Oral versus intravenous acetaminophen for perioperative pain management in adult patients undergoing non-cardiac surgery: A quantile segmented regression analysis.

STUDY OBJECTIVE: Determine whether preferential use of perioperative enteral acetaminophen is associated with changes in perioperative pain, narcotic administration, or time to meeting criteria for post anesthesia care unit (PACU) discharge, compared to preferential parenteral administration. DESIGN: Retrospective Cohort with quantile segmented regression analysis. Groups determined by date of surgery, one year pre-initiative and one year post-initiative. SETTING: Operating room and PACU of a tertiary academic medical center. PATIENTS: Adult (age > 18 years), ASA status 1-5, non-pregnant patients undergoing non-cardiac surgery of less than six hours duration admitted to the PACU postoperatively. INTERVENTIONS: A multidisciplinary initiative to preferentially utilize enteral over parenteral acetaminophen. MEASUREMENTS: The primary outcome was narcotic consumption in the PACU. Secondary outcomes were intraoperative narcotic administration, pain score on PACU admission and discharge, and time to meeting criteria for PACU discharge. RESULTS: 24,701 patients were included in the analysis; 12,379 had surgery prior to the initiative and 12,322 after. Enteral acetaminophen administration increased preoperatively from 13.49% to 26.84%, and postoperatively from 43.16% to 51.45%, while intraoperative parenteral APAP use dropped from 43.23% to 6.81%. Quantile Segmented regression analysis after adjusting for period (pre versus postintervention), day, age, gender, inpatient status, and ASA class demonstrated a decrease in adjusted median perioperative acetaminophen dose (-175 mg P < 0.001), with no significant difference in level change of intraoperative or PACU narcotic administration. There was no significant difference in median time to meet criteria for PACU discharge, though there was a significant change in the slope, (-0.36, p = 0.007.) Median pain scores measured on a standard 0-10 numeric rating scale at PACU admission did not change, while median pain scores at PACU discharge decreased slightly (-0.24 p < 0.001). There was no change in the probability of PONV. CONCLUSION: In adult patients undergoing non-cardiac surgery of <6 h duration, preferential use of enteral rather than parenteral acetaminophen is associated with non-inferior outcomes in narcotic requirements, pain scores, time to PACU discharge, and probability of PONV when compared with routine parenteral administration. Further studies are needed to validate these findings.

Microwave-assisted synthesis and in vitro stability of N-benzylamide non-steroidal anti-inflammatory drug conjugates for CNS delivery.

More effective delivery of non-steroidal anti-inflammatory drugs (NSAIDs) to the brain could treat the underlying inflammatory pathology of a range of CNS diseases and conditions. Use of a blood-brain barrier shuttle such as the N-benzylamide moiety, which has been largely unexplored for this purpose, could improve the brain bioavailabilities of NSAIDs. A series of novel N-benzylamide NSAID conjugates was synthesized via a three-step process with a microwave-assisted bimolecular nucleophilic substitution as the final step. We explored conditions to promote substitution over a competing elimination reaction, which was successfully suppressed with isopropyl alcohol solvent. All molecules exhibit physicochemical properties consistent with those of brain-penetrant molecules. Furthermore, they exhibit long (>48 h) half-lives in phosphate-buffered saline (PBS; pH 7.4) and short to moderate half-lives in human plasma. N-Benzylamide NSAID conjugates represent promising CNS drug discovery leads.