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.

Exploring anaesthetists' views on the carbon footprint of anaesthesia and identifying opportunities and challenges for reducing its impact on the environment.

A shift in practice by anaesthetists away from anaesthetic gases with high global warming potential towards lower emission techniques (e.g. total intravenous anaesthesia) could result in significant carbon savings for the health system. The purpose of this qualitative interview study was to understand anaesthetists' perspectives on the carbon footprint of anaesthesia, and views on shifting practice towards more environmentally sustainable options. Anaesthetists were recruited from four hospitals in Western Sydney, Australia. Data were organised according to the capability-opportunity-motivation model of behaviour change. Twenty-eight anaesthetists were interviewed (July-September 2021). Participants' age ranged from 29 to 62 years (mean 43 years), 39% were female, and half had completed their anaesthesia training between 2010 and 2019. Challenges to the wider use of greener anaesthetic agents were identified across all components of the capability-opportunity-motivation model: capability (gaps in clinician skills and experience, uncertainty regarding research evidence); opportunity (norms, time, and resource pressures); and motivation (beliefs, habits, responsibility and guilt). Suggestions for encouraging a shift to more environmentally friendly anaesthesia included access to education and training, implementing guidelines and audit/feedback models, environmental restructuring, improving resource availability, reducing low value care, and building the research evidence base on the safety of alternative agents and their impacts on patient outcomes. We identified opportunities and challenges to reducing the carbon footprint of anaesthesia in Australian hospitals by way of system-level and individual behavioural change. Our findings will be used to inform the development of communication and behavioural interventions aiming to mitigate carbon emissions of healthcare.

Anesthesia and Intubation of Preadolescent Mouse Pups for Cardiothoracic Surgery.

Murine surgical models play an important role in preclinical research. Mechanistic insights into myocardial regeneration after cardiac injury may be gained from cardiothoracic surgery models in 0-14-day-old mice, the cardiomyocytes of which, unlike those of adults, retain proliferative capacity. Mouse pups up to 7 days old are effectively immobilized by hypothermia and do not require intubation for cardiothoracic surgery. Preadolescent (8-14-day-old) mouse pups, however, do require intubation, but this is challenging and there is little information regarding anesthesia to facilitate intubation. Here, we present dosage regimens of ketamine/xylazine/atropine in 10-day-old C57BL/6J mouse pups that allow endotracheal intubation, while minimizing animal mortality. Empirical titration of ketamine/xylazine/atropine dosage regimens to body weight indicated that the response to anesthesia of mouse pups of different weights was non-linear, whereby doses of 20/4/0.12 mg/kg, 30/4/0.12 mg/kg, and 50/6/0.18 mg/kg facilitated intubation of pups weighing between 3.15-4.49 g (n = 22), 4.50-5.49 g (n = 20), and 5.50-8.10 g (n = 20), respectively. Lower-body-weight pups required more intubation attempts than heavier pups (p < 0.001). Survival post-intubation correlated with body weight (59%, 70%, and 80% for low-, mid-, and high-weight groups, respectively, R2 = 0.995). For myocardial infarction surgery after intubation, a surgical plane of anesthesia was induced with 4.5% isoflurane in 100% oxygen and maintained with 2% isoflurane in 100% oxygen. Survival post-surgery was similar for the three weight groups at 92%, 86%, and 88% (p = 0.91). Together with refinements in animal handling practices for intubation and surgery, and minimizing cannibalization by the dam post-surgery, overall survival for the entire procedure (intubation plus surgery) correlated with body weight (55%, 60%, and 70% for low-, mid-, and high-weight groups, respectively, R2 = 0.978). Given the difficulty encountered with intubation of 10-day old pups and the associated high mortality, we recommend cardiothoracic surgery in 10-day-old pups be restricted to pups weighing at least 5.5 g.

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.

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.

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.

Near-infrared spectroscopy for detection of vascular compromise in paediatric supracondylar fractures.

Children suffering supracondylar fractures of the humerus are at risk of vascular compromise, which is currently assessed clinically, although other modalities such as angiography, pulse oximetry, Doppler ultrasound and magnetic resonance angiography have been used. We sought to ascertain whether tissue haemoglobin oxygenation (StO2) measurement could distinguish between patients with and without clinical vascular compromise following supracondylar fractures of the humerus. We prospectively observed StO2 using near-infrared spectroscopy in 29 paediatric patients with supracondylar fractures requiring operative manipulation. The injured and uninjured volar forearm compartments were monitored immediately before and after fracture reduction. The relationship between StO2 in the injured and uninjured limb, and the presence of pre-operative vascular compromise was assessed. Seven out of 29 children presented with vascular compromise. Patients with clinical vascular compromise had significantly lower pre-reduction StO2 (63.5% ± 15%, mean ± standard deviation), compared to those without compromise (80.9% ± 10%). StO2 normalized following surgery in all children with vascular compromise. These improvements in muscle StO2 were associated, in all patients, with the clinical return of pulses and resolution of neurological symptoms if present. StO2 monitoring can identify patients with clinical vascular compromise, can identify the return of adequate perfusion following operative correction of supracondylar fractures, and may be a useful adjunct to clinical assessment.

New technologies in pediatric anesthesia.

This article reviews potential pediatric applications of 3 new technologies. (1) Pulse oximetry-based hemoglobin determination: Hemoglobin determination using spectrophotometric methods recently has been introduced in adults with varied success. This non-invasive and continuous technology may avoid venipuncture and unnecessary transfusion in children undergoing surgery with major blood loss, premature infants undergoing unexpected and complicated emergency surgery, and children with chronic illness. (2) Continuous cardiac output monitoring: In adults, advanced hemodynamic monitoring such as continuous cardiac output monitoring has been associated with better surgical outcomes. Although it remains unknown whether similar results are applicable to children, current technology enables the monitoring of cardiac output non-invasively and continuously in pediatric patients. It may be important to integrate the data about cardiac output with other information to facilitate therapeutic interventions. (3) Anesthesia information management systems: Although perioperative electronic anesthesia information management systems are gaining popularity in operating rooms, their potential functions may not be fully appreciated. With advances in information technology, anesthesia information management systems may facilitate bedside clinical decisions, administrative needs, and research in the perioperative setting.

Cardiac output measurement in pediatric anesthesia.

Maintenance of cardiovascular stability is crucial to safe anesthetic practice, but measurement of cardiac output has been technically challenging, particularly in pediatric patients. Cardiovascular monitoring has therefore generally relied upon pressure-based measurements, as opposed to flow-based measurements. The measurement of cardiac output under anesthesia and in critical care has recently become easier as a result of new techniques of measurement. This article reviews the basic concepts of and rationale for cardiac output monitoring, and then describes the techniques available for monitoring in clinical practice.