While opioids pose an essential element of perioperative pain management, potential side effects as well as the escalation in therapeutic opioid use have rendered this entity a public health concern. Despite the fact that opioid related adverse effects are well established, population based data linking opioid dose levels to perioperative complications is largely missing. We therefore we sought to investigate the association between opioid prescription levels and perioperative outcomes using nationwide population based data of patients undergoing high volume orthopedic surgeries. We hypothesized that increased opioid amounts would be associated with a higher risk for postoperative complications.
Data was extracted from the national Premier Perspective database (2006-2013) on N=1,035,570 elective cases of patients undergoing lower joint arthroplasties and N=220,946 cases of spinal fusions. The study protocol was approved by the Institutional Review Boards of the Hospital for Special Surgery and Icahn School of Medicine at Mount Sinai. Multilevel multivariable logistic regression models measured associations between opioid dose prescription and postoperative outcomes, including myocardial infarction, and bradycardia, respiratory, gastrointestinal, and urinary complications, pulmonary embolism, deep venous thrombosis, cerebrovascular accident, postoperative infection, cost of hospitalization and length of hospital stay. Outcomes were studied by quartile of dispensed dose.
Compared to the lowest quartile of opioid dosing, high opioid prescription was associated with a more than 50% increased odds for gastrointestinal complications, deep venous thrombosis, and postoperative infections (p<0.001) in lower joint arthroplasties. Odds were increased by almost 30% for pulmonary embolism and more than more than 15% for respiratory and urinary complications (p<0.001). Higher opioid dose was not associated with increased risk for myocardial infarction. Moreover, the odds for cerebrovascular complications were significantly decreased by more than 25% with higher opioid use compared to opioid doses at the lowest percentile (p=0.003). In the spinal fusion cohort, which required significantly higher opioid dosages in general, findings were similar, but less pronounced.
Overall, higher opioid dose was associated with an increase in most, but not all postoperative complications, with the strongest effect seen for gastrointestinal, thromboembolic, and infectious complications. Less pronounced dose dependent effects were observed after spine fusions, despite higher opioid use in general, which could indicate a threshold in complication risk within the studied opioid dose range. Moreover, the lack of differences by low, medium or high opioid dose in the spine population, could suggest a risk plateau within higher opioid levels. Importantly, the impact on complication odds may not be uniform, as opioids may lack a negative impact or potentially even confer protective effects in terms of cerebrovascular events and myocardial infarction. Moreover, these findings are supported by current scientific mechanistic evidence and provide a foundation for formal testing of hypotheses in clinical trials in the context of balancing analgesia and side effects.