Corinne Lejus

Hydrocortisone Therapy for Patients With Multiple Trauma: The Randomized Controlled HYPOLYTE Study

CONTEXT The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown. OBJECTIVE To test the efficacy of hydrocortisone therapy in trauma patients. DESIGN, SETTING, AND PATIENTS Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France. INTERVENTION Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response. MAIN OUTCOME MEASURE Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death. RESULTS One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, -9%; 95% CI, -16% to -3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, -5% to 11%; P = .44). CONCLUSION In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00563303.

Continuous controlled-infusion of hypertonic saline solution in traumatic brain-injured patients: a 9-year retrospective study

IntroductionDescription of a continuous hypertonic saline solution (HSS) infusion using a dose-adaptation of natremia in traumatic brain injured (TBI) patients with refractory intracranial hypertension (ICH).MethodsWe performed a single-center retrospective study in a surgical intensive care unit of a tertiary hospital. Fifty consecutive TBI patients with refractory ICH treated with continuous HSS infusion adapted to a target of natremia. In brief, a physician set a target of natremia adapted to the evolution of intracranial pressure (ICP). Flow of NaCl 20% was a priori calculated according to natriuresis, and the current and target natremia that were assessed every 4 hours.ResultsThe HSS infusion was initiated for a duration of 7 (5 to 10) (8 ± 4) days. ICP decreased from 29 (26 to 34) (31 ± 9) mm Hg at H0 to 20 (15 to 26) (21 ± 8) mm Hg at H1 (P < 0.05). Cerebral perfusion pressure increased from 61 (50 to 70) (61 ± 13) mm Hg at H0 up to 67 (60 to 79) (69 ± 12) mm Hg at H1 (P < 0.05). No rebound of ICH was reported after stopping continuous HSS infusion. Natremia increased from 140 (138 to 143) (140 ± 4) at H0 up to 144 (141 to 148) (144 ± 4) mmol/L at H4 (P < 0.05). Plasma osmolarity increased from 275 (268 to 281) (279 ± 17) mmol/L at H0 up to 290 (284 to 307) (297 ± 17) mmol/L at H24 (P < 0.05). The main side effect observed was an increase in chloremia from 111 (107 to 119) (113 ± 8) mmol/L at H0 up to 121 (117 to 124) (121 ± 6) mmol/L at H24 (P < 0.05). Neither acute kidney injury nor pontine myelinolysis was recorded.ConclusionsContinuous HSS infusion adapted to close biologic monitoring enables long-lasting control of natremia in TBI patients along with a decreased ICP without any rebound on infusion discontinuation.

Balanced versus chloride-rich solutions for fluid resuscitation in brain-injured patients: a randomised double-blind pilot study

IntroductionWe sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury.MethodsWe conducted a single-centre, two-arm, randomised, double-blind, pilot controlled trial in Nantes, France. Patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8) or subarachnoid haemorrhage (World Federation of Neurosurgical Society grade III or higher) who were mechanically ventilated were randomised within the first 12 hours after brain injury to receive either isotonic balanced solutions (crystalloid and hydroxyethyl starch; balanced group) or isotonic sodium chloride solutions (crystalloid and hydroxyethyl starch; saline group) for 48 hours. The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours.ResultsForty-two patients were included, of whom one patient in each group was excluded (one consent withdrawn and one use of forbidden therapy). Nineteen patients (95%) in the saline group and thirteen (65%) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours (hazard ratio = 0.28, 95% confidence interval [CI] = 0.11 to 0.70; P = 0.006). In the saline group, pH (P = .004) and strong ion deficit (P = 0.047) were lower and chloraemia was higher (P = 0.002) than in the balanced group. Intracranial pressure was not different between the study groups (mean difference 4 mmHg [-1;8]; P = 0.088). Seven patients (35%) in the saline group and eight (40%) in the balanced group developed intracranial hypertension (P = 0.744). Three patients (14%) in the saline group and five (25%) in the balanced group died (P = 0.387).ConclusionsThis study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions. Even if the study was not powered sufficiently for this endpoint, intracranial pressure did not appear different between groups.Trial registrationEudraCT 2008-004153-15 andNCT00847977The work in this trial was performed at Nantes University Hospital in Nantes, France.

Pupillary reflex measurement predicts insufficient analgesia before endotracheal suctioning in critically ill patients

IntroductionThis study aimed to evaluate the pupillary dilatation reflex (PDR) during a tetanic stimulation to predict insufficient analgesia before nociceptive stimulation in the intensive care unit (ICU).MethodsIn this prospective non-interventional study in a surgical ICU of a university hospital, PDR was assessed during tetanic stimulation (of 10, 20 or 40 mA) immediately before 40 endotracheal suctionings in 34 deeply sedated patients. An insufficient analgesia during endotracheal suction was defined by an increase of ≥1 point on the Behavioral Pain Scale (BPS).ResultsA total of 27 (68%) patients had insufficient analgesia. PDR with 10 mA, 20 mA and 40 mA stimulation was higher in patients with insufficient analgesia (P <0.01). The threshold values of the pupil diameter variation during a 10, 20 and 40 mA tetanic stimulation to predict insufficient analgesia during an endotracheal suctioning were 1, 5 and 13% respectively. The areas (95% confidence interval) under the receiver operating curve were 0.70 (0.54 to 0.85), 0.78 (0.61 to 0.91) and 0.85 (0.721 to 0.954) with 10, 20 and 40 mA tetanic stimulations respectively. A sensitivity analysis using the Richmond Agitation Sedation Scale (RASS) confirmed the results. The 40 mA stimulation was poorly tolerated.ConclusionsIn deeply sedated mechanically ventilated patients, a pupil diameter variation ≥5% during a 20 mA tetanic stimulation was highly predictable of insufficient analgesia during endotracheal suction. A 40 mA tetanic stimulation is painful and should not be used.

Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes

While almost anesthetics are metabolized by the cytochrome P450 (CYP) 3A4, some major volatile ones such as halothane and sevoflurane are metabolized by CYP2E1 in humans. To determine whether 2,6-diisopropylphenol (propofol), a widely used intravenous anesthetic agent, known to inhibit CYP3A4 and CYP1A2, also inhibits CYP2E1, 6-OH hydroxylation of chlorzoxazone, a prototypical CYP2E1 substrate, was estimated using two pools of human microsomes and one pool of porcine microsomes from seven livers. Basal human enzyme activities were characterized by a V(max) of 1426+/-230 and 288+/-29 pmol min(-1)mg(-1) protein and a K(m) of 122+/-47 and 149+/-42 microM, while the corresponding porcine activities were associated with a V(max) of 352+/-42 pmol min(-1)mg(-1) protein and a K(m) of 167+/-38 microM. A competitive inhibition of CYP2E1 by propofol was observed with low inhibition constants in the therapeutic range in both porcine (19 microM) and human (48 microM) liver microsomes. These in vitro results suggest that propofol could have a protective effect on toxic metabolite activation of compounds catalyzed by CYP2E1.

The Microbiology of Community-acquired Peritonitis in Children.

Background: Microbiologic data are lacking regarding pediatric community-acquired peritonitis (CAP). Methods: We conducted a 2-year retrospective single center study. Consecutive children undergoing CAP surgery were included. Microbiology and antimicrobial susceptibility of peritoneal isolates were analyzed. Results: A total of 70 children from 3 months to 14 years of age were included. A total of 123 bacterial isolates were analyzed. Escherichia coli was the predominant aerobic organism (51% of isolates); 54.8% were susceptible to amoxicillin whereas 90.3% were susceptible to amoxicillin-clavulanate. Anaerobes accounted for 29% of isolates, and 94.3% of strains were susceptible to amoxicillin-clavulanate and 68.5% were susceptible to clindamycin. Pseudomonas aeruginosa was present in 6% of isolates and in 10% of children. The presence of E. coli resistant to amoxicillin or to amoxicillin-clavulanate was the only independent risk factor associated with postoperative peritonitis. Conclusion: Microbiology of pediatric CAP is similar to adult CAP with a predominancy of E. coli and anaerobes. P. aeruginosa in peritoneal samples had no apparent influence on the outcome.

A retrospective study about cerebral near-infrared spectroscopy monitoring during paediatric cardiac surgery and intra-operative patient blood management☆

OBJECTIVES Cerebral non-invasive monitoring of oxygen saturation by near-infrared spectroscopy (rSO2) during paediatric cardiac surgery is supposed to decrease the risk of neurological complications. Since haemoglobin level is one of the factors changing rSO2, we aimed to explore if rSO2 monitoring influences intra-operative RBC (red blood cell) transfusion threshold and volumes, as well as the duration of ICU stay. METHODS The design was a retrospective analysis involving 91 children less than 2 years of age (including 16 neonates) with a congenital heart disease requiring surgical treatment with or without cardiopulmonary bypass from January 2006 to August 2009. Systematic rSO2 monitoring was introduced after September 2007 (n=56). The independent factors associated with the intra-operative transfusion threshold haemoglobin (Hb) level>9.5g/dL, total volume of intra-operative RBC transfusion<30mL/kg and ICU stay<6 days were identified by multivariate analysis logistic regression. Data were expressed as medians (25-75%). RESULTS Cardiac malformations and demographic characteristics were similar in both periods. Two independent factors, weight and rSO2 monitoring, were identified as independent factors associated with the three end-points. The transfusion threshold, total transfusion volume and ICU stay with and without rSO2 were 9.8 (8.9 to 10.3) versus 8.7 (8.2 to 9.6) g/dL (P<0.0001), 20 (14-49) versus 36 (22.5-51.5) mL/kg (P=0.0165) and 5 (3-8) versus 7 (5-10.7) days (P=0.0084), respectively. CONCLUSION rSO2 monitoring changed our transfusion strategy with an earlier transfusion but a reduced total RBC volume and decreased the length of ICU stay.

Pulse pressure variations to guide fluid therapy in donors: A multicentric echocardiographic observational study ☆ ☆☆ ★

PURPOSE Preload responsiveness parameters could be useful in the hemodynamic management of septic shock. METHODS A multicentric prospective echocardiographic observational study was conducted from March 2009 to August 2011. Clinically brain-dead subjects were included. Pulse pressure variations (ΔPPs) were recorded. Cardiac index, variation of the maximum flow velocity of aortic systolic blood flow, and right ventricular function parameters were evaluated via transthoracic echocardiography. Fluid responsiveness was defined by at least 15% cardiac index increase, 30 minutes after a 500-mL colloid solution infusion. The number of organs harvested was recorded. RESULTS Twenty-five subjects were included. Pulse pressure variation could not discriminate responders (n=15) from nonresponders (n=10). The best ΔPP threshold (20%) could discriminate responders with a sensitivity of 100% and a specificity of 40%. Variation of the maximum flow velocity of aortic systolic blood flow, tricuspid annular plane systolic excursion, and right ventricle dilation could not discriminate responders from nonresponders. Eighteen subjects underwent organ harvesting. The number of organs harvested was higher in responders (3.5 [3-5]) than in nonresponders (2.5 [2-3]; P=.03). CONCLUSIONS A ΔPP threshold of 13% is insufficient to guide volume expansion in donors. The best threshold is 20%. Fluid responsiveness monitoring could enhance organ harvesting.

What is the accuracy of the high-fidelity METI Human Patient Simulator physiological models during oxygen administration and apnea maneuvers?

BACKGROUND: A widely used physiological simulator is generally accepted to give valid predictions of oxygenation status during disturbances in breathing associated with anesthesia. We compared predicted measures with physiological measurements available in the literature, or derived from other models. METHODS: Five studies were selected from the literature which explored arterial oxygenation, with or without preoxygenation, in clinical situations or through mathematical modeling as well as the evolution of the fraction of expired oxygen (FEO2) during preoxygenation maneuvers. Scenarios from these studies were simulated on the METI-Human Patient Simulator™ simulator, and the data were compared with the results in the literature. RESULTS: Crash-induction anesthesia without preoxygenation induces an O2 pulse saturation (SpO2) decrease that is not observed on the METI simulator. In humans, after 8 minutes of apnea, SpO2 decreased below 90% while the worst value was 95% during the simulation. The apnea time to reach 85% was less with obese patients than with healthy simulated patients and was shortened in the absence of preoxygenation. However, the data in the literature include METI simulator confidence interval 95% values only for healthy humans receiving preoxygenation. The decrease in PaO2 during 35-second apnea started at end-expiration was slower on the METI simulator than the values reported in the literature. FEO2 evolution during preoxygenation maneuvers on the METI simulator with various inspired oxygen fractions (100%, 92%, 84%, and 68%) was very close to those reported in humans when perfect mask seal is provided. In practice, this seal is impossible to obtain on the METI simulator. CONCLUSIONS: SpO2 decreased much later during apnea on the METI simulator than in a clinical situation, whether preoxygenation was performed or not. The debriefing after simulation of critical situations or the use of the METI simulator to test a new equipment must consider these results.