Mortality and morbidity after total intravenous anaesthesia versus inhalational anaesthesia: a systematic review and meta-analysis.

Background: General anaesthesia is provided to more than 300 million surgical patients worldwide, every year. It is administered either through total intravenous anaesthesia, using only intravenous agents, or through inhalational anaesthesia, using volatile anaesthetic agents. The debate on how this affects postoperative patient outcome is ongoing, despite an abundance of published trials. The relevance of this topic has grown by the increasing concern about the contribution of anaesthetic gases to the environmental impact of surgery. We aimed to summarise all available evidence on relevant patient outcomes with total intravenous anaesthesia versus inhalational anaesthesia. Methods: In this systematic review and meta-analysis, we searched PubMed/Medline, Embase and Cochrane Central Register of Controlled trials for works published from January 1, 1985 to August 1, 2023 for randomised controlled trials comparing total intravenous anaesthesia using propofol versus inhalational anaesthesia using the volatile anaesthetics sevoflurane, desflurane or isoflurane. Two reviewers independently screened titles, abstracts and full text articles, and assessed risk of bias using the Cochrane Collaboration tool. Outcomes were derived from a recent series of publications on consensus definitions for Standardised Endpoints for Perioperative trials (StEP). Primary outcomes covered mortality and organ-related morbidity. Secondary outcomes were related to anaesthetic and surgical morbidity. This study is registered with PROSPERO (CRD42023430492). Findings: We included 317 randomised controlled trials, comprising 51,107 patients. No difference between total intravenous and inhalational anaesthesia was seen in the primary outcomes of in-hospital mortality (RR 1.05, 95% CI 0.67-1.66, 27 trials, 3846 patients), 30-day mortality (RR 0.97, 95% CI 0.70-1.36, 23 trials, 9667 patients) and one-year mortality (RR 1.14, 95% CI 0.88-1.48, 13 trials, 9317 patients). Organ-related morbidity was similar between groups except for the subgroup of elderly patients, in which total intravenous anaesthesia was associated with a lower incidence of postoperative cognitive dysfunction (RR 0.62, 95% CI 0.40-0.97, 11 trials, 3834 patients) and a better score on postoperative cognitive dysfunction tests (standardised mean difference 1.68, 95% CI 0.47-2.88, 9 trials, 4917 patients). In the secondary outcomes, total intravenous anaesthesia resulted in a lower incidence of postoperative nausea and vomiting (RR 0.61, 95% CI 0.56-0.67, 145 trials, 23,172 patients), less emergence delirium (RR 0.40, 95% CI 0.29-0.56, 32 trials, 4203 patients) and a higher quality of recovery score (QoR-40 mean difference 6.45, 95% CI 3.64-9.25, 17 trials, 1835 patients). Interpretation: The results indicate that postoperative mortality and organ-related morbidity was similar for intravenous and inhalational anaesthesia. Total intravenous anaesthesia offered advantages in postoperative recovery. Funding: Dutch Society for Anaesthesiology (NVA).

Influence of nitrous oxide added to general anaesthesia on postoperative mortality and morbidity: a systematic review and meta-analysis.

BACKGROUND: Nitrous oxide (N2O) is a common adjuvant to general anaesthesia. It is also a potent greenhouse gas and causes ozone depletion. We sought to quantify the influence of N2O as an adjuvant to general anaesthesia on postoperative patient outcomes. METHODS: We searched Medline, EMBASE, and Cochrane Central for works published from inception to July 6, 2023. RCTs comparing general anaesthesia with or without N2O were included. Risk ratios (RRs) and standardised mean differences (SMDs) were calculated, along with 95% confidence intervals (CIs), using a random-effects model. Outcomes were derived from the Standardised Endpoints for Perioperative Medicine (StEP) outcome set. Primary outcomes were mortality and organ-related morbidity, and secondary outcomes were anaesthetic and surgical morbidity. RESULTS: Of 3305 records, 179 full-text articles were assessed, and 71 RCTs, totalling 22 147 patients, were included in the meta-analysis. Addition of N2O to general anaesthesia did not influence postoperative mortality or most morbidity outcomes. N2O increased the incidence of atelectasis (RR 1.62, 95% CI 1.24 to 2.12) and postoperative nausea and vomiting (RR 1.27, 95% CI 1.15 to 1.40), and decreased intraoperative opioid consumption (SMD -0.19, 95% CI -0.35 to -0.04) and time to extubation (MD -2.17 min, 95% CI -3.32 to -1.03 min). CONCLUSIONS: N2O did not influence postoperative mortality or most morbidity outcomes. Considering the environmental effects of N2O, these findings confirm that current policy recommendations to limit its use do not affect patient safety. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42023443287.

Randomized Controlled Trials in ICU in the Four Highest-Impact General Medicine Journals.

OBJECTIVE: To study ICU trials published in the four highest-impact general medicine journals by comparing them with concurrently published non-ICU trials in the same journals. DATA SOURCES: PubMed was searched for randomized controlled trials (RCTs) published between January 2014 and October 2021 in the New England Journal of Medicine , The Lancet , the Journal of the American Medical Association , and the British Medical Journal. STUDY SELECTION: Original RCT publications investigating any type of intervention in any patient population. DATA EXTRACTION: ICU RCTs were defined as RCTs exclusively including patients admitted to the ICU. Year and journal of publication, sample size, study design, funding source, study outcome, type of intervention, Fragility Index (FI), and Fragility Quotient were collected. DATA SYNTHESIS: A total of 2,770 publications were screened. Of 2,431 original RCTs, 132 (5.4%) were ICU RCTs, gradually rising from 4% in 2014 to 7.5% in 2021. ICU RCTs and non-ICU RCTs included a comparable number of patients (634 vs 584, p = 0.528). Notable differences for ICU RCTs were the low occurrence of commercial funding (5% vs 36%, p < 0.001), the low number of RCTs that reached statistical significance (29% vs 65%, p < 0.001), and the low FI when they did reach significance (3 vs 12, p = 0.008). CONCLUSIONS: In the last 8 years, RCTs in ICU medicine made up a meaningful, and growing, portion of RCTs published in high-impact general medicine journals. In comparison with concurrently published RCTs in non-ICU disciplines, statistical significance was rare and often hinged on the outcome events of just a few patients. Increased attention should be paid to realistic expectations of treatment effects when designing ICU RCTs to detect differences in treatment effects that are reliable and clinically relevant.

Statistical robustness of randomized controlled trials in high-impact journals has improved but was low across medical specialties.

OBJECTIVES: To determine whether the statistical fragility of randomized controlled trials (RCTs) in high-impact journals has improved in the last decade and to perform an umbrella review of all published data on the Fragility Index (FI) across medical specialties. STUDY DESIGN AND SETTING: The FI was calculated for all eligible RCTs published from 2014-2021 in the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, the British Medical Journal, and the Annals of Internal Medicine. Trials reporting dichotomous, statistically significant, superiority results were eligible. All previously published systematic reviews on the FI were included in the umbrella review and analyzed by medical (sub) specialty. RESULTS: Of 2,544 screened RCTs, 643 were eligible for the FI analysis. These had a median sample size of 625 (interquartile range [IQR]: 265-2,056), a median FI of 12 (IQR: 3-28), and a median Fragility Quotient of 0.015 (IQR: 0.004-0.045). This is an improvement compared with the median FI of 8 (IQR: 3-18) of RCTs published a decade earlier in the same five journals (P < 0.001). The umbrella review included 57 publications across 15 different medical specialties, with a total of between 10 and 692 RCTs for each specialty. The median FI ranged between two and four for all disciplines. CONCLUSION: In the last decade, the median statistical robustness of RCTs published in high-impact journals has improved, yet the unchanged lower bound of the interquartile range reveals that statistical significance in 25% of trials is still dependent on three or less events. The umbrella review revealed that statistical fragility is prevalent across all medical specialties. The FI is an easy-to-understand metric that can be used to supplement reported P values and help readers look beyond merely reaching statistical significance.

High incidence of outcome switching observed in follow-up publications of randomized controlled trials: Meta-research study.

OBJECTIVES: To determine the incidence of outcome switching in follow-up publications of randomized controlled trials. Outcome switching leads to bias where treatment benefits are more likely to be overestimated or based on chance. STUDY DESIGN AND SETTING: Meta-research study including all follow-up publications 2014-2018 in the New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, and the British Medical Journal. Two independent reviewers compared the primary outcomes of follow-up publications with the original RCT publication and the trial protocol. RESULTS: Seventy-eight follow-up publications were identified. Thirty-one (40%) used different primary outcomes in the follow-up publication compared with the original RCT. In seventeen (55%) of these the outcome switch was neither pre-specified nor explained in the journal publication. The incidence of outcome switching in follow-up studies rose to 70% when preceded by outcome switching in the corresponding initial RCT (P< 0.001). CONCLUSION: In this study, outcome switching occurred in 40% of follow-up publications of previously published RCTs. The majority is neither pre-specified nor explained.

Appreciation of literature by the anaesthetist: A comparison of citations, downloads and Altmetric Attention Score.

BACKGROUND: Different metrics exist to evaluate the impact of a paper. Traditionally, scientific citations are leading, but nowadays new, internet-based, metrics like downloads or Altmetric Attention Score receive increasing attention. We hypothesised a gap between these metrics, reflected by a divergence between scientific and clinical appreciation of anaesthesia literature. METHODS: We collected the top 100 most cited and the top 100 most downloaded articles in Acta Anaesthesiologica Scandinavica (AAS) and Anesthesia & Analgesia (A&A) published between 2014 and 2018. We analysed the relationship between the average number of citations per year, downloads per year and Altmetric Attention Score. RESULTS: For both AAS and A&A, a significant correlation between the 100 most cited articles and their downloads (r = .573 and .603, respectively, P < .001) was found. However, only a poor correlation with Altmetric Attention Score was determined. For the 100 most downloaded articles, download frequency did not correlate with their number of citations (r = .035 and .139 respectively), but did correlate significantly with the Altmetric Attention Score (r = .458 and .354, P < .001). CONCLUSION: Highly cited articles are downloaded more frequently. The most downloaded articles, however, did not receive more citations. In contrast to the most cited articles, more frequently downloaded papers had a higher Altmetric Attention Score. Thus, a 'trending' anaesthesia paper is not a prerequisite for scientific appreciation, reflecting a gap between clinical and scientific appreciation of literature.