Sedatives, Analgesics Not Linked to Adverse Neurodevelopment in Neonates After Cardiac Surgery

Deborah Brauser

January 22, 2010

January 22, 2010 (Miami Beach, Florida) — Sedatives and analgesics given to neonates right before and after cardiac surgery are not associated with adverse neurodevelopmental outcomes, such as mental, motor, and vocabulary delays, according to the results of a new cohort study presented here at the Society of Critical Care Medicine (SCCM) 39th Critical Care Congress.

The study, which received one of the Congress' Annual Scientific Awards, was presented by first author Gonzalo Garcia Guerra, MD, assistant clinical professor in the Department of Pediatrics at the University of Alberta, Stollery Children's Hospital in Edmonton, and part of the Western Canadian Complex Pediatric Therapies Project Follow-Up Group.

According to the presentation, "although animal models have suggested detrimental effects of anesthetic drugs on the developing brain, it's been unclear whether those results could be extrapolated to human neonates."

"A lot of the current data suggest that that association would apply only to preterm babies," co-investigator Ari Joffe, MD, associate clinical professor of pediatrics at the University of Alberta/Stollery Children's Hospital and fellow member of the Western Canadian research collaborative, told Medscape Critical Care. "To our knowledge, this is the first study to examine this relationship in full-term neonates having cardiac surgery."

No Drugs Associated With Adverse Outcomes

For this study, the investigators retrospectively evaluated data from 95 neonates who underwent open heart surgery between April 2003 and December 2006 and survived.

"We looked back during this time at all the opioids, benzodiazepines, ketamine, and chloral hydrates received by each neonate, and added that to our database," explained Dr. Joffe. "We then adjusted for various factors, such as heart lesion, preoperative and postoperative severity of illness, and intraoperative factors, during the cardiac surgery to see if there was an association between these drug exposures and developmental outcome at 2 years of age."

Other variables evaluated include dose during hospitalization and number of days the drug was given. Neurodevelopmental outcome measures included the Adaptive Behavior Assessment System (ABAS) General Adaptive Composite score, the ABAS motor subscore, Bayley Scale of Infant Development (BSID) measures of mental and motor delay (score <70), and the BSID vocabulary delay (score <15th percentile).

Results showed that none of the drugs given for sedation and analgesia, in terms of their cumulative amount or daily dose, were associated with any adverse neurodevelopmental outcomes in the patients.

"We thought these results were reassuring, but I don't think they were really surprising," said Dr. Joffe. "The animal models are probably more equivalent to humans who are preterm, and our patients were all term neonates. Our study does not address preterm babies, but at least in these children, the findings are reassuring. Of course, ideally, these results should be confirmed by further studies."

He noted that it would be "virtually impossible not to give these drugs in these situations. These babies are critically ill and no one would want to hold back sedation and analgesia drugs. So it's a relief to see that in our findings there's no indication to change practice."

He reported that the investigators plan to continue following up with the children from the study. "We were looking at 2-year outcomes. As the children get older, we plan to look at their 5-year neurodevelopmental outcomes to make sure there's nothing more subtle there."

Heartening Results

"I thought it was of great interest that the authors were able to discern whether or not the use of sedatives and analgesics in this patient population had an impact on their long-term development," said session comoderator Bruce Greenwald, MD, FCCM, FAAP, professor of clinical pediatrics and chief of the Division of Pediatric Critical Care Medicine at Cornell University Weill Medical College in New York City, and Critical Care Congress cochair.

"It was heartening for me and the [SCCM] audience to learn that these drugs that we use regularly appear to be safe and that the authors were unable to find any negative consequences of their use. In fact, it would cause a great change in many of the practices of pediatric intensivists if they had found that these drugs are associated with long-term developmental problems," said Dr. Greenwald, who was not involved with the study.

"One would hope that if there was a consistent long-term negative association, reports to the [US Food and Drug Administration] and the weight of the evidence would alert the public," added Dr. Greenwald. "Interestingly, this was the first study that I know of that was directly geared toward answering this question."

He noted that although the study was of reasonable size, the results would be more useful and convincing if the study had been larger. "However, this is a difficult study to do, especially in neonates — to follow them for several years after this type of surgery. So although it would be wonderful if a larger study could be done at some point, this is a nice beginning."

Dr. Greenwald said that some of the more interesting questions that came up during the presentation included whether the authors looked at the duration of cardiopulmonary bypass or the duration of deep hypothermia that might have been used in the operating room on these patients. "In fact, they have a whole lot of data that they did not present because of the time constraints of the presentation format. I think many anxiously await the publication of an article that details some the aspects of the study not reported here. I look forward to reading that myself."

The registry from this follow-up study was funded by Alberta Health and Wellness. Dr. Joffe and Dr. Greenwald have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 39th Critical Care Congress: Abstract 25. Presented January 10, 2010.


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