Sample size estimation in clinical trials using ventilator-free days as the primary outcome: a systematic review.

BACKGROUND: Ventilator-free days (VFDs) are a composite endpoint increasingly used as the primary outcome in critical care trials. However, because of the skewed distribution and competitive risk between components, sample size estimation remains challenging. This systematic review was conducted to systematically assess whether the sample size was congruent, as calculated to evaluate VFDs in trials, with VFDs' distribution and the impact of alternative methods on sample size estimation. METHODS: A systematic literature search was conducted within the PubMed and Embase databases for randomized clinical trials in adults with VFDs as the primary outcome until December 2021. We focused on peer-reviewed journals with 2021 impact factors greater than five. After reviewing definitions of VFDs, we extracted the sample size and methods used for its estimation. The data were collected by two independent investigators and recorded in a standardized, pilot-tested forms tool. Sample sizes were calculated using alternative statistical approaches, and risks of bias were assessed with the Cochrane risk-of-bias tool. RESULTS: Of the 26 clinical trials included, 19 (73%) raised "some concerns" when assessing risks of bias. Twenty-four (92%) trials were two-arm superiority trials, and 23 (89%) were conducted at multiple sites. Almost all the trials (96%) were unable to consider the unique distribution of VFDs and death as a competitive risk. Moreover, significant heterogeneity was found in the definitions of VFDs, especially regarding varying start time and type of respiratory support. Methods for sample size estimation were also heterogeneous, and simple models, such as the Mann-Whitney-Wilcoxon rank-sum test, were used in 14 (54%) trials. Finally, the sample sizes calculated varied by a factor of 1.6 to 17.4. CONCLUSIONS: A standardized definition and methodology for VFDs, including the use of a core outcome set, seems to be required. Indeed, this could facilitate the interpretation of findings in clinical trials, as well as their construction, especially the sample size estimation which is a trade-off between cost, ethics, and statistical power. Systematic review registration PROSPERO ID: CRD42021282304. Registered 15 December 2021 ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021282304 ).

Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial.

BACKGROUND: Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis. METHODS: A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30. RESULTS: Between June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15-30] and 30 days [18-30], respectively; median absolute difference of - 0.0 days, 95% CI - 3.3 to 3.3; p = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5-28] versus 6 days [2-13], p = 0.02). CONCLUSIONS: In a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02126332 , April 30, 2014.

Predicting intraoperative hypotension: from hope to hype and back to reality.

The analysis of arterial pressure waveforms with machine learning algorithms has been proposed to predict intraoperative hypotension. The ability to forecast arterial hypotension 5-15 min ahead of the fall in blood pressure allows clinicians to be pro-active instead of reactive, and could potentially decrease postoperative morbidity. However, the predictive value of machine learning algorithms has been overestimated due to selection bias in several clinical studies, and they might not be superior to mere observation of arterial pressure. Continuous blood pressure monitoring enables immediate detection of hypotension, and giving fluid, vasopressors or inotropes to patients who are not yet (and might never become) hypotensive based on an algorithm is questionable. Finally, recent prospective interventional studies suggest that reducing intraoperative hypotension does not improve postoperative outcomes.

Intraoperative blood pressure: could less be more?

Retrospective observational studies have reported a significant association between intraoperative hypotension and postoperative morbidity. However, association does not imply causation, and whether preventing intraoperative hypotension can improve patient outcome remains to be demonstrated. In this issue of the British Journal of Anaesthesia, D'Amico and colleagues meta-analysed 10 prospective randomised trials comparing low (≤60 mm Hg) and higher mean arterial pressure targets during anaesthesia and surgery. They did not observe an increase in postoperative morbidity and mortality in the low target group. In contrast, they reported a statistically significant (but not clinically relevant) reduction in postoperative cardiac arrhythmia and hospital length of stay when targeting mean arterial pressure ≤60 mm Hg. These findings suggest that during most surgical cases, intraoperative hypotension is a marker of the severity, frailty, or both rather than a mediator of postoperative complications.

One-year patient outcomes based on lung morphology in acute respiratory distress syndrome: secondary analysis of LIVE trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes. METHODS: This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up. RESULTS: A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes. CONCLUSION: Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities. TRIAL REGISTRATION: NCT02149589; May 29, 2014.

Hydroxyethyl Starch for Fluid Management in Patients Undergoing Major Abdominal Surgery: A Systematic Review With Meta-analysis and Trial Sequential Analysis.

BACKGROUND: In critically ill patients, warnings about a risk of death and acute kidney injury (AKI) with hydroxyethyl starch (HES) solutions have been raised. However, HES solutions may yet have a role to play in major abdominal surgery. This meta-analysis and trial sequential analysis (TSA) aimed to investigate the effect of HES intravascular volume replacement on the risk of AKI, intraoperative blood transfusion, and postoperative intra-abdominal complications compared to crystalloid intravascular volume replacement. METHODS: In this meta-analysis and TSA, we searched for randomized controlled trials (RCTs) comparing intraoperative HES intravascular volume replacement to crystalloid intravascular volume replacement in adult patients undergoing major abdominal surgery. Primary outcome was 30-day AKI, defined as a binary outcome according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, combining stages 1, 2, and 3 into an AKI category versus no AKI category (stage 0). Secondary outcomes included rates of intraoperative blood transfusion and postoperative intra-abdominal complications. We used random effects models to calculate summary estimates. We used relative risk (RR) as summary measure for dichotomous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome (P value <.05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes (P value <.01 was considered statistically significant). RESULTS: Seven RCTs including 2398 patients were included. HES intravascular volume replacement was not associated with an increased risk of 30-day AKI (RR = 1.22, 95% CI, 0.94-1.59; P = .13), when compared to crystalloid intravascular volume replacement. According to TSA, this analysis was underpowered. HES intravascular volume replacement was associated with higher rates of blood transfusion (RR = 1.57 99% CI, 1.10-2.25; P = .001), and similar rates of postoperative intra-abdominal complications (RR = 0.76 99% CI, 0.57-1.02; P = .02). CONCLUSIONS: In this meta-analysis to focus on HES intravascular volume replacement in major abdominal surgery, HES intravascular volume replacement was not associated with a higher risk of 30-day AKI when compared to crystalloid intravascular volume replacement. However, CI and TSA do not exclude harmful effects of HES intravascular volume replacement on the renal function.

Characteristics and outcomes of patients undergoing anesthesia while SARS-CoV-2 infected or suspected: a multicenter register of consecutive patients.

BACKGROUND: There are limited data to detail the perioperative anesthetic management and the incidence of postoperative respiratory complications among patients requiring an anesthetic procedure while being SARS-CoV-2 positive or suspected. METHODS: An observational multicenter cohort study was performed including consecutive patients who were SARS-CoV-2 confirmed or suspected and who underwent scheduled and emergency anesthesia between March 17 and May 26, 2020. RESULTS: A total of 187 patients underwent anesthesia with SARS-CoV-2 confirmed or suspected, with ultimately 135 (72.2%) patients positive and 52 (27.8%) negative. The median SOFA score was 2 [0; 5], and the median ARISCAT score was 49 [36; 67]. The major respiratory complications rate was 48.7% (n = 91) with 40.4% (n = 21) and 51.9% (n = 70) in the SARS-CoV-2-negative and -positive groups, respectively (p = 0.21). Among both positive and negative groups, patients with a high ARISCAT risk score (> 44) had a higher risk of presenting major respiratory complications (p < 0.01 and p = 0.1, respectively). DISCUSSION: When comparing SARS-COV-2-positive and -negative patients, no significant difference was found regarding the rate of postoperative complications, while baseline characteristics strongly impact these outcomes. This finding suggests that patients should be scheduled for anesthetic procedures based on their overall risk of postoperative complication, and not just based on their SARS-CoV-2 status.

Automated closed-loop versus standard manual oxygen administration after major abdominal or thoracic surgery: an international multicentre randomised controlled study.

INTRODUCTION: Hypoxaemia and hyperoxaemia may occur after surgery, with related complications. This multicentre randomised trial evaluated the impact of automated closed-loop oxygen administration after high-risk abdominal or thoracic surgeries in terms of optimising the oxygen saturation measured by pulse oximetry time within target range. METHODS: After extubation, patients with an intermediate to high risk of post-operative pulmonary complications were randomised to "standard" or "automated" closed-loop oxygen administration. The primary outcome was the percentage of time within the oxygenation range, during a 3-day frame. The secondary outcomes were the time with hypoxaemia and hyperoxaemia under oxygen. RESULTS: Among the 200 patients, time within range was higher in the automated group, both initially (≤3 h; 91.4±13.7% versus 40.2±35.1% of time, difference +51.0% (95% CI -42.8-59.2%); p<0.0001) and during the 3-day period (94.0±11.3% versus 62.1±23.3% of time, difference +31.9% (95% CI 26.3-37.4%); p<0.0001). Periods of hypoxaemia were reduced in the automated group (≤3 days; 32.6±57.8 min (1.2±1.9%) versus 370.5±594.3 min (5.0±11.2%), difference -10.2% (95% CI -13.9--6.6%); p<0.0001), as well as hyperoxaemia under oxygen (≤3 days; 5.1±10.9 min (4.8±11.2%) versus 177.9±277.2 min (27.0±23.8%), difference -22.0% (95% CI -27.6--16.4%); p<0.0001). Kaplan-Meier analysis depicted a significant difference in terms of hypoxaemia (p=0.01) and severe hypoxaemia (p=0.0003) occurrence between groups in favour of the automated group. 25 patients experienced hypoxaemia for >10% of the entire monitoring time during the 3 days within the standard group, as compared to the automated group (p<0.0001). CONCLUSION: Automated closed-loop oxygen administration promotes greater time within the oxygenation target, as compared to standard manual administration, thus reducing the occurrence of hypoxaemia and hyperoxaemia.

Balanced Opioid-free Anesthesia with Dexmedetomidine versus Balanced Anesthesia with Remifentanil for Major or Intermediate Noncardiac Surgery.

BACKGROUND: It is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil. METHODS: Patients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting. RESULTS: The study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay. CONCLUSIONS: This trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia.

Blunt Chest Trauma and Regional Anesthesia for Analgesia of Multitrauma Patients in French Intensive Care Units: A National Survey.

BACKGROUND: Chest injuries are associated with mortality among patients admitted to the intensive care unit (ICU) and require multimodal pain management strategies, including regional anesthesia (RA). We conducted a survey to determine the current practices of physicians working in ICUs regarding RA for the management of chest trauma in patients with multiple traumas. METHODS: An online questionnaire was sent to medical doctors (n = 1230) working in French ICUs, using the Société Française d'Anesthésie Réanimation (SFAR) mailing list of its members. The questionnaire addressed 3 categories: general characteristics, practical aspects of RA, and indications and contraindications. RESULTS: Among the 333 respondents (response rate = 27%), 78% and 40% of 156 respondents declared that they would consider using thoracic epidural analgesia (TEA) and thoracic paravertebral blockade (TPB), respectively. The main benefits declared for performing RA were the ability to have effective analgesia, a more effective cough, and early rehabilitation. For 70% of the respondents, trauma patients with a theoretical indication of RA did not receive TEA or TPB for the following reasons: the ICU had no experience of RA (62%), no anesthesiologist-intensivist working in the ICU (46%), contraindications (27%), ignorance of the SFAR guidelines (19%), and no RA protocol available (13%). In this survey, 95% of the respondents thought the prognosis of trauma patients could be influenced by the use of RA. CONCLUSIONS: While TEA and TPB are underused because of several limitations related to the patterns of injuries in multitrauma patients, lack of both experience and confidence in combination with the absence of available protocols appear to be the major restraining factors, even if physicians are aware that patients' outcomes could be improved by RA. These results suggest the need to strengthen initial training and provide continuing education about RA in the ICU.

Lung Ultrasound Findings in the Postanesthesia Care Unit Are Associated With Outcome After Major Surgery: A Prospective Observational Study in a High-Risk Cohort.

BACKGROUND: Postoperative pulmonary complications are associated with increased morbidity. Identifying patients at higher risk for such complications may allow preemptive treatment. METHODS: Patients with an American Society of Anesthesiologists (ASA) score >1 and who were scheduled for major surgery of >2 hours were enrolled in a single-center prospective study. After extubation, lung ultrasound was performed after a median time of 60 minutes by 2 certified anesthesiologists in the postanesthesia care unit after a standardized tracheal extubation. Postoperative pulmonary complications occurring within 8 postoperative days were recorded. The association between lung ultrasound findings and postoperative pulmonary complications was analyzed using logistic regression models. RESULTS: Among the 327 patients included, 69 (19%) developed postoperative pulmonary complications. The lung ultrasound score was higher in the patients who developed postoperative pulmonary complications (12 [7-18] vs 8 [4-12]; P < .001). The odds ratio for pulmonary complications in patients who had a pleural effusion detected by lung ultrasound was 3.7 (95% confidence interval, 1.2-11.7). The hospital death rate was also higher in patients with pleural effusions (22% vs 1.3%; P < .001). Patients with pulmonary consolidations on lung ultrasound had a higher risk of postoperative mechanical ventilation (17% vs 5.1%; P = .001). In all patients, the area under the curve for predicting postoperative pulmonary complications was 0.64 (95% confidence interval, 0.57-0.71). CONCLUSIONS: When lung ultrasound is performed precociously <2 hours after extubation, detection of immediate postoperative alveolar consolidation and pleural effusion by lung ultrasound is associated with postoperative pulmonary complications and morbi-mortality. Further study is needed to determine the effect of ultrasound-guided intervention for patients at high risk of postoperative pulmonary complications.

Effects of adding a combined femoral and sciatic nerve block with levobupivacaine and clonidine to general anaesthesia in femoropopliteal bypass surgery: A randomised, double-blind, controlled trial.

BACKGROUND: Adding a regional block to general anaesthesia can prevent postoperative pain and improve peripheral circulation. OBJECTIVE: To seek improved postoperative analgesia and care due to a long-acting combined femoral and sciatic nerve block in patients undergoing femoropopliteal bypass surgery. DESIGN: A randomised, double-blind, controlled trial. SETTING: Vascular surgery unit of a French university hospital. PATIENTS: Forty-four adults scheduled for bypass surgery under general anaesthesia. INTERVENTION: Patients were allocated to receive either an active nerve block with 20 ml of 0.375% levobupivacaine and clonidine 0.5 µg kg, or a simulated (sham) block only, but with local anaesthesia of the skin, before general anaesthesia. General anaesthesia was standardised with propofol, then sevoflurane and sufentanil adjusted according to clinical need. Postoperative analgesia was standardised with paracetamol 1 g every 6 h, and intravenous morphine, initially titrated in the postanaesthesia care unit and then patient-controlled. Oral analgesics were repeated up to day 3. MAIN OUTCOME MEASURES: The primary outcome was morphine consumption during the first 24 postoperative hours. In a subgroup of postoperative patients distal tissue oxygen saturation was recorded at the lateral side of the blocked calf. RESULTS: Patients in the active group received less intra-operative sufentanil (median dose 25 vs. 41 µg), needed less morphine during the first 24 h (15 vs. 27 mg) and 72 (20 vs. 35 mg) postoperative hours, than in the control group. They also had less pain on movement, but pain at rest, the tissue oxygen saturation and other rehabilitation outcomes were unaffected by the treatment. Tolerance outcomes were also similar between groups. CONCLUSION: Combining the two regional blocks improves the quality of postoperative care in this frail population, probably by reducing the amount of peri-operative opioid. TRIAL REGISTRATION: ClinicalTrials.gov (ref. NCT01785693).

Effect of Hydroxyethyl Starch vs Saline for Volume Replacement Therapy on Death or Postoperative Complications Among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial.

Importance: It is not known if use of colloid solutions containing hydroxyethyl starch (HES) to correct for intravascular deficits in high-risk surgical patients is either effective or safe. Objective: To evaluate the effect of HES 130/0.4 compared with 0.9% saline for intravascular volume expansion on mortality and postoperative complications after major abdominal surgery. Design, Setting, and Participants: Multicenter, double-blind, parallel-group, randomized clinical trial of 775 adult patients at increased risk of postoperative kidney injury undergoing major abdominal surgery at 20 university hospitals in France from February 2016 to July 2018; final follow-up was in October 2018. Interventions: Patients were randomized to receive fluid containing either 6% HES 130/0.4 diluted in 0.9% saline (n = 389) or 0.9% saline alone (n = 386) in 250-mL boluses using an individualized hemodynamic algorithm during surgery and for up to 24 hours on the first postoperative day, defined as ending at 7:59 am the following day. Main Outcomes and Measures: The primary outcome was a composite of death or major postoperative complications at 14 days after surgery. Secondary outcomes included predefined postoperative complications within 14 days after surgery, durations of intensive care unit and hospital stays, and all-cause mortality at postoperative days 28 and 90. Results: Among 826 patients enrolled (mean age, 68 [SD, 7] years; 91 women [12%]), 775 (94%) completed the trial. The primary outcome occurred in 139 of 389 patients (36%) in the HES group and 125 of 386 patients (32%) in the saline group (difference, 3.3% [95% CI, -3.3% to 10.0%]; relative risk, 1.10 [95% CI, 0.91-1.34]; P = .33). Among 12 prespecified secondary outcomes reported, 11 showed no significant difference, but a statistically significant difference was found in median volume of study fluid administered on day 1: 1250 mL (interquartile range, 750-2000 mL) in the HES group and 1500 mL (interquartile range, 750-2150 mL) in the saline group (median difference, 250 mL [95% CI, 83-417 mL]; P = .006). At 28 days after surgery, 4.1% and 2.3% of patients had died in the HES and saline groups, respectively (difference, 1.8% [95% CI, -0.7% to 4.3%]; relative risk, 1.76 [95% CI, 0.79-3.94]; P = .17). Conclusions and Relevance: Among patients at risk of postoperative kidney injury undergoing major abdominal surgery, use of HES for volume replacement therapy compared with 0.9% saline resulted in no significant difference in a composite outcome of death or major postoperative complications within 14 days after surgery. These findings do not support the use of HES for volume replacement therapy in such patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02502773.

Shedding light on perioperative hemodynamic monitoring.

Given the number of clinical studies and meta-analyses investigating the impact of cardiac output-guided hemodynamic management on the postoperative outcome of patients undergoing high-risk surgery, clinicians should already have a fair idea of the clinical and economic benefits. However, this is still a matter of debate, there are still large outcome studies going on, and surveys and audits have shown that clinical adoption remains low. Rational patient selection, more affordable monitoring solutions, and the personalization of therapeutic strategies are desirable to ensure that cardiac output monitoring adds value and becomes part of the routine anesthesia management of high-risk surgical patients.

Monitoring tissue perfusion: a pilot clinical feasibility and safety study of a urethral photoplethysmography-derived perfusion device in high-risk patients.

Continuous monitoring of tissue perfusion in patients with hemodynamic instability remains challenging because of the lack of tools available. Through using urethral photoplethysmography, the urethral perfusion index (uPI) could allow tissue perfusion monitoring through a modified urinary catheter. The first objective of our study was to evaluate the feasibility and safety of the IKORUS UP (Advanced Perfusion Diagnostics, Villeurbanne, France), a new device in the field. The secondary objectives were to evaluate the performance (duration and signal quality) of the IKORUS UP probe and to assess the uPI variations during hemodynamic events during major abdominal surgery. "STEP UP" was a prospective, multicenter, observational study. The inclusion criteria were age 18 years or older with signed informed consent and admitted to intensive care unit (ICU) with hemodynamic instability or high-risk surgical patient. Thirty patients were included in the study, 26 in the operating room, and four in the ICU. Of these patients, 28 were analyzed. For the primary outcome, six (21%) patients had pain scores assessed at insertion of and 22 (79%) at withdrawal of the catheter. The mean EVA score was 1.5 (IQ 1-2) and 0.7 (IQ 0-1), respectively, with the highest score being 3. One (4%) minor urethral bleeding and one (4%) catheter-associated urinary tract infection were reported. The IKORUS UP probe remained in the urethra for an average of 172 h (IQ40-328). The median signal measurement time was 33 h (IQ 5.2-46). The signal quality was recorded as good or excellent for 99% (IQ 82-100) of the insertion duration. The signal quality index was 93% (IQ 87-96) with a signal-to-noise ratio of 26 (IQ 21-36). We observed clinically relevant variations in the uPI over time during hemodynamic events or therapeutic interventions, with a strong cross-correlation with macrohemodynamic variables in some patients, while others did not display macrohemodynamic changes. The IKORUS UP probe was well tolerated and allowed urethral perfusion monitoring. Clinically relevant changes in tissue perfusion could be recorded during the observational period. Trial Registration: ( www.clinicaltrials.gov NCT03410069) registered January 25, 2018.

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial.

BACKGROUND: Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients. METHODS: We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253. FINDINGS: Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported. INTERPRETATION: In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury. FUNDING: French Ministry of Health and the Société Française d'Anesthésie Réanimation.

Lung-protective ventilation for the surgical patient: international expert panel-based consensus recommendations.

Postoperative pulmonary complications (PPCs) occur frequently and are associated with substantial morbidity and mortality. Evidence suggests that reduction of PPCs can be accomplished by using lung-protective ventilation strategies intraoperatively, but a consensus on perioperative management has not been established. We sought to determine recommendations for lung protection for the surgical patient at an international consensus development conference. Seven experts produced 24 questions concerning preoperative assessment and intraoperative mechanical ventilation for patients at risk of developing PPCs. Six researchers assessed the literature using questions as a framework for their review. The modified Delphi method was utilised by a team of experts to produce recommendations and statements from study questions. An expert consensus was reached for 22 recommendations and four statements. The following are the highlights: (i) a dedicated score should be used for preoperative pulmonary risk evaluation; and (ii) an individualised mechanical ventilation may improve the mechanics of breathing and respiratory function, and prevent PPCs. The ventilator should initially be set to a tidal volume of 6-8 ml kg-1 predicted body weight and positive end-expiratory pressure (PEEP) 5 cm H2O. PEEP should be individualised thereafter. When recruitment manoeuvres are performed, the lowest effective pressure and shortest effective time or fewest number of breaths should be used.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

Cardiac Arrest and Mortality Related to Intubation Procedure in Critically Ill Adult Patients: A Multicenter Cohort Study.

OBJECTIVES: To determine the prevalence of and risk factors for cardiac arrest during intubation in ICU, as well as the association of ICU intubation-related cardiac arrest with 28-day mortality. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Sixty-four French ICUs. PATIENTS: Critically ill patients requiring intubation in the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the 1,847 intubation procedures included, 49 cardiac arrests (2.7%) occurred, including 14 without return of spontaneous circulation (28.6%) and 35 with return of spontaneous circulation (71.4%). In multivariate analysis, the main predictors of intubation-related cardiac arrest were arterial hypotension (systolic blood pressure < 90 mm Hg) prior to intubation (odds ratio = 3.406 [1.797-6.454]; p = 0.0002), hypoxemia prior to intubation (odds ratio = 3.991 [2.101-7.583]; p < 0.0001), absence of preoxygenation (odds ratio = 3.584 [1.287-9.985]; p = 0.0146), overweight/obesity (body mass index > 25 kg/m; odds ratio = 2.005 [1.017-3.951]; p = 0.0445), and age more than 75 years old (odds ratio = 2.251 [1.080-4.678]; p = 0.0297). Overall 28-day mortality rate was 31.2% (577/1,847) and was significantly higher in patients who experienced intubation-related cardiac arrest than in noncardiac arrest patients (73.5% vs 30.1%; p < 0.001). After multivariate analysis, intubation-related cardiac arrest was an independent risk factor for 28-day mortality (hazard ratio = 3.9 [2.4-6.3]; p < 0.0001). CONCLUSIONS: ICU intubation-related cardiac arrest occurs in one of 40 procedures with high immediate and 28-day mortality. We identified five independent risk factors for cardiac arrest, three of which are modifiable, possibly to decrease intubation-related cardiac arrest prevalence and 28-day ICU mortality.

Personalization of arterial pressure in the perioperative period.

PURPOSE OF REVIEW: This review aims to discuss recent findings on the relationship between intraoperative arterial hypotension and organ dysfunction in surgical patients and examines the available evidence for personalizing blood pressure (BP) management as a strategy to improve patient outcome. RECENT FINDINGS: Hypotension contributes to oxygen supply-demand mismatch and may cause an ischemia-reperfusion injury which may manifest as organ dysfunction. Evidence is accumulating suggesting that hypotension is associated with acute postoperative myocardial and kidney injury, and increased risk of mortality in surgical patients. In contrast to traditional BP management in which BP targets are empirically chosen, personalized BP management aims at individualizing BP targets according to individual patient physiology considering clinical conditions that may influence organ pressure-flow autoregulation. Recent randomized data provide clinically meaningful findings that a treatment strategy aims at targeting individualized BP values which may help improving outcome in surgical patients. SUMMARY: Hypotension is a common complication in surgical patients and is an important trigger of organ injury in surgical patients. Personalized BP management may contribute at reducing postoperative organ dysfunction in surgical patients.