SPA Spring Meeting Reviews

Sunday Session I - Year-In-Review: Best Pediatric Anesthesia Research

By Constance L. Monitto, MD
Johns Hopkins University School of Medicine

The Sunday morning sessions began with “Year-In-Review: Best Pediatric Anesthesia Research” moderated by Dr. Olutoyin Olutoye from Texas Children’s Hospital. The speakers included Susan M. Goobie, MD, FRCPC, (Boston Children’s Hospital), Andrew Davidson, MBBS, MD, FANZCA, (Royal Children's Hospital in Melbourne, Australia), and Laszlo Vutskits, MD, PhD, (University Hospitals of Geneva).

Dr. Goobie started the session discussing articles of interest from Anesthesia & Analgesia chosen by her colleague Dr. James DiNardo. The first article was Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery with Cardiopulmonary Bypass by Ingrande et al. Dr. Goobie noted that there is little pharmacokinetic data to guide dosing regimens for surgical site infection prophylaxis in infants undergoing cardiac surgery. In this study, plasma concentrations of vancomycin and cefazolin were measured in two cohorts of infants undergoing cardiac surgery with cardiopulmonary bypass (CPB). Mixed-effects pharmacokinetic models were constructed and simulations were performed to define an appropriate dosing regimen necessary to maintain effective antibiotic concentrations. The authors found that prophylactic treatment using vancomycin 15 mg/kg with 12-hour re-dosing or cefazolin 30 mg/kg with 4-hour re-dosing maintained antibiotic serum levels above the susceptibility cutoffs for susceptible staphylococci. Further, continuous infusions were not necessary and the effect of CPB on pharmacokinetics was negligible.

The second article discussed was Perioperative Outcomes and Surgical Case Volume in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Observational Study From the Pediatric Craniofacial Collaborative Group. The aim of this study was to use the power of big data to examine the effect of surgical case volume on perioperative outcomes. Analyzing data from 33 participating institutions, Fernandez and colleagues found that high volume surgical centers used fewer central lines and more antifibrinolytics. They identified an inverse relationship between case volume and total perioperative blood donor exposures. However, no significant relationship was found between surgical case volume and the incidence of major postoperative complications or hospital length of stay.

Gaver and colleagues’ article Retrospective Analysis of the Safety and Efficacy of Sugammadex Versus Neostigmine for the Reversal of Neuromuscular Blockade in Children was discussed next. In this retrospectively-matched, case-controlled study of patients from birth through adolescence, the authors found fewer episodes of bradycardia with sugammadex than neostigmine. Within age groups, sugammadex demonstrated faster completion of operation with the greatest difference observed in the neonatal population. Importantly, looking for anaphylaxis using surrogate measures, the authors found no difference between the two drugs.

Raising the question of whether infants with pyloric stenosis should have a nasogastric tube placed prior to surgery, Dr. Goobie proceeded to summarize the findings of Lee and colleagues’ paper Retrospective Cohort Study on the Optimal Timing of Orogastric Tube/Nasogastric Tube Insertion in Infants with Pyloric Stenosis. In this multicenter retrospective cohort study, data was extracted from the medical records of over 400 patients who underwent pyloromyotomy. The authors found that oro- or nasogastric tube placement on admission was associated with a longer time to electrolyte correction in infants with abnormal laboratory values on presentation. It was also associated with a longer time until infants were ready for surgery (based on electrolyte values) and a longer postoperative hospital stay.

Dr. Goobie closed her presentation by discussing Beyond Anesthesia Toxicity: Anesthetic Considerations to Lessen the Risk of Neonatal Neurological Injury by McCann et al. This review article summarizes types of brain injury in preterm and term infants and their key pathways. In addition, it addresses pathogenic pathways including hypo- and hypercapnia, hyperoxia, hypoxia, hypotension, hypoglycemia, and hyperthermia that may modify risk. Finally, Dr. Goobie noted the importance of blood pressure management and cerebral autoregulation and their impact on perioperative neurotoxicity.

Dr. Goobie was followed by Dr. Davidson, Editor-in-Chief of Paediatric Anaesthesia, who touched on nine articles published by the journal that he felt would be of interest to the audience. Appropriately, he started with The Society for Pediatric Anesthesia Recommendations for the Use of Opioids in Children During the Perioperative Period by Cravero and colleagues. This document was written by a taskforce appointed to evaluate available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. This objective led Dr. Davidson to discuss the nuances of different types of guidelines. The three types he considered were clinical practice standards, which he contended are not guidelines, clinical practice guidelines, which provide a recommendation, and clinical practice statements, which provide a majority expert consensus. He advised the audience that when evaluating guidelines, they should consider their utility, trustworthiness, transparency and how they were generated.

He next moved on to Ho and colleagues’ editorial Estimating the Risk of Aspiration in Gas Induction for Infantile Pyloromyotomy. This article discusses the statistical limitations of the “Rule of 3” or the “Rule of 4” when estimating a confidence interval using small sample size data to evaluate the risk of rare events. They argue that in Bayesian logic, context is important and prior events should be incorporated when using new data to make inferences.

The third article was Duration of Preoperative Clear Fluid Fasting and Peripheral Intravenous Catheterization in Children: A Single-center Observational Cohort Study of 9693 Patients by Galves et al. In this study, the authors found that clear liquid fasting time was not associated with multiple intravenous insertion attempts in children receiving general anesthesia. However, other factors such as patient age, ethnicity, time of day, and ASA Physical Status classification showed a greater association with the risk of multiple intravenous line insertion attempts.

Dr. Davidson next discussed Morrison et al.’s special interest review article Stroke Management in Children. Acute ischemic stroke is rare in children. Initial treatment may involve anti‐thrombotic therapy. Alternatively, some affected children may benefit from mechanical thrombectomy, as is performed in adults. However, unlike adults, this procedure requires general anesthesia when performed on pediatric patients. As summarized by Dr. Davidson, Morrison’s paper discusses the potential for pre-procedural imaging, preoperative assessment looking for patient comorbidities, and intraoperative considerations including risks and benefits of arterial line placement, strategies for blood pressure management, and PaO2 and PaCO2 targets. Finally, the authors discuss the influence of time pressure in managing this emergency and advocate utilizing a unified concise stroke pathway to optimize care.

In Accuracy of Pediatric Cricothyroid Membrane Identification by Digital Palpation and Implications for Emergency Front of Neck Access, Dr. Davidson reported that Fennessy and colleagues determined that accurate identification of the location of the cricothyroid membrane (using ultrasound as a reference standard) by anesthesiologists occurred in only about one-third of all attempts, a finding that has implications for the technical approach to emergency front of neck access.

The next two articles both addressed the topic of allergies. In An Update on Allergy and Anaphylaxis in Pediatric Anesthesia, Stepanovic and colleagues reviewed the pathophysiology of hypersensitivity reactions and the implications for anesthesia of food allergy, atopy, and family history of allergy in children. Common triggers of perioperative anaphylaxis and the process of expert allergy testing following a suspected case of anaphylaxis in children were also discussed. In Allergy Alerts - The Incidence of Parentally Reported Allergies in Children Presenting for General Anesthesia, Sommerfield and colleagues sought to determine the incidence and nature of parent-reported allergies in children presenting for surgery and its significance for anesthetists. Reviewing over 1,000 pediatric patients, they found that 15.8% had parent-reported allergies, less than half were specialist confirmed, and less than 1% of drug sensitivities were likely to significantly alter anesthesia practice. However, Dr. Davidson noted that given the morbidity associated with anaphylaxis, providing conservative care remains reasonable.

Soneru and colleagues addressed the question of whether apneic oxygenation extended time to desaturation during intubation by inexperienced learners in their article Apneic Nasal Oxygenation and Safe Apnea Time During Pediatric Intubations by Learners. In their prospective observational study, the authors provided apneic oxygen via nasal cannula and found that the intervention significantly delayed desaturation to SpO2 95%, leading Dr. Davidson to conclude that their study demonstrated that the intervention was both simple and safe.

Dr. Davidson finished with the paper Pediatric Airway Dimensions - A Summary and Presentation of Existing Data by Dave and colleagues. In this systematic review of publications containing original data on pediatric airway dimensions, the authors found heterogeneous data on pediatric airway dimensions, making it impossible to compile standard reference values. Data was obtained using multiple techniques, and Dr. Davidson noted that there was no agreed upon superior measurement technique.

The final speaker was Dr. Vutskits, who summarized five of the best pediatric papers published in Anesthesiology over the past year. He began with Opioid Sensitivity in Children With and Without Obstructive Sleep Apnea by Montana et al. Testing the hypothesis that children with obstructive sleep apnea (OSA) have an increased sensitivity to opioids, the authors studied children with and without OSA who were administered a remifentanil infusion. Measuring remifentanil plasma levels, ventilation (respiratory rate and end-tidal C02) and pupillary response, they found no differences in the remifentanil concentration-miosis relation and no difference in ventilatory parameters between the two groups. However, Dr. Vutskits observed that the study was not designed to test clinical relevance.

The second article he presented was Pappas and colleagues’ manuscript δ-Oscillation Correlates of Anesthesia Induced Unconsciousness in Large-scale Brain Networks of Human Infants. The aim of this study was to identify changes in functional connectivity of the infant brain during anesthesia by analyzing multichannel EEG recordings. The authors found that sevoflurane decreased functional connectivity at the δ-frequency in infants less than four months of age when comparing anesthesia with emergence. Dr. Vutskits suggested that the authors’ findings may help guide depth of anesthesia management in very young patients in the future.

Dr. Vutskits’ third topic was Hypoxemia, Bradycardia, and Multiple Laryngoscopy Attempts During Anesthetic Induction in Infants: A Single-center, Retrospective Study. Conducting a retrospective chart analysis, Galves and colleagues evaluated the relationship between laryngoscopy attempts and the incidence of hypoxemia or bradycardia during induction of anesthesia. They identified over 1,300 patients who met inclusion criteria. Analyzing data from the 16% who had multiple direct laryngoscopy attempts, they found an association between multiple laryngoscopy attempts and hypoxemia but not bradycardia, pointing to an association between multiple direct laryngoscopy attempts and adverse events.

A second paper focusing on airway management was Assessment of Common Criteria for Awake Extubation in Infants and Young Children by Templeton et al. The aim of this observational study was to prospectively evaluate routine practice surrounding awake extubation and the predictive value of commonly used criteria. The authors found that successful extubation occurred in almost 93% of cases in their observational cohort. Facial grimace, purposeful movement, conjugate gaze, eye opening and tidal volume greater than 5 ml/kg were individually associated with success, while combining these five factors resulted in a positive predictive value of 100%.

The final paper Dr. Vutskits summarized was Pediatric Perioperative Mortality in Kenya: A Prospective Cohort Study from 24 Hospitals. To establish a baseline pediatric perioperative mortality rate and factors associated with mortality in Kenya, Newton and colleagues designed a prospective cohort study and measured 24-hour, 48-hour, and 7-day perioperative mortality. Collecting 132 data elements and analyzing more than 6,000 pediatric surgical cases at 24 hospitals, cumulative mortality rates were 0.8% at 24 hours, 1.1% at 48 hours, and 1.7% at 7 days. Factors associated with increased 7-day mortality were ASA Physical Status > II, night or weekend surgery, and not having the Safe Surgery Checklist performed. Dr. Vutskits commended this study as demonstrating that quality improvement efforts can allow analysis and intervention focused on region-specific issues.

The Year in Review was followed by “Updates from SPA Young Investigator Research Award Recipients” moderated by Charles Berde MD, PhD, (Boston Children’s Hospital). During this session, Laura Downey, MD, (Emory University School of Medicine) and Lance Relland, MD, PhD (Nationwide Children’s Hospital) provided the audience with a summary of their ongoing research.

The title of Dr. Downey’s talk was In Vivo Effects of Fibrinogen Concentrate (FC) Versus Cryoprecipitate on the Neonatal Fibrin Network Structure after Cardiopulmonary Bypass. She began her presentation by noting that between 15% and 25% of PICU patients are transfused with packed red blood cells (PRBCs), but patients who undergo cardiac surgery receive the majority of blood products. Cardiac surgery patients with excessive bleeding have increased rates of transfusion, infection, need for additional surgery, length of intubation and duration of PICU admission. Further, there are specific risks for bleeding after CPB including patient age, weight, surgical complexity, hypothermia, hemodilution and an immature coagulation system. Focusing on the coagulation system, she noted that the most common hemostatic derangement in excessive bleeding is an acute acquired hypofibrinogenemia.

In light of this, Dr. Downey questioned whether use of FC could be advantageous by allowing physicians to achieve a target fibrinogen level with decreased volume administration and minimal risk of infection, allergic reaction or immunologic sensitization. While prior research by Galas and colleagues suggested no benefit, Dr. Downey’s own research published in 2019 found that patients who received FC received less PRBCs than those who received cryoprecipitate, and that the impact might be more significant in high risk patients. However, there are structural differences between adult and neonatal fibrinogen and when the two types are mixed, clots are slower to degrade. This observation raises the question of whether the source of fibrinogen can affect clot structure, degradation time or clinical outcome.

To help answer this question, Dr. Downey is in the midst of enrolling 36 full term neonates to test the hypothesis that, when compared to clots formed from transfused cryoprecipitate, FC clots will have similar structural characteristics but will be degraded faster by the neonatal fibrinolytic system. Subjects having elective cardiac surgery will be randomized to receive either FC or cryoprecipitate after CPB. Clots are formed ex vivo from patient samples at four time points and assessed for structural and functional integrity. To date, Dr. Downey has enrolled nine patients and preliminary results have shown a decrease in post-CPB blood products in the FC group and comparable rates of adverse events. However, it is too early to draw definitive conclusions. In closing, Dr. Downey touched on the challenges of neonatal research and possible future directions for her work.

Dr. Relland’s research interests relate to pediatric pain, and his presentation was titled Effect of a Vibratory Stimulus to Mitigate Nociception-specific Responses to Skin Puncture in Neonates. Dr. Relland noted that over one million neonates are exposed to iatrogenic pain annually, and that noxious stimuli can have long-term effects. However, assessing pain in infants is challenging. An EEG can potentially measure the effects of nociceptive inputs by assessing the EEG event related potential (ERP) – a stimulus-dependent response. Dr. Relland hypothesized that a non-painful vibratory stimulus would lead to a decrease in the mean amplitude of the EEG nociceptive-specific response.

In his randomized controlled trial, 36 to 52-week post-gestational age infants with no recent exposure to opioids or sedatives underwent heel lance or heel lance plus a vibratory stimulus. Subjects were assessed with time-locked recording of ERP, as well as facial expression (using video recording), and reflex withdrawal. Study enrollment has now been completed and preliminary results suggest a significant decrease in nociceptive response to skin puncture with the vibratory stimulus. In addition, when coding facial expressions stimulus-related eye findings have been more consistent than those related to the mouth, but facial coding has not been completed. Finally, Dr. Relland discussed possible future directions in his research including optimizing his intervention regarding the timing of the vibratory stimulus and the type of lancet used.

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