Intravenous Acetaminophen Research Articles

Impact of opioids on P2Y12 receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial.

AimsPlatelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI.Methods and resultsThe Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37–215) vs. 175 (63–228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32–509) vs. 60 ng/mL (13–206), P = 0.007], immediately after primary PCI [326 ng/mL (94–791) vs. 115 ng/mL (38–326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281–974) vs. 372 ng/mL (95–635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1–5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3–7); P = 0.96].ConclusionThe iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

Opioid-Sparing Effect of Liposomal Bupivacaine and Intravenous Acetaminophen in Colorectal Surgery

BackgroundThis study evaluated the opioid-sparing effect of liposomal bupivacaine and intravenous acetaminophen in colorectal surgery. Materials and methodsThis study was a retrospective, 2 × 2 factorial cohort conducted at an academic medical center from May 2016 to February 2018. Patients undergoing open or minimally invasive colorectal resection were included. Exclusion criteria were age <18 y, surgery after second hospital day, ostomy, and allergy to acetaminophen, opioids, or bupivacaine. Intraoperative liposomal bupivacaine and intravenous acetaminophen administration within 18 h after surgery were evaluated. The primary outcome was intravenous morphine milligram equivalents administered within 24 h after surgery. A linear regression model adjusted for American Society of Anesthesiologists score, enhanced recovery after surgery management, open surgery, opioid use before surgery, and height was used for the primary analysis. ResultsAmong 486 included patients, 193 received both liposomal bupivacaine and intravenous acetaminophen, 93 received liposomal bupivacaine only, 104 received intravenous acetaminophen only, and 96 did not receive either. On average, patients received 21 (SD = 31) morphine equivalents over 24 h. Intraoperative liposomal bupivacaine was associated with a reduction of morphine equivalents (adjusted change −11, 95% CI −17 to −6), but intravenous acetaminophen was not (2, 95% CI −3 to 7). Intraoperative liposomal bupivacaine was associated with a reduction of length of stay (adjusted change = −1.2 d, 95% CI −2.1 to −0.3), but intravenous acetaminophen was not (adjusted change = 1.5 d, 95% CI 0.7 to 2.2). ConclusionsLiposomal bupivacaine was associated with a significant reduction of opioid use within 24 h after colorectal surgery, but intravenous acetaminophen was not.

Increasing non-opioid pain management in the cancer patient presenting to the emergency department.

237 Background: The opioid epidemic is claiming more than 115 lives daily in the US (1). Pain is commonly the chief complaint of cancer patients presenting to the emergency department (ED) and aggressively managed with opioids. A recent study of cancer patients presenting to the ED showed they were also at high risk for opioid misuse (2). Non-opioid analgesia is often avoided from concerns of masking fevers, intolerance due to nausea/vomiting, or bleeding risk in thrombocytopenia. Our aim was to identify opportunities to reduce opioid use while safely alleviating pain in patients presenting to the Emergency Department of a comprehensive cancer center. Methods: Following the PDSA model, baseline data on current opioid use was obtained and perceived barriers to non-opioid analgesia were identified through questionnaires. Comfort level with non-opioid analgesia in cancer patients and current pain management practice was also queried. Patients eligible for non-opioid analgesia (solid tumors, no fever, pain score &lt; 7) were then identified through retrospective chart review and the prevalence of contraindications for non-opioid (renal/liver failure, thrombocytopenia, oral intolerance) and patient preference for opioids was calculated. This data and opportunities to use non-opioid analgesia was shared with providers in education sessions. Medication order panels were modified to provide easy access to oral and intravenous acetaminophen (APAP) and nonsteroidal anti-inflammatory drugs (NSAIDs). After two months the change in opioid prescribing was calculated. Results: Providers self-reported barriers to prescribing opioids as: low platelets, patient preference, and poor oral intake. Of 237 patients presenting to the MDA Emergency Department with complaints of pain between January 2018 and May 2018, 76 (32%) were eligible for non-opioid analgesia. Only 3 patients had absolute contraindications to both APAP or NSAIDs. After provider education, order entry simplification and prescribing guidance, the use of non-opioid analgesia rose from 3.9% to 9.4%. Patient satisfaction with pain control rose from 57.4 to 60.4 % following the intervention based on Press Ganey results. Conclusions: There is opportunity for non-opioid acute pain management in the solid tumor patients. Contraindications to non-opioid analgesia are uncommon. In the emergency department, safe pain relief can be provided by non-opioids such as NSAIDs and APAP.

Intraoperative Administration of Intravenous Dexmedetomidine and Acetaminophen for Improved Postoperative Pain Management in Primary Palatoplasty

BACKGROUND: Effective pain management for primary palatoplasty (PP) is critical to minimizing risk for postoperative complications including hemorrhage and airway loss. Administration of intravenous (IV) dexmedetomidine and IV acetaminophen is a successful intraoperative analgesic with the additional benefit of being an opioid-sparing technique. The current study assesses the efficacy of intraoperative use of these medications in managing pain after PP. METHODS: We reviewed our ongoing prospective database of patients undergoing PP from April 2009 to July 2018. We excluded patients who did not receive both medications or received additional intraoperative ketorolac. Patients were divided into those who received intraoperative IV dexmedetomidine and IV acetaminophen (Group 1) and those who did not (Group 2). Outcome variables included postoperative narcotic use by morphine milligram equivalents (MME), time to oral intake, need for supplemental oxygen, length of stay (LOS), and rate of complications (eg, bleeding requiring exploration or readmission) within the 30-day postoperative period. Baseline characteristics were compared in both groups. Continuous variables were compared using t test for normally distributed data and Mann-Whitney U test for skewed data, whereas categorical variables were compared using chi-square test or Fisher’s exact test. Multivariable linear regression was used to analyze continuous outcomes, and multivariable Poisson regression with robust variance estimation was used to analyze binary outcomes. RESULTS: One hundred ninety-three patients met inclusion criteria (Group 1, N = 54; Group 2, N = 139). Median age at PP was 11.7 (interquartile range, 10.4–15.5) months for Group 1 and 11.3 (interquartile range, 9.8–14.2) months for Group 2 (P = 0.13). Baseline characteristics such as weight, gender, type of palatoplasty, Veau classification, syndromic diagnosis, and prior use of Latham device were consistent between groups. ASA scores were found significantly different (ASA 1: 11.1% versus 29.7%, ASA 2: 75.9% versus 61.6%, ASA 3: 13.0% versus 8.7%, for Groups 1 and 2, respectively; P = 0.02). Group 1 required significantly lower doses of postoperative acetaminophen (mean dose: 71.0 mg/kg, 95% CI: 57.8–84.3 versus 90.9 mg/kg, 95% CI: 82.7–99.1; P = 0.01), as well as lower fentanyl requirements in the recovery room (mean dose: 0.68 µg/kg, 95% CI: 0.48–0.88 versus 1.18 µg/kg, 95% CI: 1.06–1.31; P < 0.001). Although Group 1 patients had shorter LOS, shorter duration to oral intake, lower pain scores, less narcotic requirements for breakthrough pain, and less 30-day complication rates (1.8% versus 5.0%; P = 0.45), these differences did not reach statistical significance. CONCLUSION: The addition of intraoperative IV dexmedetomidine and IV acetaminophen during PP provides effective perioperative pain control, resulting in statistically significant decreased need for postoperative pain medication. Our study also documents an overall trend for decrease in LOS, time to oral intake, pain scores, total narcotic requirements, and postoperative complications. These results warrant larger studies to confirm the statistical significance of some variables.

Comparison of analgesic efficacy of acetaminophen monotherapy versus acetaminophen combinations with either pethidine or parecoxib in patients undergoing laparoscopic cholecystectomy: a randomized prospective study.

Aim To investigate analgesic effect of three different regimens of combination of analgesics administered to patients undergoing laparoscopic cholecystectomy. Methods Patients undergoing laparoscopic cholecystectomy were randomly allocated to one of three groups on admission, depending of a prescribed post-operative analgesic regimen. Patients allocated to the group A received a combination of intravenous (IV) acetaminophen and intramuscular (IM) pethidine, patients in the group B received a combination of IV acetaminophen and IV parecoxib, and the patients of the group C received IV acetaminophen monotherapy. Analgesic therapy was administered at regular intervals. Pain was evaluated utilizing the numeric rating scale (NRS) at 5 time points: the first assessment was done at 45 minutes, the second, third, fourth and fifth at 2, 6, 12, and 24 hours post-administration, respectively. Postoperative pain intensity was measured by NRS within the groups and between the groups at each time they analysed using one-way repeat measured ANOVA and Post Hoc Test-Bonferroni Correlation. Results A total of 316 patients were enrolled. The analgesic regimens of groups A and B (combination regimens consisting of IV acetaminophen and intramuscular pethidine and IV acetaminophen and IV parecoxib, respectively) were found to be of equivalent efficacy (p=1.000). In contrast, patients in group C (acetaminophen monotherapy) had higher NRS scores, compared to both patients in groups A (p<0.01) and B (p<0.01). Conclusion This study confirms the notion of a significant opioid-sparing effect of parecoxib in postoperative pain management after laparoscopic cholecystectomy.

Effects of preemptive analgesia with intravenous acetaminophen on postoperative pain relief in patients undergoing third molar surgery: a prospective, single-blind, randomized controlled trial.

Background The efficacy of preemptive analgesia in managing postoperative pain remains controversial. The aim of this study was to compare the efficacy of intravenous (IV) acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar. Material and Methods This prospective randomized clinical trial included 120 patients. The patients were assigned to one of three groups: the preoperative-treatment group (pre-group), which received 1000 mg of IV acetaminophen 20 min before surgery; the postoperative-treatment group (post-group), which received 1000 mg of IV acetaminophen after surgery; the no-treatment group (control-group), which did not receive any analgesic. Rescue analgesic (60 mg loxoprofen) was issued to each patient, with instructions on self-administration if needed. For the rescue medication usage, the time of first loxoprofen usage and the total amount of loxoprofen consumption were obtained for a 17-hour period after surgery. We measured pain using the visual analogue scale at 1 hour and at 2, 3, 4, 5, and 15 hours after surgery. Results There was no significant difference in pain level among the three groups at any time interval. However, the pre-group demonstrated significantly lower rescue analgesic consumption and longer time until initial administration. Conclusions Administration of IV acetaminophen before third molar surgery provides more effective pain control than postoperative administration and no treatment. Key words:Preemptive analgesia, acetaminophen, impacted third molar, pain relief, randomized controlled trial.

S2467 Acute Liver Failure Associated With Therapeutic Doses of Intravenous Acetaminophen

INTRODUCTION: Drug induced liver injury is an uncommon, but important phenomenon responsible for nearly half of all acute liver failure (ALF) cases in the US. The majority of these cases are due to Acetaminophen (APAP) which is hepatotoxic in a dose-dependent pattern. Current guidelines suggest that daily dosing of less than 4 grams a day is safe. However, this dose can be hepatotoxic in patients with underlying liver disease, longer duration of use or malnutrition. The following case demonstrates therapeutic acetaminophen dosing causing acute liver failure. CASE DESCRIPTION/METHODS: A 67-year-old Caucasian female with a BMI of 19.7 kg/m2.was admitted for bowel obstruction due to adenocarcinoma in the sigmoid colon. She had no history of liver disease, alcohol use, acetaminophen use and had normal aminotransferases on admission. The patient remained hemodynamically stable while a pre-surgical evaluation was conducted. She received an average of 3-4g/day of IV APAP for pain over 4 days and was on a liquid diet. On hospital day 5, laboratory evaluation showed an INR of 6.1, which was notably 1.0 before admission, and her liver chemistries were markedly elevated in a hepatocellular pattern. The patient had new psychomotor slowing meeting criteria for ALF. She was not a transplant candidate. Her acetaminophen level was 58.9 mcg/mL 2-hours after her last dose. APAP was discontinued and IV NAC was started. Evaluation of other causes of liver failure to include ultrasound of liver and serologic evaluation for EBV, CMV, HSV, HAV, HBV, HEV, AIH, and Wilson’s disease were unremarkable. Review of her medical record did not reveal any medications to explain her acute liver failure. The patient was closely monitored in the ICU and the coagulopathy, mental status and liver chemistries all improved. A presumptive diagnosis of APAP induced ALF was made. She subsequently underwent an open colectomy without complication. DISCUSSION: While generally safe in therapeutic dosing, we present a case of IV APAP causing ALF. Therapeutic dosing causing hepatoxicity has been associated with malnourishment, low BMI, advanced age, fasting, and longer duration of use. IV APAP has slightly different pharmacodynamics that may increase this risk but has been rarely described. This patient’s fasting state, age and malnutrition likely contributed to ALF. Similar to patient’s with cirrhosis, lower dosing (< 2 G/day) may be more appropriate in this patient population.Table 1.: Hospital Course with Laboratory Data.Figure 1.: Hospital Course with Laboratory Data.Figure 2.: Acetomenophen Dosing during admission.

Effectiveness of scheduled intravenous acetaminophen in the postoperative pain management of video-assisted thoracic surgery.

The scheduled administration of intravenous acetaminophen (scheduled-IV-AcA) is one of the more effective multimodal analgesic approaches for postoperative pain in abdominal/orthopedic surgeries. However, there is little evidence concerning scheduled-IV-AcA after general thoracic surgery, especially when limited to video-assisted thoracoscopic surgery (VATS). We investigated the efficacy of scheduled-IV-AcA administration in patients after undergoing VATS. Ninety-nine patients who underwent VATS lobectomy or segmentectomy via an 8-cm access window and 1 camera port were retrospectively reviewed by categorizing them into groups either with scheduled-IV-AcA (Group AcA: n = 29) or without it (Group non-AcA: n = 70). Group AcA received 1g of IV-AcA every 6h from the end of the operation until the end of POD2. Postoperative pain was measured using a numeric rating scale (NRS) three times per day until discharge. NRS scores were significantly lower in Group AcA with motion (on POD1 to the first point of POD2) than in Group non-AcA. Group non-AcA was also more likely to use additional analgesics than Group AcA (39% vs. 17%, p = 0.058). Scheduled-IV-AcA administration is a safe and effective multimodal analgesic approach in patients undergoing VATS pulmonary resection via an 8-cm access window.

64. Intravenous vs oral acetaminophen administration in perioperative care of one- and two-level LLIFs with instrumented posterior lumbar fusion: a comparative effectiveness study

BACKGROUND CONTEXT Since 2000, the annual death toll from opioid associated overdose has increased by over 300%. To reduce the opioid consumption, physicians have used alternative approaches, which have proven to not only be effective, but also reduce the side effects such as nausea, constipation, and addiction. IV acetaminophen has been shown to successfully accomplish the reduction in opioid use, however, it is an expensive alternative. Testing the efficacy of IV acetaminophen vs its oral formulation will likely modify future postoperative pain management regimens while also addressing cost-effectiveness. PURPOSE To prospectively evaluate clinical outcomes and determine the cost effectiveness of IV vs oral (PO) acetaminophen following lumbar circumferential spine surgery. We hypothesize that IV acetaminophen will perform better than PO in terms of length of stay, morphine equivalence, and change in VAS scores from baseline. STUDY DESIGN/SETTING A prospective, single-center, randomized control trial. PATIENT SAMPLE Patients between the ages of 18-85 who underwent circumferential lumbar fusion surgery, while failing conservative treatment for more than 6 months were included in the study. Patients were excluded if they had already undergone lumbar surgery at the index level(s), were diagnosed with osteoporosis, had dysphagia prohibiting oral administration, or had a history of substance abuse. OUTCOME MEASURES Outcome measures included opioid equivalence, length of hospital stay, VAS measurements, and Oswestry Disability Index (ODI) scores. METHODS Once enrolled, patients were randomized to either the IV or PO acetaminophen treatment groups. Preoperatively, patients completed a baseline analgesic regimen questionnaire, surveys including VAS, SF-12, and ODI, and were administered their first acetaminophen dose within three hours of first incision. Postoperatively, patients received seven subsequent doses of their assigned acetaminophen, with access to supplemental analgesics if needed. Analgesic usage and VAS scores were monitored until discharge. Surveys were completed at six weeks and six months follow-up. RESULTS Average daily opioid consumption for the IV group was significantly lower than the PO group during the immediate postoperative period. Average length of stay was similar between groups, 3.3 days for PO and 3.7 days for IV. VAS back and leg scores were not statistically different between groups, however, both groups experienced a decrease by more than the minimally clinically important difference (MCID) of 12 points from baseline. ODI also decreased by the MCID at the 6-month follow-up, which was defined as 12.8% for ODI. CONCLUSIONS Along with an overall reduction in opioid usage, patient-reported outcomes depict successful improvement of pain management with the use of IV acetaminophen following circumferential spinal fusion surgery. Furthermore, despite the large discrepancy between the two formulations in cost-to-perceived-benefit ratio, the significant reduction of opioid usage and, therefore, its associated costs, provides a far less dramatic divergence. The continued testing of the efficacy of IV acetaminophen vs its oral formulation will likely modify future postoperative pain management regimens while also addressing the opioid epidemic plaguing communities across the US. FDA DEVICE/DRUG STATUS OFIRMEV (Approved for this indication).

Evidence for the Efficacy of an Opioid-Sparing Effect of Intravenous Acetaminophen in the Surgery Patient: A Systematic Review.

Intravenous (IV) acetaminophen is used in multimodal analgesia to reduce the amount and duration of opioid use in the postoperative setting. A systematic review of published randomized controlled trials was conducted to define the opioid-sparing effect of IV acetaminophen in different types of surgeries. Eligible studies included prospective, randomized, double-blind trials of IV acetaminophen compared with either a placebo- or active-treatment group in adult (age ≥18 years) patients undergoing surgery. Trials had to be published in English in a peer-reviewed journal. A total of 44 treatment cohorts included in 37 studies were included in the systematic analysis. Compared with active- or placebo-control treatments, IV acetaminophen produced a statistically significant opioid-sparing effect in 14 of 44 cohorts (32%). An opioid-sparing effect was more common in placebo-controlled comparisons. Of the 28 placebo treatment comparisons, IV acetaminophen produced an opioid-sparing effect in 13 (46%). IV acetaminophen produced an opioid-sparing effect in only 6% (one out of 16) of the active-control groups. Among the 16 active-control groups, opioid consumption was significantly greater with IV acetaminophen than the active comparator in seven cohorts and not significantly different than the active comparator in eight cohorts. The results of this systematic analysis demonstrate that IV acetaminophen is not effective in reducing opioid consumption compared with other adjuvant analgesic agents in the postoperative patient. In patients where other adjuvant analgesic agents are contraindicated, IV acetaminophen may be an option.

Intravenous acetaminophen vs intravenous ibuprofen to close a patent ductus arteriosus closure: A pilot randomized controlled trial.

Intravenous acetaminophen vs intravenous ibuprofen to close a patent ductus arteriosus closure: A pilot randomized controlled trial.

COMPARISON OF POST OPERATIVE PAIN WITH EFFICACY OF INTRAVENOUS ACETAMINOPHEN VERSUS KETAMINE AMONG PATIENTS UNDERGOING ABDOMINAL HYSTERECTOMY

Objective; To determine the effectiveness in terms of postoperative pain with intravenous acetaminophen versus ketamine among women undergoing abdominal hysterectomy. Material and Methods; A total of 114 women undergoing abdominal hysterectomy were taken in this study. The study was conducted at Akhtar Saeed Trust Hospital, Lahore and Nishtar Hospital Multan. Data was analyzed with statistical analysis program (SPSS version 21). Analysis was done to compare proportion of acetaminophen group and ketamine group. Chi-square test was applied to compare both groups in terms of efficacy taken p ≤0.05 as significant. Results; Our study comprised of 114 ladies undergoing abdominal hysterectomy, mean age of the study cases was 54.13 ± 6.89 years (with minimum age of the patients was 39 years while maximum age was 68 years). Majority of our study cases i.e. 92 (80.7 %) had parity more than 3 and American Society of Anesthesiology (ASA) score level 1 in 93 (81.6%). Sixty one (53.1%) belonged to rural areas, while mean duration of surgery was 72.80 ± 11.32 minutes. Mean BMI level in our study cases was noted to be 23.98 ±4.17 Kg/m 2 and obesity was present in 34 (29.8%) of our study cases. Efficacy was noted in 60 (52.6 %) of our study cases. Efficacy was 73.7% study cases in group A while 18 (31.6%) in group B (p=0.000). Conclusion; Our study results support the use of intravenous acetaminophen (IVA) for pain management in patients undergoing abdominal hysterectomy compared with ketamine. Intravenous acetaminophen is safe, reliable and effective for the pain management in postoperative abdominal hysterectomy patients which was associated with shorter hospital stay and cost effective for the suffering families. No adverse reactions were noted in this study with the use of intravenous acetaminophen. Keywords; Intravenous acetaminophen, Ketamine, Abdominal Hysterectomy. DOI: 10.7176/JMPB/67-04 Publication date: August 31 st 2020

In Reply to the Letter to the Editor Regarding “Intravenous Acetaminophen (Paracetamol) for Postcraniotomy Pain; Systematic Review and Meta-analysis of Randomized Clinical Trials”

In Reply to the Letter to the Editor Regarding “Intravenous Acetaminophen (Paracetamol) for Postcraniotomy Pain; Systematic Review and Meta-analysis of Randomized Clinical Trials”

Inpatient Perioperative Formulary Restriction of Intravenous Acetaminophen at Vizient Partner Hospitals: A National Survey of Pharmacists.

Purpose: Despite potential benefits of intravenous (i.v.) administration of acetaminophen (APAP), consistent outcome data are lacking. This, combined with the higher acquisition cost of the drug, has led to variation in i.v. APAP management strategies. This project evaluated the contemporary formulary status and restrictions of i.v. APAP in the perioperative setting. Methods: A survey focusing on i.v. APAP formulary restriction in the perioperative setting was developed by the Vizient Pharmacy Research Committee and distributed to Vizient Pharmacy Program participant listservs for Pharmacy Directors or Drug Information Pharmacists. The four survey domains included hospital characteristics, perioperative i.v. APAP formulary status and prescribing restrictions, perioperative i.v. APAP use, and perioperative i.v. APAP medication use evaluation (MUE) results. Responses were collected and summarized, and primary outcomes were evaluated using Fisher's exact test. Results: A total of 1195 surveys were distributed with a response rate of 19%. Respondents were equally distributed between academic medical centers (AMC) and non-academic medical centers (non-AMC). Two cohorts were examined: those with i.v. APAP on formulary and those without. The non-AMCs showed a larger proportion of hospitals with the medication on formulary (P = .041). Regarding formulary decision-making, the AMCs were more considerate of value. Several different practices were employed to limit or restrict i.v. APAP. Conclusion: A survey of directors of pharmacy and drug information specialists revealed that the majority of hospitals have i.v. APAP on formulary for perioperative use, but use is restricted. Differences in i.v. APAP formulary practices between AMCs and non-AMCs warrant further consideration.

Effect of Intravenous Acetaminophen on Postoperative Hypoxemia After Abdominal Surgery

Opioid-induced ventilatory depression and hypoxemia is common, severe, and often unrecognized in postoperative patients. To the extent that nonopioid analgesics reduce opioid consumption, they may decrease postoperative hypoxemia. To test the hypothesis that duration of hypoxemia is less in patients given intravenous acetaminophen than those given placebo. Randomized, placebo-controlled, double-blind trial conducted at 2 US academic hospitals among 570 patients who were undergoing abdominal surgery, enrolled from February 2015 through October 2018 and followed up until February 2019. Participants were randomized to receive either intravenous acetaminophen, 1 g (n = 289), or normal saline placebo (n = 291) starting at the beginning of surgery and repeated every 6 hours until 48 postoperative hours or hospital discharge, whichever occurred first. The primary outcome was the total duration of hypoxemia (hemoglobin oxygen saturation [Spo2] <90%) per hour, with oxygen saturation measured continuously for 48 postoperative hours. Secondary outcomes were postoperative opioid consumption, pain (0- 10-point scale; 0: no pain; 10: the most pain imaginable), nausea and vomiting, sedation, minimal alveolar concentration of volatile anesthetic, fatigue, active time, and respiratory function. Among 580 patients randomized (mean age, 49 years; 48% women), 570 (98%) completed the trial. The primary outcome, median duration with Spo2 of less than 90%, was 0.7 (interquartile range [IQR], 0.1-5.1) minutes per hour among patients in the acetaminophen group and 1.1 (IQR, 0.1-6.6) minutes per hour among patients in the placebo group (P = .29), with an estimated median difference of -0.04 (95% CI,-0.18 to 0.11) minutes per hour. None of the 8 secondary end points differed significantly between the acetaminophen and placebo groups. Mean pain scores within initial 48 postoperative hours were 4.2 (SD, 1.8) in the acetaminophen group and 4.4 (SD, 1.8) in the placebo group (difference, -0.28; 95% CI, -0.71 to 0.15); median opioid use in morphine equivalents was 50 mg (IQR, 18-122 mg) and 58 mg (IQR, 24-151 mg) , respectively, with a ratio of geometric means of 0.86 (95% CI, 0.61-1.21). Among patients who underwent abdominal surgery, use of postoperative intravenous acetaminophen, compared with placebo, did not significantly reduce the duration of postoperative hypoxemia over 48 hours. The study findings do not support the use of intravenous acetaminophen for this purpose. ClinicalTrials.gov Identifier: NCT02156154.

Role of intravenous acetaminophen in pediatric anterior cruciate ligament reconstruction

BackgroundIntravenous acetaminophen is used as part of a multimodal analgesia regimen for a variety of surgical procedures. In 2015, we implemented a standardized clinical management guideline for patients undergoing anterior cruciate ligament reconstruction. In this study we investigate the clinical impact of intravenous acetaminophen in pediatric patients undergoing arthroscopic anterior cruciate ligament reconstruction managed with and without intravenous acetaminophen. The primary hypothesis of this study was that patients managed with intraoperative intravenous acetaminophen would require less total in-hospital opioid medications. MethodsIn this retrospective cohort study, we compared all patients aged 10 to 21 years of age who underwent arthroscopic anterior cruciate ligament reconstruction at any of the Children's Hospital of Philadelphia locations between December 1, 2015 and November 30, 2017. The patients were grouped based on the administration of an intraoperative dose of intravenous acetaminophen (Group A) or those managed without intraoperative intravenous acetaminophen (Group B). ResultsWe identified 318 patients who underwent an arthroscopic anterior cruciate ligament reconstruction. Patients were similar in age, gender, weight, and duration of surgery. When we grouped the patients based on location of surgery (main hospital vs. ambulatory surgery center), we found that the dose of total in-hospital opioid was not significantly different between the Group A and Group B at the main hospital [difference of mean (95% CI) 0.013 (-0.005, 0.032), p = 0.16); and at the ambulatory surgery center [difference of mean (95% CI) 0.002 (-0.008, 0.011), p = 0.99). ConclusionsIn this cohort, we found that the addition of intravenous acetaminophen to a multimodal pain regimen for anterior cruciate ligament reconstruction surgery is not associated with a reduction in total in-hospital opioid use. This finding may be related to the concomitant use of peripheral nerve blocks and intravenous ketorolac.

Efficacy of Intravenous Acetaminophen as Adjunct Post-Operative Analgesic in Cardiac Surgery: A Retrospective Study

The dose-dependent adverse events associated with post-operative opioid use may be reduced when opioids are used in conjunction with intravenous acetaminophen. The purpose of this study was to compare outcomes in median sternotomy patients receiving intravenous acetaminophen in addition to intravenous opioids versus intravenous opioids only. A retrospective study was conducted on 122 adult patients undergoing median sternotomy at a regional tertiary-referral center. Data collected included patient demographics, length of stay, opioid and intravenous acetaminophen use, adverse effects, and transition time to oral pain medication. There was no difference between groups in demographics, preoperative risk scores, operative procedures, intravenous opioid consumption, transition time to oral pain medications, or length of stay. Acetaminophen use was associated with lower rates of atrial fibrillation (7.0% vs. 24.6%, p = 0.009) and nausea/vomiting (8.9% vs. 32.3%, p = 0.002), but higher rates of urinary retention (15.8% vs. 3.1%, p = 0.014), constipation (50.0% vs. 20.0%, p = 0.001) and respiratory depression (7.1% vs. 0.0%, p = 0.043). Intravenous acetaminophen was not associated with a reduction in length of stay or opioid consumption, but was associated with lower rates of atrial fibrillation, nausea, and vomiting. Additional studies are needed to determine if intravenous acetaminophen administration reduces atrial fibrillation in this population.

The Efficacy and Safety of Acetaminophen in Total Joint Arthroplasty: Systematic Review and Direct Meta-Analysis

BackgroundOral and intravenous (IV) acetaminophen has become widely used perioperatively as part of a multi-modal pain management protocol for primary total joint arthroplasty (TJA). The purpose of our study is to evaluate the efficacy and safety of acetaminophen in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management. MethodsWe searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published prior to September 2019 on acetaminophen in primary TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of acetaminophen. ResultsIn total, 1287 publications were critically appraised yielding 17 publications representing the best available evidence for analysis. Oral and IV acetaminophen demonstrates the ability to safely reduce postoperative pain and opioid consumption during the inpatient hospital stay. No evidence was available to assess the efficacy and safety of oral acetaminophen after discharge. ConclusionModerate evidence supports the use of oral and IV acetaminophen as a non-opioid adjunct for pain management during the inpatient hospitalization. Strong evidence supports the safety of oral and IV acetaminophen when appropriately administered to patients undergoing primary TJA. Although there is lack of robust evidence for use of acetaminophen following discharge, it remains a low-cost and low-risk option as part of a multimodal pain regimen.

A randomized trial of intravenous acetaminophen versus indomethacin for treatment of hemodynamically significant PDAs in VLBW infants.

Objective was to compare the rate of successful treatment of hsPDA based on echocardiogram criteria after use of IV acetaminophen or IV indomethacin in very low-birthweight infants. The study was a multi-center, randomized controlled trial. Infants born prior to 32 weeks with birthweight ≤ 1500 g were included if PDA treatment was indicated within the 21 days after birth. hsPDA was defined by strict echocardiogram criteria. Eligible infants were randomized to treatment with either IV acetaminophen or IV indomethacin. Of 86 eligible infants, 17 infants were randomized to acetaminophen and 20 to indomethacin. One (5.9%) hsPDA in the acetaminophen group had successful treatment compared to 11 (55%) in the indomethacin group (p = 0.002). Eight (47%) in the acetaminophen group and 3 (15%) in the indomethacin group received transcatheter PDA closure (p = 0.07). IV indomethacin was more effective than IV acetaminophen for treatment of hsPDAs. More infants in the acetaminophen group received transcatheter closure.

Is P&T Ready to Add Rapid Cycle Analytics to Formulary?

Purpose: The intent of this article is to evaluate a novel approach, using rapid cycle analytics and real world evidence, to optimize and improve the medication evaluation process to help the formulary decision making process, while reducing time for clinicians. Summary: The Pharmacy and Therapeutics (P&T) Committee within each health system is responsible for evaluating medication requests for formulary addition. Members of the pharmacy staff prepare the drug monograph or a medication use evaluation (MUE) and allocate precious clinical resources to review patient charts to assess efficacy and value. We explored a novel approach to evaluate the value of our intravenous acetaminophen (IV APAP) formulary admittance. This new methodology, called rapid cycle analytics, can assist hospitals in meeting and/or exceeding the minimum criteria of formulary maintenance as defined by the Joint Commission Standards. In this particular study, we assessed the effectiveness of IV APAP in total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. We assessed the correlation to same-stay opioid utilization, average length of inpatient stay and post anesthesia care unit (PACU) time. Conclusion: We were able to explore and improve our organization's approach in evaluating medications by partnering with an external analytics expert to help organize and normalize our data in a more robust, yet time efficient manner. Additionally, we were able to use a significantly larger external data set as a point of reference. Being able to perform this detailed analytical exercise for thousands of encounters internally and using a data warehouse of over 130 million patients as a point of reference in a short time has improved the depth of our assessment, as well as reducing valuable clinical resources allocated to MUEs to allow for more direct patient care. This clinically real-world and data-rich analytics model is the necessary foundation for using Artificial or Augmented Intelligence (AI) to make real-time formulary and drug selection decisions.