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Apnea in the early postoperative period was reduced in infants undergoing inguinal herniorrhaphy who received regional anesthesia compared with general anesthesia.1 The study found that the strongest predictor of apnea was prematurity.
The complication of postoperative apnea is a known risk in neonates, and premature neonates are known to be at higher risk. This study compared spinal and general anesthesia (GA) to determine if spinal anesthesia (SA) reduced the risk of apnea as a secondary aim. In the future, neurodevelopmental outcomes at age five years will be examined for equivalence.
“The overall study, which evaluates the long term developmental effects of general anesthesia, is critically important to assure that we are not causing long term harm to a susceptible population,” said Daniel Davis, MD, Professor of Clinical Medicine and Department of Emergency Medicine Director at the University of California San Diego Center for Resuscitation Science. He was not involved in the study but commented as an outside expert in an interview.
“This particular analysis is important not only to establish the relative risks and benefits of general anesthesia versus regional anesthesia in a young population, but also to help define optimal post-operative monitoring strategies for these patients.”
This prospective trial randomized 722 infants undergoing inguinal herniorrhaphy to either regional anesthesia (RA) or GA on a 1:1 ratio between 2007 and 2013. The randomization was based on gestational age at birth, with three blocks: 26-29 weeks; 30-36 weeks, 6 days; and 37 weeks and more. The study included 28 sites in seven countries.
The intent-to-treat (ITT) analysis included 361 patients in the RA arm and 358 in the GA arm. The study included 394 premature infants and 325 term infants.
Early apnea lessened with regional anesthesia
At least one apnea was recorded for 25 patients (3%), including 10 in the RA arm and 15 in the GA arm. The apnea occurred most frequently in the early postoperative period, particularly in the GA group.
The odds of apnea in the overall time period up to 12 hours after surgery were not altered by receiving RA or GA (OR = 0.63; 95% CI, 0.31-1.30; p=.2133 by ITT).
Notably, the odds of early apnea were less in the RA arm than the GA arm (OR = 0.20; 95% CI, 0.05-0.91; p=.0367 by ITT). Also, the RA arm had less odds for needing a significant intervention for early apnea (OR = 0.09; 95% CI, 0.01-0.64; p=.0164). These effects were greater by analysis as per-protocol.
The level of intervention was lower for apnea in the RA arm. Among the infants who had postoperative apnea, such interventions as tactile stimulation, supplemental oxygen, bag mask ventilation, or CPR occurred for 86% in the GA arm and 50% in the RA arm. Among the nine (1.3%) children who required positive pressure ventilation or cardiopulmonary resuscitation within five days of surgery, six who had this event within 30 minutes of surgery were in the GA arm (1.7% of the GA arm).
Notably, two infants in the RA did not have apnea in the postanesthesia care unit but had multiple apneic episodes that started 6-7 hours postoperatively on the inpatient ward. These were treated with continuous positive airway pressure or bag and mask ventilation with transfer to intensive care.
Apnea incidence was not increased by a brief exposure to anesthesia or sedation in the RA arm, though if a full GA was administered, the risk of apnea approached that of a planned GA.
Risk factors for apnea
Overall, the apnea rate was relatively low. Among all infants, the absolute risk reduction for early apnea with allocation to the RA was 0.03 (95% CI, 0.004-0.05). For preterm infants, the absolute risk reduction for early apnea with allocation to RA was 0.04 (95% CI, 0.004-0.08). For term infants, the absolute risk reduction for early apnea was 0.006 (95% CI, -0.006-0.02).
All cases of apnea except one occurred in ex-premature infants. The incidence of apnea was 0.3% in term infants and 6.1% in preterm infants. Apnea risk was associated with prematurity (OR=21.87; 95% CI, 4.38-109.24), decreasing gestational age at birth, decreasing weight, decreasing postmenstrual age, a history of recent apnea, ever receiving methylxanthine, ever receiving ventilation through a tracheal tube, and ever needing oxygen support. Early apnea had similar risk factors, though less evidence was found for an association with a history of recent apnea or ever requiring ventilation with a tracheal tube.
How regional anesthesia affects apnea risk
“In this trial, there was no evidence that RA reduced the overall risk of observed apnea. In subgroup analyses, RA did reduce the risk of early postoperative apnea; however, there was no evidence that RA reduced the risk of late apnea,” stated the study authors in the discussion.
The apnea after RA was likely of lesser clinical importance, since RA reduced the degree of postoperative oxygen desaturation and the level of intervention for apnea.
Commentary
An accompanying commentary criticized the study for the lack of standardized postoperative monitoring, which likely resulted in a high likelihood for missed events and late detection of apnea with increased need for life-saving interventions such as bag mask ventilation.2 It was suggested that standardized, high-reliable postoperative monitoring might have prevented the nearly 2% incidence of life-threatening events in the study.
The commentary also noted that 19% of infants in the ITT RA arm were converted to GA or RA with sedation, which is an appreciable failure rate. The rate of apnea after RA with sedation was similar to that of RA alone.
References
1. Davidson AJ, et al. Anesthesiology. 2015; 123:38-54.
2. Kurth DC and Cote CJ. Anesthesiology. 2015; 123:15-17.
