Response

This letter highlights several important issues. The use of intravenous epinephrine in cardiopulmonary resuscitation (CPR) in the Neonatal Intensive Care Unit (NICU) is potentially life saving. The current neonatal recommendations and guidelines for CPR in extremely low birthweight (ELBW) infants are, however, not evidence based, having been extrapolated from data obtained from more mature populations. While outcome data following NICU CPR demonstrate improved survival in more mature infants and following brief episodes,1 all our infants had “prolonged” CPR, receiving intravenous epinephrine according to standard guidelines.2 Infant survival was no better even when a clear precipitating cause was identified. The uniformly poor outcome following CPR demonstrated in the study population should make us continue to question the benefits of this intervention in infants ≤750 g birthweight.

We agree that the use of intravenous epinephrine as a first line inotropic agent is not routine practice in most NICUs. In our population, 17% of infants received it as first-line therapy, while in 83% of infants it was administered as a second-line agent. Of concern, the overall use of intravenous epinephrine increased over time despite an absence of published clinical evidence. The authors further expand on biologically plausible arguments why high doses of intravenous epinephrine both administered for inotropic support and in the CPR setting may be potentially disadvantageous in the most immature infants.

Exposure of infants in our study to both these aggressive interventions occurred almost exclusively in the early neonatal period, with a median age of death in all groups being <7 days. While it is difficult to comment on the “appropriateness” of therapy from this retrospective study, the suggestion that high-dose intravenous epinephrine caused a prolongation of the dying process is concerning.

These data on CPR and intravenous epinephrine as an inotrope highlight the possible pitfalls in extrapolating data obtained from more mature human populations and experimental animal models, and applying the results directly to the premature infant with an immature cardiovascular system.

We therefore would advocate caution in the use of these potentially life saving therapies in the high-risk ELBW population ≤750 g birthweight in the absence of evidence detailing proven benefit, and suggest the risks, benefits and appropriateness of these interventions be considered on a case-by-case basis for each individual infant.

References

  1. 1

    Chamnanvanakij S, Perlman JM . Outcome following cardiopulmonary resuscitation in the neonate requiring ventilatory assistance. Resuscitation 2000;45:173–180.

  2. 2

    Niermeyer S, Kattwinkel J, Van Reempts P, et al. International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines. Pediatrics 2000;106:E29.

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Campbell, M., Byrne, P. Response. J Perinatol 25, 225 (2005). https://doi.org/10.1038/sj.jp.7211249

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