Short-term outcomes in infants following general anesthesia with low-dose sevoflurane/dexmedetomidine/remifentanil versus standard dose sevoflurane (The TREX trial).

BACKGROUND: The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. METHODS: This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups. RESULTS: There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae. CONCLUSIONS: These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.

Effect of perioperative management on early graft function in living donor paediatric kidney transplantation.

BACKGROUND: Paediatric kidney transplantation has an increased risk of surgical and vascular complications, with intensive care monitoring required postoperatively. This study aimed to determine if perioperative management affects early graft function in living donor paediatric kidney transplantation. METHODS: Clinical data was extracted from the electronic medical record for living donor kidney transplants at two paediatric centres covering the state of New South Wales (NSW), Australia from 2009 to 2021. Estimated glomerular filtration rate (eGFR) of 7 days and 1-month post-transplant were calculated as measures of early graft function. RESULTS: Thirty-nine eligible patients (female n (%) 13 (33%)) with a median (IQR) age of 6 (3-9) years and pre-transplant eGFR of 7 (6-10) mL/min/1.73 m2 were analysed. Mean (SD) central venous pressure (CVP) after revascularisation was 11 (4) mmHg. Intraoperatively, mean volume of fluid administered was 84 (39) mL/kg, and 34 (87%) patients received vasoactive agents. Average systolic blood pressure (BP) in the first 24-h post-transplant was 117 (12) mmHg. Postoperatively, median volume of fluid administered in the first 24 h was 224 (159-313) mL/kg, and 17 (44%) patients received vasoactive agents. Median eGFR 7 days and 1-month post-transplant were 115 (79-148) and 103 (83-115) mL/min/1.73 m2, respectively. Linear regression analyses demonstrated that after adjusting for age, the average CVP after revascularisation and average systolic BP in the first 24-h post-transplant were not associated with eGFR in the first month post-transplant. CONCLUSIONS: Targeted intraoperative and postoperative fluid and haemodynamic characteristics were achieved but did not correlate with early graft function.

Pediatric anesthesia in Mongolia and Thailand.

INTRODUCTION AND HISTORY: In Mongolia, pediatric anesthesia has advanced during the past 25 years through expanded, standardized education programs and international collaboration. Pediatric anesthesia is a recognized specialty, covering all surgical services, including cardiac and transplant, using physicians and nurses. TRAINING: The pediatric anesthesia fellowship is 6 months after 2 years of residency; pediatric nurse anesthesia training is 6 months. CONCLUSION: As a Low- and Middle-Income Country (LMIC) with low population density and extreme weather, the challenges include insufficient equipment, supplies, and clinician numbers, matching few clinicians to many varied patient locations, and covering surgical emergencies over distance and weather. In Thailand, education and training in pediatric anesthesia remain a focus: Pediatric anesthesia is an official subspecialty, the fellowship is accredited, using a competency-based curriculum with milestones of Direct Observation of Procedural Skills and Entrusted Professional Activities. The Bangkok Anesthesia Regional Training Center (BARTC)-Pediatrics, jointly sponsored by the World Federation of Societies of Anesthesiologists (WFSA) and the Society for Pediatric Anesthesia (SPA), have expanded training to anesthesiologists worldwide. Challenges include difficulty balancing service workload and education, as well as attracting pediatric anesthesia fellows due to the strong private sector job market.

Isoelectric Electroencephalography in Infants and Toddlers during Anesthesia for Surgery: An International Observational Study.

BACKGROUND: Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. The authors hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. METHODS: Fifteen hospitals enrolled patients age 36 months or younger for surgery using sevoflurane or propofol anesthetic. Frontal four-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life variables were analyzed for association with isoelectric events. RESULTS: Isoelectric events occurred in 32% (206 of 648) of patients, varied significantly among sites (9 to 88%), and were most prevalent during pre-incision (117 of 628; 19%) and surgical maintenance (117 of 643; 18%). Isoelectric events were more likely with infants younger than 3 months (odds ratio, 4.4; 95% CI, 2.57 to 7.4; P < 0.001), endotracheal tube use (odds ratio, 1.78; 95% CI, 1.16 to 2.73; P = 0.008), and propofol bolus for airway placement after sevoflurane induction (odds ratio, 2.92; 95% CI, 1.78 to 4.8; P < 0.001), and less likely with use of muscle relaxant for intubation (odds ratio, 0.67; 95% CI, 0.46 to 0.99; P = 0.046]. Expired sevoflurane was higher in patients with isoelectric events during preincision (mean difference, 0.2%; 95% CI, 0.1 to 0.4; P = 0.005) and surgical maintenance (mean difference, 0.2%; 95% CI, 0.1 to 0.3; P = 0.002). Isoelectric events were associated with moderate (8 of 12, 67%) and severe hypotension (11 of 18, 61%) during preincision (odds ratio, 4.6; 95% CI, 1.30 to 16.1; P = 0.018) (odds ratio, 3.54; 95% CI, 1.27 to 9.9; P = 0.015) and surgical maintenance (odds ratio, 3.64; 95% CI, 1.71 to 7.8; P = 0.001) (odds ratio, 7.1; 95% CI, 1.78 to 28.1; P = 0.005), and lower Pediatric Quality of Life scores at baseline in patients 0 to 12 months (median of differences, -3.5; 95% CI, -6.2 to -0.7; P = 0.008) and 25 to 36 months (median of differences, -6.3; 95% CI, -10.4 to -2.1; P = 0.003) and 30-day follow-up in 0 to 12 months (median of differences, -2.8; 95% CI, -4.9 to 0; P = 0.036). Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs. propofol). CONCLUSIONS: Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension.

Off-label use of dexmedetomidine in paediatric anaesthesiology: an international survey of 791 (paediatric) anaesthesiologists.

PURPOSE: The purpose of this international study was to investigate prescribing practices of dexmedetomidine by paediatric anaesthesiologists. METHODS: We performed an online survey on the prescription rate of dexmedetomidine, route of administration and dosage, adverse drug reactions, education on the drug and overall experience. Members of specialist paediatric anaesthesia societies of Europe (ESPA), New Zealand and Australia (SPANZA), Great Britain and Ireland (APAGBI) and the USA (SPA) were consulted. Responses were collected in July and August 2019. RESULTS: Data from 791 responders (17% of 5171 invitees) were included in the analyses. Dexmedetomidine was prescribed by 70% of the respondents (ESPA 53%; SPANZA 69%; APAGBI 34% and SPA 96%), mostly for procedural sedation (68%), premedication (46%) and/or ICU sedation (46%). Seventy-three percent had access to local or national protocols, although lack of education was the main reason cited by 26% of the respondents not to prescribe dexmedetomidine. The main difference in dexmedetomidine use concerned the age of patients (SPA primarily < 1 year, others primarily > 1 year). The dosage varied widely ranging from 0.2-5 µg kg-1 for nasal premedication, 0.2-8 µg kg-1 for nasal procedural sedation and 0-4 µg kg-1 intravenously as adjuvant for anaesthesia. Only ESPA members (61%) had noted an adverse drug reaction, namely bradycardia. CONCLUSION: The majority of anaesthesiologists use dexmedetomidine in paediatrics for premedication, procedural sedation, ICU sedation and anaesthesia, despite the off-label use and sparse evidence. The large intercontinental differences in prescribing dexmedetomidine call for consensus and worldwide education on the optimal use in paediatric practice.

Lighting a candle, or cursing the darkness? Delivering a climate friendly anaesthetic.

With up to 7% of national emissions coming from health care in industrial nations, and volatile anaesthetics and nitrous oxide being particularly effective greenhouse gases, anaesthetists can potentially reduce their medical carbon footprint substantially. Operating theatres create 25% of hospital waste, and there are many other avenues for 'greening' in the perioperative environment, including recycling and avoiding unnecessary operations. However, it is vital to understand how to produce a real change in practice that continues into the future and is normalised. Health-care choices we make in 2021 cannot be allowed to lead to a climate catastrophe in 2050.

Statistical Analysis Plan for "An international multicenter study of isoelectric electroencephalography events in infants and young children during anesthesia for surgery".

This Statistical Analysis Plan details the statistical procedures to be applied for the analysis of data for the multicenter electroencephalography study. It consists of a basic description of the study in broad terms and separate sections that detail the methods of different aspects of the statistical analysis, summarized under the following headings (a) Background; (b) Definitions of protocol violations; (c) Definitions of objectives and other terms; (d) Variables for analyses; (e) Handling of missing data and study bias; (f) Statistical analysis of the primary and secondary study outcomes; (g) Reporting of study results; and (h) References. It serves as a template for researchers interested in writing a Statistical Analysis Plan.

An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study.

BACKGROUND: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours. METHODS: Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used. RESULTS: One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg). CONCLUSION: A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.

Neuromonitoring in paediatric anaesthesia.

PURPOSE OF REVIEW: There has been a steady advance in neuromonitoring during anaesthesia. Inevitably much of the research is first done in adults and later in children. This review will focus on the recent paediatric publications (2017-2019) in two areas of neuromonitoring - measuring anaesthesia effect and cerebral perfusion and oxygenation. RECENT FINDINGS: For EEG-derived depth monitors, the main recent advances have been in better understanding their performance in infants. For the first time, large multichannel EEG studies on infants have focused on understanding the basic principles of how anaesthesia impacts on the EEG of the developing brain in a way different to the older brain. Nociception monitors are beginning to be studied in children. In the area of optical neuromonitoring, studies show that cerebral desaturation during both general and spinal anaesthesia in infants is uncommon in neonates and infants. Further work emphasizes the importance of CO2 levels on cerebral oxygenation, and demonstrates impaired cerebral autoregulation in premature infants undergoing laparotomies. SUMMARY: The impact of anaesthesia on the EEG of small infants has some gross similarities to older children but there are fundamental differences, which mandate separate calibration of anaesthesia depth monitors. The role of nociception monitors in children has yet to be defined. Cerebral oxygenation monitoring during paediatric anaesthesia is improving our understanding of cerebral perfusion in this period, but as with almost all monitoring, evidence that its use improves outcome is not yet available.

An International, Multicenter, Observational Study of Cerebral Oxygenation during Infant and Neonatal Anesthesia.

BACKGROUND: General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia-ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants. METHODS: This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline); for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg); and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%). RESULTS: The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation; American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze. CONCLUSIONS: Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.

The impact of general anesthesia on child development and school performance: a population-based study.

BACKGROUND: There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood. AIMS: The aim of this data linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood. METHODS: We included children born in New South Wales, Australia of 37+ weeks' gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade-3 school test results in 2008-2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests. RESULTS: Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.07-1.29); or scoring below the national minimum standard in numeracy (aOR: 1.34; 95% CI: 1.21-1.48) and reading (aOR: 1.23; 95% CI: 1.12-1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained. CONCLUSION: Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations.

Using a pulse oximeter to determine clinical depth of anesthesia-investigation of the utility of the perfusion index.

BACKGROUND: Peripheral vasodilation is a well-recognized side effect of general anesthesia, and induces changes in the amplitude of the pulse plethysmograph (PPG) waveform. This can be continuously quantitaed using the Perfusion Index (PI), a ratio of the pulsatile to nonpulsatile signal amplitude in the PPG waveform. We hypothesized that the perfusion index would rise with the induction of anesthesia in children, and fall with emergence, and performed a prospective, observational study to test this. AIM: Our primary aim was to test whether the different clinical stages of anesthesia were associated with changes in the perfusion index, and the secondary aim was to test the correlation between the normalized perfusion index and the MAC value. METHODS: Twenty-one patients between the ages of 1 and 18 undergoing minor procedures with no anticipated painful stimuli were recruited. Patients with significant illnesses were excluded. Data collection commenced with a preinduction baseline, and data were collected continuously, with event marking, until completion of the anesthesia and removal of the pulse oximeter. Data collected included perfusion index, heart rate, and anesthetic gas concentration values. A normalized perfusion index was calculated by subtracting the initial baseline perfusion index value from all perfusion index values, allowing changes, from a standardized initial baseline value of zero, to be analyzed. RESULTS: During induction, the mean normalized perfusion index rose from 0.0 to 4.2, and then declined to 0.470 when the patients returned to consciousness. P < 0.001 using repeated measures anova test. The normalized perfusion index was correlated with MAC values (r2 = 0.33, 95% CI 0.18-0.47, P < 0.01). CONCLUSION: The perfusion index changed significantly during different stages of anesthesia. There is a significant correlation between the perfusion index, measured by pulse oximetry, and the MAC value, in pediatric patients undergoing minor procedures.

Cerebral oxygen saturation and tissue hemoglobin concentration as predictive markers of early postoperative outcomes after pediatric cardiac surgery.

BACKGROUND: Near-infrared spectroscopy (NIRS) provides an assessment of cerebral oxygenation and tissue hemoglobin concentration. AIM: The aim of this study was to investigate whether the cerebral oxygenation and hemoglobin concentration measured with NIRS could predict outcomes after pediatric cardiac surgery. METHOD: We conducted a retrospective observational study in 399 patients who underwent pediatric cardiac surgery. Associations were determined between postoperative outcome and preoperative and postoperative cerebral tissue oxygenation index (TOI), postoperative normalized tissue hemoglobin index (nTHI), concentration changes in oxygenated hemoglobin (Δ[HbO2 ]) and deoxygenated hemoglobin (Δ[HHb]). RESULTS: Thirty-nine children had major postoperative morbidity and 12 died. Using Spearman's correlation analysis, postoperative lower TOI and higher Δ[HHb] were associated with longer stays in the Intensive Care Unit (ICU) (r = -0.48, P < 0.001, r = 0.31, P < 0.001, respectively) and longer duration of intubation (r = -0.48, P < 0.001, r = 0.31, P < 0.001, respectively) and higher probability of death determined by the Risk Adjusted Classification for Congenital Heart Surgery (RACHS-1) (r = -0.39, P < 0.001, r = 0.23, P < 0.001, respectively). In multivariate regression analysis, postoperative TOI was independently associated with major morbidity and mortality and Δ[HHb] was independently associated with major morbidity. In receiver operating characteristic analysis, postoperative TOI and Δ[HHb] predicted major morbidity (Area under the curve [AUC] = 0.72, 0.68, respectively) and mortality (AUC = 0.81, 0.69, respectively). CONCLUSION: Lower TOI or higher [HHb] at the end of surgery and higher RACHS-1 category predicted worse outcomes.

Can transcutaneous near infrared spectroscopy detect severe hepatic ischemia: a juvenile porcine model.

BACKGROUND: Vascular complications following pediatric liver transplantation occur in 8-10% of cases, and no continuous, non-invasive monitoring for this problem exists. Near infrared spectroscopy (NIRS) allows non-invasive, continuous, transcutaneous assessment of hemoglobin oxygenation (StO2 ) 1-4 cm below the skin surface. AIMS: We hypothesized that transcutaneous NIRS would be able to detect severe hepatic ischemia, and tested this in an animal model using 15-20 kg and 5-7 kg juvenile pigs. MATERIALS AND METHODS: Direct liver surface and transcutaneous hepatic tissue hemoglobin oxygen saturation (StO2 ) were measured during occlusions of the hepatic artery and portal vein. Changes in hepatic delivery of oxygen (HepDO2 ) were calculated for each ischemic challenge and compared to changes in direct liver surface (DirHepStO2 ) and transcutaneous liver StO2 measurements (CutHepStO2 ). RESULTS: In the 15-20 kg animals during complete occlusion, CutHepStO2 decreased by 6.0(±4.9)%, whilst DirHepStO2 decreased by 83.7(±7.2)%. In the 5-7 kg animals during complete occlusion, CutHepStO2 decreased by 27.4(±8.5)%, whilst DirHepStO2 decreased by 82.8(±4.6)%. CONCLUSION: Transcutaneous hepatic StO2 monitoring cannot reliably detect severe hepatic ischemia in a juvenile porcine model, although a stronger and potentially useful signal is seen in 5-7 kg pigs. Trials of this technology should be currently restricted to situations where the organ is less than 1 cm from the skin surface, corresponding to infants of <10 kg.

Evidence of cardiac functional reserve upon exhaustion during incremental exercise to determine VO2max.

BACKGROUND: There remains considerable debate regarding the limiting factor(s) for maximal oxygen uptake (VO2max). Previous studies have shown that the central circulation may be the primary limiting factor for VO2max and that cardiac work increases beyond VO2max. AIM: We sought to evaluate whether the work of the heart limits VO2max during upright incremental cycle exercise to exhaustion. METHODS: Eight trained men completed two incremental exercise trials, each terminating with exercise at two different rates of work eliciting VO2max (MAX and SUPRAMAX). During each exercise trial we continuously recorded cardiac output using pulse-contour analysis calibrated with a lithium dilution method. Intra-arterial pressure was recorded from the radial artery while pulmonary gas exchange was measured continuously for an assessment of oxygen uptake. RESULTS: The workload during SUPRAMAX (mean±SD: 346.5±43.2 W) was 10% greater than that achieved during MAX (315±39.3 W). There was no significant difference between MAX and SUPRAMAX for Q (28.7 vs 29.4 L/min) or VO2 (4.3 vs 4.3 L/min). Mean arterial pressure was significantly higher during SUPRAMAX, corresponding to a higher cardiac power output (8.1 vs 8.5 W; p<0.06). CONCLUSIONS: Despite similar VO2 and Q, the greater cardiac work during SUPRAMAX supports the view that the heart is working submaximally at exhaustion during an incremental exercise test (MAX).