Pediatric Anesthesiology 2018 Reviews

Sunday Session II: Best Pediatric Anesthesia Research

Reviewed by Constance L. Monitto, MD
Charlotte Bloomberg Children’s Center
Johns Hopkins Medical Institutions

Data registries, anesthesia-related neurotoxicity, the use of ultrasound, quality and process improvement, and childhood obesity were among the recurring themes in the many articles presented during the Editor’s Picks session and summarized below.

Jorge Galvez, MD, MBI (Children’s Hospital of Philadelphia), Associate Editor of Anesthesiology, started the discussion with a whirlwind presentation of eight articles describing research undertaken in countries around the world. In the first article, Burjek and colleagues (1) reported the results of an observational, multicenter cohort study of over 1600 children in which they compared the success rates of fiberoptic intubation via a supraglottic airway and videolaryngoscopy in children with difficult airways. Analyzing data from the Pediatric Difficult Intubation Registry, the authors found that fiberoptic intubation and videolaryngoscopy had similar first attempt success rates, but in infants a higher first attempt success rate was reported with fiberoptic intubation. Complication rates were similar in the two groups, but the incidence of hypoxemia was lower when continuous ventilation through a supraglottic airway was employed.

Neurotoxicity was the focus of Hu and colleagues’ retrospective study of children born in Minnesota between 1996 and 2000 (2). The authors used propensity matching to test the hypothesis that multiple, but not single, exposures to general anesthesia before age three years would be associated with adverse neurodevelopmental outcomes. Supporting their hypothesis, they found that multiple anesthetic exposures were associated with an increased frequency of learning disabilities and attention-deficit/hyperactivity disorder as well as decreases in cognitive ability and academic achievement. Single exposures, on the other hand, were associated with modest decreases in reading and language achievement but not cognitive ability. Although consistent with previous studies, the authors emphasized that they cannot determine whether anesthesia is causal or just associated with these neurodevelopmental outcomes.

Although general anesthesia during infancy is associated with neurocognitive abnormalities, mechanisms of injury are not well defined. This led Olbrecht and colleagues (3) to undertake a prospective, multicenter study of infants aged < 6 months having general anesthesia looking at the incidence of low cerebral oxygenation as measured by near-infrared spectroscopy. Collecting data on > 400 infants, the authors found that mild and moderate low cerebral saturation was frequent, but severe low cerebral saturation was uncommon. Low mean arterial pressure was also common but not well associated with low cerebral saturation. These findings led the authors to conclude that prolonged, unrecognized severe desaturation is not likely to explain the development of anesthesia-associated neurocognitive abnormalities.

Focusing on a second registry, Dr. Galvez next summarized the results of one of the multiple studies published this year by members of the Pediatric Craniofacial Collaborative Group (4). Analysis of data from 1,223 cases (935 children aged < 24 months) revealed that 95% of children aged < 24 months and 79% of children aged > 24 months received at least one transfusion and utilization of blood conservation techniques was highly variable. Perioperative complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries, but no deaths were reported. Based on their findings, which included large variability in perioperative management and significant complications, the authors suggested that targets for improvement exist.

The next three studies presented described the use of ultrasound. Chreschan and colleagues (5) reported the results of a retrospective single-center analysis that evaluated the effectiveness of supraclavicular in-plane, real-time ultrasound-guided cannulation of the brachiocephalic vein in preterm infants. Studying 142 neonates weighing between 0.59 and 2.5kg, they reported an overall success rate of 94% and a 70% success rate with a single cannulation attempt. Lower infant weight and targeting the right brachiocephalic vein were associated with the more attempts being needed.

A single center, prospective, randomized controlled trial of 120 children < 5 years of age undergoing cardiac surgery found that perioperative lung ultrasound examination followed by ultrasound-guided recruitment maneuvers helped decrease postoperative desaturation events and shorten the duration of mechanical ventilation, supporting a role for this modality in the management of pediatric patients undergoing cardiac surgery (6). Finally, Kim and colleagues reported on a study evaluating the posterior tibial artery as an alternative arterial cannulation site to the radial artery in small children (7).

Looking at the anatomy of posterior tibial artery, the authors found that its diameter was similar to the radial artery, and it had a larger cross-sectional area. Furthermore, comparing the success rate of ultrasound-guided arterial cannulation they found the first attempt success rates of posterior tibial and radial artery cannulation were similar, supporting its use as a reasonable alternative to the radial artery for ultrasound-guided arterial cannulation in small children.

Ever the fan of technology, in closing Dr. Galvez recommended the audience read a brief “Mind to Mind” creative writing article titled “Texting Under Anesthesia” about an interaction between a patient, a family, an anesthesiologist – and a cell phone (8).  In addition, he informed the audience that further information regarding the articles presented was posted on Twitter at #AnesJC (Twitter Journal Clubs).

James A. DiNardo, MD (Boston Children’s Hospital), Pediatric Anesthesiology section editor for Anesthesia and Analgesia next presented his choices for the journal’s best pediatric articles of 2017 to 2018. Beginning with the statement “You do not need consultants to improve process,” Dr. DiNardo presented a diverse series of papers to support his point. Working with the Department of Materials Management, anesthesiologists at Children’s National Health System in Washington, DC, applied Six Sigma and Lean methodologies including DMAIC (define, measure, analyze, improve, control) to identify pediatric anesthesia supply chain problems and address deficiencies (9). Interestingly, they used daily distance walked by anesthesia technicians and number of callouts for missing supplies as measurements which they analyzed before and after implementing improvements in anesthesia cart design. Using this approach, they were able to demonstrate improvements that were sustained at a year after implementation of changes.

The primary aim of the second study presented was to enact interventions to increase the rate of adverse incident reporting by pediatric anesthesiologists at Stanford’s Lucile Packard Children’s Hospital (10). The rationale for this project was to help identify risks and opportunities for improvement by improving reporting. Global and SMART (specific, measurable, achievable, realistic and timely) aims were identified, and a key driver diagram was developed to guide an improvement initiative. Run charts were used to track progress as multiple interventions were made. Electronic mandatory incident reporting data entry and an initiative to understand and address reporting barriers and motivators were associated with sustained increases in the adverse event reporting rate.

In a second paper from the Pediatric Craniofacial Collaborative Group, outcomes were compared between endoscopic-assisted and open repair in infants with craniosynostosis (11). Using propensity scoring, the authors analyzed data from 1382 infants < 12 months of age and found reduced utilization of blood and coagulation products, lower median blood donor exposure, decreased anesthesia time, surgical duration, ICU days, and hospital length of stay in the endoscopic group.  These findings demonstrated advantages of endoscopic-assisted craniofacial surgery for young infants that the authors hypothesize may result in improved outcomes and increased safety.

Anesthesia-related neurotoxicity was also the focus of a large retrospective, longitudinal data set study of over 38,000 children from New York and Texas, in which the effect of exposure to anesthesia at an age ≤ 5 years for a single minor surgical procedure was evaluated across 11 separate age categories (12).

The goal of this study was to determine whether the timing of exposure to anesthesia was associated with increased subsequent risk of diagnoses for any mental disorder. The authors found that children who underwent minor surgery requiring anesthesia had a small but statistically significant increased risk of mental disorder diagnoses and developmental delay and attention deficit/hyperactivity disorder, but timing of the surgical procedure did not alter this risk. They concluded that their findings do not support the concept of delaying a minor procedure to reduce long-term neurodevelopmental risks of anesthesia in children.

In an accompanying editorial, Nafiu and Davis (13) discussed the many issues that complicate interpreting data from this and other anesthesia-related neurotoxicity studies, focusing specifically on the nine criteria proposed by Sir Austin Bradford Hill to determine causality in observational or epidemiological studies (strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy).

Again in the anesthesia-related neurotoxicity realm, McCann and colleagues also published a manuscript focusing on a secondary aim of the general anesthesia compared to Spinal anesthesia (GAS) study, namely to compare rates of intraoperative hypotension between the two study arms to identify risk factors for intraoperative hypotension (14). Analyzing their data, the authors reported that the relative risk of hypotension was significantly greater by both intention to treat and per protocol analysis in the sevoflurane versus the spinal anesthesia group. Furthermore, interventions for hypotension occurred more commonly in the general anesthesia group. Group assignment, weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. This article was also published with an accompanying editorial highlighting the need to better correlate perioperative blood pressure values with immediate and longer term neurocognitive outcomes, and how the GAS and other similar studies can be helpful in evaluating this potential relationship (15).

Finally, Dr. DiNardo briefly touched on an Open Mind article by Nafiu and colleagues (16) advocating for a role for pediatric perioperative personnel in obesity prevention and its accompanying editorial (17).

David M. Polaner, MD (Children’s Hospital Colorado), Section Editor for Pediatric Anesthesia closed the session by presenting three papers which focused on physiologic research. Erb and colleagues reported the results of a prospective, observational study designed to determine whether high concentrations of sevoflurane adequately suppress laryngeal reflexes (18). Forty spontaneously breathing children, age three to seven years, were administered sevoflurane 2.5% (1 MAC) or 4.7% (ED95Intubation ) in random order, distilled water was sprayed onto the larynx under bronchoscopic view, and laryngeal and respiratory reflex responses were assessed.

Analysis of bronchoscopic images revealed that laryngospasm occurred in 18% of children at ED95Intubation while all other reflex responses were infrequent and similar at both concentrations. These results suggest that even deep levels of sevoflurane anesthesia do not fully blunt laryngeal reflexes.

Studies measuring cerebral blood flow in infants during deep hypothermia have demonstrated diminished cerebrovascular pressure autoregulation, but the coexistence of hypotension confounds the conclusion that deep hypothermia impairs autoregulation. Therefore, Goswami and colleagues studied the static rate of autoregulation between anesthetized normothermic and hypothermic neonatal piglets while hemorrhagic hypotension was induced (19). Using this model the authors demonstrated that the lower limit and static rate of autoregulation were similar in hypothermic and normothermic piglets, suggesting that hypotension is of greater importance when diminished cerebrovascular pressure autoregulation is observed.

As thoracoscopic surgeries in infants have become more common, concerns regarding the risks of intraoperative hypercapnia and acidosis have developed. To better define the impact of these metabolic perturbations, Neunhoeffer and colleagues compared the effects of thoracoscopy versus open abdominal surgery in neonates and infants on cerebral microcirculation, oxygen saturation, oxygen consumption, and cerebral fractional tissue oxygen extraction (20). During thoracoscopy an increase in arterial paCO2, and decrease in arterial pH were observed. In addition, a correlation between intrathoracic pressure exceeding 4 mm Hg and transient decrease in regional cerebral oxygen saturation was also noted. Further, periods of regional cerebral oxygen saturation below 20% from baseline were significantly more frequent during thoracoscopy. According to the authors, these findings suggest that thoracoscopic surgery may be associated with a decrease in regional cerebral oxygen saturation correlating with the applied intrathoracic pressure, and an inflation pressure > 4 mm Hg should be avoided.

Finally, Dr. Polaner recommended the audience read Anderson and Holford’s review discussing allometric scaling and what size predictors are most useful in calculating drug dosing in patients of various ages and sizes (21).

References

1. Burjek NE, Hishisaki A, et al.  Videolaryngoscopy versus Fiberoptic intubation through Supraglottic Airway in Children with a Difficult Airway, Analysis from the Multicenter Pediatric Difficult Intubation Registry. Anesthesiology. 2017 Sep;127(3):432-440.     
2. Hu D, Flick RP, et al. Association between Exposure of Young Children to procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort. Anesthesiology. 2017 Aug;127(2):227-240.   
3. Olbrecht VA, Skowno J, et al. An International, Multicenter, Observational Study of Cerebral Oxygenation during Infant and Neonatal Anesthesia. Anesthesiology. 2018 Jan;128(1):85-96.
4. Stricker PA Goobie SM, et al. Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction, A Multicenter Study from the Pediatric Craniofacial Collaborative Group. Anesthesiology. 2017 Feb;126(2):276-287.
5. Chreschan C, Graf G, et al. A Retrospective Analysis of the Clinical Effectiveness of Supraclavicular Ultrasound-guided Bracicephalic Vein (BCV) Cannulations in Preterm Infants Anesthesiology. 2018 Jan;128(1):38-43.   
6. Song IK, Kim EH, et al. Utility of Perioperative Lung Ultrasound in Pediatric Cardiac Surgery – single center prospective randomized controlled trial of 120 children younger than 5 years Anesthesiology. 2018 Apr;128(4):718-727.   
7. Kim EH, Lee JH, et al. Posterior Tibial Artery as an Alternative to the Radial Artery for Arterial Cannulation Site in Small Children. A Randomized Controlled Study. Anesthesiology. 2017 Sep;127(3):423-431.
8. Guardiola D, Guardiola M, Cook-Sather S. Texting under Anesthesia. Anesthesiology 2017; 127:192-3.
9. Roberts RJ, Wilson, AE, Quezado Z. Using Lean Six Sigma Methodology to Improve Quality of the Anesthesia Supply Chain in a Pediatric Hospital. Anesth Analg. 2017 Mar;124(3):922-924. 
10. Williams GD, Muffly MK, et al. Reporting of Perioperative Adverse Events by Pediatric Anesthesiologists at a Tertiary Children’s Hospital: Targeted Interventions to Increase the Rate of Reporting. Anesth Analg. 2017 Nov;125(5):1515-1523.   
11. Thompson DR, Zurakowski D, et al. Endoscopic versus Open Repair for Craniosynostosis in Infants using Propensity Score Matching to Compare Outcomes: A Multicenter Study from the Pediatric Craniofacial Collaborative Group. Anesth Analg. 2018 Mar;126(3):968-975.  
12. Ing C, Sun M, et al. Age at Exposure to Surgery and Anesthesia in Children and Association with Mental Disorder Diagnosis.  Anesth Analg. 2017 Dec;125(6):1988-1998.
13. Nafiu OO, Davis PJ. Association of Surgery and Anesthesia With Mental Disorder Diagnoses: What Would Sir Austin Bradford Hill Say? Anesth Analg. 2017 Dec;125(6):1845-184.
14. McCann ME, Withington DE, et al. Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study – A Prospective Randomized Trial) Anesth Analg. 2017 Sep;125(3):837-845.
15. Vutskits L, Skowno J. Perioperative Hypotension in Infants: Insights From the GAS Study. Anesth Analg. 2017 Sep;125(3):719-720.
16. Nafiu OO, Chimbira WT, Tait AR. Pediatric Preoperative Assessment: Six Million Missed Opportunities for Chldhood Obesity Education. Anesth Analg. 2018 Jan;126(1):343-345.
17. Davis PJ, Rofey DL, Goldstrohm SL. The Pediatric Elephant in the Room. Anesth Analg. 2018 Jan;126(1):21-22.
18. Erb TO, von Ungern-Sternberg BS, et al. Impact of high concentrations of sevoflurane on laryngeal reflex responses. Paediatr Anaesth. 2017 Mar;27(3):282-289.
19. Goswami D, McLeod K, et al. Static cerebrovascular pressure autoregulation remains intact during deep hypothermia. Paediatr Anaesth. 2017 Sep;27(9):911-917.
20. Neunhoeffer F, Warmann SW, et al. Elevated intrathoracic CO2 pressure during thoracoscopic surgery decreases regional cerebral oxygen saturation in neonates and infants – A pilot study. Paediatr Anaesth. 2017 Jul;27(7):752-759.
21. Anderson BJ, Holford NH. What is the best size predictor for dose in the obese child? Paediatr Anaesth. 2017 Dec;27(12):1176-1184.