Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients. METHODS: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis. RESULTS: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%). CONCLUSIONS: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

The role of collaboration in educating the global pediatric anesthesia workforce.

An estimated 1.7 billion children and adolescents do not have access to safe and affordable surgical care, and the vast majority of these are located in low-middle-income countries (LMICs). Pediatric anesthesia, a specialized field that requires a diverse set of knowledge and skills, has seen various advancements over the years and has become well-established in upper-middle and high-income countries. However, in LMICs, due to a multitude of factors including severe workforce shortages, this has not been the case. Collaborations play a vital role in increasing the capacity of pediatric anesthesiology educators and training the pediatric anesthesia workforce. These efforts directly increase access for children who require surgical intervention. Collaboration models can be operationalized through bidirectional knowledge sharing, training, resource allocation, research and innovation, quality improvement, networking, and advocacy. This article aims to highlight a few of these collaborative efforts. Specifically, the role that the World Federation of Societies of Anaesthesiologists, the Safer Anesthesia from Education program, the Asian Society of Pediatric Anaesthesiologists, Pediatric Anesthesia Training in Africa, the Paediatric Anaesthesia Network New Zealand, the Safe Pediatric Anesthesia Network and two WhatsApp™ groups (global ped anesthesia and the Pediatric Difficult Intubation Collaborative) have played in improving anesthesiology care for children.

Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis.

BACKGROUND: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as "long COVID" or "post-acute sequelae of SARS-CoV-2 infection" (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed. METHODS: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates. RESULTS: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained. CONCLUSIONS: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.

Remimazolam for Pediatric Procedural Sedation: Results of an Institutional Pilot Program.

Remimazolam, an ultra-short-acting benzodiazepine sedative, was first approved in 2020 in Japan as a general anesthetic for adults. However, its utilization in pediatric settings remains unexplored and, to date, is confined to isolated case reports due to a lack of specific pediatric labeling. The primary objective of our study was to evaluate the safety profile of remimazolam when used for procedural sedation in children following dosages established in adult protocols. Additional parameters, including dosage per kg of body weight, duration of the procedure, efficacy (measured as successful completion of the procedure), the necessity for supplemental medications, and changes in physiological parameters, such as the heart rate (HR) and mean arterial blood pressure (MAP), were assessed. Our study encompassed 48 children with an average age of 7.0 years. The objective Tracking and Reporting Outcomes of Procedural Sedation tool indicated no adverse events. In our cohort, propofol and ketamine were used as adjunctive treatments in 8 and 39 patients, respectively, with successful completion of all procedures. Notable hemodynamic variability was observed, with 88.4% of patients experiencing a ≥20% change (increase or decrease) and 62.8% experiencing a ≥30% change in MAP. Additionally, a ≥20% change in HR was observed in 54.3% of patients, and a ≥30% change was observed in 34.8% of patients. Nevertheless, none of the patients required pharmacological intervention to manage these hemodynamic fluctuations. Our findings suggest that remimazolam, when supplemented with propofol or ketamine, could offer a safe and effective pathway for administering procedural sedation in pediatric populations.

Remimazolam as an Adjunct to General Anesthesia in Children: Adverse Events and Outcomes in a Large Cohort of 418 Cases.

Remimazolam was first approved in 2020 as a general anesthetic for adults and still does not have pediatric labeling. Our study will be the first pilot program that administers remimazolam as an adjunct to a general endotracheal anesthetic in children. Between August 2020 and December 2022, electronic medical records were collected for all children who received remimazolam during anesthesia. The remimazolam dosing regimen was extrapolated from the adult package insert, with intravenous induction doses of 12 mg/kg/h administered until the desired effect was achieved. Subsequent infusions were given at a rate of 1-2 mg/kg/h, accompanied by intermittent boluses of 0.2 mg/kg, with all dosing adjustments made according to the anesthesiologist's clinical discretion. A total of 418 children (mean 4.6 yrs, 68.7% ASA 1 and 2) underwent surgeries which averaged 81.2 min. A total of 75.2% of patients had greater than a 20% change (increase or decrease) in MAP (lowest or highest) from baseline, and 203 (49.3%) patients had greater than a 30% change (increase or decrease) in MAP (lowest or highest) from baseline. A total of 5% received ephedrine to treat unanticipated hemodynamic variability. Discharge criteria were met within an average of 13.8 min after arrival at the post-anesthesia care unit. Remimazolam may offer the benefits of rapid recovery following general endotracheal anesthesia. The risk of hemodynamic variability which necessitates and responds to ephedrine should be anticipated.

Epidemiology of adverse events attributed to airway management in paediatric anaesthesia: protocol for the prospective, multicentre, registry-based, cross-sectional Japan Pediatric Difficult Airway in Anesthesia study (J-PEDIA).

INTRODUCTION: Failure to secure an airway during general anaesthesia is a major cause of adverse events (AEs) in children. The safety of paediatric anaesthesia may be improved by identifying the incidence of AEs and their attributed risk factors. The aim of the current study is to obtain real-world data on the incidence of adverse peri-intubation events and assess their association with patient characteristics (including the prevalence of difficult airway features) and choice of anaesthesia management. These data can be used to develop a targeted education programme for anaesthesia providers towards quality improvement activities. METHODS AND ANALYSIS: This prospective, multicentre, registry-based, cross-sectional study will be conducted in four tertiary care hospitals in Japan from June 2022 to May 2025. Children <18 years of age undergoing surgical and/or diagnostic test procedures under general anaesthesia or sedation by anaesthesiologists will be enrolled in this study. Data on patient characteristics, discipline of anaesthesia providers and methodology of airway management will be collected through a standardised verification system. The exposure of interest is the presence of difficult airway features defined based on the craniofacial appearance. The primary and secondary endpoints are all AEs associated with airway management and reduced peripheral capillary oxygen saturation values. Potential confounders are related to the failure to secure the airway and variations in the anaesthesia providers' levels, adjusted using hierarchical multivariable regression models with mixed effects. The sample size was calculated to be approximately 16 000 assuming a 99% probability of obtaining a 95% Wilson CI with±0.3% of the half-width for the 2.0% of the incidence of critical AEs. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board at Aichi Children's Health and Medical Center (2021051). The results will be reported in a peer-reviewed journal and a relevant academic conference. TRIAL REGISTRATION NUMBER: UMIN000047351.

Sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reports.

Although the recommended preoperative cessation period for sodium-glucose cotransporter 2 inhibitors (SGLT2is) changed in 2020 (from 24 h to 3-4 days preoperatively) to reduce the risk of SGLT2i-associated perioperative ketoacidosis (SAPKA), the validity of the new recommendation has not been verified. Using case reports, we assessed the new recommendation effectiveness and extrapolated precipitating factors for SAPKA. We searched electronic databases up to June 1, 2022 to assess SAPKA (blood pH < 7.3 and blood or urine ketone positivity within 30 days postoperatively in patients taking SGLT2i). We included 76 publications with 99 cases. The preoperative SGLT2i cessation duration was reported for 59 patients (59.6%). In all cases with available cessation periods, the SGLT2is were interrupted < 3 days preoperatively. No SAPKA cases with > 2-day preoperative cessation periods were found. Many case reports lack important information for estimating precipitating factors, including preoperative SGLT2i cessation period, body mass index, baseline hemoglobin A1c level, details of perioperative fluid management, and type of anesthesia. Our study suggested that preoperative SGLT2i cessation for at least 3 days could prevent SAPKA. Large prospective epidemiologic studies are needed to identify risk factors for SAPKA.

Anesthetic management with remimazolam for a pediatric patient with Duchenne muscular dystrophy.

RATIONALE: With Duchenne muscular dystrophy (DMD) being the most common and most severe type of muscular dystrophy, DMD patients are at risk for complications from general anesthesia due to impaired cardiac and respiratory functions as the pathological condition progresses. In recent years, advances in multidisciplinary treatment have improved the prognosis of DMD patients, and the number of patients requiring surgery has increased. Remimazolam is a benzodiazepine derivative similar to midazolam. Its circulatory stability and the fact that it has an antagonist make it superior to propofol.There are no reports of pediatric patients with DMD undergoing total intravenous anesthesia with remimazolam. PATIENT CONCERNS: A 4-year boy was scheduled for single-incision laparoscopic percutaneous extraperitoneal closure for inguinal hernia under general anesthesia, but the surgery was postponed because his serum creatine phosphokinase level was extremely high. DIAGNOSIS: He was diagnosed with DMD. According to the results of the genetic test, exon deletion of the DMD gene was detected using multiplex ligation-dependent probe amplification, although he had no symptoms of DMD except for elevated serum levels of creatine phosphokinase, etc. INTERVENTION: He was admitted for the same surgical purpose. Anesthesia was induced with 3 mg of intravenously administered remimazolam. He lost the ability to respond to verbal commands. After the intravenous administration of 100 µg of fentanyl, a continuous infusion of remifentanil (1.0 µg/kg/min) and remimazolam (15 mg/h) was started, and the endotracheal tube was inserted smoothly after the administration of 10 mg of rocuronium with which the muscle twitches disappeared in train-of-four monitoring. At the end of the surgery, 15 mg of flurbiprofen was administered intravenously. After surgery, we injected 40 mg of sugammadex to confirm a train-of-four count of 100%. OUTCOMES: Although the dose of remimazolam was reduced to 5 mg/h 30 minutes before the end of the surgery, it took 20 minutes after the discontinuation of remimazolam for the patient to open his eyes upon verbal command. On postoperative Day 2, he was discharged from the hospital without any complications. LESSONS: Remimazolam was shown to be safe to use for general anesthesia in a pediatric patient with DMD.

Multicentre prospective observational study of sodium-glucose cotransporter-2 inhibitor-associated postoperative ketoacidosis: the SAPKA study protocol.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycaemic agents that promote urinary glucose excretion in the renal proximal tubule and have cardio-protective and renal-protective properties. However, there are several safety concerns related to increased risks of hypoglycaemic, urinary tract infections and ketoacidosis. Ketoacidosis is a potentially fatal complication that often presents as euglycaemic ketoacidosis during SGLT2 inhibitor treatment. Furthermore, invasive treatment and related surgical stress may increase the risk of ketogenesis. Therefore, this study aims to clarify the incidence of SGLT2 inhibitor-associated postoperative ketoacidosis (SAPKA) among patients who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit 750 adult Japanese patients with diabetes who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. Urine samples will be collected on postoperative days 0, 1, 2 and 3. Blood gas analysis will be performed when urine ketone positivity is detected. The incidence of postoperative ketoacidosis will be identified based on urine ketone positivity and a blood pH of ≤7.3. The study will also collect data to identify risk factors for SAPKA. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committee of Kyorin University (approval number: 785, 26 October 2020) and local ethical approval will be required at each participating centre. Study findings will be submitted to peer-reviewed journals and abstracts will be submitted to relevant national and international meetings. TRIAL REGISTRATION NUMBER: UMIN000042795.

Surgical symptomatic knowledge among medical staff and community health workers in rural Cambodia: a descriptive study for workforce improvement.

Objective: The surgical workforce needs to at least double by 2030. To increase the workforce, training for non-physician healthcare professionals and community health workers (CHWs) in rural areas is promising to decrease the numbers of untreated surgical patients. Nevertheless, few studies have been conducted on surgical activities of non-physician healthcare professionals and CHWs in rural Cambodia. We sought to measure the level of knowledge of surgical symptoms, and identify factors associated with it. A questionnaire survey was administered to people in rural areas of Kratie Province to determine their knowledge of surgical symptoms, and to strengthen the surgical workforce among medical staff and CHWs. Patient/Materials and Methods: To evaluate the knowledge of surgical symptoms among medical staff and CHWs, a self-reported questionnaire was administered to medical staff, CHWs, and villagers in a rural area of Kratie province, Cambodia. The rating score of the number of correct answers among medical staff, CHWs, and villagers was set as the primary outcome. Results: A total of 91 participants, including 31 medical staff, 24 CHWs, and 36 villagers, completed the survey. The median scores for knowledge of symptoms indicative of surgery were 8 (7-8) [median (interquartile range)] in medical staff, 8 (7-8.5) in CHWs, and 8.5 (8-9) in villagers. There was no significant difference in the scores of surgical symptoms among each of the occupational groups. The group of people who recognized low subjective knowledge of surgical symptom by themselves had significantly higher objective score of knowledge of surgical symptom. Conclusion: Knowledge of surgical symptoms among medical staff and CHWs was inadequate. To at least double the surgical workforce by 2030 successfully, accurate evaluation and improvement of surgical symptomatic knowledge among medical staff in rural areas is crucial.

Effect of forced-air warming by an underbody blanket on end-of-surgery hypothermia: a propensity score-matched analysis of 5063 patients.

BACKGROUND: Underbody blankets have recently been launched and are used by anesthesiologists for surgical patients. However, the forced-air warming effect of underbody blankets is still controversial. The aim of this study was to determine the effect of forced-air warming by an underbody blanket on body temperature in anesthetized patients. METHODS: We retrospectively analyzed 5063 surgical patients. We used propensity score matching to reduce the bias caused by a lack of randomization. After propensity score matching, the change in body temperature from before to after surgery was compared between patients who used underbody blankets (Under group) and those who used other types of warming blankets (Control group). The incidence of hypothermia (i.e., body temperature < 36.0 °C at the end of surgery) was compared between the two groups. A p value < 0.05 was considered to indicate statistical significance. RESULTS: We obtained 489 propensity score-matched pairs of patients from the two groups, of whom 33 and 63 had hypothermia in the Under and Control groups, respectively (odds ratio: 0.49, 95% confidence interval: 0.31-0.76, p = 0.0013). CONCLUSIONS: The present study suggests that the underbody blanket may help reduce the incidence of intraoperative hypothermia and may be more efficient in warming anesthetized patients compared with other types of warming blankets. TRIAL REGISTRATION: UMIN Clinical Trials Registry (Identifier: UMIN000022909 ; retrospectively registered on June 27, 2016).

Use of remifentanil in general anesthesia for neonatal non-cardiac surgery: a case series.

OBJECTIVE: This case series aimed to summarize our experience in usage of remifentanil in neonates undergoing non-cardiac surgery. BACKGROUND: Physiology of neonates and infants is different from that of adults. Immaturity of their vital organ systems narrows a safety margin of perioperative management including anesthesia. Remifentanil has favorable characteristics for pediatrics such as short duration of action and rapid elimination. Although remifentanil was introduced into clinical practice since 1996, its application to neonatal anesthesia has not been validated yet. METHODS: This is a 14-month retrospective case series of neonates receiving remifentanil during non-cardiac surgery at a tertiary care pediatric hospital in Japan. Patients' characteristics, intraoperative data, and complications were retrieved from medical records. RESULTS: A total of 68 neonates underwent non-cardiac surgery under general anesthesia, of whom 48 received remifentanil. Infusion rate was 0.14 (0.04-0.35) mcg/kg/min (median, range). No intractable adverse events including postoperative apnea were detected. CONCLUSION: Remifentanil is generally feasible to neonatal surgical population.

Efficacy of prophylactic doses of intravenous nitroglycerin in preventing myocardial ischemia under general anesthesia: A systematic review and meta-analysis with trial sequential analysis.

STUDY OBJECTIVE: To evaluate the efficacy of intravenous nitroglycerin (TNG) in preventing intraoperative myocardial ischemia (MI) under general anesthesia. Moreover, we analyzed the hemodynamic changes in heart rate (HR), mean blood pressure (MBP), and pulmonary capillary wedge pressure (PCWP) associated with TNG administration both before and after the induction of anesthesia. DESIGN: Meta-analysis. SETTING: Operating room, cardiac surgery or non-cardiac surgery, all surgeries were elective measurements. We performed a computerized search of articles on PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using Review Manager. The data from the individual trials were combined using a random-effects model to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) with 95% confidence interval (CI). We conducted trial sequential analysis (TSA). The primary outcome was the incidence of MI and the secondary outcomes were hemodynamic changes (HR, MBP, and PCWP). MAIN RESULTS: Using electronic databases, we selected 10 trials with a total of 353 patients for our review. Prophylactic intravenous TNG did not significantly decrease the incidence of MI (RR=0.61; CI, 0.33 to 1.13; P=0.12; I2=55). TSA corrected the CI to 0.05 to 7.39 and showed that 9.5% of the required information size was achieved. In terms of hemodynamic changes, intravenous TNG significantly reduced MBP in comparison with the placebo (MBP pre-induction: WMD=-7.27; 95% CI -14.2 to -0.33; P=0.04; I2=97%; MBP post-induction: WMD=-5.13; 95% CI -9.17 to -1.09; P=0.01; I2=73%). CONCLUSIONS: Our analyses showed that prophylactic intravenous TNG does not reduce the incidence of intraoperative MI. Moreover, TSA suggests that further studies are necessary to confirm the results (GRADE: very low). Prophylactic doses of intravenous TNG significantly reduced the MBP both pre and post anesthesia induction (GRADE: very low).

Weekend versus weekday admission and short-term mortality: A meta-analysis of 88 cohort studies including 56,934,649 participants.

It is widely accepted that higher mortality related to weekend admissions basically exists; however, there has been no systematic exploration of whether weekend admissions are associated with higher risk of death in patients on the basis of certain diagnoses, geographic regions, and study subtypes.A meta-analysis was performed according to the reporting guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE Compliant). Literature search was conducted using electronic databases. Primary outcome was short-term (≤30-day) mortality. Patients were divided into 7 regions (North America, South America, Europe, Asia, Oceania, Africa, and Antarctica) for subgroup analyses and into 7 categories evaluating 24 major diagnoses. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated with DerSimonian and Laird random-effects models.Eighty-eight studies including 56,934,649 participants met our inclusion criteria. Overall pooled adjusted and crude OR of weekend to weekday admission for short-term mortality was 1.12 (95% CI, 1.07-1.18; I = 97%) and 1.16 (95% CI, 1.14-1.19; I = 97%), respectively. In subgroup analyses, higher risk of death on the weekend was significantly identified in patients living in all five continents (North America, South America, Europe, Asia, and Oceania). However, significant weekend effect was identified only in 15 of 24 diagnostic groups. Patients admitted on the weekend were more likely to die in an emergency situation (crude OR = 1.17, 95% CI, 1.12-1.22).Although weekend admissions were associated with higher risk of death compared with weekday admissions on all five continents, the effect was limited to certain diagnostic groups and admission subtypes. Weekend effect remains highly heterogeneous and limited, suggesting that further well-conducted cohort studies might be informative.

Factors affecting extubation time following pediatric ambulatory surgery: an analysis using electronic anesthesia records from an academic university hospital.

BACKGROUND: In pediatric general anesthesia, our goal should be quicker extubation to facilitate rapid turnover in the operating room without compromising on safety and quality of anesthesia. Although many studies have focused on improving safety and pursuing a higher quality of recovery, factors related to anesthesia emergence remain unclear. We must, therefore, identify factors that influence the process of emergence from general anesthesia in children. FINDINGS: We retrospectively examined 148 children (aged 1-6 years, American Society of Anesthesiologists physical status: 1-2) who had undergone <2 h of ambulatory surgery. Clinical measures included time from the end of surgery to extubation (extubation time), age, height, weight, surgical time, mean indirect blood pressure during surgery, mean heart rate during surgery, mean end-tidal carbon dioxide during surgery (mETCO2), mean body temperature during surgery (mBT), and total amount of fentanyl. Anesthetic procedures involved sevoflurane or propofol. Multiple regression analysis revealed that mETCO2 (p < 0.01) and mBT (p < 0.01) were independent clinical factors associated with extubation time following pediatric ambulatory surgery. CONCLUSIONS: This study of 148 pediatric patients demonstrated that anesthesia emergence may be associated with mBT and mETCO2 following pediatric ambulatory surgery. These results show that perioperative vital signs are important in the prevention of delayed emergence for pediatric patients.