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Opioid Use After Cardiac Surgery in Children With Down Syndrome*

Van Driest, Sara L. MD, PhD1; Shah, Anushi MS2; Marshall, Matthew D. PharmD3; Xu, Hua PhD2,4; Smith, Andrew H. MD, MSCI1; McGregor, Tracy L. MD, MSCI1,5; Kannankeril, Prince J. MD, MSCI1

Pediatric Critical Care Medicine: November 2013 - Volume 14 - Issue 9 - p 862–868
doi: 10.1097/PCC.0b013e31829f5d9d
Cardiac Intensive Care

Objectives: To determine the cumulative opioid doses administered to patients with Down syndrome after cardiac surgery and compare them with patients without Down syndrome.

Design: Retrospective observational comparative study.

Setting: PICU in a university-affiliated freestanding pediatric teaching hospital.

Patients: Infants and children who presented to our institution for heart surgery after July 1, 2008, and met the following criteria: 1) no opioid medications for 48 hours prior to surgery, 2) sternotomy approach with primary closure, and 3) no additional operative procedures in the 5 days after surgery. All patients with Down syndrome were included, and patients without Down syndrome with similar age, type of cardiac lesion, and length of surgical procedure were selected in a ~2:1 ratio, blinded to opioid exposure.

Interventions: None.

Measurements and Main Results: Clinical and demographic data were extracted from electronic medical record data. Univariate analyses and multivariate linear regression modeling were performed to determine the influence of Down syndrome, patient characteristics, and clinical covariates on weight-adjusted opioid dose. The differences in median cumulative opioid doses between those with Down syndrome (n = 44) and those without Down syndrome (n = 77) were not significant in the first 24 hours (+0.39 mg/kg [95% CI, –0.45 to +1.39 mg/kg]) or 96 hours (+0.54 mg/kg [95% CI, –0.59 to +2.07 mg/kg]) after surgery. Age, cardiac bypass time, benzodiazepines, and neuromuscular blocking agents were significantly correlated with opioid dose, but Down syndrome, gender, pain score, creatinine, acetaminophen, nonsteroidal anti-inflammatory drugs, and steroid medications were not. Patients with Down syndrome had longer hospital stays; in multivariate analysis, higher opioid exposures in the first 96 hours after surgery and higher peak serum creatinine values correlated with longer hospitalization.

Conclusions: This cohort did not provide evidence for opioid resistance in patients with Down syndrome. Younger age, longer cardiac bypass time, exposure to benzodiazepines, and neuromuscular blockade did correlate with increased opioid doses after cardiac surgery.

Supplemental Digital Content is available in the text.

1Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN.

2Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN.

3Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN.

4The University of Texas School of Biomedical Informatics at Houston, Houston, TX.

5Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN.

* See also p. 899.

This work was performed in the Monroe Carell Jr. Children’s Hospital at Vanderbilt and Vanderbilt University Medical Center.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by grant UL1 RR024975 from National Center for Research Resources/National Institutes of Health (NIH). Vanderbilt Institute for Clinical and Translational Research. Dr. Van Driest has been supported by NIH/National Institute of General Medical Sciences Clinical Pharmacology Training Program (5T32 GM007569-33). Ms. Shah and Dr. Xu are supported by NIH/National Cancer Institute (grant R01CA141307). Dr. Smith is supported by American Heart Association Clinical Research Program Grant (12CRP10560001). Dr. McGregor is supported by NIH/National Institute of Environmental Health Sciences (grant K12 ES015855).

Dr. Van Driest received grant support from NCRR/NIH grant UL1 RR024975 and NIH/NIGMS 5T32 GM007569-33. Drs. Shah, Marshall, Xu, Smith, and Kannankeril received grant support from NCRR/NIH grant UL1 RR024975. Dr. McGregor received grant support from NCRR/NIH grant UL1 RR024975, NIH/NIEHS grant K12 ES015855, and NIH/NICHD.

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©2013The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies