Serge Molliex

Do Antifibrinolytics Reduce Allogeneic Blood Transfusion in Orthopedic Surgery

Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, or ϵ-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; ϵ-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28–0.64) for aprotinin and 0.17 (0.11–0.24) for tranexamic acid. Results suggest a dose–effect relation with tranexamic acid. ϵ-Aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.

Target-controlled versus manually-controlled infusion of propofol for direct laryngoscopy and bronchoscopy.

Few studies have compared the clinical profile of target-controlled infusions of propofol with that of manually-controlled infusions. Fifty-four ASA physical status I or II patients scheduled for an elective otorhinolaryngology endoscopy performed under general anesthesia with spontaneous ventilation were enrolled in this prospective randomized study to compare the clinical outcome of such administrations. Before induction, all patients received a single alfentanil bolus dose (10 &mgr;g/kg). Propofol administration was adapted to maintain absence of movement, hemodynamic stability, and efficient spontaneous ventilation. When compared with the Manually-Controlled Infusion group, in the Target-Controlled Infusion group there were fewer movements at insertion of the laryngoscope (14.8% vs. 44.4%), improved hemodynamic stability (largest variations of mean arterial blood pressure <10% of control values, versus 20%), fewer episodes of apnea, and less respiratory acidosis after endoscopy (pH = 7.37 ± 0.05 and Paco2 = 50 ± 7 mm Hg versus pH = 7.28 ± 0.06 and Paco2 = 58 ± 9 mm Hg); the recovery was also shorter (time to opening eyes or verbal response, 4.6 ± 2.0 min and 6.8 ± 2.5 min versus 10.8 ± 7.3 min and 15.7 ± 7.1 min). Propofol consumption was comparable in the two groups. Targeting the effect-site concentration improved the time course of the propofol drug effect during direct laryngoscopy performed during spontaneous ventilation when compared with manual infusion.

De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit

IntroductionMost data on de-escalation of empirical antimicrobial therapy has focused on ventilator-associated pneumonia. In this retrospective monocentric study, we evaluated de-escalation as part of a global strategy of empiric antibiotherapy management irrespective of the location and the severity of the infection. The goal of this trial was to assess the application of a de-escalation strategy and the impact in terms of re-escalation, recurrent infection and to identify variables associated with de-escalation.MethodsAll consecutive patients treated with empiric antibiotic therapy and hospitalized in the intensive care unit for at least 72 hours within a period of 16 months were included. We compared the characteristics and outcome of patients who have experienced de-escalation therapy with those who have not.ResultsA total of 116 patients were studied corresponding to 133 infections. Antibiotic therapy was de-escalated in 60 cases (45%). De-escalation, primarily accomplished by a reduction in the number of antibiotics used, was observed in 52% of severe sepsis or septic shock patients. Adequate empiric antibiotic and use of aminoglycoside were independently linked with de-escalation. De-escalation therapy was associated with a significant reduction of recurrent infection (19% vs 5% P = 0.01). Mortality was not changed by de-escalation.ConclusionsAs part of a global management of empiric antibiotherapy in an intensive care unit, de-escalation might be safe and feasible in a large proportion of patients.

Halogenated Anesthetics Reduce Interleukin-1β-induced Cytokine Secretion by Rat Alveolar Type II Cells in Primary Culture

Background Alveolar epithelial type II (ATII) cells participate in the intraalveolar cytokine network by secreting cytokines and are widely exposed to volatile anesthetics during general anesthesia. The aim of the current study was to evaluate the effects of halothane, enflurane, and isoflurane on rat ATII cell cytokine secretions in ATII primary cell cultures. Methods Alveolar epithelial type II primary cell cultures were obtained from adult rat lungs. ATII cells were stimulated by recombinant murine interleukin-1&bgr; (rmIL-1&bgr;) to mimic an inflammatory response, and immediately exposed for various duration to different concentration of halothane, enflurane, or isoflurane. Interleukin-6, macrophage inflammatory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1) protein concentrations were then measured in cell culture supernatants. Recombinant mIL-1&bgr;-stimulated ATII cells exposed to air served as control. Results Halothane, isoflurane, and enflurane (1 minimum alveolar concentration [MAC], 4 h) decreased rmIL-1&bgr;-stimulated ATII cell secretions of interleukin-6, MIP-2, and MCP-1, but did not modify total protein secretion. Halothane exposure decreased rmIL-1&bgr;-stimulated ATII cell secretions of interleukin-6, MIP-2, and MCP-1 in a dose- and time-dependent manner. Total protein concentrations remained unchanged except at 1.5 MAC of halothane, and no cytotoxic effect could be evidenced by lactate dehydrogenase release. These effects were transient as rmIL-1&bgr;-stimulated ATII cell secretions of interleukin-6 and MIP-2 progressively reached control values between 4 and 24 h after the end of halothane exposure. However, MCP-1 inhibition persisted until 24 h. rmIL-1&bgr;-induced MIP-2 and tumor necrosis factor-&agr; mRNA expression were decreased by 36 and 24%, respectively, after halothane exposure. Conclusions The current study shows that exposure of rmIL-1&bgr;-stimulated ATII cells to volatile anesthetics reversibly alters their cytokine secretion. Therefore, volatile anesthesia, by modulating pulmonary epithelial cell secretion of inflammatory cytokines, might affect the lung inflammatory response.

Wavelet transform of heart rate variability to assess autonomic nervous system activity does not predict arousal from general anesthesia

PurposeThe relationship between autonomic nervous system (ANS) activity and general anesthesia has been explored. Studies have demonstrated partial recovery of heart rate variability (HRV), representative of ANS activity in the postoperative period, but the arousal period has not been precisely studied. The goals of this study were to analyze modifications of ANS activity during general anesthesia and, more particularly, around the arousal period, to look for predictors of arousal.MethodsWe analyzed HRV changes using wavelet transform, a time-frequency analysis that, in contrast to Fourier transform, is able to assess abrupt changes of ANS activity. Seventeen patients (mean ♂ SD age: 40.9 ♂ 16.4 yr) under general anesthesia for hip or knee surgery, were included in the study. The analysis began one hour before anesthesia, focussed on eye opening, and ended three hours after arousal.ResultsThere was a dramatic decrease in HRV after induction, that extended throughout anesthesia and represented a decrease in global autonomic regulation with, however, a relative predominance of vagal tone. At the moment of eye opening, there was an abrupt change in HRV, representing a sudden shift of ANS balance towards the predominance of sympathetic activity, while none of these indices changed seconds before arousal.ConclusionsWavelet analysis of HRV appears to be powerful tool to precisely assess instantaneous changes of HRV during anesthesia. Using this method, there were no identifiable precursory HRV indices of arousal.RésuméObjectifOn connaît la relation entre l’activité du système nerveux autonome (SNA) et l’anesthésie générale. Des études ont démontré la récupération postopératoire partielle de la variabilité de la fréquence cardiaque (VFC), représentant l’activité du SNA, mais le retour à la conscience n’a pas été précisément étudié. Les objectifs de la présente étude sont d’analyser les modifications de l’activité du SNA pendant l’anesthésie générale et, plus particulièrement, la période entourant le retour à la conscience, afin de découvrir des prédicteurs de réveil.MéthodeNous avons analysé les changements de VFC en utilisant la transformée par ondelettes, une analyse temps-fréquence qui, contrairement à la transformée de Fourier, permet d’évaluer les changements brusques de l’activité du SNA. Dixsept patients (âge moyen ♂ écart type : 40,9 ♂ 16,4 ans), sous anesthésie générale pour une intervention à la hanche ou au genou, ont participé à l’étude. L’analyse, centrée sur l’ouverture des yeux, a débuté une heure avant l’anesthésie et s’est terminée trois heures après le retour à la conscience.RésultatsAprès l’induction de l’anesthésie, il s’est produit une baisse marquée de la VFC qui s’est prolongée tout au long de l’anesthésie et qui représentait une diminution de la régulation autonome globale accompagnée, toutefois, d’une relative prédominance du tonus vagal. À l’ouverture des yeux, il y a eu un changement brusque de la VFC, indice d’un décalage soudain dans l’équilibre du SNA vers une prédominance de l’activité sympathique, alors qu’aucun de ces indices n’avait changé quelques secondes avant le réveil.ConclusionL’analyse par ondelettes de la VFC s’est révélée un outil puissant pour évaluer de façon précise les modifications de la VFC pendant l’anesthésie. Cette méthode n’a pas montré d’indices précurseurs identifiables de VFC de réveil.

Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial

Importance Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain. Objective To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction. Design, Setting, and Participants The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016). Interventions Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient’s resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery. Main Outcomes and Measures The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery. Results Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = .02; absolute risk difference, −14%, 95% CI, −25% to −2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality. Conclusions and Relevance Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction. Trial Registration clinicaltrials.gov Identifier: NCT01536470

A Comparison of Target- and Manually Controlled Infusion Propofol and Etomidate/Desflurane Anesthesia in Elderly Patients Undergoing Hip Fracture Surgery

Elderly patients have a higher risk of developing adverse drug reactions during anesthesia, especially anesthesia affecting cardiovascular performance. In this prospective randomized study we compared quality of induction, hemodynamics, and recovery in elderly patients scheduled for hip fracture surgery and receiving either etomidate/desflurane (ETO/DES) or target-controlled (TCI) or manually controlled (MAN) propofol infusion for anesthesia. Sixteen patients were anesthetized with ETO (0.4 mg/kg) followed by DES titrated from an initial end-tidal concentration of 2.5%. Eighteen patients received propofol TCI at an initial plasma concentration of 1 &mgr;g/mL and titrated upwards by 0.5-&mgr;g/mL steps. Fifteen patients received a bolus induction of propofol 1 mg/kg over 60 s followed by an infusion initially set at 5 mg · kg−1 · h−1. All received a bolus (20 &mgr;g/kg) followed by an infusion of 0.4 &mgr;g · kg−1 · min−1 alfentanil. According to hemodynamics, concentrations of DES or propofol (TCI group) and propofol infusion rate (MAN group) were respectively adjusted by a step of 20% and 50%. In the TCI and ETO/DES groups, the time spent at a mean arterial blood pressure within 15% and 30% of baseline values was more than 60% and 80% of anesthesia time, whereas in the MAN group it was <30% and 60%, respectively. In the MAN group more anesthetic drug adjustments were recorded (6.4 ± 2.8 versus 2.5 ± 1.2 [ETO/DES] and 2.6 ± 1 [TCI]). TCI improves the time course of propofols hemodynamic effects in elderly patients.

Cervical epidural anesthesia is associated with increased cancer-free survival in laryngeal and hypopharyngeal cancer surgery: a retrospective propensity-matched analysis.

Background and Objectives Regional anesthesia preserves perioperative immune competence and may reduce the risk of recurrence and metastasis after cancer surgery. Cervical epidural anesthesia provides adequate analgesia for head and neck cancer surgery, but its impact on cancer recurrence is unknown. Methods This study was a single-center retrospective cohort study of patients undergoing larynx or hypopharynx cancer surgery between January 1984 and December 2008. One hundred eleven patients had general anesthesia combined with intraoperative and postoperative cervical epidural; 160 had general anesthesia alone with postoperative morphine. From this cohort, matched pairs were selected using a propensity score to balance potential confounders of receiving epidural anesthesia. The primary end point was the length of cancer-free survival after surgery until September 2009. Results Propensity-based matching produced 65 pairs. Matching was effective in achieving balance between groups for each of the preoperative variables collected. Combined epidural and general anesthesia (68% 5-year cancer-free survival; 95% confidence interval [CI], 57%–82%) was associated with significantly increased cancer-free survival compared with general anesthesia alone (37% 5-year cancer-free survival; 95% CI, 25%–54%) with a corresponding adjusted hazard ratio of 0.49 (95% CI, 0.25–0.96; P = 0.04). Patients in the epidural group had an increased overall survival compared with the non–epidural group (P = 0.03). Conclusions The association between cervical epidural anesthesia and increased cancer-free survival found in this retrospective study should be an important hypothesis to further investigate in head and neck cancer surgery.

Optimal low-molecular-weight heparin regimen in major orthopaedic surgery A meta-analysis of randomised trials

Low-molecular-weight heparins (LMWH) are routinely used for thromboprophylaxis in major lower limb orthopaedic surgery. However the optimal LMWH regimen, offering the greatest efficacy with an acceptable risk of bleeding, has not been clearly established with regard to dose and timing of treatment initiation. We performed a meta-analysis of all available randomised trials comparing LMWH to placebo. Relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated. By means of subgroup analysis, we evaluated the consistency of the results according to the timing of treatment initiation (preoperative versus postoperative) and dose of LMWH used (low doses, i.e. 4000 anti-Xa IU or below versus high doses). The possibility of a dose-effect relationship of LMWH was also evaluated by meta-regression. Thirteen studies were included (1925 patients). In four studies, LMWH treatment was started postoperatively. Daily LMWH doses ranged from 3000 anti-Xa IU to over 6000 anti-Xa IU. Compared to placebo, LMWH significantly reduced the risk of asymptomatic deep-vein thrombosis (DVT) (RR=0.51, 95% CI=[0.45-0.59], p<0.001) without significantly increasing the risk of major haemorrhage (RR=0.80 [0.36-1.79], p=0.58). We found no convincing evidence that starting prophylaxis preoperatively was associated with a significantly reduced risk of asymptomatic DVT relative to starting postoperatively. Our results showed a strong correlation between the risk of DVT and LMWH dose (meta-regression, test of slope p=0.03). These findings are tentative because the comparisons are across trials, but nevertheless suggest that the different LMWH regimens currently recommended are effective and safe.

Repérage de la membrane cricothyroïdienne en phase d’apprentissage : valeur ajoutée de l’échographie ?

OBJECTIVES Emergency cricothyroidotomy is recommended as life-saving maneuver when mask ventilation and tracheal intubation are impossible. It requires the puncture of the cricothyroid membrane (CTM) whose clinical identification is difficult. The objective of this study is to evaluate if ultrasound can help locating the CTM by comparing palpation and ultrasonographic evaluation. PATIENTS AND METHODS After ultrasound localization of CTM by a referent physician in two overweight volunteers, twelve residents without prior anatomy recall, defined by palpation an entry point for CTM. After a rapid training in CTM ultrasound localization, residents identified an ultrasound-guided puncture point. For each puncture site were registered: relevance, time and ease to localization. Six months later, residents renewed clinical and ultrasound identification of CTM on the same subjects. RESULTS The CTM was accurately identified by palpation and ultrasound by 46% and 100% of residents respectively (P<0.05). Six months later, residents remained more effective identifying CTM with ultrasound than with palpation (78% vs. 33%) (P<0.05). Time to localization of CTM by palpation in the 2 volunteers was 15 s [11-18] and 24 s [9-39] (average [CI 95%]) whereas it was 21 s [16-25 s] and 28 s [19-36] by ultrasound respectively (ns). The ultrasound identification of CTM was also considered easier than clinical identification. CONCLUSION Following a limited training phase, ultrasound allowed a more effective localization of CTM by residents when compared to clinical palpation in overweight patients. This benefit remained significant when assessment was repeated 6 months later.