Comparative Analysis of Inpatient Costs for Obstetrics and Gynecology Surgery Patients Treated With IV Acetaminophen and IV Opioids Versus IV Opioid-only Analgesia for Postoperative Pain.

BACKGROUND: Recovery from obstetrics and gynecology (OB/GYN) surgery, including hysterectomy and cesarean section delivery, aims to restore function while minimizing hospital length of stay (LOS) and medical expenditures. OBJECTIVE: Our analyses compare OB/GYN surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia with those who received IV opioid-only analgesia and estimate differences in LOS, hospitalization costs, and opioid consumption. METHODS: We performed a retrospective analysis of the Premier Database between January 2009 and June 2015, comparing OB/GYN surgery patients who received postoperative pain management with combination IV acetaminophen and IV opioids with those who received only IV opioids starting on the day of surgery and continuing up to the second postoperative day. We performed instrumental variable 2-stage least-squares regressions controlling for patient and hospital covariates to compare the LOS, hospitalization costs, and daily opioid doses (morphine equivalent dose) of IV acetaminophen recipients with that of opioid-only analgesia patients. RESULTS: We identified 225 142 OB/GYN surgery patients who were eligible for our study of whom 89 568 (40%) had been managed with IV acetaminophen and opioids. Participants averaged 36 years of age and were predominantly non-Hispanic Caucasians (60%). Multivariable regression models estimated statistically significant differences in hospitalization cost and opioid use with IV acetaminophen associated with $484.4 lower total hospitalization costs (95% CI = -$760.4 to -$208.4; P = 0.0006) and 8.2 mg lower daily opioid use (95% CI = -10.0 to -6.4), whereas the difference in LOS was not significant, at -0.09 days (95% CI = -0.19 to 0.01; P = 0.07). CONCLUSION: Compared with IV opioid-only analgesia, managing post-OB/GYN surgery pain with the addition of IV acetaminophen is associated with decreased hospitalization costs and reduced opioid use.

Intravenous acetaminophen in bariatric surgery: effects on opioid requirements.

BACKGROUND: Opioids are commonly used after bariatric surgery for pain control because of their potent analgesic effects. Nevertheless, the morbidly obese patient has increased risk for developing adverse effects produced by opioids (such as sedation, apnea, hypoxemia, ileus, and vomiting). Intravenous acetaminophen (IVA) has been evaluated in some specialties showing a reduction in opioid consumption. The purpose of this study was to evaluate the effect on opioid consumption when IVA is administered in bariatric surgery patients. MATERIAL AND METHODS: A retrospective study was performed in patients who underwent bariatric surgery. Group A included those patients who received IVA perioperatively and group B those who did not. The amount of opioids administered was calculated and compared for each group. RESULTS: Group A included 38 cases (44.7%) and group B included 47 cases (55.3%). A comparison was performed in terms of age (P = 0.349), body mass index (P = 0.311), gender (P = 0.890), American Society of Anesthesiologist score (P = 0.438), total surgical time (P = 0.497), perioperative complications (P = 0.786), number of procedures per surgeon (P = 0.08), and type of surgical procedure (P ≤ 0.01). Group A had a mean 24-h total opioid dose of 99.5 mg, whereas group B of 164.6 mg (P = 0.018). Group A received 39.5% less opioids than group B. A post hoc analysis determined a statistical power of 0.74. CONCLUSIONS: IVA used perioperatively can decrease opioid consumption in patients after bariatric surgery. Randomized trials are needed to corroborate these results.

Assessing efficacy of intravenous acetaminophen for perioperative pain control for oocyte retrieval: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the effect of preoperative intravenous (IV) acetaminophen versus oral (PO) acetaminophen or placebo on postoperative pain scores and the time to discharge in women undergoing oocyte retrieval. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Single academic fertility center. PATIENT(S): Women aged 18-43 years undergoing oocyte retrieval. INTERVENTION(S): Randomization to preoperative 1,000 mg IV acetaminophen and PO placebo (group A), IV placebo and 1,000 mg PO acetaminophen (group B), or IV and PO placebo (group C) MAIN OUTCOME MEASURE(S): Difference in patient-reported postoperative visual analog scale pain scores from baseline and the time to discharge. RESULT(S): Of the 159 women who completed the study, there were no differences in the mean postoperative pain score differences or the time to discharge. Although not statistically significant, the mean postoperative opioid dose requirement in group A was lower than that in groups B and C (0.24 vs. 0.59 vs. 0.58 mg IV morphine equivalents, respectively) due to fewer women in group A requiring rescue pain medication (8% vs. 19% vs. 15%, respectively). Group A also reported less constipation when compared with groups B and C (19% vs. 33% vs. 40%, respectively). The rates of postoperative nausea were similar, and there were no differences in embryology or early pregnancy outcomes between the study groups. CONCLUSION(S): Preoperative IV acetaminophen for women undergoing oocyte retrieval did not reduce postoperative pain scores or shorten the time to discharge when compared with PO acetaminophen or placebo and, thus, cannot currently be recommended routinely in this patient population. CLINICAL TRIAL REGISTRATION NUMBER: NCT03073980.

The analgesic efficacy of IV acetaminophen for acute postoperative pain in C-section patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: The rate of cesarean delivery is on the rise in the USA. Satisfactory postoperative analgesia remains a top priority for cesarean delivery. Multimodal analgesia with a reduction in opioid consumption and improvement in patient satisfaction is a goal for anesthesiologists caring for this patient population. Our study sought to assess whether IV acetaminophen in four divided doses over 24 h decreased pain scores and opioid requirements in patients undergoing cesarean delivery with neuraxial anesthesia. METHODS: 66 patients undergoing elective cesarean delivery under spinal anesthesia with hyperbaric bupivacaine 12 mg, fentanyl 10 µg, and preservative-free morphine 150 µg were randomized to receive either IV acetaminophen or IV placebo for four consecutive doses in the first 24 h postoperatively. The need for rescue medication using morphine equivalence, pain scores, patient satisfaction, and side effects were assessed by a blinded researcher in the first 24 and 48 h postoperatively. RESULTS: There was no difference in opioid requirements in the acetaminophen versus placebo group, 44.32 ± 23 mg versus 47.59 ± 28 mg (p = .607), respectively at 24 h. There was also no difference at 48 h, 57.95 ± 20 mg versus 56.59 ± 22 mg (p = .795). Postoperative pain scores, patient satisfaction, and adverse events were similar in both groups as well. CONCLUSIONS: The results of this study failed to demonstrate any additional benefits of administering multiple doses of IV acetaminophen for treating postoperative pain in patients who have undergone CS surgery and receiving intra-thecal morphine as part of their anesthesia and analgesia. TRIAL REGISTRY NUMBER: NCT02069184.

Prospective, Double-blind Evaluation of Perioperative Intravenous Acetaminophen and Ketorolac for Postoperative Pain and Opioid Consumption After Endoscopic Carpal Tunnel Release.

Background: The current opioid epidemic highlights the need for pain management strategies to decrease or eliminate postoperative use of opioid medications. The purpose of this study was to determine if perioperative administration of intravenous (IV) acetaminophen and/or IV ketorolac decreases postoperative pain and opioid consumption after endoscopic carpal tunnel release. Methods: In all, 44 subjects were enrolled in this randomized, double-blind, placebo-controlled study from October 2015 to April 2017 and divided into 4 treatment arms: placebo, IV acetaminophen, IV ketorolac, or both IV acetaminophen and IV ketorolac. Patients recorded pain at 8-hour intervals on an 11-point scale and daily opioid use for 7 days after surgery. Analysis of variance and Kruskal-Wallis tests were used to compare mean pain scores and opioid consumption. Results: Mean pain scores over the 7-day study period were lower in the placebo and IV acetaminophen groups. Patients in the placebo and acetaminophen groups reported less pain than those in the ketorolac and combination groups on postoperative days 6 and 7. Patients administered IV acetaminophen had lower daily mean opioid usage. In all, 50% of the patients did not take any opioids after surgery. Conclusions: There are small, statistically significant differences in postoperative pain and opioid consumption supporting the use of IV acetaminophen for pain control after endoscopic carpal tunnel release, though these results are likely not clinically relevant. We recommend continued investigation into multimodal pain management in upper extremity surgery as well as limiting the number and quantity of opioid prescriptions provided to patients postoperatively.

The role of intravenous acetaminophen in post-operative pain control in head and neck cancer patients.

OBJECTIVE: This study investigated the role of intravenous acetaminophen for alleviation of postoperative pain after surgical resection of head and neck cancers. METHODS: A single-center study was conducted, which investigated a prospective group of 48 participants who underwent surgery between April 2016 and May 2017 and postoperatively received scheduled IV acetaminophen (1 g every 6 hours for 4 doses) plus the standard opioid PCA and breakthrough narcotics. These were compared to a similar retrospective cohort of 51 patients who had surgery between January 2014 to March 2015 and only received an opioid patient controlled analgesia (PCA) pump and breakthrough narcotics. Outcome measures included averaged pain scores, total amount of narcotics received (in morphine equivalents), and number of PCA attempts measured in 8-hour intervals over the first 24 hours, as well as duration of PCA and length of stay. Statistical measures included descriptive analysis and gamma regression analysis. RESULTS: The acetaminophen group achieved equally low pain scores (0.8 ± 1.2 vs. 1.0 ± 1.3, P = .408) with significantly less total narcotics in the first 8 hours after surgery (13.5 ± 13.3 vs. 22.5 ± 21.5 MEs, P = .014). This group had a significantly decreased length of stay (7.8 ± 4.6 vs. 10.6 ± 7.6 days, P = .03). CONCLUSION: This study demonstrates that intravenous acetaminophen may play a role in reducing the total narcotic requirement in the first 8 hours after surgery and contribute to a decreased length of stay and potentially decrease cost to the patient and hospital overall. Future research should be aimed at comparing these groups in a randomized control study/setting. LEVEL OF EVIDENCE: 3.

Improved Outcomes Associated With the Use of Intravenous Acetaminophen for Management of Acute Post-Surgical Pain in Cesarean Sections and Hysterectomies.

BACKGROUND: Post-surgical pain impacts many patient outcomes. Effective pain management increasingly relies on multimodal analgesia regimens in which acetaminophen (APAP) is a key component. The aim of our study was to examine the impact of oral APAP versus intravenous (IV) APAP as a component of post-surgical pain management after Cesarean sections and hysterectomies. METHODS: A retrospective analysis of the Cerner HealthFacts® database (from January, 2011 to December, 2015) was conducted to compare outcomes of Cesarean section and hysterectomy surgery patients who received oral APAP to those who received IV APAP post-surgically. Length of stay (LOS), daily morphine milligram equivalent (MME) consumption, the presence of potential opioid-related adverse events (ORADEs), and total pharmacy costs were assessed. Adjusted results were derived using inverse probability weighted regression adjustment (IPW-RA) estimators based on covariates that included demographics, comorbidities, patient clinical characteristics, and hospital characteristics. RESULTS: The study identified 29,124 Cesarean section patients (24,612 oral APAP; 4,512 IV APAP) and 9,767 hysterectomy surgery patients (5,586 oral APAP; 4,181 IV APAP). Compared to the oral APAP group, the IV APAP group had reductions in adjusted LOS (Cesarean section: -11.7% days (P < 0.001), hysterectomy: -11.8% days (P = 0.005)), lowered adjusted daily MME consumption from day 0 to day 3 (Cesarean section: -1.6 mg (P < 0.001), hysterectomy: -1.7 mg (P = 0.014)), and reduced risk of ORADEs for Cesarean sections (relative risk of 0.45, P < 0.001). Total pharmacy costs were not significantly different between the two APAP groups. CONCLUSIONS: Post-surgical pain managed with IV APAP in patients undergoing Cesarean section or hysterectomy was associated with shorter LOS, reduced risk of ORADEs, and lower opioid consumption compared to patients managed with oral APAP, without adversely impacting total pharmacy costs.

Acute hepatotoxicity associated with therapeutic doses of intravenous acetaminophen.

BACKGROUND: IV acetaminophen at 4 g per day is considered safe, producing no hepatic failure in more than 1400 cases. Oxidation of acetaminophen forms a reactive intermediate that binds to cellular proteins resulting in acetaminophen-protein adducts (APAP-CYS). Serum concentrations of APAP-CYS have been found to correlate with acetaminophen-induced hepatotoxicity. We report a case of hepatotoxicity associated with therapeutic doses of IV acetaminophen, with elevated serum APAP-CYS. CASE DETAILS: The patient was a 92-year-old, 68 kg woman without known hepatic disease or ethanol abuse. On hospital day 3 she underwent laparoscopic reduction of internal hernias under general anesthesia. Surgery was uncomplicated and postoperatively she was treated with subcutaneous heparin and IV acetaminophen, 1 g every 6 h for almost 4 days (total dose = 13 g). At the start of therapy, transaminases were normal. On hospital day 5, she was noted to have marked transaminase elevations (AST: 4698 IU/L; ALT: 3914 IU/L) with increases in INR (1.68), ammonia (60 mcg/dL), and total bilirubin (1.8 mg/dL). Serum acetaminophen concentration was 15.3 mcg/mL 26 h after her last dose. Acetaminophen was discontinued and IV acetylcysteine was given and continued at the second maintenance dose rate for a second 16-hour infusion, at which time transaminases, INR, ammonia and total bilirubin were all improving. The patient was discharged 2 days later. Serum APAP-CYS concentrations in serum samples obtained during her hospitalization were elevated (peak = 4.81 µM on hospital day 5; expected range for therapeutic dosing <1.1 µM). CASE DISCUSSION: We have identified a case of acute liver injury associated with therapeutic dosing of IV acetaminophen. The serum APAP-CYS concentrations are consistent with that seen in cases of hepatotoxicity following repeated supratherapeutic acetaminophen ingestion. Several factors that likely contributed to her susceptibility included advanced age, post-operative status, a likely catabolic state and multiple acetaminophen doses over several days. These uncommon circumstances limit the generalizability of risk. We believe the findings are most consistent with acetaminophen-induced liver injury. CONCLUSION: This case illustrates a potential hazard of IV acetaminophen and demonstrates the potential utility of APAP-CYS adducts in evaluating causality in acute liver injury.

Comparative Analysis of Length of Stay and Inpatient Costs for Orthopedic Surgery Patients Treated with IV Acetaminophen and IV Opioids vs. IV Opioids Alone for Post-Operative Pain.

INTRODUCTION: Recovery from orthopedic surgery is oriented towards restoring functional health outcomes while reducing hospital length of stay (LOS) and medical expenditures. Optimal pain management is a key to reaching these objectives. We sought to compare orthopedic surgery patients who received combination intravenous (IV) acetaminophen and IV opioid analgesia to those who received IV opioids alone and compared the two groups on LOS and hospitalization costs. METHODS: We performed a retrospective analysis of the Premier Database (Premier, Inc.; between January 2009 and June 2015) comparing orthopedic surgery patients who received post-operative pain management with combination IV acetaminophen and IV opioids to those who received only IV opioids starting on the day of surgery and continuing up to the second post-operative day. The quarterly rate of IV acetaminophen use for all hospitalizations by hospital served as the instrumental variable in two-stage least squares regressions controlling for patient and hospital covariates to compare the LOS and hospitalization costs of IV acetaminophen recipients to opioid monotherapy patients. RESULTS: We identified 4,85,895 orthopedic surgery patients with 1,74,805 (36%) who had received IV acetaminophen. Study subjects averaged 64 years of age and were predominantly non-Hispanic Caucasians (78%) and female (58%). The mean unadjusted LOS for IV acetaminophen patients was 3.2 days [standard deviation (SD) 2.6] compared to 3.9 days (SD 3.9) with only IV opioids (P < 0.0001). Average unadjusted hospitalization costs were $19,024.9 (SD $13,113.7) for IV acetaminophen patients and $19,927.6 (SD $19,578.8) for IV opioid patients (P < 0.0001). These differences remained statistically significant in our instrumental variable models, with IV acetaminophen associated with 0.51 days shorter hospitalization [95% confidence interval (CI) -0.58 to -0.44, P < 0.0001] and $634.8 lower hospitalization costs (95% CI -$1032.5 to -$237.1, P = 0.0018). CONCLUSION: Compared to opioids alone, managing post-orthopedic surgery pain with the addition of IV acetaminophen is associated with shorter LOS and decreased hospitalization costs. FUNDING: Mallinckrodt Pharmaceuticals.

Postmarketing review of intravenous acetaminophen dosing based on Food and Drug Administration prescribing guidelines.

STUDY OBJECTIVES: To evaluate the appropriateness of intravenous acetaminophen dosing-prescribed dose, frequency, duration, and indication-based on United States Food and Drug Administration (FDA)-approved prescribing guidelines and to evaluate the adverse effect profile of intravenous acetaminophen. DESIGN: Retrospective chart review. SETTING: United States Navy medical center. PATIENTS: Three hundred patients who received intravenous acetaminophen from August 1, 2011, to August 1, 2012. MEASUREMENTS AND MAIN RESULTS: The indications, dose, frequency, and duration of intravenous acetaminophen were recorded for each patient. Adverse effects of intravenous acetaminophen were analyzed by thoroughly reviewing any adverse effects documented, including nausea, vomiting, headache, or any symptom specifically attributed to the drug. Baseline liver function tests, including aspartate aminotransferase and alanine aminotransferase levels, and elevations 3 times the upper limit of normal during intravenous acetaminophen therapy were recorded. The average patient weight was 78±21 kg, with 12 patients (4%) weighing less than 50 kg and 288 (96%) patients weighing 50 kg or greater. Two hundred forty-one patients (80%) were appropriately dosed, whereas 59 (20%) patients were not appropriately dosed based on the FDA-approved dosing. No patients exceeded the FDA-approved maximum daily dosing recommendations for intravenous acetaminophen (4 g). Sixty-five patients (22%) received intravenous acetaminophen for longer than 24 hours. Intravenous acetaminophen was well tolerated, without any reported adverse effects, including the commonly reported adverse effects of nausea, vomiting, headache, and insomnia. Ten patients (3%) had a documented history of liver disease and did not experience any adverse effects or increases in liver function tests after the administration of intravenous acetaminophen. CONCLUSION: Intravenous acetaminophen appeared to be a safe and effective analgesic and antipyretic agent. Dosing for patients weighing less than 50 kg needs to be appropriately weight adjusted. Intravenous acetaminophen can be used alone or in conjunction with opioids and other analgesics. Limitations of this study include its retrospective design, inability to assess outcomes of reducing opioid use, and short-term observation period.

Opioid use in knee arthroplasty after receiving intravenous acetaminophen.

BACKGROUND: Intravenous (IV) acetaminophen may be an effective component of multimodal postoperative pain management. The primary objective of this study was to evaluate the impact of IV acetaminophen on total opioid use in postoperative patients. The secondary objective was to evaluate the effect of IV acetaminophen on hospital length of stay. METHODS: This retrospective, case-control study evaluated the impact of IV acetaminophen on total opioid use in surgical patients. Patients were included if they received at least one perioperative dose of IV acetaminophen and underwent a surgical knee procedure. Controls were matched and randomly selected based on procedure type, age, and severity of illness. Postoperative opioids were converted into oral morphine equivalents, and overall use was compared between groups. RESULTS: One hundred patients were enrolled, with 25 patients receiving IV acetaminophen and 75 matched controls. A total of 135 mg versus 112.5 mg oral morphine equivalents were used in the IV acetaminophen group and control group, respectively (p=0.987). There were 45 mg/day oral morphine equivalents used in the IV acetaminophen group versus 37.5 mg in the control group (p=0.845). The median hospital length of stay in both groups was 3 days (p=0.799). CONCLUSION: IV acetaminophen did not significantly decrease postoperative opioid use in patients who underwent surgical knee procedures. In addition, there was a nonsignificant trend toward increased opioid use in the IV acetaminophen group. There was no significant difference in hospital length of stay between the IV acetaminophen group and the control group. These findings require further study in larger patient populations and in other orthopedic procedures that typically require longer hospital stays.

Multimodal analgesia reduces narcotic requirements and antiemetic rescue medication in laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: After bariatric surgery, patients are at risk for narcotic-related side effects. Multimodal pain management strategies should be used when possible to reduce the consumption of narcotic medication. The purpose of this study was to investigate whether multimodal analgesia reduces narcotic consumption and may have an influence on opioid-related side effects in patients undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB). METHODS: In this retrospective data analysis, we examined the data of a total of 181 consecutive patients undergoing LRYGB. In January 2011, i.v. acetaminophen became clinically available. Hydromorphone patient controlled analgesia (PCA) was replaced by i.v. acetaminophen and i.v. ketorolac (TNT-Tylenol and Toradol). The first 89 patients received postoperative hydromorphone PCA (PCA group). The next 92 patients received i.v. acetaminophen and i.v. ketorolac every 6 hours for the first 24 hours (TNT group). In the TNT group, 8 patients were excluded in the analysis. RESULTS: There were no differences in clinical characteristics between the groups except for smoking history. Patients treated with PCA required 4.2 mg hydromorphone in the postoperative period. Patients in the TNT group required 1.1 mg hydromorphone. This was a statistically significant reduction of opioids by 73.8%. After discharge from postanesthesia care unit, 34.8% of patients required antiemetic rescue medication (AERM) compared with 20.2% in the TNT group (P<.001). The relative risk (AERM/no AERM) in the postoperative period after postanesthesia care unit discharge is 1.75 (95% CI, 1.05-2.92). CONCLUSION: This study suggests that a multimodal analgesic regimen (TNT) can reduce postoperative narcotic consumption, which may lead to a reduction in the number of patients requiring AERM.