Anesthesia and analgesia have been found to reduce morbidity and mortality in newborns after surgery.1,2 Although general anesthetics have been linked to “developmentally regulated increases in perinatal apoptosis and long term deleterious behavioral changes,” neuraxial anesthetics and analgesics are associated with fewer systemic adverse effects, according to a review published in Anesthesia & Analgesia.3,4
Despite findings that support the tolerability and efficacy of such agents, there is a dearth of evidence demonstrating improved clinical outcomes in neonates and infants, and there have been few assessments of their safety in terms of spinal toxicity in the early developmental period.
In neonates, epidural or intrathecal delivery of neuraxial agents, most commonly opioids, as well as clonidine, dexmedetomidine, ketamine, midazolam, and neostigmine, may be used to supplement and limit the use of general anesthesia for perioperative analgesia, or as a sole anesthetic for surgery of the abdomen or lower limb. A 2006 survey showed an increase in the number of central blocks performed on neonates (5.6% vs 3.4% from the previous 1994 survey) and infants <6 months (30% vs 16.5%).5 In another study, spinal anesthetics in neonates accounted for 30% of the total procedures performed at 1 center in France.6
Although the available evidence precludes firm conclusions because of insufficient data and variability in study design, reported benefits of neuraxial delivery in infants and neonates include reduced respiratory complications such as postoperative apnea, reductions in circulating stress hormones, maintenance of cardiovascular stability, reduced hospital stay, and improved surgical outcomes.7-11
While the incidence of severe complications caused by pediatric neuraxial analgesia is low, it is elevated in neonates and infants, with 0.4% vs 0.1% for neuraxial blocks in general, and 1.1% vs 0.49% for epidural blocks specifically.5,12 Another potential disadvantage of this approach is the risk for infection and neurological injury, although evidence indicating substantial rates of such events is not available.
In the 2012 review, the authors point to findings from their rodent studies in this area to illustrate that, for further advances, systematic preclinical assessments are needed regarding the comparative safety of various agents, with particular attention on “the therapeutic ratio of the neuraxially delivered agent, the developmental time of exposure to the agent, and assessment of neuropathology (apoptosis, myelination, gliosis and dendritic morphology) and long term functional outcomes.” In addition, because there is no exact match between developmental phases of rodent and human neonates, preclinical models evaluating the safety of neuraxial agents should include a variety of developmental ages.
In clinical practice, when “considering the choice of spinal analgesic adjuvants, many provide similar analgesia but not all have undergone systematic evaluations of spinal toxicity, and changing practice to include only agents with the widest demonstrable safety margin can be achieved without compromising clinical care,” the authors concluded.
Clinical Pain Advisor followed up with 1 of the authors of the review, Tony L. Yaksh, PhD, a professor in the Department of Anesthesiology and the Department of Pharmacology at the University of California, San Diego, to gain additional insights into this topic.
Clinical Pain Advisor: What prompted you and your coauthor to write this review?
Dr Yaksh: Newborn humans often require surgical interventions, such as for cardiac problems. There was a time in the early 1970s when it was thought that babies did not have the appropriate neural substrate for perceiving pain. Early work found that was not true and that babies, similar to adults, survived better with appropriate surgical anesthesia. So, through the early 1980s, there was an increasing utilization of general anesthesia; for example, gaseous anesthetics, injectable systemic anesthetics. In the early 1990s, there was a growing appreciation of the possibility that general anesthetics might have adverse effects on neonatal brain development. Although this effect is controversial, it has given many in neonatal anesthesiology pause for thought.
My coauthor, Suellen M. Walker, MBBS, PhD, is a pediatric anesthesiologist [at University College London] who is interested in neonatal pain and anesthesia; specifically, the role of spinal drug delivery in medicating such patients. [This] is readily achieved with a high degree of safety and has value only in that the drug effects are limited to the spinal cord. Further, the density of anesthesia and analgesia achievable by the spinal delivery of drugs is typically superior to that which can be achieved by a systemically administered drug. This all argues strongly for an increased utilization of neuraxial anesthesia.
Yet an important issue has been the question of how safe the spinal route is in the neonate. Until the work that Dr Walker and I have undertaken on neonatal safety in rats, there was no formal evaluation of spinal drug safety in the newborn. Accordingly, we had argued that proposing an increased utilization of spinal delivery in the newborn without such safety data might be an example of jumping from the frying pan into the fire. Accordingly, several years ago we initiated self-funded studies to develop the neonatal rat model.
This article originally appeared on Clinical Pain Advisor