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BackgroundPost-induction anaesthesia often promotes intraoperative hypotension (IOH) that can worsen postoperative outcomes. This study aims to assess the benefit of norepinephrine versus ephedrine at the induction of anaesthesia to prevent postoperative complications following major abdominal surgery by preventing IOH.Methods and analysisThe EPON STUDY is a prospective single-centre randomised controlled trial with the planned inclusion of 500 patients scheduled for major abdominal surgery at the Amiens University Hospital. The inclusion criteria are patients aged over 50 years weighing more than 50 kg with an American Society of Anesthesiologists physical status score of ≥2 undergoing major abdominal surgery under general anaesthesia. Patients are allocated either to the intervention group (n=250) or the standard group (n=250). In the intervention group, the prevention of post-induction IOH is performed with norepinephrine (dilution to 0.016 mg/mL) using an electric syringe pump at a rate of 0.48 mg/h (30 mL/h) from the start of anaesthesia and then titrated to achieve the haemodynamic target. In the control group, the prevention of post-induction IOH is performed with manual titration of ephedrine, with a maximal dose of 30 mg, followed by perfusion with norepinephrine. In both groups, the haemodynamic target to maintain is a mean arterial pressure (MAP) of 65 mm Hg or 70 mm Hg for patients with a medical history of hypertension. An intention-to-treat analysis will be performed. The primary outcome is the Clavien–Dindo score assessed up to 30 days postoperatively. The secondary endpoints are the length of hospital stay and length of stay in an intensive care unit/postoperative care unit; postoperative renal function; postoperative cardiovascular, respiratory, neurological, haematological and infectious complications at 1 month; and volume of intraoperative vascular filling and mortality at 1 month.Ethics and disseminationEthical approval was obtained from the committee of protection of the persons of Ile de France in May 2021 (number 21 05 41). The authors will be involved in disseminating the research findings (through attending conferences and co-authoring papers). The results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences.Trial registration number NCT05276596.

BackgroundNorepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors’ distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion.MethodsA prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion.ResultsThirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [− 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p < 0.001) with norepinephrine infusion, being classified as VW responders. The VW responders improved cardiac index (from 1.8 (0.6) L min−1 m−2 to 2.2 (0.5) L min−1 m−2, p = 0.002), capillary refill time (from to 4.2 (1.1) s to 3.1 (1) s, p = 0.006), and pCO2 gap (from 9 [7;10] mmHg to 6 [4;8] mmHg, p = 0.04). No baseline parameters were able to predict the VW response to norepinephrine. In comparison, VW non-responders did not significantly change the VW (from 5 [-5;16] mmHg to -2 [-12;15] mmHg, p = 0.17), cardiac index (from 1.6 (0.3) L min−1 m−2 to 1.8 (0.4) L min−1 m−2, p = 0.09) and capillary refill time (from 4.1 (1) s to 3.7 (1.4), p = 0.44).ConclusionsIn post-cardiac surgery patients with vasoplegic arterial hypotension, the vascular waterfall is low. Norepinephrine did not systematically restore the vascular waterfall. Increase of the vascular waterfall was associated with an improvement of laboratory and clinical parameters of tissue perfusion.

A fluid challenge can generate an infraclinical interstitial syndrome that may be detected by the appearance of B-lines by lung ultrasound. Our objective was to evaluate the appearance of B-lines as a diagnostic marker of preload unresponsiveness and postoperative complications in the operating theater. We conducted a prospective, bicentric, observational study. Adult patients undergoing abdominal surgery were included. Stroke volume (SV) was determined before and after a fluid challenge with 250 mL crystalloids (Delta-SV) using esophageal Doppler monitoring. Responders were defined by an increase of Delta-SV > 10% after fluid challenge. B-lines were collected at four bilateral predefined zones (right and left anterior and lateral). Delta-B-line was defined as the number of newly appearing B-lines after a fluid challenge. Postoperative pulmonary complications were prospectively recorded according to European guidelines. In total, 197 patients were analyzed. After a first fluid challenge, 67% of patients were responders and 33% were non-responders. Delta-B-line was significantly higher in non-responders than responders [4 (2–7) vs 1 (0–3), p < 0.0001]. Delta-B-line was able to diagnose fluid non-responders with an area under the curve of 0.74 (95% CI 0.67–0.80, p < 0.0001). The best threshold was two B-lines with a sensitivity of 80% and a specificity of 57%. The final Delta-B-line could predict postoperative pulmonary complications with an area under the curve of 0.74 (95% CI 0.67–0.80, p = 0.0004). Delta-B-line of two or more detected in four lung ultrasound zones can be considered to be a marker of preload unresponsiveness after a fluid challenge in abdominal surgery. The objectives and procedures of the study were registered at Clinicaltrials.gov (NCT03502460; Principal investigator: Stéphane BAR, date of registration: April 18, 2018).

Indirect measurement of the respiratory exchange ratio (RER) has been shown to predict the occurrence of postoperative complications after major open non-cardiac surgery. Our main objective was to demonstrate the ability of the RER, indirectly measured by the anaesthesia respirator, to predict the occurrence of postoperative complications following laparoscopic surgery. We performed an observational, prospective and monocentric study. Haemodynamic and respiratory parameters were collected at several timepoints to calculate the RER by a non-volumetric method: RER = (FetCO2–FiCO2)/(FiO2–FetO2). Fifty patients were prospectively included. Nine patients (18%) had at least one postoperative complication. The mean RER was significantly higher for the subgroup of patients with complications than the subgroup without (1.04 ± 0.27 vs 0.88 ± 0.13, p < 0.05). The RER could predict the occurrence of post-operative complications with an area under the ROC curve of 0.73 (95% CI 0.59–0.85, p = 0.021). The best cut off was 0.98, with a sensitivity of 56% and a specificity of 88%. One hour after insufflation, the FiO2–FetO2 difference was significantly lower and the RER was significantly higher in the complications subgroup than in the subgroup without complications (4.4/− 1.6% vs 5.8/− 1.2%, p = 0.001 and 0.95 [0.85–1.04] vs 0.83 [0.75–0.92], p = 0.04, respectively). The RER measured during laparoscopic surgery can predict the occurrence of postoperative complications.Trial registration The objectives and procedures of the study was registered at Clinicaltrials.gov (NCT03751579); date: November 23, 2018.

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.

This post-hoc analysis of a randomized controlled trial was undertaken to establish the determinants of postoperative complications and acute kidney injury in high-risk noncardiac surgery patients supported with hemodynamic treatment strategies. We conducted a post-hoc analysis of patients enrolled in the OPtimization Hemodynamic Individualized by the respiratory QUotiEnt (OPHIQUE) trial. Operating rooms in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. We enrolled 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia. All patients were treated according to hemodynamic treatment strategies which included cardiac output optimization by titration of fluid challenge and targeted systolic blood pressure to remain within ±10% of the reference value. We assessed the association between pre-operative and intra-operative exposure of interest with a composite primary outcome of major complications or death within seven days following surgery using a multivariable logistic regression model. We also assessed the association between these exposures of interest and acute kidney injury. The data of 341 patients were analyzed. In multivariate analysis, the factors independently associated with the primary outcome were age (OR = 1.04 (1.01–1.06), P = 0.002), preoperative hemoglobin concentration (OR = 0.85 (0.75–0.96), P = 0.012), non-vascular surgery (OR = 0.30 (0.17–0.53), P < 0.0001), and intraoperative surgical complications (OR = 2.08 (1.02–4.24), P = 0.046). The factors independently associated with postoperative acute kidney injury were age (OR = 1.04 (1.01–1.08), P = 0.008), preoperative creatinine concentration (OR = 1.01 (1.00–1.01), P = 0.049), non-vascular surgery (OR = 0.36 (0.20–0.66), P = 0.001), and intraoperative surgical complications (OR = 3.36 (1.50–7.55), P = 0.031). Surgical complications, a lower preoperative hemoglobin concentration, age, and vascular surgery were associated with postoperative complications in a high-risk noncardiac surgery population supported with hemodynamic treatment strategies. •The prevalence of complications was high for patients treated according to hemodynamic treatment strategy.•factors associated with complications in this population were age, the preoperative hemoglobin and surgical complications.•These factors were associated with outcome in this population treated according to hemodynamic treatment strategy.•Neither blood pressure, cardiac output, intraoperative volume, nor norepinephrine dose were associated with complications.

The purpose of this study was to determine whether dynamic elastance E-Adyn derived from echocardiographic measurements of stroke volume variations can predict the success of a one-step decrease of norepinephrine dose. In this prospective single-center study, 39 patients with vasoplegic syndrome treated with norepinephrine and for whom the attending physician had decided to decrease norepinephrine dose and monitored by thermodilution were analyzed. E-Adyn is the ratio of pulse pressure variation to stroke volume variation and was calculated from echocardiography stroke volume variations and from transpulmonary thermodilution. Pulse pressure variation was obtained from invasive arterial monitoring. Responders were defined by a decrease in mean arterial pressure (MAP)>10% following norepinephrine decrease. The median decrease in norepinephrine was of 0.04 [0.03-0.05] mu g kg(-1) min(-1). Twelve patients (31%) were classified as pressure responders with a median decrease in MAP of 13% [12-15%]. E-Adyn was lower in pressure responders (0.40 [0.24-0.57] vs 0.95 [0.77-1.09], p<0.01). E-Adyn was able to discriminate between pressure responders and non-responders with an area under the curve of 0.86 (CI95% [0.71 to1.0], p<0.05). The optimal cut-off was 0.8. E-Adyn calculated from the echocardiographic estimation of the stroke volume variation and the invasive arterial pulse pressure variation can be used to discriminate pressure response to norepinephrine weaning. Agreement between E-Adyn calculated from echocardiography and thermodilution was poor. Echocardiographic E-Adyn might be used at bedside to optimize hemodynamic treatment.

[...]the duration of exposure to surgery was the factor most highly associated with hyperlactatemia. (d) Despite a similar DO2, haemoglobin values were lower for patients experiencing hyperlactatemia, suggesting a role for insufficient microvascular O2 delivery. (e) Finally, hyperlactatemia was associated with tissue acidosis and higher values for the venoarterial pCO2gap/arteriovenous O2 content difference ratio and respiratory exchange ratio, suggesting microvascular hypoperfusion with tissue metabolic uncoupling [4]. [...]hyperlactatemia may not only be explained by low blood flow but also by time-dependent surgical trauma with disturbances of microvascular O2 delivery, metabolic acidosis, and low arterial haemoglobin content. Lactate < 3 mmol l−1 N = 366 Lactate ≥ 3 mmol l−1 N = 68 p-value Clinical parameters Temperature, °C 35.8 ± 0.8 35.9 ± 0.8 0.54 Heart rate, bpm 73 [64–85] 86 [73–95] <0.001 MAP, mmHg 75 [69–85] 72 [66–81] 0.10 PPV, % 8 [5–11] 9 [6–13] 0.06 Cardiac index, l min−1 m−2 2.7 [2.3–3.5] 2.8 [1.9–3.4] 0.23 Respiratory exchange ratio 0.82 [0.75–0.94] 0.98 [0.80–1.21] <0.001 Systemic parameters PaO2, mmHg 158 [120–197] 177 [129–197] 0.11 PvO2, mmHg 58 [46–63] 59 [51–73] <0.001 PaCO2, mmHg 40 [37–44] 41 [37–46] 0.39 PvCO2, mmHg 46 [42–50] 46 [42–51] 0.71 PCO2gap, mmHg 5.7 [3.8–7.8] 5.8 [3.3–8.2] 0.66 CaO2, ml 16.2 [14.6–17.6] 14.8 [12.6–16.6] <0.001 CvO2, ml 13.2 [11.5–14.6] 12.4 [10.0–15.1] 0.08 DavO2, ml 2.9 [1.8–3.8] 2.2 [1.4–3.5] 0.008 pCO2gap/DavO2, mmHg ml−1 2.0 [1.2–3.3] 2.3 [1.7–4.6] 0.02 SaO2, % 99 [98–99] 99 [98–99] 0.14 SvO2, % 83.1 [77.1–88.5] 86.0 [81.7–91.2] 0.002 DO2, ml min−1 m−2 480 [374–672] 461 [310–865] 0.95 VO2, ml min−1 m−2 88 [51–136] 76 [33–143] 0.28 Arterial lactate, mmol l−1 1.3 [1.0–1.8] 3.9 [3.4–5.7] <0.001 Arterial Haemoglobin, g dl−1 11.7 ± 1.8 10.5 ± 2.1 <0.001 Acid basic balance Arterial pH 7.35 [7.31–7.39] 7.26 [7.22–7.33] <0.001 Venous pH 7.32 [7.28–7.35] 7.24 [7.19–7.30] <0.001 Arterial bicarbonates, mmol l−1 23.1 ± 2.6 19.7 ± 4.0 <0.001 Arterial base excess, mmol l−1 −2.7 [−4.5– –1.1] −7.4 [−9.9– –4.4] <0.001 Table 1 Comparison of clinical and biological parameters in the overall population according to the presence of hyperlactatemia.

Purpose: To evaluate the ability of an algorithm based on dynamic arterial elastance to decrease the duration of norepinephrine treatment. Methods: We performed a prospective, open-label, randomized study in patients requiring norepinephrine for vasoplegic syndrome after cardiac surgery with cardiopulmonary bypass. Patients were randomized to an algorithm-based intervention group or a control group. The primary outcome was the duration of norepinephrine treatment. The secondary outcomes included the total dose of norepinephrine, the length of stay (LOS) in the ICU, central venous oxygen saturation, arterial lactate levels, arrhythmia and diuresis. Results: Of 130 included patients, 118 were analysed on an intention-to-treat basis (intervention group: n = 59; control group: n = 59). On inclusion, the intervention and control groups did not differ significantly in terms of demographic characteristics, surgical data or the prior duration of norepinephrine treatment [5 h (4-10) vs. 5 h (5-7), respectively; P = 0.543]. The cumulative duration of norepinephrine treatment after inclusion was shorter in the intervention group than in the control group [17 h (13-26)] vs. 39 h (19-58), respectively; (P < 0.001). The cumulative dose of norepinephrine and the LOS in the ICU were also lower in the intervention group (P < 0.05). There were no intergroup differences for other outcomes (the sepsis-related organ failure score, central venous oxygen saturation, arrhythmia, and arterial lactate levels). Conclusion: A haemodynamic algorithm based on dynamic arterial elastance was associated with a shorter duration of norepinephrine treatment and a shorter LOS in the ICU. Use of the algorithm did not alter perfusion parameters or increase the volume of fluid infused.

Background Observational studies have suggested that a high respiratory exchange ratio (RER) is associated with the occurrence of postoperative complications. The study’s primary objective is to demonstrate that the incidence of postoperative complications is lower in an interventional group (patients monitored using a hemodynamic algorithm that incorporates the RER) than in a control group (treated according to standard practice). Methods We shall perform a prospective, multicenter, randomized, open-label, superiority trial of consecutive patients undergoing major noncardiac surgery (i.e., abdominal, vascular, and orthopedic surgery). The control group will be treated according to the current guidelines on standard hemodynamic care. The interventional group will be treated according to an algorithm based on the RER. The primary outcome will be the occurrence of at least one complication in the 7 days following surgery. The secondary outcomes will be the length of hospital stay, the total number of complications per patient, the 30-day mortality, the total intraoperative volume of fluids administered, and the Sequential [sepsis-related] Organ Failure Assessment (SOFA) score and laboratory data measured on postoperative days 1, 2, and 7. A total of 350 patients will be included. Discussion In the operating theater, the RER is potentially a continuously available, easy-to-read, indirect marker of tissue hypoperfusion and postoperative complications. If the RER does predict the occurrence of tissue hypoperfusion, it will help the physician to provide personalized hemodynamic management and limit the side effects associated with excessive hemodynamic optimization (volume overload, vasoconstriction, etc.). Trial registration ClinicalTrials.gov NCT03852147 . Registered on February 25, 2019