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Complications with opioid-based postoperative pain management have led to guideline recommendations for a multimodal analgesia strategy incorporating nonopioid agents. We evaluated the opioid-sparing effect of intravenous acetaminophen in patients undergoing transapical transcatheter aortic valve replacement.A multimodal pain management strategy that incorporated intravenous acetaminophen was retrospectively evaluated in 43 patients undergoing transapical transcatheter aortic valve replacement between November 2012 and March 2014. Before intravenous acetaminophen formulary availability, 23 patients received standard postoperative pain management interventions including intravenous narcotics and oral narcotics/acetaminophen. After intravenous acetaminophen availability, 20 patients received intravenous acetaminophen (4 g/d, ≥4 doses) and supplemental intravenous and nonacetaminophen oral narcotics. Daily narcotic dose (standardized to morphine equivalents), drug cost, and hospital length of stay were compared between groups.Baseline characteristics were similar between intravenous acetaminophen (n = 20) and nonintravenous acetaminophen (n = 23) patients including the Society of Thoracic Surgery mortality risk (10.5% vs 9.0%, P = 0.3). The median number of intravenous acetaminophen doses was 6.5 (interquartile range = 4.0–18.5), with a median cost per patient of US $221 (interquartile range = $136–$629). Patients who received intravenous acetaminophen used significantly fewer morphine equivalents on postoperative day 0 compared with patients not receiving intravenous acetaminophen (22.5 vs 45.0 morphine equivalents, P = 0.03) and had a shorter median length of stay (5.0 vs 7.0 days, P = 0.007). After adjusting for the Society of Thoracic Surgery risk, intravenous acetaminophen continued to be associated with a reduction in median postoperative length of stay [−1.9 days (95% confidence interval = −0.9 to −8.2 days), P = 0.049].In patients undergoing transapical transcatheter aortic valve replacement, a multimodal pain management strategy incorporating intravenous acetaminophen was associated with reductions in narcotic use on the day of surgery and overall length of stay.