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Abstract Introduction In elderly patients, goal-directed haemodynamic therapy (GDHT), depth of anaesthesia monitoring and lung-protective ventilation have been shown to improve postoperative outcomes. The aim of this study was to evaluate current practices concerning strategies of anaesthesia optimisation in patients aged ≥ 75 years. Patients and methods A multicentre observational study was performed from February to May 2015 in 23 French academic centres. On 30 consecutive days in each centre, patients ≥ 75 years with at least one major comorbidity undergoing elective or emergency procedures (femoral-neck fractures surgery, intraperitoneal abdominal surgery or vascular surgery) were included. Patient characteristics and data related to GHDT, management of hypotension, monitoring of temperature and depth of anaesthesia, lung ventilation, point of care haemoglobin testing were collected. Results In total, 807 patients were included. Only 2% of patients [95% CI: 1–3] received GHDT in full accordance with guidelines. Depth of anaesthesia monitoring was largely performed (53% [95% CI: 50–56]). The multifaceted strategy of lung-protective ventilation combining low tidal volumes (6–8 mL/kg), PEEP of 5–8 cm cmH 2 O, and repeated recruitment manoeuvres, was performed in only 4% [95% CI: 3–5] of patients. A centre effect was a major determinant of variation concerning implementation of these strategies. Discussion In patients' ≥ 75 years, strategies of anaesthesia optimisation are not in accordance with eligible guidelines. Implementation of these techniques varies independently of factors related to the patient or the type of surgery and may be dependent on the generated constraints. [ABSTRACT FROM AUTHOR]

Highlights from the article: Keywords: Quality improvement; Perioperative care pathways; Emergency abdominal surgery; Postoperative mortality The patient-level process measures concerning the ten key components of the care pathway in the usual care group revealed a high average rate of implementation, between 47% and 90%. Quality improvement, Perioperative care pathways, Emergency abdominal surgery, Postoperative mortality.

Background. Unfractionated heparin is administered in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Anticoagulation monitoring is recommended, with an anti-activated factor X (anti-Xa) targeting 0.3 to 0.7 IU/mL. Owing to heparin's heterogeneous pharmacokinetic properties, anti-Xa is unpredictable, generating a challenge in anticoagulation practices. The aim of this study was to build a pharmacokinetic model of heparin accounting for potential confounders, and derive an optimized dosing regimen for a given anti-Xa target. Methods. Adult patients undergoing VA-ECMO were included between January 2020 and June 2021. Anticoagulation was managed with an initial 100 IU/kg heparin loading dose followed by a continuous infusion targeting 0.2 to 0.7 IU/mL anti-Xa. The data were split into model development and model validation cohorts. Statistical analysis was performed using a nonlinear mixed effects modeling population approach. Model-based simulations were performed to develop an optimized dosing regimen targeting the desired anti-Xa. Results. A total of 74 patients were included, with 1703 anti-Xa observations. A single-compartment model best fitted the data. Interpatient variability for distribution volume was best explained by body weight, C-reactive protein and ECMO indication (post-cardiotomy shock or medical cardiogenic shock), and interpatient variability for elimination clearance was best explained by serum creatinine and C-reactive protein. Simulations using the optimized regimen according to these covariates showed accurate anti-Xa target attainment. Conclusion. In adult patients on VA-ECMO, heparin's effect increased with serum creatinine and medical indication, whereas it decreased with body weight and systemic inflammation. We propose an optimized dosing regimen accounting for key covariates, capable of accurately predicting a given anti-Xa target. [ABSTRACT FROM AUTHOR]

Background: Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH. Few covariates were identified probably owing to a lack of statistical power. This study aims to address these limitations through a meta-analysis of individual data from two studies. Methods: An individual patient data meta-analysis was conducted using data from two single-center prospective observational studies, where different UFH types were used for anticoagulation. A pharmacodynamic/pharmacodynamic model of UFH was developed using a non-linear mixed-effects approach. Time-varying covariates such as hemodilution and fluid infusions during a cardiopulmonary bypass were considered. Results: Activities of UFH's anti-activated factor/anti-thrombin were best described by a two-compartment model. Unfractionated heparin clearance was influenced by body weight and the specific UFH type. Volume of distribution was influenced by body weight and pre-operative fibrinogen levels. Pharmacodynamic data followed a log-linear model, accounting for the effect of hemodilution and the pre-operative fibrinogen level. Equations were derived from the model to personalize UFH dosing based on the targeted activated clotting time level and patient covariates. Conclusions: The population model effectively characterized UFH's pharmacokinetics/pharmacodynamics in cardiopulmonary bypass patients. This meta-analysis incorporated new covariates related to UFH's pharmacokinetics/pharmacodynamics, enabling personalized dosing regimens. The proposed model holds potential for individualization using a Bayesian estimation. [ABSTRACT FROM AUTHOR]

Background: Potential methods for objective assessment of postoperative pain include the Analgesia Nociception Index™ (ANI), a real-time index of the parasympathetic tone, the pupillary light reflex (PLR), and the variation coefficient of pupillary diameter (VCPD), a measure of pupillary diameter (PD) fluctuations. Until now, the literature is divided as to their respective accuracy magnitudes for assessing a patient's pain. The VCPD has been demonstrated to strongly correlate with pain in an obstetrical population. However, the pain induced by obstetrical labour is different, given its intermittent nature, than the pain observed during the postoperative period. The aim of the current study was to compare the respective values of these variables at VAS scores ≥4.Methods: After approval by the Ethics Committee, 345 patients aged on average 50 (SD 17) yr (range: 18-91 yr) of age were included. The protocols of general anaesthesia and postoperative analgesia were left to the anaesthetist's discretion. Some 40 min after tracheal intubation, VAS, ANI, PD, PLR, and VCPD values were recorded.Results: VCPD correlates more strongly (r=0.78) with pain as assessed with the VAS than ANI (r=-0.15). PD and PLR are not statistically correlated with VAS. The ability of VCPD to assess the pain of patients (VAS≥4) is strong [area under the curve (AUC): 0.92, confidence interval (CI): 0.89-0.95], and better than for ANI (AUC: 0.39, CI: 0.33-0.45).Conclusions: Our study suggests that VCPD could be a useful tool for monitoring pain in conscious patients during the postoperative period.Clinical Trial Registration: NCT03267979. [ABSTRACT FROM AUTHOR]

The question of environmentally sustainable perioperative medicine represents a new challenge in an era of cost constraints and climate crisis. The French Society of Anaesthesia and Intensive Care (SFAR) recommends stroke volume optimization in high-risk surgical patients. Pulse contour techniques have become increasingly popular for stroke volume monitoring during surgery. Some require the use of specific disposable pressure transducers (DPTs), whereas others can be used with standard DPTs. Quantify and compare the carbon footprint and cost of pulse contour techniques using specific and standard DPTs on a yearly basis and at a national level. We estimated the number of high-risk surgical patients monitored every year in France with a pulse contour technique, and the plastic waste, carbon footprint and cost associated with the use of specific and standard DPTs. When compared to pulse contour techniques working with a standard DPT, techniques requiring a specific DPT are responsible for an increase in carbon dioxide emission estimated at 65–83 tons/yr and for additional hospital cost estimated at €67 million/yr. If, as recommended by the SFAR, all high-risk surgical patients were monitored, the difference would reach 179–227 tons/yr for the environmental impact and €187 million/yr for the economic impact. From an environmental and economic standpoint, pulse contour techniques working with standard DPTs should be recommended for the perioperative hemodynamic monitoring of high-risk surgical patients. [ABSTRACT FROM AUTHOR]

Objective: Postoperative lymphopenia has been proposed as a risk factor for postoperative infections but has never been identified as such in a multivariate analysis. Postoperative pneumonia (POP) is one of the most common complications after lung cancer surgery and is associated with a worse outcome. We aimed to evaluate the association between postoperative lymphopenia and POP after lung cancer surgery. Methods: Patients admitted for lung cancer surgery (lobectomy, bilobectomy, or pneumonectomy) aged ≥ 18 years and with no history of an immunosuppressive state were eligible for inclusion. Lymphocyte counts were determined in blood drawn on the day before surgery and at postoperative days 1, 3 and 7. POP diagnosis was based on clinical, biological and radiological data. A logistic regression model adjusted on currently described risk factors for POP was used to explain the onset of this condition. Results: Two hundred patients were included, of whom 43 (21.5%) developed POP. Preoperative lymphocyte count was 1.8±0.6x109 cells/L and 2.0±0.7x109 cells/L in patients with and without POP, respectively (P = .091). In both groups, the lymphocyte count nadir occurred at postoperative day 1. In multivariate analysis, lymphopenia at postoperative day 1 was significantly associated with increased risk of POP (odds ratio: 2.63, 95% CI [1.03–5.40]). POP rate at postoperative day 7 was higher in patients presenting low lymphocyte counts (≤1.19x109 cells/L) at postoperative day 1 (P = .003). Conclusions: Our study showed that lymphopenia following lung cancer surgery was maximal at postoperative day 1 and was associated with POP. [ABSTRACT FROM AUTHOR]

These studies revealed about a 20% increase in mortality associated with deep anaesthesia, but the result was statistically significant only for studies with a one-year follow-up duration, and not significant for studies with a 30-day follow-up duration. In another observational study, intraoperative EEG suppression, a marker of deep anaesthesia, was a predictor of postoperative mortality only if it coincided with a low MAP [6]. Patients in the intervention group received EEG- or BIS-guidance, with or without an explicit goal of "light" anaesthesia, while patients in the control group received routine care without monitoring, or "deep" anaesthesia with EEG or BIS monitoring. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Background: Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss.Methods: This prospective, double-blind, parallel-arm, randomized, superiority study was conducted in 168 patients undergoing unilateral primary hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of tranexamic acid followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus-infusion group) or placebo (bolus group) for 8 h. The primary outcome was calculated perioperative blood loss up to day 5. Erythrocyte transfusion was implemented according to a restrictive transfusion trigger strategy.Results: The mean perioperative blood loss was 919 ± 338 ml in the bolus-plus-infusion group (84 patients analyzed) and 888 ± 366 ml in the bolus group (83 patients analyzed); mean difference, 30 ml (95% CI, -77 to 137; P = 0.58). Within 6 weeks postsurgery, three patients in each group (3.6%) underwent erythrocyte transfusion and two patients in the bolus group experienced distal deep-vein thrombosis. A meta-analysis combining data from this study with those of five other trials showed no incremental efficacy of additional perioperative administration of tranexamic acid.Conclusions: A preoperative bolus of tranexamic acid, associated with a restrictive transfusion trigger strategy, resulted in low erythrocyte transfusion rates in patients undergoing hip arthroplasty. Supplementary perioperative administration of tranexamic acid did not achieve any further reduction in blood loss. [ABSTRACT FROM AUTHOR]

ICU patients with SARS-CoV-2-related pneumonia are at risk to develop a central dysautonomia which can contribute to mortality and respiratory failure. The pupillary size and its reactivity to light are controlled by the autonomic nervous system. Pupillometry parameters (PP) allow to predict outcomes in various acute brain injuries. We aim at assessing the most predictive PP of in-hospital mortality and the need for invasive mechanical ventilation (IV). We led a prospective, two centers, observational study. We recruited adult patients admitted to ICU for a severe SARS-CoV-2 related pneumonia between April and August 2020. The pupillometry was performed at admission including the measurement of baseline pupillary diameter (PD), PD variations (PDV), pupillary constriction velocity (PCV) and latency (PDL). Fifty patients, 90 % males, aged 66 (60–70) years were included. Seven (14 %) patients died in hospital. The baseline PD (4.1 mm [3.5; 4.8] vs 2.6 mm [2.4; 4.0], P = 0.009), PDV (33 % [27; 39] vs 25 % [15; 36], P = 0.03) and PCV (3.5 mm.s−1 [2.8; 4.4] vs 2.0 mm.s−1 [1.9; 3.8], P = 0.02) were significantly lower in patients who will die. A PD value <2.75 mm was the most predictive parameter of in-hospital mortality, with an AUC = 0.81, CI 95 % [0.63; 0.99]. Twenty-four (48 %) patients required IV. PD and PDV were significantly lower in patients who were intubated (3.5 mm [2.8; 4.4] vs 4.2 mm [3.9; 5.2], P = 0.03; 28 % [25; 36 %] vs 35 % [32; 40], P = 0.049, respectively). A reduced baseline PD is associated with bad outcomes in COVID-19 patients admitted in ICU. It is likely to reflect a brainstem autonomic dysfunction. [Display omitted] • Pupillary parameters PD, PDV and slope were found significantly lower in COVID-19 patients who will die. • A reduced baseline PD <2.75 mm is the most predictive parameter of in-hospital mortality. • PD and PDV were also associated with the need for invasive mechanical ventilation with greater significance for PD. • A reduced PD could result from a central autonomic impairment related to a brainstem dysfunction in severe COVID-19 patients. [ABSTRACT FROM AUTHOR]

Volatile anaesthetic agents are used in the vast majority of general anaesthesias performed in France. We assessed the degree of understanding of French anaesthetists with regard to the general pharmacology of these products and their understanding of the factors that govern selection of the different agents available for use in adults. A validated 13-item questionnaire was sent electronically in 2012 using files from the Société française d’anesthésie et de réanimation (Sfar). It covered four categories: general characteristics of the respondent; practical aspects of anaesthesia with volatile agents; pharmacological properties and criteria for choosing a volatile agent; risk of intra-operative awareness. Among the 981 respondents, the anaesthetic technique used by 50% was that of an intravenous induction followed by maintenance with sevoflurane. The concepts relating to the practical use of these products are well known. A fresh gas flow of less than 2 L/min is used by 96% of the respondents. However, knowledge levels are often inadequate (rate of correct answers often < 50%). This lack of knowledge pertains to current themes (climate pollution), those of debatable clinical significance, e.g. pre-conditioning, hypoxic vasoconstriction and those that concern scientific theory (medullary action). However, a lack of knowledge is also observed with regard to basic pharmacology (respiratory, vascular, neurological or pharmacokinetic effects). There is no significant difference in the mode of practice. The experience of the anaesthetist (measured by number of years post diploma) resulted in a number of differences in response to many aspects of the questionnaire but these were minor. These results suggest the need for an improvement both in the initial and continued training of anaesthetists with respect to volatile anaesthetic agents. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics. Methods This work is based on a single-centre, double-blinded, randomized, placebo-controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach. Results The free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance. Conclusions Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery. [ABSTRACT FROM AUTHOR]

Abstract: Nitric oxide (NO) is believed to play a key role in adverse microvascular changes during sepsis. A deficit in NO has been evoked as a potential mechanism of microcirculatory deterioration in the early phase of septic shock. The aim of this study was to evaluate simultaneously and continuously both hepatic microcirculation and local NO production during early experimental sepsis. Wistar male rats were divided into two groups: a sepsis group undergoing cecal ligation and puncture (CLP) peritonitis and a control group undergoing sham surgery. Hepatic microcirculation was continuously monitored using a laser Doppler probe and local nitric oxide (NO) production by means of a specific electrode. Constitutive and inducible NO synthase production was assessed 2h after surgery, at onset of shock, and at 2 and 3h after shock. In control animals, hepatic microcirculatory perfusion and NO production remained stable throughout the experiment. In septic animals, whereas a fall in microcirculatory perfusion was noted as early as 2h after CLP, NO concentration remained stable and further increased after the onset of shock. At this time, inducible NO synthase was the only isoform significantly elevated. In this non-resuscitated experimental model of sepsis, an absolute liver deficit of NO could not explain the early adverse changes in the local microvascular system. [Copyright &y& Elsevier]

Mechanisms of postoperative sleep architecture disturbances and sleep-disordered breathing are uncertain. The authors hypothesised that patients undergoing surgery under regional anaesthesia without opioids used for postoperative analgesia would experience lesser changes in these parameters than patients operated under general anaesthesia with per- and postoperative opioids. After ethical approval and informed consent, patients undergoing total hip replacement were included in a prospective, randomised trial comparing 3 groups of patients: (1) S-LPB group receiving spinal anaesthesia and postoperative analgesia by lumbar plexus block; (2) GA-PCA group receiving general anaesthesia and postoperative analgesia by morphine patient-controlled analgesia; (3) GA-LPB group receiving general anaesthesia and postoperative analgesia by lumbar plexus block. Outcome measurements were polysomnographic parameters of sleep architecture and sleep-disordered breathing. Eighteen patients completed the 5-night study protocol (preoperative night: N-1, postoperative nights: N1 to N4). The percentage of rapid eye movement (REM) sleep decreased by 49% and 47% during N1 in the GA-PCA and GA-LPB groups respectively. A rebound phenomenon of more than 40% in the GA-PCA group and 25% in the GA-LPB group was observed during N2 and N3. Apnoea hypopnoea index (AHI) and the number of arousals per hour were significantly increased during N2 and N3 when compared with N-1 in the GA-groups. No sleep architecture disturbances and no sleep-disordered breathing were measured in the S-LPB group. Postoperative sleep architecture and breathing pattern were disturbed in GA groups. Both were preserved under spinal anaesthesia associated with a free opioid postoperative analgesia. [ABSTRACT FROM AUTHOR]

Introduction L’existence de protocoles de transfusion massive permet de réduire les délais d’initiation de la transfusion, les défaillances d’organes et les complications postopératoires chez le polytraumatisé. Le CHUSE est doté d’une salle de déchocage et de procédures adaptées depuis 2010. En 2014, suite à l’évaluation du taux de PSL détruits non transfusés (DNT), le département d’anesthésie-réanimation a mis en place une stratégie d’amélioration des pratiques. Méthode Un audit clinique a été réalisé selon les référentiels HAS avec un 1 er tour rétrospectif sur 2014,période pendant laquelle l’EFS délivrait en UV 2 mallettes de 3 CGR O et 3 PFC. En 2015, une stratégie avec 3 mallettes de 2 CGR O et 1 de 2 PFC a été mise en place. Une campagne d’information a été menée par les intervenants du déchocage aux professionnels de terrain. Un 2 e audit prospectif de juin 2015 à juin 2016 a été réalisé. Résultats Le 1 er tour a mis en évidence 21 CGR DNT au déchocage, soit 14 % des CGR DNT du CHU et 27 PFC DNT, soit 25 % des PFC DNT du CHU en 2014. Suite au nouveau protocole, les résultats comparant 2 périodes d’évaluation de 10 mois pour une activité de déchocage similaire entre les deux tours montre un passage d’un taux de 32,6 % de mallettes CGR partiellement utilisées au 1 er d’audit à 4 % au deuxième tour d’audit et d’un taux de 60 % de mallettes PFC partiellement utilisées au 1 er tour à 12,5 % au 2 e tour. Soit entre 2 tours similaires de 10 mois, un passage de 21 CGR DNT à 3 CGR DNT et de 24 PFC DNT à 4 PFC DNT. Conclusion Le nouveau protocole de délivrance des PSL associé à une information aux personnels impliqués a permis une réduction notable des PSL DNT. Cette action est un projet d’EPP, reconnu comme tel. Cette nouvelle stratégie s’intègre dans une démarche économique mais aussi éthique auprès des donneurs de sang. La mise en place de ce nouveau protocole n’a pas perturbé la prise en charge des patients au sein du déchocage et a reçu un avis favorable des équipes. [ABSTRACT FROM AUTHOR]