Remembering the classics: Post-Anesthesia Apnea in the Newborn

Charles J. Cote, MD (and Myron Yaster MD)

I was reading the history of pediatric anesthesia article by Drs. Chrisine Mai and Paul Firth the other day highlighting the career of Dr. Charles (“Charlie”) Cote and thought, “wouldn’t it be great to have Charlie, A Smith award winner, summarize one of his key papers and tell us the back story of how it happened.  Soooo, without any further ado…Myron Yaster MD

Original Article

C J Coté, A Zaslavsky, J J Downes, C D Kurth, L G Welborn, L O Warner, S V Malviya. Postoperative apnea in former preterm infants after inguinal herniorrhaphy. A combined analysis. Anesthesiology; 1995 Apr;82(4):809-22. PMID: 7717551

Original Article (from history of peds anesthesia project)

Firth PG, Mai CL. The evolution of pediatric sedation and anesthesia patient safety: An interview with Dr Charles J. "Charlie" Cote. Paediatr Anaesth. 2020 Nov;30(11):1183-1190. PMID: 3356980

This classic paper on postanesthetic apnea in the newborn has been the source reference for this topic for many years.  The back story is interesting.  In 1977, when I was a fellow, a former preterm infant had undergone bilateral inguinal herniorrhaphies under general anesthesia with halothane at the Children’s Hospital of Philadelphia (CHOP).  He was observed for two hours in the PACU and then transported back to his floor with his mom and a transport person.  Upon arrival he was asystolic and not resuscitatable. Obviously, this shocked all of us to the core. Shortly thereafter, Dr. Jack Downes, the legendary chairman of the Department of Anesthesia at CHOP (see: Christine L Mai, Mark S Schreiner, Paul G Firth, Myron Yaster. The development of pediatric critical care medicine at The Children's Hospital of Philadelphia: an interview with Dr. John J. 'Jack' Downes. Paediatr Anaesth . 2013 Jul;23(7):655-64. PMID: 23679061), discussed the case with his friend, Dr. David Steward, Chair at the Hospital for Sick Children in Toronto, who was at CHOP as a visiting professor. On his return home, Dr. Steward examined his experiences and published the first retrospective case series (Steward DJ: Preterm infants are more prone to complications following minor surgery than are term infants. Anesthesiology 56:304-306, 1982, PMID: 7065438) illustrating a high incidence of post anesthesia respiratory complications in this patient population. 

The following year I and my colleagues published the first prospective study on this topic (Liu LMP, Coté CJ, Goudsouzian NG, et al: Life-threatening apnea in infants recovering from anesthesia. Anesthesiology 59:506-510, 1983 PMID: 6650906).  We found that in a mixed population of full term and preterm infants undergoing a variety of procedures that “anesthetics may unmask a defect in ventilatory control of prematurely born infants younger than 41-46 weeks conceptual age who have a preanesthetic history of idiopathic apnea.”  After these two papers, a series of prospective studies from a variety of institutions carried out over several years reported similar findings and some new observations, most importantly an apparent relationship of apnea with anemia. The editor of Anesthesiology at the time asked me to review the data and perform a meta-analysis.  It was clear that insufficient detail was available from the published papers to perform this type of analysis, but the authors of these papers agreed to send me their original data for a more detailed review.  This resulted in the classic paper cited above (PMID: 7717551).

The collegiality of all contributing authors allowed the statistician (Allan Zaslavsky) to take these data and develop multiple models (all patients, those with anemia, and those with obvious apnea in PACU).  The findings of this analysis are still valid in current day practice: the analysis revealed that the incidence of postoperative apnea was inversely proportional to gestational age at birth and postconceptual age at the time of surgery.  Anemia (hematocrit < 30%) was an independent risk factor. The authors concluded: “the probability of apnea in nonanemic infants free of recovery-room apnea is not less than 5%, with 95% statistical confidence until postconceptual age was 48 weeks with gestational age 35 weeks. This risk is not less than 1%, with 95% statistical confidence, for that same subset of infants, until postconceptual age was 56 weeks with gestational age 32 weeks or postconceptual age was 54 weeks and gestational age 35 weeks. Older infants with apnea in the recovery room or anemia also should be admitted and monitored”. This analysis supported the previous observations of Kurth et al (Kurth CD, Spitzer AR, Broennle AM, Downes JJ: Postoperative apnea in preterm infants. Anesthesiology 66:483-488, 1987 PMID: 3565813) and their data were in fact part of the final analysis cited above.

Interestingly, a more recent publication comparing the incidence of apnea following spinal vs general anesthesia (a spin off of The GAS Study)(Davidson AJ, Morton NS, Arnup SJ, et al: Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study—Comparing Apnea and Neurodevelopmental Outcomes, a Randomized Controlled Trial. Anesthesiology July 2015, Vol. 123, 38–54. PMID: 26001033) reported a lower incidence of early apnea with spinal but not an absence of apnea. They concluded that: “Regional anesthesia in infants undergoing inguinal herniorrhaphy reduces apnea in the early postoperative period. Cardiorespiratory monitoring should be used for all ex-premature infants.” Interestingly, life threatening apnea was still associated with the more modern inhalation agent sevoflurane.  Thus, despite all the advances in NICU treatment (inhaled surfactant, improved ventilation strategies, etc) this population is still at risk for developing post anesthesia apnea. Good science does not lie. 

Charles J. Cote MD

PS: As a 4th year medical student, I was a visiting student at Penn and CHOP in 1976 on an anesthesia clerkship.  It’s a long and funny story that I’d be delighted to tell, at the bar, during a SPA meeting. One of the first people I met was Charlie who was a fellow at the time.  As a fly on the wall, I watched in amazement as he and Dr. David Jobes performed the first right internal jugular vein, central line catheter placements using the Seldinger wire technique, in a newborn about to undergo cardiac surgery.  Small world!  Myron Yaster MD