Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study.

BACKGROUND: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. METHODS: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. RESULTS: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. CONCLUSIONS: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone. CLINICAL TRIAL REGISTRATION: EudraCT: 2012-004219-30; NCT01882530.

An elevated respiratory quotient predicts complications after cardiac surgery under extracorporeal circulation: an observational pilot study.

Following cardiac surgery, hyperlactatemia due to anaerobic metabolism is associated with an increase in both morbidity and mortality. We previously found that an elevated respiratory quotient (RQ) predicts anaerobic metabolism. In the present study we aimed to demonstrate that it is also associated with poor outcome following cardiac surgery. This single institution, prospective, observational study includes all those patients that were consecutively admitted to the intensive care unit (ICU) after cardiac surgery with cardiopulmonary bypass, that had also been monitored using pulmonary artery catheter. Data were recorded at admission (H0) and after one hour (H1) including: oxygen consumption ([Formula: see text]), carbon dioxide production ([Formula: see text]), RQ ([Formula: see text]), lactate levels and mixed venous oxygen saturation ([Formula: see text]). The primary endpoint was defined as mortality at 30 days. Comparison of the area under the curve (AUC) for receiver operating characteristic curves was used to analyze the prognostic predictive value of RQ, lactate levels and [Formula: see text], in terms of patient outcome. We studied 151 patients admitted to the ICU between May 2015 and February 2016. Seventy eight patients experienced a worse than expected outcome in the post-operative period, and among those seven died. RQ at H1 in non-survivors ([Formula: see text]) was higher than in survivors ([Formula: see text]; p = 0.02). The AUC for RQ to predict mortality was 0.77 (IC95% [0.70-0.84]), with a threshold value of 0.76 (sensitivity 64%, specificity 100%). By comparison, the AUC for lactate levels was significantly superior (AUClact 0.89, IC95% [0.83-0.93], p = 0.02). In this study, elevated RQ appeared to be predictive of mortality after cardiac surgery with CPB.

Extracorporeal life support for massive pulmonary embolism during pregnancy.

Massive pulmonary embolism is a leading cause of death during pregnancy. While the prevention of thromboembolic disease during the peripartum period is codified, there is no consensus regarding its treatment. We report two cases of pregnant women who had massive pulmonary embolisms (PE) and shock treated with veno-arterial extracorporeal life support (ECLS) and heparin therapy.Haemodynamic and oxygenation parameters were rapidly restored. The patients completely recovered and the pregnancies continued. The patients did not develop pulmonary hypertension. ECLS can be considered as a successful treatment option of massive pulmonary embolism during pregnancy.

Reduction of red blood cell transfusion with a patient blood management protocol in urological and visceral surgery: a before-after study.

BACKGROUND: Although Patient Blood Management (PBM) is recommended by international guidelines, little evidence of its effectiveness exists in abdominal surgery. The aim of this study was to evaluate the benefits of the implementation of a PBM protocol on transfusion incidence and anaemia-related outcomes in major urological and visceral surgery. METHODS: In this before-after study, a three-pillar PBM protocol was implemented in 2020-2021 in a tertiary care centre, including preoperative correction of iron-deficiency anaemia, intraoperative tranexamic acid administration, and postoperative restrictive transfusion. A historical cohort (2019) was compared to a prospective cohort (2022) after the implementation of the PBM protocol. The primary outcome was the incidence of red blood cell transfusion intraoperatively or within 7 days after surgery. RESULTS: Data from 488 patients in the historical cohort were compared to 499 patients in the prospective cohort. Between 2019 and 2022, screening for iron deficiency increased from 13.9% to 69.8% (p < 0.01), tranexamic acid administration increased from 9.5% to 84.6% (p < 0.01), and median haemoglobin concentration before transfusion decreased from 77 g.L-1 to 71 g.L-1 (p = 0.02). The incidence of red blood cell transfusion decreased from 11.5% in 2019 to 6.6% in 2022 (relative risk 0.58, 95% CI 0.38-0.87, p = 0.01). The incidence of haemoglobin concentration lower than 100 g.L-1 at discharge was 24.2% in 2019 and 21.8% in 2022 (p = 0.41). The incidence of medical complications was comparable between the groups. CONCLUSION: The implementation of a PBM protocol over a two-year period was associated with a reduction of transfusion in major urological and visceral surgery.

Endobronchial closure of bronchopleural fistula with Amplatzer PFO device.

Bronchopleural fistula (BPF) is a feared postoperative complication of pneumonectomy that carries significant morbidity and mortality. BPF can be treated by various surgical and medical techniques. Endobronchial techniques have been used for the delivery of biological glue, sealants, coils, and covered stents with variable degrees of success, depending on the size of the fistula. A recent case report described the endobronchial closure of a BPF through the implantation of an Amplatzer ASD device, commonly used for transcatheter closure of atrial septal defects. In this case report, we describe closure of a BFP using the Amplatzer PFO device.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

Early postoperative bleeding after isolated coronary bypasses: Changes over a period of 20 years - An observational study.

OBJECTIVES: The objectives were to analyze the evolution of the postoperative bleeding after coronary artery bypass grafting and to determine which factors impacted on this evolution. METHODS: This is a single-center retrospective study including 4590 patients undergoing coronary bypass surgery between 1995 and 2017. The study period was divided into 3 same-sized periods. We analyzed the evolution of the bleeding according to: the chest volume bleeding over the first 24hours, the severity and the rate of transfusion during the hospital stay. Intrahospital outcomes were compared between "minor" and "major" bleedings. The risk factors of major bleeding were analyzed by multiple logistic regression. RESULTS: The chest volume decreased particularly during the first years of the study period. Major bleedings decreased over the periods (7.3%, 4.9% and 3.8% respectively, P<0.0001), as did the rate of transfusion (26.4%, 23.5% and 19.6% respectively, P<0.0001). Major bleedings were correlated with hospital mortality (8.2% versus 1.1%, P<0.0001). The risk factors of major bleeding were the period 1 (1995 to 2003), a renal failure, a resternotomy, the EuroSCORE, the hematocrit prior to cardiopulmonary bypass and the duration of cardiopulmonary bypass. CONCLUSIONS: Postoperative bleeding decreased mainly in the 1990s. Progressive changes in bleeding prevention and blood recovery, surgical techniques, haemoglobin threshold for transfusion decision and practitioners' experience have contributed to these results and must be continued to optimize the postoperative outcomes.

Tranexamic acid in hip fracture surgery: a randomized controlled trial.

BACKGROUND: Hip fracture surgery may be associated with substantial blood loss. This study was designed to assess the efficacy and safety of the use of tranexamic acid in hip fracture surgery for the reduction of erythrocyte transfusion. METHODS: The study pertains to a randomized double-blind study with blinded adjudication of outcomes. Patients requiring surgery for an isolated hip fracture of less than 48 h received saline or tranexamic acid 15 mg kg(-1) given at skin incision and 3 h later. Primary efficacy outcome was erythrocyte transfusion from surgery up to day 8. Transfusion was administered according to a standardized protocol (Hb<9 g dl(-1)). Safety criterion was a composite of symptomatic and asymptomatic vascular events up to 6 weeks. RESULTS: Fifty-seven patients were randomized to tranexamic acid and 53 to placebo. The rate of erythrocyte transfusion was 42% with tranexamic acid and 60% with placebo (P=0.06). Preoperative haemoglobin value, age, and type of surgery were risk factors for erythrocyte transfusion independent of treatment group. The probability of vascular events at 6 weeks was 16% in the tranexamic acid group and 6% in the placebo group (P=0.10). A meta-analysis combining this study with previous trials showed that tranexamic acid significantly reduced erythrocyte transfusion in hip fracture surgery although efficacy was lower than that observed in hip or knee arthroplasty. CONCLUSIONS: In hip fracture surgery, tranexamic acid reduces erythrocyte transfusion but may promote a hypercoagulable state. Thus, further evaluation of safety is required before recommending the off-label use of tranexamic acid.

Serious adverse events and deaths linked to poor ventilator use: A report of four closed claims.

Through this series of four closed claims, we highlight examples of accidents stemming from poor ventilator use. We then review the main issues in this regard as reported in the literature and by learned societies. This case series has led us to emphasise the need for safety procedures involving systematic checks prior to use, declaration and analysis of the risk, as well as feedback and teaching regarding ventilation systems.

Bleeding complications following peripheral regional anaesthesia in patients treated with anticoagulants or antiplatelet agents: A systematic review.

BACKGROUND: Patients on either antiplatelet or anticoagulant therapy may need procedures performed under peripheral nerve blocks in preference to general anaesthesia techniques. The risk of bleeding associated with peripheral nerve blocks under these circumstances remains unknown. This systematic review evaluates the incidence of bleeding complications following peripheral nerve blocks in patients receiving antiplatelet and/or anticoagulant medication. METHOD: All English, French and Spanish publications on peripheral nerve blocks in patients receiving antiplatelet and/or anticoagulant medication, from 1978 to 2018 from various sources including Pubmed, were reviewed. Publications on neuraxial anaesthesia (spinal or epidural) and eye blocks were excluded. RESULTS: Twenty-four articles were selected, including six observational studies and 18 case reports. Patients received antiplatelet agents only, in 4 studies, anticoagulants only in 14 studies, and both in 6 studies. In the observational studies, 80 bleeding complications (haematoma or minor bleeding at the puncture site) were identified following 9738 peripheral nerve blocks. Amongst case reports, 15 bleeding complications were noted following 50 peripheral nerve blocks. Bleeding complications were reported mostly with lumbar plexus blocks (1 requirement for blood transfusion, 1 catheter embolization, 1 surgical exploration and 1 death). The overall estimate of the incidence of bleeding complications was 0.82% (0.64%-1.0%). CONCLUSION: This systematic review found that bleeding complications following peripheral nerve blocks were rare in patients receiving antiplatelet and/or anticoagulant medication.

Integrating a pharmacist into an anaesthesiology and critical care department: Is this worthwhile?

Background Operating rooms and Intensive Care Units are places where an optimal management of drugs and medical devices is required. Objective To evaluate the impact of a dedicated pharmacist in an academic Anaesthesiology and Critical Care Department. Setting This study was conducted in the Anaesthesiology and Critical Care Department of Grenoble University Hospital. Method Between November 2013 and June 2017, the drug-related problems occurring in three Intensive Care Units and their corrections by a full-time clinical pharmacist were analyzed using a structured order review instrument. Pharmaceutical costs in the Anaesthesiology and Critical Care Department were analyzed over a 7 year period (2010-2016), during which automated dispensing systems and recurrent meetings to review indications of medications and medical devices were implemented in the department. Main outcome measure Analysis of two issues: correcting drug-related problems and containing pharmaceutical costs. Results A total of 324 drug-related problems were identified. The most frequent problem concerned anti-infective agents (45%), and this was mainly due to the over-dosage of drugs (30%). Dosage adjustments were the most frequent interventions performed by the pharmacist (43%). Over the 7 year period, pharmaceutical costs decreased by 9% (€365,469), while the care activity of the department increased by 55% (+ 12,022 surgical procedures and + 1424 admissions in the ICU). Conclusion Integrating a pharmacist into the Anaesthesiology and Critical Care Department was associated with interventions to correct drug-related problems and containing pharmaceutical costs. Pharmacists should play a central role in such medical environments, to optimize the use of drugs and medical devices.

Management of antiplatelet therapy for non elective invasive procedures of bleeding complications: proposals from the French working group on perioperative haemostasis (GIHP), in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR).

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.

[Rupture of a thoracic aortic aneurysm into the right pleural cavity]. / Rupture d'anévrisme de l'aorte thoracique descendante dans la cavité pleurale droite.

Rupture of an aneurysm of the descending thoracic aorta into the right pleural cavity is an uncommon event and its prognosis is rapidly fatal. Its diagnosis is difficult and it may remain unrecognized. We report the case of a 66-year-old patient with a haemorrhagic shock associated with a spontaneous right haemothorax. A ruptured aneurysm of the descending thoracic aorta was diagnosed during the surgical procedure.

[Pain management in subarachnoid haemorrhage: a survey of French analgesic practices]. / Prise en charge des céphalées secondaires aux hémorragies sous-arachnoïdiennes dans les centres de neurochirurgie français.

OBJECTIVE: Pain management in patients having a subarachnoid haemorrhage was assessed in French intensive care unit of neurosurgical centres. STUDY DESIGN: Nationwide survey. METHODS: A standardized postal questionnaire was sent to senior doctor of every neurosurgical centres in France inquiring pain scores assessment, analgesics used and their routes of administration, centre's opinion about efficacy of pain management. RESULTS: Of the 34 centres, 24 returned completed questionnaires. Fifty four per cent of the centres evaluated pain intensity with a non valid pain score. In the case of patients in the comatose, pain was not evaluated in fifty four per cent of the centres. Paracetamol and morphine were the most currently used analgesics drugs. Morphine was administered subcutaneously by 75% of the centres. Six centres used also PCA. Thirty-seven percent of the centres were reluctant to use opioids and 75% to use NSAIDS. CONCLUSION: The majority of the centres considered pain management in patient suffering from subarachnoid haemorrhage (SAH) was not optimal and stressed the need to establish a well validated pain rating scale dedicated to SAH patients.

[Prevention of venous thromboembolism in surgery and obstetrics]. / Prévention de la maladie thromboembolique veineuse périopératoire et obstétricale.

The French Society of anaesthesiology and intensive care has chosen a high level methodology to issue professional Recommendations on perioperative and obstetrical venous thromboembolism prophylaxis. In addition with a short review on mechanical and pharmacological prophylaxis, all surgical and obstetrical settings have been studied. The initiation and duration of prophylaxis have been particularly debated in close relation with the level of surgical risk. A large group of experts has been involved in this process. More than 150 other experts have participated in the reading process. Didactic tables have been added to help the prescription.

[Management of direct oral anticoagulants for invasive procedures]. / Gestion des anticoagulants oraux directs pour un acte invasif.

Three new Direct Oral Anticoagulants (DOACs), rivaroxaban, apixaban and dabigatran etexilate are available on the French market. Management of DOAC-induced bleeding risk remains challenging. For elective procedures with high hemorrhagic risk, a last DOAC intake five days before procedure ensures complete elimination in all patients. Heparin bridging therapy should be proposed only to patients at high thrombotic risk. For elective procedures with low hemorrhagic risk, the DOAC intake of the night before procedure should be omitted. For urgent procedures with high bleeding risk, DOAC plasmatic concentration can be helpful: concentration lower than 30 ng/mL should enable performing the procedure; a high concentration is associated with a higher bleeding risk, especially if higher than 400 ng/mL. In case of massive bleeding, no antidote is approved yet; activated prothrombin concentrates or non-activated 4-factors prothrombin concentrates could be considered.

Prone position affects stroke volume variation performance in predicting fluid responsiveness in neurosurgical patients.

BACKGROUND: Stroke volume variation (SVV) during mechanical ventilation predicts preload responsiveness. We hypothesized that the prone position would alter the performance of this dynamic indicator. METHODS: Two parallel groups of ventilated neurosurgical patients with low tidal volume (6-8 ml.kg-1) were studied before surgical incision. SVV was measured at T0, T15 and T30 min during a fluid volume expansion (250 mL hetastarch 6% over 30 min) with patients in either the supine (N.=29; Supine group) or prone position (N.=23; Prone group). Fluid responsiveness was defined as an increase in the stroke volume index (SVI) of ≥20% at T30. Receiver-operating characteristics (ROC) curves were generated for SVV. RESULTS: Prone positioning significantly increased SVV. Volume expansion in the Prone group increased SVI but led to a decline in SVV from 16% (12-22; median, 25-75th percentile) at T0 to 9% (8-13%) at T30. These effects on SVI and SVV were more pronounced compared to those obtained in the Supine group (P ≤0.05). Fluid responsiveness was predicted by SVV >12% at T0 (sensitivity 88%, specificity 62%) in the Supine group. In the Prone group, the area under the ROC curve of SVV (0.53; 95% confidence interval 0.27-0.79) did not allow the determination of a threshold SVV value. CONCLUSION: In ventilated patients with low tidal volume, a prone position may have a direct effect on the heart that alters the performance of SVV in predicting fluid responsiveness. External factor such as prone position renders difficult the interpretation of SVV as a dynamic indicator of cardiac preload.

[Managing antithrombotic therapy in vitreoretinal surgery]. / Comment gérer les antithrombotiques en chirurgie vitréorétinienne ?

Given the growing number of patients on antithrombotic therapy we are increasingly confronted with the management of this therapy before, during and after vitreoretinal surgery. In the absence of a consensus, the decision to withdraw antithrombotic therapy is based on the cardiovascular thromboembolism risk versus the theoretical risk of bleeding if the antithrombotic treatment is continued. As suggested by the literature, antiplatelet therapy (acetylsalicylic acid or clopidogrel) may be safely continued for vitreoretinal surgery, including retinal detachment repair. However, the risk/benefit ratio for patients being treated with two antiplatelet therapies is unknown. It appears that an International Normalized Ratio (INR) less than 3 for patients treated with anticoagulant therapy does not increase the perioperative risk of ocular bleeding. This risk has not been evaluated in patients treated by new antithrombotic therapies (prasugrel, ticagrelor as antiplatelet medication, or dabigatran, rivaroxaban, apixaban as anticoagulant therapy), and there is a need to study it further.

Carotid artery mechanical properties of Dahl salt-sensitive rats.

We evaluated the mechanical properties of the carotid artery in anesthetized Dahl rats with or without long-term treatment with the diuretic compound indapamide. The mechanical properties of the carotid artery were evaluated by establishing pressure-volume curves in situ in vivo before and after total relaxation of arterial smooth muscle by potassium cyanide. Dahl salt-sensitive and salt-resistant rats were fed either a low (0.4%) or high (7%) NaCl diet for 5 weeks. In each group, half the rats received for the same period of time oral treatment with indapamide (3 mg/kg per day). Blood pressure, heart rate, and pressure-volume curves were studied at the end of the 5-week period. In untreated Dahl salt-sensitive rats, the pressure-volume curve of the carotid artery was shifted to the right compared with that in untreated Dahl salt-resistant rats. The finding was observed even after potassium cyanide and regardless of the NaCl diet (P < .01 between Dahl salt-sensitive and -resistant rats). Indapamide was able to prevent the development of hypertension in Dahl salt-sensitive rats receiving a high NaCl diet (185 +/- 7 versus 146 +/- 8 mm Hg in untreated and treated Dahl salt-sensitive rats with a high NaCl diet, P < .0005). In the other groups, indapamide had no effect on blood pressure. Indapamide treatment increased carotid arterial static compliance in Dahl salt-sensitive rats with a high or low NaCl diet and to a lesser extent in Dahl salt-resistant rats. The increase was observed even after total relaxation of carotid arterial smooth muscle by potassium cyanide.(ABSTRACT TRUNCATED AT 250 WORDS)