The effectiveness of ambulatory continuous popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia in patients undergoing foot or ankle surgery (CAREFREE trial); a randomized, open label, non-inferiority trial.

STUDY OBJECTIVE: Management of pain after foot and ankle surgery remains a concern for patients and healthcare professionals. This study determined the effectiveness of ambulatory continuous popliteal sciatic nerve blockade, compared to standard of care, on overall benefit of analgesia score (OBAS) in patients undergoing foot or ankle surgery. We hypothesized that usage of ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care. DESIGN: Single center, randomized, non-inferiority trial. SETTING: Tertiary hospital in the Netherlands. PATIENTS: Patients were enrolled if ≥18 years and scheduled for elective inpatient foot or ankle surgery. INTERVENTION: Patients were randomized to ambulatory continuous popliteal sciatic nerve blockade or standard of care. MEASUREMENTS: The primary outcome was the difference in OBAS, which includes pain, side effects of analgesics, and patient satisfaction, measured daily from the first to the third day after surgery. A non-inferiority margin of 2 was set as the upper limit for the 90% confidence interval of the difference in OBAS score. Mixed-effects modeling was employed to analyze differences in OBAS scores over time. Secondary outcome was the difference in opioid consumption. MAIN RESULTS: Patients were randomized to standard of care (n = 22), or ambulatory continuous popliteal sciatic nerve blockade (n = 22). Analyzing the first three postoperative days, the OBAS was significantly lower over time in the ambulatory continuous popliteal sciatic nerve blockade group compared to standard of care, demonstrating non-inferiority (-1.9 points, 90% CI -3.1 to -0.7). During the first five postoperative days, patients with ambulatory continuous popliteal sciatic nerve blockade consumed significantly fewer opioids over time compared to standard of care (-8.7 oral morphine milligram equivalents; 95% CI -16.1 to -1.4). CONCLUSIONS: Ambulatory continuous popliteal sciatic nerve blockade is non-inferior to standard of care with single shot popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia.

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.

Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review.

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

Preoperative Glycosylated Haemoglobin Screening to Identify Older Adult Patients with Undiagnosed Diabetes Mellitus-A Retrospective Cohort Study.

More than 25% of older adults in Europe have diabetes mellitus. It is estimated that 45% of patients with diabetes are currently undiagnosed, which is a known risk factor for perioperative morbidity. We investigated whether routine HbA1c screening in older adult patients undergoing surgery would identify patients with undiagnosed diabetes. We included patients aged ≥65 years without a diagnosis of diabetes who visited the preoperative assessment clinic at the Amsterdam University Medical Center and underwent HbA1c screening within three months before surgery. Patients undergoing cardiac surgery were excluded. We assessed the prevalence of undiagnosed diabetes (defined as HbA1c ≥ 48 mmol·mol-1) and prediabetes (HbA1c 39-47 mmol·mol-1). Using a multivariate regression model, we analysed the ability of HbA1c to predict days alive and at home within 30 days after surgery. From January to December 2019, we screened 2015 patients ≥65 years at our clinic. Of these, 697 patients without a diagnosis of diabetes underwent HbA1c screening. The prevalence of undiagnosed diabetes and prediabetes was 3.7% (95%CI 2.5-5.4%) and 42.9% (95%CI 39.2-46.7%), respectively. Preoperative HbA1c was not associated with days alive and at home within 30 days after surgery. In conclusion, we identified a small number of patients with undiagnosed diabetes and a high prevalence of prediabetes based on preoperative HbA1c screening in a cohort of older adults undergoing non-cardiac surgery. The relevance of prediabetes in the perioperative setting is unclear. Screening for HbA1c in older adult patients undergoing non-cardiac surgery does not appear to help predict postoperative outcome.

Chemotherapy-induced peripheral neuropathy models constructed from human induced pluripotent stem cells and directly converted cells: a systematic review.

ABSTRACT: Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for chemotherapy-induced peripheral neuropathy (CIPN) research, resulting in the description of numerous CIPN models constructed from human neurons. This systematic review provides a critical analysis of available models and their methodological considerations (ie, used cell type and source, CIPN induction strategy, and validation method) for prospective researchers aiming to incorporate human in vitro models of CIPN in their research. The search strategy was developed with assistance from a clinical librarian and conducted in MEDLINE (PubMed) and Embase (Ovid) on September 26, 2023. Twenty-six peer-reviewed experimental studies presenting original data about human reprogrammed nonmotor neuron cell culture systems and relevant market available chemotherapeutics drugs were included. Virtually, all recent reports modeled CIPN using nociceptive dorsal root ganglion neurons. Drugs known to cause the highest incidence of CIPN were most used. Furthermore, treatment effects were almost exclusively validated by the acute effects of chemotherapeutics on neurite dynamics and cytotoxicity parameters, enabling the extrapolation of the half-maximal inhibitory concentration for the 4 most used chemotherapeutics. Overall, substantial heterogeneity was observed in the way studies applied chemotherapy and reported their findings. We therefore propose 6 suggestions to improve the clinical relevance and appropriateness of human cellular reprogramming-derived CIPN models.

Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.

Prescriptions and use of glucagon-like peptide-1 (GLP-1) receptor agonists are increasing dramatically, as indications are expanding from the treatment of diabetes mellitus to weight loss for people with obesity. As GLP-1 receptor agonists delay gastric emptying, perioperative healthcare practitioners could be concerned about an increased risk for pulmonary aspiration during general anaesthesia. We summarise relevant medical literature and provide evidence-based recommendations for perioperative care for people taking GLP-1 receptor agonists. GLP-1 receptor agonists delay gastric emptying; however, ongoing treatment attenuates this effect. The risk of aspiration during general anaesthesia is unknown. However, we advise caution in patients who recently commenced on GLP-1 receptor agonists. After over 12 weeks of treatment, standard fasting times likely suffice to manage the risk of pulmonary aspiration for most otherwise low-risk patients.

Different Analgesia Techniques for Postoperative Pain in Children Undergoing Abdominal Surgery for Intractable Constipation: A Retrospective Cohort Study in a Single Tertiary Children's Hospital.

Functional constipation in the pediatric population is a prevalent issue that is usually well managed. However, in rare cases, conservative treatment fails, and surgical intervention is necessary. This retrospective cohort study aimed to describe and compare different perioperative analgesic techniques in children undergoing major abdominal surgery for intractable constipation. Conducted between 2011 and 2021, this study enrolled patients under 18 years old who underwent initial major abdominal surgery for intractable constipation (i.e., creation of ostomy or subtotal colectomy). Patients were categorized according to the perioperative analgesic technique (i.e., systemic, neuraxial, or truncal block). Of 65 patients, 46 (70.8%) were female, and the median age was 13.5 [8.8-16.1] years during initial major abdominal surgery. Systemic analgesia was used in 43 (66.2%), neuraxial in 17 (26.2%), and truncal blocks in 5 (7.7%) of the surgeries. Patients with neuraxial analgesia reported less postoperative pain (median [interquartile range] numeric rating scale (NRS) 2.0 [0-4.0]), compared to systemic analgesia (5.0 [2.0-7.0], p < 0.001) and to truncal blocks (5.0 [3.0-6.5], p < 0.001). In this preliminary investigation, neuraxial analgesia appears to be the most effective approach to reducing acute postoperative pain in pediatric patients undergoing major abdominal surgery for intractable functional constipation. However, well-designed studies are warranted.

Adductor canal block techniques do not lead to involvement of sciatic nerve branches: a radiological cadaveric study.

INTRODUCTION: Low and high volume mid-thigh (ie, distal femoral triangle) and distal adductor canal block approaches are frequently applied for knee surgical procedures. Although these techniques aim to contain the injectate within the adductor canal, spillage into the popliteal fossa has been reported. While in theory this could improve analgesia, it might also result in motor blockade due to coverage of motor branches of the sciatic nerve. This radiological cadaveric study, therefore, investigated the incidence of coverage of sciatic nerve divisions after various adductor canal block techniques. METHODS: Eighteen fresh, unfrozen and unembalmed human cadavers were randomized to receive ultrasound-guided distal femoral triangle or distal adductor canal injections, with 2 mL or 30 mL injectate volume, on both sides (36 blocks in total). The injectate was a 1:10 dilution of contrast medium in local anesthetic. Injectate spread was assessed using whole-body CT with reconstructions in axial, sagittal and coronal planes. RESULTS: No coverage of the sciatic nerve or its main divisions was found. The contrast mixture spread to the popliteal fossa in three of 36 nerve blocks. Contrast reached the saphenous nerve after all injections, whereas the femoral nerve was always spared. CONCLUSIONS: Adductor canal block techniques are unlikely, even when using larger volumes, to block the sciatic nerve, or its main branches. Furthermore, injectate reached the popliteal fossa in a small minority of cases, yet if a clinical analgesic effect is achieved by this mechanism is still unknown.

Analgesia in esophagectomy: a narrative review.

Background and Objective: Optimal pain management for esophagectomy facilitates prevention of postoperative complications such as pneumonia, but also chronic pain. Historically, multimodal intravenous analgesia was employed. In the last decades, regional anesthesia including epidural and paravertebral analgesia is frequently used. In this narrative review, we provide a comprehensive overview of the available evidence for the different analgesia regimens for esophagectomy. Methods: A search was conducted in the PubMed/MEDLINE database in November 2022. Only reports in English or Dutch were included. Editorials or articles lacking full text were excluded. A review of different analgesia regimens after esophagectomy is provided. Key Content and Findings: Epidural analgesia (EA) was suggested to reduce postoperative pneumonia and prevent chronic postsurgical pain (CPSP) as compared to opioid-based systemic analgesia and was considered the gold standard of pain management for esophagectomy. In the last decades, the side-effects of EA became more evident. Next to mild or moderate side-effects such as hypotension and urinary retention, several reports emphasized the incidence of serious neurologic complications to be much higher than estimated before. In addition, minimally invasive surgery fostered that other regional analgesia (RA) techniques are potential alternatives for EA. Paravertebral catheter placement can be performed under videoscope view during the thoracic phase of esophagectomy, making it a safe and easily placed block. Evidence on the effectiveness of erector spinae plane block (ESPB) is limited in this context. Conclusions: Several analgesia regimens after esophagectomy are described. EA is most common, however paravertebral analgesia is a good alternative. Other techniques are also gaining ground but randomized clinical trials are lacking. Future studies should focus on the efficacy of paravertebral and erector spinae blocks for postoperative pain management for esophagectomy.

The Effectiveness of Adductor Canal Block Compared to Femoral Nerve Block on Readiness for Discharge in Patients Undergoing Outpatient Anterior Cruciate Ligament Reconstruction: A Multi-Center Randomized Clinical Trial.

This study evaluated the effect of adductor canal block (ACB) versus femoral nerve block (FNB) on readiness for discharge in patients undergoing outpatient anterior cruciate ligament (ACL) reconstruction. We hypothesized that ACB would provide sufficient pain relief while maintaining motor strength and safety, thus allowing for earlier discharge. This was a randomized, multi-center, superiority trial. From March 2014 to July 2017, patients undergoing ACL reconstruction were enrolled. The primary outcome was the difference in readiness for discharge, defined as Post-Anesthetic Discharge Scoring System score ≥ 9. Twenty-six patients were allocated to FNB and twenty-seven to ACB. No difference in readiness for discharge was found (FNB median 1.8 (95% CI 1.0 to 3.5) vs. ACB 2.9 (1.5 to 4.7) hours, p = 0.3). Motor blocks and (near) falls were more frequently reported in patients with FNB vs. ACB (20 (76.9%) vs. 1 (3.7%), p < 0.001, and 7 (29.2%) vs. 1 (4.0%), p = 0.023. However, less opioids were consumed in the post-anesthesia care unit for FNB (median 3 [0, 21] vs. 15 [12, 42.5] oral morphine milligram equivalents, p = 0.004) for ACB. Between patients with FNB or ACB, no difference concerning readiness for discharge was found. Despite a slight reduction in opioid consumption immediately after surgery, FNB demonstrates a less favorable safety profile compared to ACB, with more motor blocks and (near) falls.

The effectiveness of a transitional pain service in patients undergoing surgery with an increased risk of developing chronic postsurgical pain (TRUSt study). A randomized clinical trial.

STUDY OBJECTIVE: Poorly controlled acute postsurgical pain is associated with delayed recovery, chronic postsurgical pain (CPSP), chronic opioid use and impaired functioning in daily activities. The aim was to determine the effectiveness of a transitional pain service (TPS) to improve quality of recovery for patients at risk of CPSP. We hypothesized that a TPS improves the quality of recovery in patients at risk of CPSP. DESIGN: Single-center, pragmatic, randomized, superiority trial. SETTING: Tertiary hospital in the Netherlands. PATIENTS: Assessed for eligibility if ≥18 years of age, undergoing elective surgery, and had an increased risk of developing CPSP. After being stratified for sex, 176 patients were included. INTERVENTION: Patients were randomized to receive TPS or standard of care (SOC). TPS was a multidisciplinary intervention providing a patient-tailored perioperative pain management plan, throughout all phases of surgery. MEASUREMENTS: The primary outcome was the difference in quality of recovery on the third postoperative day, measured by the Quality of Recovery (QoR)-15 questionnaire. Secondary outcomes include the between group differences in opioid consumption. MAIN RESULTS: The primary outcome was available in 169 (96.0%) patients. No difference between groups was found in QoR-15 on the third postoperative day (mean difference 2.0, 95% CI -5.5 to 9.4, p = 0.607). A decrease in opioid usage (compared to baseline) was observed in chronic opioid users, the median [IQR] reduction in total daily oral morphine milligram equivalents (MME) for TPS was -30 [-60, 0] at three and - 29.3 [-65.6, 0] at six months, whereas SOC had a median reduction of 0 [-56, 0] at three, and 0 [-60, 7.5] at six months. CONCLUSIONS: TPS did not significantly affect short-term quality of recovery but might improve long-term outcomes, such as the incidence of chronic pain, opioid consumption, and functioning in daily life. However, sample size in the present study was too small to provide solid evidence for this positive signal.

Does Regular Practice with a "Flexible Bronchoscopy Simulator" Improve Fibreoptic Intubation Skills in Experts and Novices? A Randomized Controlled Study.

BACKGROUND: The appropriate management of a "difficult airway" remains a challenge for novices and experienced anaesthetists. With the current available airway technologies, e.g., video laryngoscopy, flexible bronchoscopy (fibreoptic intubation (FOI)) for endotracheal intubation is decreasing, likely diminishing caregiver skills. We investigated whether bronchoscopy simulator training improved FOI skills. METHODS: 72 volunteers, consisting of anaesthetists, anaesthesia residents, and nurses, performed six exercises on a bronchoscopy simulator. At baseline and after 12 months, the six exercises included one serious game (to train agility), two basic airways, and three difficult airways. After a baseline assessment, subjects were randomly allocated to the intervention group (with) or control group without bronchoscopy simulator training every six weeks for 10 min using a preloaded serious game. The primary outcome was the difference in the time to reach the carina after 12 months, as measured objectively by the simulator. The level of stress and FOI confidence after 12 months were secondary outcomes. RESULTS: The control and intervention groups had a similar time to reach the carina in difficult airway cases and the reported stress levels, at baseline and 12 months, showed no difference. In contrast, the intervention group's self-reported confidence in FOI skills improved more. CONCLUSIONS: Although participants rated higher in confidence, practicing FOI skills on an airway simulator with an agility game did not increase their performance in simulated challenging airway instances.

A radiological cadaveric study of obturator nerve involvement and cranial injectate spread after different approaches to the fascia iliaca compartment block.

Whether the fascia iliaca compartment block (FICB) involves the obturator nerve (ON) remains controversial. Involvement may require that the injectate spreads deep in the cranial direction, and might thus depend on the site of injection. Therefore, the effect of suprainguinal needle insertion with five centimeters of hydrodissection-mediated needle advancement (S-FICB-H) on ON involvement and cranial injectate spread was studied in this radiological cadaveric study. Results were compared with suprainguinal FICB without additional hydrodissection-mediated needle advancement (S-FICB), infrainguinal FICB (I-FICB), and femoral nerve block (FNB). Seventeen human cadavers were randomized to receive ultrasound-guided nerve block with a 40 mL solution of local anesthetic and contrast medium, on both sides. Injectate spread was objectified using computed tomography. The femoral and lateral femoral cutaneous nerves were consistently covered when S-FICB-H, S-FICB or FNB was applied, while the ON was involved in only one of the 34 nerve blocks. I-FICB failed to provide the same consistency of nerve involvement as S-FICB-H, S-FICB or FNB. Injectate reached most cranial in specimens treated with S-FICB-H. Our results demonstrate that even the technique with the most extensive cranial spread (S-FICB-H) does not lead to ON involvement and as such, the ON seems unrelated to FICB. Separate ON block should be considered when clinically indicated.

Opioid-free anesthesia: A systematic review and meta-analysis.

STUDY OBJECTIVE: To evaluate all available evidence thus far on opioid based versus opioid-free anesthesia and its effect on acute and chronic postoperative pain. DESIGN: Systematic review and meta-analysis of randomized clinical trials. SETTING: Operating room, postoperative recovery room and ward. PATIENTS: Patients undergoing general anesthesia. INTERVENTIONS: After consulting MEDLINE, EMBASE and Cochrane database, studies which compared opioid free anesthesia (OFA) with opioid based anesthesia (OBA) were included (last search April 15th 2022). MEASUREMENTS: Primary outcomes were acute and chronic pain scores in NRS or VAS. Secondary outcomes were quality of recovery and postoperative opioid consumption. Risk of bias was assessed using the RoB2 tool and a random effects model for the meta-analysis was conducted. MAIN RESULTS: We identified 1245 citations, of which 38 studies met our inclusion criteria. There is moderate quality evidence showing no clinically relevant difference of Numeric Rating Scale (NRS) scores or opioid consumption in the postoperative period (pooled mean difference of 0.39 points with a CI of 0.19-0.59 and 4.02 MME with a CI of 1.73-6.30). We found only one small-sized study reporting no effect of opioid-free anesthesia on chronic pain. The quality of recovery was superior in patients with opioid-free anesthesia (mean difference of 8.26 points), however, this pooled analysis was comprised of only two studies. Postoperative nausea and vomiting (PONV) occurred less in opioid-free anesthesia, but bradycardia was more frequent. CONCLUSIONS: We concluded that we cannot recommend one strategy over the other. Future studies could focus on quality of recovery as outcome measure and adequately powered studies on the effects of opioid-free anesthesia on chronic pain are eagerly awaited.

A multimodal pain protocol for treatment of vaso-occlusive crisis in patients with sickle cell disease: Implementation and evaluation.

OBJECTIVES: Pain management during a vaso-occlusive crisis (VOC) for patients with sickle cell disease (SCD) remains a major challenge and strongly depends on opioids. We developed a multimodality pain protocol for rapid, opioid-sparing pain treatment of VOC and evaluated its feasibility. METHODS: Patients were included for evaluation if they were ≥18 years, diagnosed with SCD and visited the emergency department (ED) because of VOC between July 2018 and December 2020. Primary evaluation outcome was the feasibility of multimodal pain analgesia (i.e., the use of at least two analgesics with different underlying mechanisms of action). RESULTS: A total of 131 SCD patients visited the ED because of VOC with a total of 550 ED presentations, of which 377 were eventually hospitalised. A total of 508 (92.4%) ED presentations and 374 (99.2%) hospital admissions received multimodal pain treatment. Time to first administration of an opioid was median [IQR] 34.0 [21.0-62.0] minutes. CONCLUSION: The implementation of a pain protocol using multimodal analgesia for VOC in patients with SCD appeared to be feasible and facilitated rapid administration of opioids. Controlled trials are needed to investigate the effectiveness of multimodal analgesia on pain and should focus on patient reported outcome measures.

The Effect of Preoperative Disability, Cognitive Impairment, Frailty and Opioid Use on Acute Postoperative Pain in Older Patients Undergoing Surgery A Prospective Cohort Study.

Globally, life expectancy is increasing, leading to more surgeries being performed in older patients. Postoperative pain is associated with complications after surgery. The aim of this study is to explore potential age-related risk factors for acute postoperative pain in older patients undergoing surgery. This was a prospective, single-center study. Patients ≥65 years, with and without disability, as defined by the WHO Disability Assessment Schedule 2.0, undergoing elective surgery, were compared. Primary outcome was the postoperative pain (ie, numeric rating scale (NRS) score) on the first postoperative day. Secondary outcomes were postoperative pain and pain trajectories in patients with and without mild cognitive impairment (MCI), frailty, preoperative opioid use, and new-onset disability after surgery. Between February 2019 and July 2020, 155 patients were enrolled. On the first day after surgery, postoperative pain did not differ between patients with and without disability. NRS scores differed between patients with-, and without MCI on the first (P = .01), and second postoperative day (P < .01). Patients who used opioids before surgery reported higher median NRS score on the first (P < .001) and second (P < .01) postoperative day. Out of a total of 1816 NRS scores, 2 pain clusters were identified. Acute postoperative pain did not differ between patients with or without preoperative disability and frailty in older patients undergoing surgery. Reduced postoperative pain in older patients with MCI warrants further investigation. The PIANO study (Comparison of Postoperative NeurocognitiveFunction in Older Adult Patients with and without Diabetes Mellitus) was registered with www.clinicaltrialregister.nl (search term: Which can predict memory problems after surgery better; blood sugar levels or memory before surgery?). PERSPECTIVE: This study explored risk factors for acute postoperative pain in older patients. No differences in postoperative pain were observed in patients with or without preexistent disability or frailty, however, patients with mild cognitive impairment experienced reduced pain. We suggest to simplify pain assessment in this group and take functional recovery into account.

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.

Current practice in the perioperative management of patients with diabetes mellitus: a narrative review.

The prevalence of diabetes is increasing, and patients with diabetes mellitus have both an increased likelihood of requiring surgery and of developing postoperative complications when they do. We summarise available evidence underpinning current guidelines on preoperative assessment and optimisation, perioperative management of prescribed insulin and oral hypoglycaemic medication, intraoperative glycaemic control, and postoperative patient care.