis. The 152 patients without aspiration syndrome did not receive antibiotics. Conclusions: Among comatose patients receiving mechanical ventilation, those without clinical, laboratory, or radiologic evidence of bacterial aspiration pneumonia did not require antibiotics. In those with suspected bacterial aspiration pneumonia, stopping empirical antibiotic therapy when routine telescopic plugged catheter sampling recovered no microorganisms was nearly always effective. This strategy may be a valid alternative to routine full-course antibiotic therapy. Only half the patients with suspected bacterial aspiration pneumonia had this diagnosis confirmed by telescopic plugged catheter sampling.

Coronary angiography after cardiac arrest: useful for whom?

Dear Editor, Dankiewicz et al. [1] report no survival benefit of early coronary angiography (CAG) in patients without ST elevation after cardiac arrest. We congratulate them for this new subgroup analysis of the landmark TTM trial [2]. However, we have concerns about their interpretation of the results. First, the frequency of significant culprit-lesion identification by CAG in the TTM trial is affected by the population characteristics selected using two criteria: suspected cardiac cause and suspected acute ischemia. In the Utstein Style, medical cause is a category but cardiac cause only a subcategory, within which the cardiac diagnoses are not specified. All the observational cohort studies showing superiority of CAG over no CAG included out-of-hospital cardiac arrests (OHCA) due to cardiac causes but did not describe the methods used to diagnose these cardiac causes. Prevalences of coronary artery disease vary with the diagnostic methods. Early CAG and/or CT identified a cause in only 59 % of patients with OHCA [3]. In the study by Dankiewicz et al. [1], late CAG was performed in 94/292 (32 %) patients who did not undergo early CAG. This high crossover rate may have induced underestimation of CAG benefits in the group with early CAG. Second, OHCA of presumed cardiac cause was an inclusion criterion for the TTM trial [2]. Nevertheless, only 63 % of patients underwent CAG in the ICU and 44 % had attempted percutaneous coronary intervention (PCI). However, in some studies successful PCI, but not CAG, was associated with the outcome. Dankiewicz et al. [1] report that only 96 (38 %) of 252 early-CAG-group patients underwent successful PCI. This point indicates selection of patients to early-CAG based on a high probability of chronic myocardial ischemia, regardless of whether acute infarction was diagnosed. It probably indicates better tolerance of ischemia–reperfusion injury in this subgroup compared to groups with other causes of cardiac arrest (e.g., pulmonary embolism). A secondary analysis of our single-center cardiac arrest cohort [4] showed that PCI, but not CAG, was associated with decreased mortality and improved 6-month outcomes (Fig. 1, v test). Performing CAG without PCI unnecessarily delays temperature management [5], gas exchange optimization, and anticoagulant therapy. Considerable effort has been expended to standardize neurological prognostication after cardiac arrest. Now, the time has come to standardize patient selection for CAG. Over 10 years ago, the GRACE score was developed to guide management decisions in patients with acute coronary syndrome. A similar approach may be helpful after cardiac arrest. A score designed to rule out

Long-term quality of life in adult patients surviving purpura fulminans: an exposed-unexposed multicenter cohort study

Background Long-term Health-related Quality of Life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. Methods A French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 ICUs for a PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, SAPS II and gender with septic shock survivors (unexposed group). HR-QOL was assessed during a phone-interview using the SF-36 questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R) and the Activity of Daily Living (ADL) and Instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. Results Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 [35-83] and 44 [35-72] months of ICU discharge, respectively (p=0.23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median [quartile1-quartile3]=47 [36-53] vs. 54 [36-57]; p=0.18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n=12/37, 32%) exhibited lower PCS (34 [24-38] vs. 52 [42-56]; p=0.001) and IADL scores (7 [4-8] vs. 8 [7-8]; p=0.021) as compared to non-amputated patients. Conclusion Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. Clinical Trials NCT03216577.