Effect of non-steroidal anti-inflammatory drugs on the management of postoperative pain after cardiac surgery: a multicenter, randomized, controlled, double-blind trial (KETOPAIN Study).

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for the management of acute postoperative pain as part of a multimodal strategy to reduce opioid use, relieve pain, and reduce chronic pain in non-cardiac surgery. However, significant concerns arise in cardiac surgery due to the potential adverse effects of NSAID including increased bleeding and acute kidney injury (AKI). We hypothesized that NSAIDs are effective against pain and safe in the early postoperative period following cardiac surgery, taking contraindications into account. METHODS: The KETOPAIN trial is a prospective, double blind, 1:1 ratio, versus placebo multicentric trial, randomizing 238 patients scheduled for cardiac surgery. Written consent will be obtained for all participants. The inclusion criterion is patients more than 18 years old undergoing for elective cardiac surgery under cardiopulmonary bypass (CPB). Patients will be allocated to the intervention (ketoprofen) group (n = 119) or the control (placebo) group (n = 119). In the intervention group, in addition to the standard treatment, patients will receive NSAIDs (ketoprofen) at a dose of 100 mg each 12 h 48 h after. The control group, in addition to the standard treatment, will receive a placebo of NSAIDs every 12 h for 48 h after surgery. An intention-to-treat analysis will be performed. The primary endpoint will be the intensity of acute postoperative pain at rest at 24 h from the end of surgery. Pain will be assessed using the numerous rating scale. The secondary endpoints will be postoperative pain on coughing during chest physiotherapy, postoperative pain until day 7, the pain trajectory between day 3 and day 7, cumulative opioid consumption within 48 h after surgery, nausea and vomiting, the occurrence of postoperative pulmonary complications within the first 7 days after surgery, neuropathic pain at 3 months, and quality of life at 3 months. DISCUSSION: NSAIDs function as non-selective, reversible inhibitors of the cyclooxygenase enzyme and play a role in a multimodal pain management approach. While there are recommendations supporting the use of NSAIDs in major non-cardiac surgery, recent guidelines do not favor their use in cardiac surgery. However, this is based on low-quality evidence. Major concerns regarding NSAID use in cardiac surgery patients are potential increase in postoperative bleeding or AKI. However, few studies support the possible use of NSAIDs without the risk of bleeding and/or AKI. Also, in a recent French survey, many anesthesiologists reported using NSAIDs in cardiac surgery. To date, no large randomized study has been conducted to evaluate the efficacy of NSAIDs in the management of postoperative pain in cardiac surgery. The expected outcome of this study is an improvement in the management of acute postoperative pain in cardiac surgery with a multimodal strategy including the use of NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT06381063. Registered on April 24, 2024.

Evaluating pre-anesthesia assessment performance in residency: the reliability of standardized patient methods.

Background: Pre-anesthesia assessment clinic (PAC) is known to increase safety and quality in the perioperative period. However, PAC teaching during anesthesiology residency is a challenge. The objective of this study was to assess the reliability of a simulation score grid using a standardized patient on the PAC performance of anesthesiology residents. Methods: A score grid, including the 4 components of the PAC (clinical evaluation, perioperative strategy, information and communication) was validated by a group of 5 senior anesthesiologists. Anesthesiology residents (> one year) and attending anesthesiologists were included. The same simulation sequence with the same standardized patient was conducted in a simulation dedicated consultation room. The simulation sequence was followed by a debriefing session with the 2 professors (anesthesiology and communication) and each anesthesiology resident. The main outcome was the overall grid score out of a maximum score of 300 and the correlation of this score with experience in anesthesiology residency. Secondary outcomes were individual component scores according to level of experience in anesthesiology. Results: Between October 2014 and April 2016, 109 anesthesiology residents and 16 attending anesthesiologists were included in this prospective bicentric study. There was a positive correlation (p < 0.01) between level of experience and overall score on the grid score (Pearson's Coefficient = 0.52). The Pearson correlation coefficient between overall assessment and level of experience in anesthesiology was 0.46 (p < 0.01). The analysis of the sub-scores for the 4 components of the overall score (evaluation, perioperative strategy, information and communication) also identify differences between groups of experience. Conclusion: Standardized patient Simulation of PAC seems to be a reliable tool to assess PAC performance in anesthesiology residents and senior anesthesiologists. These results suggest standardized patient simulation could be used as a teaching tool for PAC.

POBS-Card, a new score of severe bleeding after cardiac surgery: Construction and external validation.

Objective: Bleeding after cardiac surgery leads to poor outcomes. The objective of the study was to build the PeriOperative Bleeding Score in Cardiac surgery (POBS-Card) to predict bleeding after cardiac surgery. Methods: We conducted a retrospective cohort study in 2 academic hospitals (2016-2019). Inclusion criteria were adult patients after cardiac surgery under cardiopulmonary bypass. Exclusion criteria were heart transplantation, assistance, aortic dissection, and preoperative hemostasis diseases. Bleeding was defined by the universal definition for perioperative bleeding score ≥2. POBS-Card score was built using multivariate regression (derivation cohort, one center). The performance diagnosis was assessed using the area under the curve in a validation cohort (2 centers) and compared with other scores. Results: In total, 1704 patients were included in the derivation cohort, 344 (20%) with bleeding. Preoperative factors were body mass index <25 kg/m2 (odds ratio [OR], 1.48 [1.14-1.93]), type of surgery (redo: OR, 1.76 [1.07-2.82]; combined: OR, 1.81 [1.19-2.74]; ascendant aorta: OR, 1.56 [1.02-2.38]), ongoing antiplatelet therapy (single: OR, 1.50 [1.09-2.05]; double: OR, 2.00 [1.15-3.37]), activated thromboplastin time ratio >1.2 (OR, 1.44 [1.03-1.99]), prothrombin ratio <60% (OR, 1.91 [1.21-2.97]), platelet count <150 g/L (OR, 1.74 [1.17-2.57]), and fibrinogen <3 g/L (OR, 1.33 [1.02-1.73]). In the validation cohort of 597 patients, the area under the curve was 0.645 [0.605-0.683] and was superior to other scores (WILL-BLEED, Papworth, TRUST, TRACK). A threshold >14 predicted bleeding with a sensitivity of 50% and a specificity of 73%. Conclusions: POBS-Card score was superior to other scores in predicting severe bleeding after cardiac surgery. Performances remained modest, questioning the place of these scores in the perioperative strategy of bleeding-sparing.

Association between volume of lung damage and endoplasmic reticulum stress expression among severe COVID-19 ICU patients.

Introduction: Links have been established between SARS-CoV-2 and endoplasmic reticulum stress (ERS). However, the relationships between inflammation, ERS, and the volume of organ damage are not well known in humans. The aim of this study was to explore whether ERS explains lung damage volume (LDV) among COVID-19 patients admitted to the intensive care unit (ICU). Materials and methods: We conducted a single-center retrospective study (ancillary analysis of a prospective cohort) including severe COVID-19 ICU patients who had a chest computed tomography (CT) scan 24 h before/after admission to assess LDV. We performed two multivariate linear regression models to identify factors associated with plasma levels of 78 kDa-Glucose-Regulated Protein (GRP78; ERS marker) and Interleukin-6 (IL-6; inflammation marker) at admission. Results: Among 63 patients analyzed, GRP78 plasma level was associated with LDV in both multivariate models (ß = 22.23 [4.08;40.38]; p = 0.0179, ß = 20.47 [0.74;40.20]; p = 0.0423) but not with organ failure (Sequential Organ Failure Assessment (SOFA) score) at admission (r = 0.03 [-0.22;0.28]; p = 0.2559). GRP78 plasma level was lower among ICU survivors (1539.4 [1139.2;1941.1] vs. 1714.2 [1555.2;2579.1] pg./mL. respectively; p = 0.0297). IL-6 plasma level was associated with SOFA score at admission in both multivariate models (ß = 136.60 [65.50;207.70]; p = 0.0003, ß = 193.70 [116.60;270.90]; p < 0.0001) but not with LDV (r = 0.13 [-0.14;0.39]; p = 0.3219). IL-6 plasma level was not different between ICU survivors and non-survivors (12.2 [6.0;43.7] vs. 30.4 [12.9;69.7] pg./mL. respectively; p = 0.1857). There was no correlation between GRP78 and IL-6 plasma levels (r = 0.13 [-0.13;0.37]; p = 0.3106). Conclusion: Among severe COVID-19 patients, ERS was associated with LDV but not with systemic inflammation, while systemic inflammation was associated with organ failure but not with LDV.

Opioid-free anaesthesia with dexmedetomidine and lidocaine versus remifentanil-based anaesthesia in cardiac surgery: study protocol of a French randomised, multicentre and single-blinded OFACS trial.

INTRODUCTION: Intraoperative opioids have been used for decades to reduce negative responses to nociception. However, opioids may have several, and sometimes serious, adverse effects. Cardiac surgery exposes patients to a high risk of postoperative complications, some of which are common to those caused by opioids: acute respiratory failure, postoperative cognitive dysfunction, postoperative ileus (POI) or death. An opioid-free anaesthesia (OFA) strategy, based on the use of dexmedetomidine and lidocaine, may limit these adverse effects, but no randomised trials on this issue have been published in cardiac surgery.We hypothesised that OFA versus opioid-based anaesthesia (OBA) may reduce the incidence of major opioid-related complications after cardiac surgery. METHODS AND ANALYSIS: Multicentre, randomised, parallel and single-blinded clinical trial in four cardiac surgical centres in France, including 268 patients scheduled for coronary artery bypass grafting under cardiac bypass, with or without aortic valve replacement. Patients will be randomised to either a control OBA protocol using remifentanil or an OFA protocol using dexmedetomidine/lidocaine. The primary composite endpoint is the occurrence of at least one of the following: (1) postoperative cognitive disorder evaluated by the Confusion Assessment Method for the Intensive Care Unit test, (2) POI, (3) acute respiratory distress or (4) death within the first 48 postoperative hours. Secondary endpoints are postoperative pain, morphine consumption, nausea-vomiting, shock, acute kidney injury, atrioventricular block, pneumonia and length of hospital stay. ETHICS AND DISSEMINATION: This trial has been approved by an independent ethics committee (Comité de Protection des Personnes Ouest III-Angers on 23 February 2021). Results will be submitted in international journals for peer reviewing. TRIAL REGISTRATION NUMBER: NCT04940689, EudraCT 2020-002126-90.

Pre-operative maintenance of angiotensin-converting enzyme inhibitors is not associated with acute kidney injury in cardiac surgery patients with cardio-pulmonary bypass: a propensity-matched multicentric analysis.

Objective: We investigated the effects of the maintenance of angiotensin-converting enzyme inhibitors (ACE inhibitors) the day of the surgery on the incidence of postoperative acute kidney injury (AKI) and cardiac events in patients undergoing cardiac surgery. Methods: We performed a multicentric observational study with propensity matching on 1,072 patients treated with ACE inhibitors. We collected their baseline demographic data, comorbidities, and operative and postoperative outcomes. AKI was defined by KDIGO (Kidney Disease: Improving Global Outcome). Results: Maintenance of an ACE inhibitor was not associated with an increased risk of AKI (OR: 1.215 (CI95%:0.657-2.24), p = 0.843, 71 patients (25.1%) vs. 68 patients (24%)). Multivariate logistic regression and sensitive analysis did not demonstrate any association between ACE inhibitor maintenance and AKI, following cardiac surgery (OR: 1.03 (CI95%:0.81-1.3)). No statistically significant difference occurs in terms of incidence of cardiogenic shock (OR: 1.315 (CI95%:0.620-2.786)), stroke (OR: 3.313 (CI95%:0.356-27.523)), vasoplegia (OR: 0.741 (CI95%:0.419-1.319)), postoperative atrial fibrillation (OR: 1.710 (CI95%:0.936-3.122)), or mortality (OR: 2.989 (CI95%:0.343-26.034)). ICU and hospital length of stays did not differ (3 [2; 5] vs. 3 [2; 5] days, p = 0.963 and 9.5 [8; 12] vs. 10 [8; 14] days, p = 0.638). Conclusion: Our study revealed that maintenance of ACE inhibitors on the day of the surgery was not associated with increased postoperative AKI. ACE inhibitor maintenance was also not associated with an increased rate of postoperative major cardiovascular events (arterial hypotension, cardiogenic shock, vasopressors use, stroke and death).

Effect of opioid-free anesthesia on post-operative period in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a propensity score matched study.

BACKGROUND: Postoperative pain after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is important. It appears essential to reduce postoperative pain and morphine consumption. METHODS: Retrospective study in a university hospital comparing patient benefiting from CRS-HIPEC under opioid-free anesthesia (OFA; dexmedetomidine) to those anesthetized with opioid anesthesia (OA; remifentanil) using a propensity score matching method. The main objective was the impact of OFA on postoperative morphine consumption in the first 24 h after surgery. RESULTS: 102 patients were included, matching on the propensity score allowed selecting 34 unique pairs analyzed. Morphine consumption was lower in the OFA group than in the OA group (3.0 [0.00-11.0] mg/24 h vs. 13.0 [2.5-25.0] mg/24 h; p = 0.02). In multivariable analysis, OFA was associated with a reduction of 7.2 [0.5-13.9] mg of postoperative morphine (p = 0.04). The rate of renal failure with a KDIGO-score > 1 was lower in the OFA group than in the OA group (12% vs. 38%; p = 0.01). There was no difference between groups concerning length of surgery/anesthesia, norepinephrine infusion, volume of fluid therapy, post-operative complications, rehospitalization or ICU readmission within 90 days, mortality, and postoperative rehabilitation. CONCLUSION: Our results suggest that OFA for CRS-HIPEC patients appears safe and is associated with less postoperative morphine use and acute kidney injury.

Overview of the current use of levosimendan in France: a prospective observational cohort study.

BACKGROUND: Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. METHOD: The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. RESULTS: The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. CONCLUSIONS: We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.

Upgrading extra corporeal life support to ECMELLA using Impella 5.0 in rescued INTERMACS 1 patients, lactate level matters!

Background: Venoarterial extra corporeal life support (ECLS) is the treatment of choice of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 1 patients, but left ventricle (LV) overload is a complication of ECLS. Unloading the LV by adding Impella 5.0 to ECLS in Impella used in combination with venoarterial extracorporeal membrane oxygenation (ECMELLA) configuration is recommended only in patients with acceptable prognosis. We investigated whether serum lactate level, a simple biological parameter, could be used as a marker to select candidates for bridging from ECLS to ECMELLA. Methods: Forty-one consecutive INTERMACS 1 patients under ECLS were upgraded to ECMELLA using Impella 5.0 pump implantation to unload the LV and were followed-up for 30 days. Demographic, clinical, imaging, and biological parameters were collected. Results: The time between ECLS and Impella 5.0 pump implantation was 9 [0-30] hours. Among these 41 patients, 25 died 6±6 days after implantation. They were older (53±12 vs. 43±12 years, P=0.01) with acute coronary syndrome as the primary etiology (64% vs. 13%, P=0.0007). In univariate analysis, patients who died exhibited a lower mean arterial pressure (74±17 vs. 89±9 mmHg, P=0.01), a higher level of troponin (24,000±38,000 vs. 3,500±5,000 mg/dL, P=0.048), a higher level of serum lactate (8.3±7.4 vs. 4.2±3.8 mmol/L, P=0.05) and more frequent cardiac arrest at admission (80% vs. 25%, P=0.03). In multivariate Cox regression analysis, a serum lactate level of >7.9 mmol/L (P=0.008) was found to be an independent predictor of mortality. Conclusions: In INTERMACS 1 patients who require urgent ECLS for restoring hemodynamics and organ perfusion, an upgrade from ECLS to ECMELLA is relevant if the serum lactate level is ≤7.9 mmol/L.

Ventriculo-arterial (un)coupling in septic shock: Impact of current and upcoming hemodynamic drugs.

Sepsis is an archetype of distributive shock and combines different levels of alterations in preload, afterload, and often cardiac contractility. The use of hemodynamic drugs has evolved over the past few years, along with the invasive and non-invasive tools used to measure these components in real time. However, none of them is impeccable, which is why the mortality of septic shock remains too high. The concept of ventriculo-arterial coupling (VAC) allows for the integration of these three fundamental macroscopic hemodynamic components. In this mini review, we discuss the knowledge, tools, and limitations of VAC measurement, along with the evidence supporting ventriculo-arterial uncoupling in septic shock. Finally, the impact of recommended hemodynamic drugs and molecules on VAC is detailed.

Evaluation of Medical Confidentiality Breaches on Twitter Among Anesthesiology and Intensive Care Health Care Workers.

BACKGROUND: With the generalization of social network use by health care workers, we observe the emergence of breaches in medical confidentiality. Our objective was to determine, among anesthesiology and intensive care health care workers, the rate of medical confidentiality breaches among professional tweets. METHODS: We performed a retrospective analysis of public Twitter data available through the official Twitter application program interface. The profiles of anesthesiology and intensive care professionals were identified thanks to keywords in their biography. All the tweets with a photograph and all the text-only tweets containing at least one specific keyword related to anesthesiology or intensive care were extracted. We selected only the tweets with a health care-related character. Then, we analyzed 10% of the tweets with a photograph and 10% of the text-only tweets extracted and noted those presenting a breach of medical confidentiality. RESULTS: After a first screening of 12,705 accounts, we manually analyzed 431 tweets with photograph(s) and 9000 text-only tweets from 1831 accounts. We found 44 (10.2%) breaches of medical confidentiality among the photographs and 76 (0.8%) among text-only tweets. These 120 problematic tweets came from 96 profiles (96/1831; 5.2%); 3.7% of North American profiles breached medical confidentiality versus 6.3% of profiles from other areas; P = .03. When comparing the distribution of the number of followers and tweets, accounts with breach of medical confidentiality tweets had more tweets and followers than profiles without (both P < .0001). CONCLUSIONS: We found a significant proportion of tweets with breach of medical confidentiality among anesthesiology and intensive care professionals accounts.

Erector Spinae Plane Block versus Paravertebral Block after Thoracic Surgery for Lung Cancer: A Propensity Score Study.

INTRODUCTION: The prevention of respiratory complications is a major issue after thoracic surgery for lung cancer, and requires adequate post-operative pain management. The erector spinae plane block (ESPB) may decrease post-operative pain. The objective of this study was to evaluate the impact of ESPB on pain after video or robot-assisted thoracic surgery (VATS or RATS). METHODS: The main outcome of this retrospective study with a propensity score analysis (PSA) was to compare the post-operative pain at 24 h at rest and at cough between a group that received ESPB and a group that received paravertebral block (PVB). Post-operative morphine consumption at 24 h and complications were also assessed. RESULTS: One hundred and seven patients were included: 54 in the ESPB group and 53 in the PVB group. The post-operative median pain score at rest and cough was lower in the ESPB group compared to the PVB group at 24 h (respectively, at rest 2 [1; 3.5] vs. 2 [0; 4], p = 0.0181, with PSA; ESPB -0.80 [-1.50; -0.10], p = 0.0255, and at cough (4 [3; 6] vs. 5 [4; 6], p = 0.0261, with PSA; ESPB -1.48 [-2.65; -0.31], p = 0.0135). There were no differences between groups concerning post-operative morphine consumption at 24 h and respiratory complications. CONCLUSIONS: Our results suggest that ESPB is associated with less post-operative pain at 24 h than PVB after VATS or RATS for lung cancer. Furthermore, ESPB is an acceptable and safe alternative compared to PVB.

Comparison of landiolol and amiodarone for the treatment of new-onset atrial fibrillation after cardiac surgery (FAAC) trial: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative atrial fibrillation (PoAF) after cardiac surgery has a high incidence of 30%, but its management is controversial. Two strategies are recommended without evidence of a superiority of one against the other: rate control with beta-blocker or rhythm control with amiodarone. Landiolol is a new-generation beta-blocker with fast onset and short half-life. One retrospective, single-center study compared landiolol to amiodarone for PoAF after cardiac surgery with a better hemodynamic stability and a higher rate of reduction to sinus rhythm with landiolol, justifying the need for a multicenter randomized controlled trial. Our aim is to compare landiolol to amiodarone in the setting of PoAF after cardiac surgery with the hypothesis of a higher rate of reduction to sinus rhythm with landiolol during the 48 h after the first episode of POAF. METHODS: The FAAC trial is a multicenter single-blind two parallel-arm randomized study, which planned to include 350 patients with a first episode of PoAF following cardiac surgery. The duration of the study is 2 years. The patients are randomized in two arms: a landiolol group and an amiodarone group. Randomization (Ennov Clinical®) is performed by the anesthesiologist in charge of the patient if PoAF is persistent for at least 30 min after correction of hypovolemia, dyskalemia, and absence of pericardial effusion on a transthoracic echocardiography done at bedside. Our hypothesis is an increase of the percentage of patients in sinus rhythm from 70 to 85% with landiolol in less than 48 h after onset of PoAF (alpha risk = 5%, power = 90%, bilateral test). DISCUSSION: The FAAC trial was approved by the Ethics Committee of EST III with approval number 19.05.08. The FAAC trial is the first randomized controlled trial comparing landiolol to amiodarone for PoAF after cardiac surgery. In case of higher rate of reduction with landiolol, this beta-blocker could be the drug of choice used in this context as to reduce the need for anticoagulant therapy and reduce the risk of complications of anticoagulant therapy for patients with a first episode of postoperative atrial fibrillation after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04223739. Registered on January 10, 2020.

Paravertebral block combined with serratus anterior plane block after video-assisted thoracic surgery: a prospective randomized controlled trial.

OBJECTIVES: Adequate pain management after thoracoscopic surgery is a major issue in the prevention of respiratory complications. The combination of the paravertebral block (PVB) with the serratus anterior plane block (SAPB) may decrease postoperative pain. The objective of this study was to evaluate the impact of the combination of PVB and SAPB on the consumption of morphine and pain after video- or robot-assisted thoracic surgery. METHODS: The main objective of this randomized controlled trial was to compare the cumulative postoperative morphine consumption at 24 h between a group having PVB (PVB group) and a group having PVB and SAPB (PV-SAPB group). Postoperative pain at 6 and 24 h and morphine-related complications were also assessed. RESULTS: A total of 112 patients were included with 56 in each group. There was no difference in median cumulative morphine consumption at 24 h between the 2 groups (P = 0.1640). At 6 h, the median postoperative pain was higher in the PVB group compared to the PV-SAPB group (3 [0; 4] vs 2 [0; 3], P = 0.0231). There were no differences between the 2 groups for pain at 24 h and morphine-related complications. CONCLUSIONS: We did not find any difference in morphine consumption between the 2 groups. Our results suggest that the combination of PVB and SAPB for video-assisted thoracic surgery or robot-assisted thoracic surgery is safe effective and reliable and could be an alternative to PVB alone in certain indications.