Literature Reviews

Preterm Versus Term Children: Analysis of sedation/anesthesia adverse events and longitudinal risk

Authors: Havidich J, Beach M, Dierdorf S, Onega T, Suresh G, Cravero J
Pediatrics. 2016 Mar;137(3):e20150463.

Reviewer(s): Michael Hooper, MD Yale New Haven Hospital; and Kevin Couloures, DO, MPH Yale New Haven Hospital

Abstract
Background:
This study was a large prospective observational study looking at sedation/anesthesia adverse events and longitudinal risk in preterm versus term children using the PRSC database. 

Methods
Observational data was collected from the PSRC database on children who had received sedation/anesthesia for diagnostic and /or therapeutic procedures outside the operating room.  There were 57,227 patients from the ages of 0 to 22 years.  All adverse events and descriptive terms were predefined.  Using logistic regression and locally weighted scatterplot regressions for analysis. 

Results
Preterm and former preterm children had higher adverse event rates (14.7% vs 8.5%) compared with children born at term.  Their analysis revealed a biphasic pattern for the development of adverse sedation/anesthesia events. Airway and respiratory adverse events were most commonly reported.  MRI scans were the most commonly performed procedures in both categories of patients.

Conclusions
Patients born preterm are nearly twice as likely as likely to develop sedation/anesthesia adverse events, and this risk continues up to 23 years of age. The authors recommended obtaining birth history during the formulation of an anesthetic/sedation plan, with heightened awareness that preterm and former preterm children may be at increased risk. Further prospective studies focusing on the etiology and prevention of adverse events in former preterm patients are warranted.

Commentary
It has been established in multiple studies that preterm children and young children, particularly those under six months of age, are at increased risk for development of adverse events, with the majority of those being less serious events such as coughing, oxygen desaturation and airway obstruction. Previous studies have also recognized that preterm infants <60 months postgestational age are at increased risk of developing apnea after anesthesia.  In this study, preterm infants had an adverse event that was nearly double (8.5% vs. 14.7%) that seen in term infants.   The majority of the increased rate was due to a greater frequency of desaturation events, coughing and airway obstruction.  These risks can be mitigated if not controlled by an experienced sedation provider but only if the history of prematurity is known.

The authors also confirmed prior studies, which have demonstrated that well organized sedation services within predominately children’s hospitals have staff that are proficient at managing the known complications.  They attributed the lack of serious adverse events despite the increased rate of all adverse events to the preparation and training of all the sedation providers.  They were also able to confirm prior work that showed that medical specialty did not affect outcomes.

The surprising development was the prolonged affect prematurity has on sedation of former preterm children in the 10 to 13 year age range, who experienced the highest percentage of adverse events.  One possible explanation could be due the higher overall dose of inhalational agents (minimal alveolar concentration) needed in this population, which is similar to that seen infants.  To better understand this phenomenon, more work should be put in to elucidate differences in these former preterm and term preteenagers.  Other measures that would help better understand why these patients are at increased risk would be routine measurement of pulmonary function prior to sedation to better understand the lung mechanics.  Pre-adolescent children with history of prematurity could also represent a unique population that require increased doses of sedation due to their behavioral/developmental problems, which then places them at higher risk for adverse events.

Sub analysis of adverse events in the 0 to 6 month category revealed that the incidence of  apnea and oxygen desaturation were significantly different.  This seems to match the data published earlier, which established that preterm infants are at increased risk for apnea with anesthesia. The majority of the patients received propofol with or without adjunctive benzodiazepine or narcotics.  Propofol may have been the confounding factor since it is known to cause apnea and the varied pharmacokinetics and pharmacodynamics could certainly explain, at least to some degree, the increased risk of apnea seen in the preterm infants.  Further work will have to be done to elicit how much prematurity of the respiratory and nervous systems contribute to the increased risk seen in the preterm cohort.

The overall arching theme of the paper that preterm infants are at risk at least until they are in their 20’s is very interesting and helpful information.  Further studies should be carried out with the degree of prematurity noted, i.e. late pre-term vs. early pre-term, to better elucidate, whether the intuitive belief, that as prematurity increases the risk of adverse events increases is actually correct.  Prior analysis of PSRC data has already shown that children under one year old have increased risk regardless of prematurity.   When children are premature and under six months of age it may be prudent to delay imaging or procedures until they are >7 months of age to help mitigate this increased risk.  Strong consideration should also be given to risk/benefit calculations for any sedated procedure.  The method of sedation should also be considered since inhalational gases had the largest effect on desaturation while propofol was more likely to cause apnea.  More work clearly needs to be done to better understand risk in this unique population but this is certainly a good start.

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