Acta Anaesthesiologica Scandinavica最新文献

Background: Peripheral nerve blocks (PNBs) are a cornerstone in postoperative pain management, reducing pain, opioid consumption, and opioid-related adverse effects. However, the duration of PNBs is limited and might result in rebound pain after block cessation. Dexamethasone, a synthetic glucocorticoid, when administered in addition to PNBs, prolongs block duration and might mitigate rebound pain. We assessed the effect of adjunct dexamethasone on pain after block cessation and rebound pain.

Methods: This is a substudy pooling data from two randomised, placebo-controlled three-arm clinical trials conducted between June 9, 2022 and May 17, 2023. Participants underwent osseous surgery of either the lower or upper limb under peripheral nerve block. Participants were allocated to dexamethasone (12 mg oral, 24 mg oral, or 12 mg intravenous) or placebo (oral or intravenous). The primary outcome was pain immediately after block cessation (Numerical Rating Scale, NRS, 0 to 10) and rebound pain (NRS ≥ 7 immediately after block cessation).

Results: Data from 159 participants were included. Fifty-six participants received placebo and 103 participants received dexamethasone. The median pain score after block cessation was 5.0 points (IQR 3.0 to 8.0) in the placebo group and 3.0 points (IQR 1.0 to 6.0) in the dexamethasone group. Rebound pain occurred in 20 of 56 participants (35.7%) in the placebo group and in 19 out of 103 participants (18.4%) in the dexamethasone group. Dexamethasone significantly reduced pain after block cessation (mean difference: -1.7 points, 95% CI: -2.6 to -0.8, p < 0.001) and the risk of rebound pain (risk ratio: 0.51, 95% CI: 0.30 to 0.88, p = 0.014) when compared to placebo. We found no association between patient satisfaction and rebound pain. However, the satisfaction measure exhibited a ceiling effect with most participants reporting maximum satisfaction and therefore the ability to detect a difference may have been limited.

Conclusions: Dexamethasone reduced pain after block cessation and the risk of rebound pain when compared with placebo.

Editorial comment: This study combined data from two randomised controlled trials, which included patients who underwent osseous surgery on either the upper or lower limb under peripheral nerve block. The trials investigated rebound pain and patient satisfaction. When administered intravenously or orally, dexamethasone reduces pain after block cessation and the occurrence of rebound pain. No significant difference in satisfaction scores was found between patients who received systemic dexamethasone and those who received a placebo.

Background: Surgical stress response initiates a complex pathophysiological cascade that alters fluid distribution and intravascular volume. In elective total hip arthroplasty (THA), the perioperative blood loss is potentially substantial, a significant part of the loss being hidden caused by tissue extravasation, residual joint blood, and hemolysis. This far conventional methods to quantify blood loss rely on either visual estimation of bleeding or formulas based on hematological and/or anthropometric parameters, both of which are considered imprecise. Accurate assessment of perioperative blood volume changes may inform more individualized postoperative fluid therapy and improve postoperative outcomes.

Methods: The study design is a single-center prospective observational cohort study with enrollment of 25 patients undergoing elective THA in a standardized fast-track setting. Perioperative blood volume will be assessed using the carbon monoxide (CO)-rebreathing method, enabling quantification of total hemoglobin mass, red cell-, plasma-, and total blood volume. Bioimpedance spectroscopy will be used to evaluate fluid distribution between intra- and extracellular compartments, as well as total body water. Measurements will be performed preoperatively before surgery (baseline), at 6 h postoperatively, and at 24 h postoperatively when feasible. Demographic data, inflammatory markers, and data on perioperative fluid administration will also be collected. The primary outcome is change in total blood volume from baseline to 6 h postoperatively. Secondary outcomes include changes in hemoglobin mass, fluid compartment shifts, and their associations with postoperative orthostatic intolerance.

Discussion: By combining CO rebreathing and bioimpedance, our study applies accurate, minimally invasive methods not previously used in surgical patients to characterize blood loss and perioperative fluid shifts. Strengths include the standardized surgical setting, detailed protocol, and transparent statistical plan, whereas limitations include the observational design, minor sample size, and exclusion of patients with major intraoperative bleeding.

Conclusion: The study will provide detailed information on the changes in perioperative blood volume and its association with orthostatic intolerance following THA. CO rebreathing may offer a precise alternative to conventional estimations of blood loss and contribute to the development of more individualized perioperative fluid management strategies in major orthopedic surgery.

Background: Feeding intolerance is common in intensive care unit (ICU) patients, but evidence supporting prokinetic use is limited. We aimed to provide international epidemiological data on the use of prokinetic agents in adult ICU patients and to explore potential associations with patient-important outcomes.

Methods: We conducted an inception cohort study between August 2024 and March 2025 in acutely admitted ICU patients in 56 ICUs across 11 countries. The primary outcome was the proportion of patients receiving prokinetic agents. Secondary outcomes included associations with baseline characteristics, serious adverse events (SAEs), days alive out of ICU/hospital, days alive without life support and 90-day mortality. Associations with SAEs, baseline characteristics and mortality were assessed using pre-specified Cox regression models, while other secondary outcomes were evaluated using adjusted linear regression. All models were adjusted for country, severity of illness, number of comorbidities, surgery and ICU admission type.

Results: Among 1440 ICU patients (median age 64 years, 56.9% male), 187 (13.0%; 95% confidence interval [CI] 11.3-14.8) received prokinetic agents during ICU stay, most commonly metoclopramide (65%). Prior abdominal surgery was associated with the initiation of prokinetic agents (hazard ratio [HR] 1.81; 95% CI 1.17-2.79). Use of prokinetic agents was statistically significantly associated with a higher hazard of experiencing a SAE (HR 1.9; 95% CI 1.3-2.8), fewer days alive out of ICU (mean difference [MD] -7.6 days; 95% CI, -13.4 to -2.2) and hospital (-13.5 days; 95% CI -18.7 to -8.4), but not with 90-day mortality (HR 0.62; 95% CI 0.3-1.2).

Conclusions: Prokinetic agents were used in 13% of ICU patients, most commonly metoclopramide and more often in those with prior abdominal surgery. Prokinetic use was associated with a higher hazard of experiencing SAEs and fewer days alive out of hospital/ICU.

Background: Intermediate-high risk pulmonary embolism (PE) represents a clinically challenging subgroup of acute PE, characterized by right ventricular dysfunction and increased risk of hemodynamic deterioration despite treatment with anticoagulation therapy. Although systemic thrombolysis may provide more rapid reperfusion, its use is limited by an increased risk of major bleeding. Catheter-based treatment strategies have emerged as potential alternatives, but their comparative efficacy and safety remain uncertain.

Objective: To assess the benefits and harms of catheter-based treatment strategies compared with contemporary control regimens, including standard anticoagulation with or without systemic thrombolysis, in patients with intermediate-high risk PE.

Methods: This protocol outlines a systematic review with Bayesian pairwise meta-analysis and network meta-analysis of randomized clinical trials evaluating catheter-based therapies for hospitalized patients with intermediate-high risk PE. Eligible interventions include catheter-directed thrombolysis, ultrasound-assisted thrombolysis, and catheter-based embolectomy. Comparators may include standard anticoagulation alone or in combination with systemic thrombolysis or other active control regimens reflecting standard of care. Searches will be conducted in relevant databases, supplemented by trial registries. Two reviewers will independently screen studies, extract data, and assess risk of bias using the Cochrane Risk of Bias 2 tool. Bayesian pairwise meta-analyses and network meta-analysis will be performed using weakly informative priors to synthesize direct and indirect evidence across interventions. Results will be reported as posterior effect estimates with 95% credible intervals. The primary outcome will be all-cause mortality. Secondary and exploratory outcomes include major bleeding as defined according to the criteria of the International Society on Thrombosis and Haemostasis within 7 days, hospital length of stay, and change in RV/LV ratio within 48 h. GRADE assessments will be performed where applicable.

Discussion: This review will synthesize direct and indirect randomized evidence on catheter-based treatment strategies for intermediate-high risk PE. The findings may help clarify the role of these interventions in contemporary management, inform future guideline recommendations, and identify persistent evidence gaps requiring further large-scale randomized trials.

Background: Pediatric in-hospital cardiac arrest is a rare event. Despite Sweden's extensive national health registries, data describing pediatric in-hospital cardiac arrest are limited. In 2018, pediatric-specific variables were introduced into the Swedish Registry for Cardiopulmonary Resuscitation. This study aimed to identify the characteristics and outcomes of pediatric IHCA at a Swedish tertiary pediatric referral hospital following implementation of these variables.

Methods: This observational cohort study included all pediatric in-hospital cardiac arrest events with initiated cardiopulmonary resuscitation (CPR) recorded at Queen Silvia Children's Hospital between 2018 and 2025. Demographic characteristics, arrest location, resuscitation variables, and survival outcomes were analyzed. Survival was assessed using Kaplan-Meier methods and Cox proportional hazard regression.

Results: A total of 125 in-hospital cardiac arrest events were included. Infants (< 1 year) represented 65.6% of cases and 57% of patients had congenital heart disease. Most arrests occurred in the intensive care unit (56.8%), followed by hospital wards (21.6%) and the operating room (16.0%). CPR was initiated within the first minute in 81.3% of cases. Return of spontaneous circulation was achieved in 90% of patients. Survival was 82% at 30 days and 68% at 1 year.

Conclusions: Pediatric in-hospital cardiac arrest occurring in highly monitored tertiary care environments has a very high rate of return of spontaneous circulation as well as survival. This study also highlights the importance of systematic registry data collection to improve understanding of pediatric in-hospital cardiac arrest and to support future benchmarking and quality improvement.

Editorial comment: In-hospital cardiac arrest is rare for pediatric patients. This retrospective cohort analysis, from one tertiary care pediatric hospital which includes a large pediatric cardiac surgery activity, presents pediatric cardiac arrest events in the hospital, along with case factors.

Background: Delirium is a frequent complication in comatose Out-of-Hospital Cardiac Arrest (OHCA) survivors requiring postresuscitation intensive care and is associated with higher mortality and longer hospitalization. Despite this, there is no established pharmacologic strategy for delirium prevention in OHCA survivors. This trial aims to evaluate if prophylactic use of olanzapine in comatose OHCA patients can reduce delirium incidence, thereby leading to a shorter duration of hospitalization.

Methods: The Danish Out-of-Hospital Cardiac Arrest (DANOCHA) trial is an investigator-initiated, multicenter, randomized, controlled trial evaluating four postresuscitation interventions in adult patients resuscitated after OHCA including administration of prophylactic olanzapine compared with placebo. Comatose adult patients with OHCA of presumed cardiac cause and sustained return of spontaneous circulation (> 20 min) will be randomized 1:1 to receive either 10 mg of olanzapine or placebo immediately after inclusion in the trial and the two following evenings for a total of three doses. The primary outcome is days alive and out of the hospital within 30 days after admission. Analysis of primary outcome will be analyzed using the Wilcoxon rank-sum test. Results will be presented as medians with interquartile ranges and 95% confidence intervals for the median difference. Inclusion began in June 2023, and the study aims to include 1000 patients from five sites over an estimated time period of 3-4 years. The trial is registered at clinicaltrials.gov (identifier: NCT05895838) and euclinicaltrials.eu (2024-515997-28-00).

Perspectives: Optimizing postresuscitation care through large-scale randomized trials is essential for improving outcomes of OHCA survivors. The findings from this part of the DANOHCA trial will provide evidence regarding the effects of prophylactic olanzapine in comatose OHCA survivors.

Trial registration: EudraCT no 2016-003265-26; EU CTIS no 2024-515997-28-00; ClinicalTrials.gov identifier NCT05895838.

Background: Post-cardiac arrest care for patients resuscitated from out-of-hospital cardiac arrest (OHCA) includes multiple pharmacological and physiological interventions, yet optimal strategies to reduce post-cardiac arrest syndrome-related morbidity and mortality remain uncertain. The DANOHCA (Danish Out-of-Hospital Cardiac Arrest) trial evaluates four such interventions-high-dose dexamethasone, prophylactic olanzapine, elevated backrest position, and early wakeup-in a factorial trial framework. This manuscript presents the complete statistical analysis plan for analyses common to all four DANOHCA interventions.

Methods: DANOHCA is an investigator-initiated, multicenter, randomized, 2 × 2 × 2 × 2 factorial clinical trial enrolling comatose adult OHCA patients with a presumed cardiac etiology who achieve sustained return of spontaneous circulation, with randomization within 180 min of return of spontaneous circulation. Participants are co-randomized to Dexamethasone versus placebo, olanzapine versus placebo, backrest elevation at 35° versus 5°, and early (≤ 6 h) versus late (28-36 h) wakeup, with pharmacological interventions blinded and physiological interventions open-label. This statistical analysis plan specifies the primary and secondary outcomes, covariate adjustment, handling of missing data, assessments of interactions between interventions, and assumption checks, with all primary analyses conducted according to the intention-to-treat principle. The analysis plan is finalized prior to completion of randomization.

Results: The primary outcomes are 90-day all-cause mortality for the dexamethasone and backrest interventions, and days alive outside hospital within 30 days for the olanzapine and early wakeup interventions, with common secondary and tertiary endpoints including mortality at later time points, neurological function, health-related quality of life, organ function, and safety outcomes. Mixed-effects regression models, Cox regression, stratified nonparametric tests, and prespecified sensitivity analyses will be applied to minimize bias and quantify intervention effects, including their associated uncertainties.

Conclusion: This predefined statistical analysis plan provides a detailed, transparent framework for the primary analyses and reporting of the DANOHCA trial.

Trial registration: Clinical Trials Information System (CTIS): 2024-515997-28-00.

Background: Postoperative complications substantially increase morbidity, mortality and healthcare costs. Understanding prognostic factors is essential for risk stratification, targeted prevention strategies, and development of prediction models.

Objectives: To identify prognostic factors for 18 major postoperative complications in 10 studied domains using the Danish TRIPLE-A database: (1) acute postoperative pain, nausea and vomiting, and need for rescue opioids; (2) persistent opioid use; (3) acute kidney injury; (4) venous thromboembolism; (5) staphylococcal surgical site infection and infections requiring antibiotic treatment; (6) three airway management complications; (7) transfusion requirements; (8) delirium; (9) new-onset postoperative atrial fibrillation; and (10) readmission, reoperation and unplanned ICU admission.

Methods: We will conduct 10 retrospective cohort studies using electronic health record data from 1.2 million surgical procedures performed in the Capital and Zealand Regions of Denmark from 2017 to 2025. Each individual complication will be identified via validated combinations of ICD-10 codes, medication administration, laboratory values, radiology examinations, and free-text mining of clinical notes. Candidate prognostic factors will be selected a priori based on literature review and clinical expertise, and will encompass patient demographics, comorbidities, surgical characteristics, anaesthetic management, vital parameters and biomarkers. We will estimate adjusted associations between candidate prognostic factors and complications using multivariable logistic regression with LASSO penalisation to reduce overfitting. Effect estimates will be reported as odds ratios with 95% confidence intervals, and the relative contribution of predictors will be assessed by changes in model discrimination (Δ-AUC). The approach for surgical procedure, calendar year, and hospital site will be determined for each study (adjustment, stratification, or inclusion as candidate predictors).

Conclusion: These studies aim to validate established prognostic factors and identify novel ones for major postoperative complications, providing a foundation for the development of individualised perioperative risk stratification models.

Background: Hemodynamic management after out-of-hospital cardiac arrest (OHCA) is critical, yet the impact of vasopressor-driven mean arterial pressure (MAP) targets on pulmonary circulation and right ventricular (RV) function remains unclear.

Methods: In this substudy of the randomized, double-blinded BOX trial, comatose OHCA survivors were allocated to low (63 mmHg) or high (77 mmHg) MAP targets. Pulmonary artery catheters (PAC) were used for serial hemodynamic assessment for 48 h after Intensive Care Unit admission. The primary endpoint was calculated pulmonary vascular resistance (PVR), secondary endpoints included pulmonary capillary wedge pressure (PCWP), pulmonary artery pulsatility index (PAPi), and RV cardiac power output (RV-CPO)-a measurement of RV pumping function.

Results: Among 730 included patients (median time randomization to PAC insertion 1.3 h), mPAP was consistently higher in the high-MAP group (mean difference 1.11-1.71 mmHg, 95% CI range 0.12-2.59). Calculated PVR was transiently lower in the high-MAP group during the first 24 h (mean difference -0.16 to -0.30, 95% CI range -0.31 to 0.11), before converging between groups. RV-CPO was lower in the low-MAP group throughout the observation period (mean difference 0.01-0.04 W [95% range 0.00-0.07], with the largest difference at 48 h. PCWP decreased in both groups but was significantly lower in the low-MAP group during the first 12 h (mean difference 1.06-1.40 mmHg, 95% CI range 0.25-2.38).

Conclusions: In comatose OHCA survivors, targeting a higher MAP increased pulmonary artery pressures, PCWP, RV-CPO, heart rate, and cardiac output. The proportionally greater increase in cardiac output over pulmonary artery pressures resulted in a decreased calculated PVR.

Trial registration: ClinicalTrials.gov identifier: NCT03141099.

Editorial comment: In this secondary analysis of a subgroup in the BOX out of hospital cardiac arrest treatment trial for oxygen level targets, blood pressure treatment target levels, higher or lower were analyzed, including central circulatory outcomes, using a pulmonary artery catheter. The higher blood pressure target group had accompanying higher pulmonary artery pressures and cardiac output, with initially a small reduction in calculated pulmonary vascular resistance.