spa-aap reviews
Sunday Session II: Best Pediatric Anesthesia Research
Reviewed by Constance L. Monitto, MD
Charlotte Bloomberg Children’s Center
Johns Hopkins Medical Institutions
Charles Berde MD, PhD (Boston Children’s Hospital) moderated Session II on Sunday, “Updates from SPA Young Investigator Research Awards.” He introduced the session by reminding the audience that pediatric anesthesia fellowships are generally only one year in duration, and, as a result, research expertise is often developed after training in an ad hoc fashion. Thus, in an effort to support research in our specialty, SPA has raised funds through the Patient Safety Education and Research Fund to provide starter grants to help foster young investigators early in their career. The inaugural grant recipients presented their preliminary data to the audience.
The first presentation was by Raj Subramanyam MD (Cincinnati Children’s Medical Center) whose research focuses on health outcomes. The goal of his project “Tonsillectomy and Clinical Adverse Events” was to study children undergoing tonsillectomy in order to identify predictors of prolonged hospital stay and post-discharge hospital visits, and subsequently to develop and validate a risk prediction algorithm.
Using a single-center prospective cohort model, he collected data on over 1,900 surgical patients cared for at CCMC. Mean patient age was 6.8 years, and over 70% had evidence of sleep disordered breathing. Seventy-one percent were originally scheduled for outpatient surgery and 1.5% required admission. Among the 13 patients who required admission following hospital discharge, the most common complaint was bleeding. Evaluating outcomes including prolonged PACU stay and perioperative complications, he identified race (African American), administration of midazolam as a premedication, and nausea as risk factors for prolonged PACU stay, while use of dexamethasone was protective for adverse events during the first three weeks after surgery.
Irfan Kathiriya, MD, PhD (UCSF Medical Center) next reported on his project, “Developmental Origins of Ventricular Septal Defects.” His goal was to study the origin of cells involved in the development of the ventricular septum and factors that regulate these cells in the hope that insights from developmental biology might have implications for future therapeutic and diagnostic options for congenital heart disease. Using a genetic lineage approach in which green fluorescent protein was used to mark ventricular progenitor cells, he was able to observe cellular migration and the effects of cell loss on both the intraventricular septum and ventricular chambers. Gene expression studies also allowed him to determine that reduced levels of Tbx5 protein lead to the development of ventricular septal defects and AV canal defects. Dr. Kathiriya plans to continue his studies using single cell genomic models to identify gene expression programs that distinguish intraventricular septum cells from those of right and left ventricular lineage, and to determine how gene signatures from intraventricular septum progenitor cells differ between normal hearts and those with congenital heart disease.
Nicholas Dalesio, MD (Johns Hopkins Children’s Center) concluded the session providing a preliminary analysis of his clinical research examining “Changes in Morphine Pharmacokinetics Due to Obesity and Obstructive Sleep Apnea in Children.” Providing some background, Dr. Dalesio reminded the audience that both obesity and obstructive sleep apnea (OSA) are important health issues for many of the children we care for.
In addition, both are often present in patients undergoing adenotonsillectomy, many of whom require opioid analgesia to treat perioperative pain. As a result, understanding the impact of these diseases on morphine pharmacokinetics is clinically relevant. He, therefore, chose to undertake a cohort study of obese and non-obese children with or without severe obstructive sleep apnea who received morphine to treat pain following tonsillectomy and adenoidectomy. Sampling blood for nine hours following morphine administration he found that children with OSA had an increased area under the curve (AUC) for morphine and its metabolites while there were inconclusive alterations caused by obesity. In addition, obese children with OSA had increased evidence of inflammation as demonstrated by elevated CRP levels as well as increased leptin levels. However, these results require further investigation regarding any relevance to postoperative respiratory complications.
In an interesting change from previous meetings in presenting this year’s best research papers, only four papers were chosen, but the findings of each study were presented by an author of the paper. The first two papers focused on the impact of general anesthesia on neurodevelopmental outcomes. Dr. Mary Ellen McCann, MD, MPH (Boston Children’s Hospital) discussed the paper “Neurodevelopmental outcome at two years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial” (Davidson et al, Lancet. 2016; 387:239-50).
As she reported, the GAS trial is a prospective, open-label, randomized controlled multisite equivalence trial in infants ranging in age from 26 to 60 weeks post conceptual age comparing inhalational anesthesia to spinal anesthesia. The study was initiated because of concerning animal studies demonstrating anesthetic-related neurotoxicity in the developing brain as well as mixed evidence from retrospective human cohort studies. While the primary hypothesis of the GAS study is that at 5 years of age IQ measurements in both groups will be equivalent, the data presented in this paper evaluated only the secondary outcome of neurodevelopment at two years of age.
In discussing the study’s findings, Dr. McCann reported that over 4,000 patients were screened to arrive at a study group of 722. Outcome data was available for 238 children in the spinal group and 294 in the general anesthesia group. Findings of the study included a success rate of approximately 80% for spinal anesthesia and an increased risk of early, but not late, apnea as well as a propensity for low blood pressure with general anesthesia. There was no evidence that anesthetic exposure of less than one hour of sevoflurane had a negative impact on neurodevelopment. Dr. McCann concluded that the strengths of the study included its international nature and that it provides prospective randomized data, while limitations included the short anesthetic exposures, difficulty in enrolling patients, and loss to follow-up.
Asking a similar question, but using a different methodology, Lena Sun, MD (Columbia University Medical Center) presented the results of the PANDA (Pediatric Anesthesia and Neuro Development Assessment) study (Sun et al. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA. 2016; 315: 2312-20).
In this ambi-directional cohort study, Dr. Sun’s group hypothesized that a single exposure to general anesthesia in healthy children less than three years of age would be associated with an increased risk for impaired global cognitive function, abnormal domain-specific neurocognitive functions, and abnormal behavior. To test their hypothesis medical billing records for children who underwent general anesthetics for hernia repair prior to age 3 (between 2000 and 2010) were screened to identify sibling pairs willing to participate in neurocognitive testing. Over 9,000 cases from 4 tertiary care hospitals were screened; 216 patients were eligible, 116 completed testing, and 105 were included in data analysis.
Using this approach, Dr. Sun and colleagues found that among healthy children with a single anesthetic exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Dr. Sun observed that a strength of this study was that it was sibling matched, while a limitation was that exposure data was retrospective. Finally, she cautioned the audience that absence of evidence is not evidence of absence, and that this study does not provide information concerning the effects of multiple or prolonged anesthetic exposures, suggesting that additional research is needed.
The third speaker was Steven Zgleszewski, MD (Boston Children’s Hospital) who presented findings from the paper “Anesthesiologist- and System-Related Risk Factors for Risk-Adjusted Pediatric Anesthesia-Related Cardiac Arrest” (Zgleszewski et al. Anesth Analg. 2016; 122: 482–489).
In this study, Dr. Zgleszewski and colleagues analyzed a prospectively collected patient cohort data set of over 300,000 anesthetics administered at Boston Children’s Hospital between 2000 and 2011. Looking specifically at anesthesia-related cardiac arrests (ARCA), they identified 72 episodes. Risk of ARCA was higher in cardiac patients and for anesthesiologists with lower annual caseloads. Dr. Zgleszewski observed that limitations of their findings included a lack of information concerning involvement of trainees in arrests as well as the limited number of overall arrests. He concluded that future steps should include a multicenter study to replicate the finding that annual days delivering anesthetics is an ARCA risk factor before changes in credentialing should be considered.
Agnes Hunyady, MD (Seattle Children’s Hospital) concluded the session by discussing “Airway management complications in children with difficult tracheal intubation from the Pediatric Difficult Intubation (PeDI) registry: A prospective cohort analysis” (Fiadjoe et al. Lancet Respir Med. 2016; 4: 37-48). This paper reported the findings of the multicenter Pediatric Difficult Intubation registry developed in 2010 to capture web-based data from 13 children’s hospitals.
The aims of the registry were to define the type and incidence of complications that arise from airway management in children with difficult tracheal intubation, to identify associations between patient, clinician and technique characteristics and the occurrence of complications, and to establish the effect of multiple intubation attempts. Reporting on 1,018 difficult intubations entered into the registry, Dr. Hunyady observed that two to five difficult intubations occurred per 1,000 anesthetics, with 80% anticipated. Twenty percent of these children had at least once complication related to the difficult intubation.
Complications included cardiac arrest (most common), hypoxemia, airway trauma, and rarely death. Risk factors for severe complications included an unanticipated difficult airway, multiple laryngoscopies, and weight less than 10 kilograms. Early transition from direct laryngoscopy to alternative devices resulted in less complications than perseverance with direct laryngoscopy. Limitations to the study included possible under-reporting, while future directions included creation of a quality improvement bundle containing measures to reduce hypoxemia and discourage repeated direct laryngoscopies as well as future research into the role of specific devices and ways to decrease complications in specific populations.
