Roland Amathieu

Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

CONTEXT Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. OBJECTIVES To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. DESIGN, SETTING, AND PATIENTS A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. INTERVENTIONS Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). CONCLUSIONS Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00320099.

An Algorithm for Difficult Airway Management, Modified for Modern Optical Devices (Airtraq Laryngoscope; LMA CTrach ™)A 2-Year Prospective Validation in Patients for Elective Abdominal, Gynecologic, and Thyroid Surgery

Background: Because algorithms for difficult airway management, including the use of new optical tracheal intubation devices, require prospective evaluation in routine practice, we prospectively assessed an algorithm for difficult airway management that included two new airway devices. Methods: After 6 months of instruction, training, and clinical testing, 15 senior anesthesiologists were asked to use an established algorithm for difficult airway management in anesthetized and paralyzed patients. Abdominal, gynecologic, and thyroid surgery patients were enrolled. Emergency, obstetric, and patients considered at risk of aspiration were excluded. If tracheal intubation using a Macintosh laryngoscope was impossible, the Airtraq laryngoscope (VYGON, Ecouen, France) was recommended as a first step and the LMA CTrach™ (SEBAC, Pantin, France) as a second. A gum elastic bougie was advocated to facilitate tracheal access with the Macintosh and Airtraq laryngoscopes. If ventilation with a facemask was impossible, the LMA CTrach™ was to be used, followed, if necessary, by transtracheal oxygenation. Patient characteristics, adherence to the algorithm, efficacy, and early complications were recorded. Results: Overall, 12,225 patients were included during 2 yr. Intubation was achieved using the Macintosh laryngoscope in 98% cases. In the remainder of the cases (236), a gum elastic bougie was used with the Macintosh laryngoscope in 207 (84%). The Airtraq laryngoscope success rate was 97% (27 of 28). The LMA CTrach™ allowed rescue ventilation (n = 2) and visually directed tracheal intubation (n = 3). In one patient, ventilation by facemask was impossible, and the LMA CTrach™ was used successfully. Conclusions: Tracheal intubation can be achieved successfully in a large cohort of patients with a new management algorithm incorporating the use of gum elastic bougie, Airtraq, and LMA CTrach™ devices.

Tracheal intubation of morbidly obese patients: a randomized trial comparing performance of Macintosh and Airtraq™ laryngoscopes

BACKGROUND The Airtraq laryngoscope is designed to allow visualization of the glottis without alignment of the oral, pharyngeal, and laryngeal axes. We hypothesized that this new airway device would facilitate tracheal intubation of morbidly obese patients. We compared tracheal intubation performance of standard Macintosh laryngoscope with the Airtraq laryngoscope in morbidly obese patients. METHODS One hundred and six consecutive ASA I-III morbidly obese patients undergoing surgery were randomized to intubation with the Macintosh laryngoscope or the Airtraq laryngoscope. Induction of anaesthesia was standardized. If tracheal intubation failed within 120 s with the Macintosh or Airtraq , laryngoscopes were switched. Success rate, SpO2, duration of tracheal intubation, and quality of airway management were evaluated and compared between the groups. RESULTS Preoperative characteristics of the patients were similar in both groups. In the Airtraq group, tracheal intubation was successfully carried out in all patients within 120 s. In the Macintosh laryngoscope group, six patients required intubation with the Airtraq laryngoscope. The mean (SD) time taken for tracheal intubation was 24 (16) and 56 (23) s, respectively, with the Airtraq and Macintosh laryngoscopes, (P<0.001). SpO2 was better maintained in the Airtraq group than in the Macintosh laryngoscope group with one and nine patients, respectively, demonstrating drops of SpO2 to 92% or less (P<0.05). CONCLUSIONS In this study, the Airtraq laryngoscope shortened the duration of tracheal intubation and prevented reductions in arterial oxygen saturation in morbidly obese patients.

Tracheal Intubation Using the Airtraq in Morbid Obese Patients Undergoing Emergency Cesarean Delivery

THE Airtraq (Prodol Meditec S.A., Vizcaya, Spain), a new disposable intubating device, was designed to provide a view of the glottis without alignment of the oral and pharyngeal axes. The Airtraq laryngoscope (AL) has recently been used in patients with normal airways 1 and in simulated difficult airways, 2 but no study has assessed its performance in difficult airway patients. After training on a manikin, five senior staff anesthesiologists covering the obstetric anesthesia unit of our university hospital performed the clinical learning process with the AL. Because of its efficiency in the case of difficult tracheal intubation, the AL was incorporated into our emergency difficult airway management algorithm as a second-step airway device in the case of failed tracheal intubation using a standard Macintosh laryngoscope. We report two cases of emergency cesarean delivery parturients in whom the trachea was rapidly intubated using the AL after failed direct laryngoscopy. We discuss the place of the AL in a difficult airway management algorithm in parturients.

Video-Assisted Versus Conventional Tracheal Intubation in Morbidly Obese Patients

BackgroundWe compared tracheal intubation characteristics and arterial oxygenation quality during airway management of morbidly obese patients whose trachea was intubated under video assistance with the LMA CTrach™ (SEBAC, Pantin, France) or the Airtraq™ laryngoscope (VYGON, Écouen, France) with that of the conventional Macintosh laryngoscope.MethodsAfter standardized induction of anesthesia, 318 morbidly obese patients scheduled for elective morbid obesity surgery received tracheal intubation with the LMA CTrach™, the Airtraq™ laryngoscope, or the conventional Macintosh laryngoscope. Duration of apnea, time to tracheal intubation, and oxygenation quality during airway management were compared between the LMA CTrach™ and the laryngoscope groups.ResultsPatients’ characteristics were similar in the three groups. The success rate for tracheal intubation was 100% with the LMA CTrach™ and the Airtraq™ laryngoscope. One patient of the Macintosh laryngoscope group received LMA CTrach™ intubation because of early arterial oxygen desaturation associated with unstable facemask ventilation. The duration of apnea was shorter with the LMA CTrach™ than that of the Airtraq™ laryngoscope and the Macintosh laryngoscope. The duration tracheal intubation was shorter with the Airtraq™ laryngoscope than with the Macintosh laryngoscopes and the LMA CTrach™. During airway management, arterial oxygenation was of better quality with the LMA CTrach™ and the Airtraq™ laryngoscope than that of the Macintosh laryngoscope.ConclusionBecause LMA CTrach™ promoted short apnea time and the Airtraq™ laryngoscope allowed early definitive airway, both video-assisted tracheal intubation devices prevented most serious arterial oxygenation desaturation evidenced during tracheal intubation of morbidly obese patients with the conventional Macintosh laryngoscope.

Improved Survival after Resuscitation with Norepinephrine in a Murine Model of Uncontrolled Hemorrhagic Shock

Background:Recent studies have challenged current guidelines on fluid resuscitation. However, studies on resuscitation using norepinephrine in uncontrolled hemorrhagic shock are lacking. The authors examined the effects of norepinephrine in combination with saline infusion in uncontrolled hemorrhage in rats. Methods:Rats subjected to a 15-min controlled hemorrhage (withdrawal of 3 ml blood/100 g body mass) followed by a 60-min uncontrolled hemorrhage (75% tail amputation) were randomly assigned to one of several treatment groups (10 rats/group) receiving different doses of norepinephrine (0 [NE0], 5 [NE5], 50 [NE50], or 500 [NE500] &mgr;g · 100 g−1 · h−1). In the four hypotensive resuscitation groups (n = 40), mean arterial pressure was not allowed to fall below 40 mmHg by titrated infusion of normal saline. In the four normotensive resuscitation groups (n = 40), it was not allowed to fall below 80 mmHg. The endpoint was survival at 210 min. Results:There was a significant difference (P < 0.05) in survival rate among groups. Among the hypotensive rats, 6 (60%) survived in the NE0 and NE5 dose groups, 9 (90%) survived in the NE50 dose group, and none survived in the NE500 dose group. Among the normotensive rats, none survived in the NE0 group, 4 (40%) survived in the NE5 dose group, all 10 (100%) survived in the NE50 group, and none survived in the NE500 group. Conclusions:The early use of norepinephrine in uncontrolled hemorrhagic shock in rats significantly improved survival when infused at a rate of 50 &mgr;g · 100 g−1 · h−1 in normotensive and hypotensive resuscitation strategies.

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).

Identification of Serum Proton NMR Metabolomic Fingerprints Associated with Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis

Purpose: Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC). Experimental Design: The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components. Results: The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up. Conclusions: Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis. Clin Cancer Res; 18(24); 6714–22. ©2012 AACR.

Difficult Intubation in Thyroid Surgery: Myth or Reality?

Thyroid surgery is considered to be a risk factor for difficult airway management. We prospectively studied 324 consecutive patients undergoing thyroid surgery to investigate the incidence of difficult intubation as evaluated by the intubation difficulty scale as well as other specific predictive factors. The overall incidence of difficult intubation was 11.1% (95% CI: 7.6–14.5). Median intubation difficulty scale was 0 (25th–75th percentile: 0; 2.7). In three predefined groups (no echographic goiter, clinically palpable goiter, and impalpable goiter), difficult intubation occurred in 10% (95% CI: 4.8–17.4), 13% (95% CI: 6.5–18.4), and 11% (95% CI: 4.7–16.8) of patients, respectively, with no statistical difference among the groups. Specific predictive criteria (palpable goiter, endothoracic goiter, airway deformation, airway compression, or thyroid malignancy) were not associated with an increased rate of difficult intubation. Classical predictive criteria (mouth opening <35 mm, Mallampati III or IV, short neck, neck mobility <80°, thyromental distance <65 mm, and a retrognathic mandible) were significantly reliable in the univariate analysis as risk factors for difficult intubation.

Metabolomic approach by 1H NMR spectroscopy of serum for the assessment of chronic liver failure in patients with cirrhosis.

Assessment of chronic liver failure (CLF) in cirrhotic patients is needed to make therapeutic decisions. A biological score is usually performed, using the Model for End-Stage Liver Disease (MELD), to evaluate CLF. Nevertheless, MELD does not take into account metabolic perturbations produced by liver-function impairment. In contrast, metabolomics can investigate many metabolic perturbations within biological systems. The purpose of this study was to assess whether metabolomic profiles of serum, obtained by proton NMR spectroscopy from cirrhotic patients, are affected by the severity of CLF. An orthogonal projection to latent-structure analysis was performed to compare MELD scores and NMR spectra of 124 patients with cirrhosis. The statistical model obtained showed a good explained variance (R(2)X = 0.87 and R(2)Y = 0.86) and a good predictability (Q(2)Y = 0.64). Metabolomic profiles showed significant differences regarding various metabolites depending of severity of CLF: levels of high-density lipoprotein and phosphocholine resonances were significantly higher in patients with mild CLF compared to severe CLF. Other metabolites such as lactate, pyruvate, glucose, amino acids, and creatinine were significantly higher in patients with severe CLF than mild CLF. Our conclusion is that metabolomic NMR analysis provides new insights into metabolic processes related to the severity of hepatic function impairment in cirrhosis.