P-069 - Characterization of Pain Management Regimens For Inpatients Receiving Bolus Ketorolac For Post-Surgical Pain Management – Results of a Retrospective Chart Audit of 597 Patient Records in 101 Hospitals Across the United States

Abstract Title: Characterization of Pain Management Regimens For Inpatients Receiving Bolus Ketorolac For Post-Surgical Pain Management – Results of a Retrospective Chart Audit of 597 Patient Records in 101 Hospitals Across the United States


Background: With over 80,000 opioid-involved deaths in the US in 2022¹, demand for effective and safe non-opioid options remains. Ketorolac, a well-established, powerful non-opioid analgesic, is the only NSAID approved to provide opioid-level analgesia. However, the pharmacokinetic profile of the bolus regimen (adult dose 30mg q6h, up to maximum of 120mg/day, elderly dose half the adult dose) causes it to have limitations: the potential for safety related risks exists during peak exposure levels; and inadequate analgesia and potential demand for rescue with opioids during end of dose trough exposure levels.



A recent chart audit of 1,005 records of surgical patients receiving bolus ketorolac showed 21% of elderly patients received greater than the recommended total daily dose, and 25% of all patients were dosed earlier than recommended – with the related risks of overexposure. Further, 48% of patients were dosed later than recommended with potential for inadequate analgesia and rescue².



NTM-001, a novel formulation of ketorolac in a premixed bag for continuous intravenous infusion over 24h, is in development for the short-term treatment of moderately-severe pain, and aims to mitigate the limitations of the bolus regimen by delivering constant exposure levels throughout treatment, with a 20% lower total daily dose of ketorolac.

Purpose/Objectives: The objective of this retrospective chart audit was to characterize analgesic regimens of post-operative inpatients, across surgical disciplines, following an index dose of bolus ketorolac. Of specific interest was the time and type of analgesic dose following the index bolus ketorolac dose, and the route of administration, by type of surgical procedure. The purpose of the audit was to determine limitations of bolus ketorolac and potential appropriate use cases for NTM-001.


Methods: US academic medical centers and community hospitals, with ≥250 beds and bolus ketorolac on the hospital formulary, were eligible for inclusion in the audit. Nurse practitioners, physician assistants, hospital pharmacists, or directors of pharmacy, typically working in surgery, operating rooms or medical-surgical departments, with proficiency in querying Electronic Medical Records (EMR) systems, were allowed to participate.



General, colon/rectal, obstetric/gynecologic, gastroenterological, maxillofacial/plastic, orthopedic, or urologic surgery patients, discharged within 12 months, who received ≥2 doses of bolus ketorolac during their stay, with a minimum length of stay of 24 hours, were eligible for inclusion. Respondents each profiled 6 charts, with no more than 2 from the same surgical category.



Patient demographics, date/time of admission/discharge, surgery type and start/end date/time were collected. Ketorolac, opioid, acetaminophen (APAP), NSAID, bupivacaine and other analgesic regimens (route, dose, date, time, and if final dose) were recorded, along with pain score, date/time where available.



For respondents able to program an EMR query, the number of surgical inpatients receiving ≥1 dose of bolus ketorolac over the last 6 months was recorded, and the number and type of procedure for those receiving ≥2 doses.



Deidentified data were collected by Outcomes Insights via a 30-minute online survey during July 2023.


Results: A total of 597 patient charts were collected and analyzed from 101 hospitals with between 200 and 1536 beds (mean 532) across the US. Responses were provided by hospital pharmacists (38%), directors of pharmacies (31%), nurse practitioners (21%) and physician assistants (11%).



The average age of patients included was 49 years, with 22% being elderly (≥65 years). 58% of patients were male, 58% white, 25% black and 18% Hispanic. Procedure types included orthopedic (24%), general (23%), gastroenterological (12%), colon/rectal (12%), obstetrics/gynecologic (11%), urologic (10%) and maxillofacial/plastic (7%), with an average length of stay of 4.7 days.



85% of index doses of bolus ketorolac were as analgesic monotherapy, 9% received concomitant IV opioid, and 2% received concomitant IV opioid and IV APAP. Approximately half (51%) of patients received their second pain management treatment early (i.e. < 5.5 hours) following the index dose of bolus ketorolac. Of those receiving their second regimen early, 50% were dosed with an opioid (35% IV, 15% oral), and 33% received an early bolus ketorolac dose. By comparison, opioids were required in only 15% of patients (8% IV, 7% oral) who did not require an early second analgesic regimen, with most (79%) receiving a 2^nd dose of bolus ketorolac at an interval recommended in the label.



Only 40% of patients treated initially with bolus ketorolac remained opioid-free by the end of the 48-hour period analyzed (i.e. 60% required opioids). Many required opioids within the first 6 to 24 hours (38% to 55%, respectively). Similar patterns were observed for both males and females, amongst adults and elderly, and across all surgery types. Patients requiring rescue analgesia within 5.5 hours of their index dose of bolus ketorolac were more likely to have received opioids at all time points (62%, 73% and 74% by 6, 24 and 48 hours respectively) and more doses on average (1.77 per patient) than patients who did not require early rescue (12%, 37%, and 45% received opioids by 6, 24, and 48 hours respectively, with a mean of 0.59 opioid doses per patient).

Conclusions/Implications for future research and/or clinical care: Bolus ketorolac is well-established in US hospitals and is the most widely used injectable non-opioid for postoperative pain. Its pharmacokinetic profile, with peaks and troughs in plasma levels, may lead to potential for side effects or inadequate analgesia. This chart audit showed patients treated initially with bolus ketorolac frequently required rescue analgesia (2^nd regimen ≤5.5 hours following initial ketorolac dose), with opioids being the most common form of rescue. These patients were more likely to receive opioids as their 2^nd analgesic regimen, were less likely to remain opioid-free during the 48-hours post-surgery, and received more opioid doses on average, than patients who did not require early rescue. This represents a strong rationale for the development of NTM-001, a novel formulation of ketorolac in a premixed bag for continuous intravenous infusion over 24 hours, with the goal of reducing the need for rescue with opioids.


References: 1. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates

2. Current Use Patterns for Ketorolac Intravenous Bolus for Post-Operative Pain in Inpatient Settings – Results of a Chart Audit in 119 Hospitals Across the United States. Steigerwald et.al, posters #112, ASHP Midyear Meeting 2020