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.

Environmental sustainability in obstetrics and gynaecology: A systematic review.

BACKGROUND: The healthcare sector is responsible for 4%-10% of global greenhouse gas emissions. Considering the broad range of care that obstetricians and gynaecologists provide, mitigation strategies within this specialty could result in significant reductions of the environmental footprint across the whole healthcare industry. OBJECTIVES: The aim of this review was to identify for what services, procedures and products within obstetric and gynaecological care the environmental impact has been studied, to assess the magnitude of such impact and to identify mitigation strategies to diminish it. SEARCH STRATEGY: The search strategy combined terms related to environmental impact, sustainability, climate change or carbon footprint, with the field of obstetrics and gynaecology. SELECTION CRITERIA: Articles reporting on the environmental impact of any service, procedure or product within the field of obstetrics and gynaecology were included. Included outcomes covered midpoint impact categories, CO2 emissions, waste generation and energy consumption. DATA COLLECTION AND ANALYSIS: A systematic literature search was conducted in the databases of MEDLINE (Ovid), Embase (Ovid) and Scopus, and a grey literature search was performed on Google Scholar and two websites of gynaecological associations. MAIN RESULTS: The scope of the investigated studies encompassed vaginal births, obstetric and gynaecological surgical procedures, menstrual products, vaginal specula and transportation to gynaecological oncologic consultations. Among the highest yielding mitigation strategies were displacing disposable with reusable materials and minimising content of surgical custom packs. The lowest yielding mitigation strategy was waste optimisation, including recycling. CONCLUSIONS: This systematic review highlights opportunities for obstetricians and gynaecologists to decrease their environmental footprint in many ways. More high-quality studies are needed to investigate the environmental impact of other aspects of women's and reproductive health care.

Environmental Impact Assessment of Reusable and Disposable Surgical Head Covers.

This life cycle assessment compares the environmental footprint of reusable surgical head covers with single-use disposable surgical head covers.

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.

Dynamic cerebral autoregulation during step-wise increases in blood pressure during anaesthesia: A nonrandomised interventional trial.

BACKGROUND: Classically, cerebral autoregulation (CA) entails cerebral blood flow (CBF) remaining constant by cerebrovascular tone adapting to fluctuations in mean arterial pressure (MAP) between ∼60 and ∼150 mmHg. However, this is not an on-off mechanism; previous work has suggested that vasomotor tone is proportionally related to CA function. During propofol-based anaesthesia, there is cerebrovascular vasoconstriction, and static CA remains intact. Sevoflurane-based anaesthesia induces cerebral vasodilation and attenuates CA dose-dependently. It is unclear how this translates to dynamic CA across a range of blood pressures in the autoregulatory range. OBJECTIVE: The aim of this study was to quantify the effect of step-wise increases in MAP between 60 and 100 mmHg, using phenylephrine, on dynamic CA during propofol- and sevoflurane-based anaesthesia. DESIGN: A nonrandomised interventional trial. SETTING: Single centre enrolment started on 11 January 2019 and ended on 23 September 2019. PATIENTS: We studied American Society of Anesthesiologists (ASA) I/II patients undergoing noncardiothoracic, nonneurosurgical and nonlaparoscopic surgery under general anaesthesia. INTERVENTION: In this study, cerebrovascular tone was manipulated in the autoregulatory range by increasing MAP step-wise using phenylephrine in patients receiving either propofol- or sevoflurane-based anaesthesia. MAP and mean middle cerebral artery blood velocity (MCA Vmean ) were measured in ASA I and II patients, anaesthetised with either propofol ( n  = 26) or sevoflurane ( n  = 28), during 10 mmHg step-wise increments of MAP between 60 and 100 mmHg. Static CA was determined by plotting 2-min averaged MCA Vmean versus MAP. Dynamic CA was determined using transfer function analysis and expressed as the phase lead (°) between MAP and MCA Vmean oscillations, created with positive pressure ventilation with a frequency of 6 min -1 . MAIN OUTCOMES: The primary outcome of this study was the response of dynamic CA during step-wise increases in MAP during propofol- and sevoflurane-based anaesthesia. RESULTS: MAP levels achieved per step-wise increments were comparable between anaesthesia regiment (63 ±â€Š3, 72 ±â€Š2, 80 ±â€Š2, 90 ±â€Š2, 100 ±â€Š3 mmHg, and 61 ±â€Š4, 71 ±â€Š2, 80 ±â€Š2, 89 ±â€Š2, 98 ±â€Š4 mmHg for propofol and sevoflurane, respectively). MCA Vmean increased more during step-wise MAP increments for sevoflurane compared to propofol ( P ≤0.001). Dynamic CA improved during propofol (0.73° mmHg -1 , 95% CI 0.51 to 0.95; P  ≤ 0.001)) and less pronounced during sevoflurane-based anaesthesia (0.21°â€ŠmmHg -1 (95% CI 0.01 to 0.42, P  = 0.04). CONCLUSIONS: During general anaesthesia, dynamic CA is dependent on MAP, also within the autoregulatory range. This phenomenon was more pronounced during propofol anaesthesia than during sevoflurane. TRIAL REGISTRATION: NCT03816072 ( https://clinicaltrials.gov/ct2/show/NCT03816072 ).

The Influence of Carbon Dioxide on Cerebral Autoregulation During Sevoflurane-based Anesthesia in Patients With Type 2 Diabetes.

BACKGROUND: Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO 2 ) (cerebrovascular CO 2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO 2 reactivity and the CA-CO 2 relationship. METHODS: We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO 2 , blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia. RESULTS: In both control and DM patients, awake CO 2 reactivity was smaller (2.8%/mm Hg CO 2 ) than during sevoflurane anesthesia (3.9%/mm Hg; P <0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO 2 ) in controls than in DM patients (1.8 deg./mm Hg CO 2 ; P <0.001) in both awake and sevoflurane-anesthetized states. CONCLUSIONS: The CA-CO 2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects.

An evidence-based roadmap to integrate planetary health education into the medical curriculum.

The urgency for action on climate change is regarded as the defining issue of our time. Planetary health education prepares future healthcare professionals to promote the health of the planet, including sustainable healthcare. This has potential benefits for the healthcare system, patients, community, and the environment. However, many educators are not confident in explaining and inspiring students and many deans and educational staff report challenges when integrating planetary health into education. The roadmap presented in this paper uses evidence from medical education literature to support medical schools with implementing this type of education. The roadmap can be used as a guide for educators, university leadership, and policy-makers in the design of planetary health education.

Reprocessing Zamak laryngoscope blades into new instrument parts; an 'all-in-one' experimental study.

Introduction: Disposable instruments in healthcare have led to a significant increase of medical waste. The aim of this study is to validate the recycling of disposable Zamak laryngoscope blades into new medical components by using a new 'all-in-one' affordable reprocessing setup as alternative for die-casting. Methods: A n "all-in-one" casting set-up was designed and built. Laryngoscope blades, recovered from two hospitals, were disinfected, melted and cast into dog-bones and into new instrument parts. The quality of the cast material was evaluated using X-ray fluorescence spectrometry. The mechanical properties were obtained by assessing the Ultimate Tensile Strength (UTS) and tensile tests. Results: A recovery of 93 % Zamak was obtained using a melting temperature of 420 °C for 3 h. The XRF Spectro data showed higher Zinc and silicon concentrations when compared with Virgin Zamak. The dog-bones tests resulted in an average UTS, Yield Strength (YS) and Young's Modulus (YM) of 236 ± 61 (MPa), 70 ± 43 and 9 ± 3, respectively, representing 82 %, 103 % and 64 % of the UTS, YS and YM of standard Zamak. Functional instrument parts with extensions and inner chambers were cast with a maximal shrinkage percentage of 1 ± 1 %. Discussion: This study demonstrates that the created "all-in-one" reprocessing method can process contaminated disposable Zamak laryngoscope blades into new raw base material and new instrument parts. Although material and surface properties can deteriorate, reprocessed Zamak still has sufficient mechanical properties and can be used to cast complex parts with sufficient dimensional tolerances and minimal shrinkage. Conclusion: A micro reprocessing method was designed and used to turn disposed laryngoscope blades into new basis material and semi-finished components. Follow up studies are needed to scale and optimize this process towards a functional alternative for die casting. It should be further investigated how this process can contribute to further medical waste reduction and a circular healthcare economy.

Pro-Con Debate: The Clinical (Ir)relevance of the Lower Limit of Cerebral Autoregulation for Anesthesiologists.

In this Pro-Con commentary article, we discuss whether the lower limit of cerebral autoregulation is clinically relevant for anesthesiologists. The central question regarding this issue is whether mean arterial blood pressure below the lower limit of autoregulation is detrimental for the brain. The Pro side argues that continuous monitoring of cerebral autoregulation has revealed an association between going below the lower limit and mortality in the critically ill patient. Conversely, the Con side argues that cerebral autoregulation is only one of various defense mechanisms of the brain that protect against cerebral hypoperfusion, and that cerebral autoregulation may be more important to protect against intracranial hypertension.

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.

Cerebral hemodynamics during sustained intraoperative hypotension.

Static cerebral autoregulation (CA) maintains cerebral blood flow (CBF) relatively constant above a mean arterial blood pressure (BPmean) of 60-65 mmHg. Below this lower limit of CA (LLCA), CBF declines along with BPmean. Data are lacking in describing how CA reacts to sustained hypotension since hypotension is usually avoided. In this study, we took advantage of a procedure requiring sustained hypotension. We assessed static CA for LLCA determination, and a more continuous CA, which counters short-term blood pressure variations. With these data, we analyzed CA during longstanding hypotension. Continuous arterial blood pressure and middle cerebral artery blood flow velocity (MCAVmean) were monitored in 23 patients that required deep intraoperative hypotension. The LLCA was determined for every patient, and BPmean below this LLCA was classified as the patient-specific hypotension. With the mean flow index (Mxa), continuous CA (Mxa-CA) was quantified. Mxa was calculated and averaged after induction of general anesthesia (baseline), every 15 min during, and 15 min after 1 h of hypotension. Functioning CA was defined as Mxa < 0.4. Data are expressed as median (25th-75th percentile). The LLCA was located at 56 (47-74) mmHg. At baseline, Mxa was 0.21 (0.14-0.32) and 0.61 (0.48-0.78) during hypotension (P < 0.01), with no appreciable change over time, n = 12. After blood pressure restoration, Mxa improved, 0.25 (0.06-0.35, n = 9). Mxa-CA became and remained disturbed during the 1 h of hypotension, and improved after blood pressure restoration. This completely reversible situation suggests no ischemic hyperemia occurs and renders an adaptation mechanism during sustained hypotension unlikely.NEW & NOTEWORTHY Intraoperative hypotension is normally avoided by anesthesiologists. However, for the Personalized External Aortic Root Support (PEARS) procedure, deep-induced hypotension is an essential requirement for the surgeon to be able to manipulate the aortic root. In this procedure, blood pressure and middle cerebral artery blood flow velocity were monitored. In this study, we assessed cerebral autoregulation during sustained hypotension, to give an insight into its behavior during hypotension.

Impact of surgery and anesthesia during early brain development: A perfect storm.

Neonatal surgery and concomitant anesthesia coincide with a timeframe of rapid brain development. The speed and complexity of early brain development superimposed on immature regulatory mechanisms that include incomplete cerebral autoregulation, insufficient free radical scavenging and an immature immune response puts the brain at risk. Brain injury may have long-term consequences for multiple functional domains including cognition, learning skills, and behavior. Neurodevelopmental follow-up studies have noted mild-to-moderate deficits in children who underwent major neonatal surgery and related anesthesia. The present review evaluates neonatal surgery against the background of neurobiological processes that unfold at a pace unparalleled by any other period of human brain development. First, a structured summary of early brain development is provided in order to establish theoretical groundwork. Next, literature on brain injury and neurodevelopmental outcome after neonatal surgery is discussed. Special attention is given to recent findings of structural brain damage reported after neonatal surgery. Notably, high-quality imaging data acquired before surgery are currently lacking. Third, mechanisms of injury are interrogated taking the perspective of early brain development into account. We propose a novel disease model that constitutes a triad of inflammation, vascular immaturity, and neurotoxicity of prolonged exposure to anesthetic drugs. With each of these components exacerbating the other, this amalgam incites the perfect storm, resulting in brain injury. When examining the brain, it seems intuitive to distinguish between neonates (i.e., <60 postconceptional weeks) and more mature infants, multiple and/or prolonged anesthesia exposure and single, short surgery. This review culminates in an outline of anesthetic considerations and future directions that we believe will help move the field forward.

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.