Perioperative acetaminophen (paracetamol): Why burn money?
Myron Yaster MD and Lynne G. Maxwell MD
Before discussing today’s PAAD by Mahon et al.1, a disclosure: Both Lynne and I were involved in the original U.S. trials of IV acetaminophen either as an investigator (LM) or as a member of the study’s data safety monitoring board (MY). As you all know, acetaminophen is a great drug with a long track record of safety and efficacy. As an essential component of multi-modal analgesia, the IV formulation allowed it to be used in patients who for one reason or another could not be given the enteral formulations (oral or rectal). The investigation and development process for the IV formulation was also unique because the original drug developer (Cadence pharmaceuticals) made testing and FDA approval in pediatric patients of all ages a priority. What a novel idea! A new analgesic dawn was upon us and as this year’s Robert M. Smith award winner, Dr. Elliot Krane, would say at investigator meetings: “acetaminophen is like ‘mother’s milk’ and should be used in virtually all pediatric surgeries.” After FDA approval, the rights to the IV formulation and its manufacturing, distribution, and marketing were sold by the original developer/sponsor to a large pharmaceutical company. It was then sold again to another company. Each sale resulted in substantial increases in drug pricing and consumer cost. Ah, the joys of capitalism!
Interestingly, several studies have shown little difference in efficacy when acetaminophen is given parenterally compared to its effectiveness when given enterally.2,3 Obviously, there are substantial differences in cost: pennies per dose for the enteral formulations compared to many dollars per dose for the IV. In today’s PAAD, Mahon et al. discuss their process improvement project to increase acetaminophen administration perioperatively. They also performed a cost analysis leading me and hopefully you to wonder: “If both the enteral and parenteral drugs produce equivalent analgesia, why spend (burn) the money on the parenteral formulation”? Myron Yaster MD
Original article
Mahon RM, Rajbhandari P, Brown TA, Engler LJ, Bhalla T. Improving perioperative acetaminophen administration for safer and cost-effective multimodal analgesia in pediatric surgery: A QI initiative. Paediatr Anaesth. 2024 Apr 5. doi: 10.1111/pan.14893. Epub ahead of print. PMID: 38578161.
The perioperative management of pain is an essential part of our pediatric anesthesia practice. Multimodal analgesia (MMA), in theory, optimizes perioperative pain control and reduces the over reliance on opioids and opioid induced side effects. Multiple classes of systemic analgesic medications are used to accomplish this including acetaminophen, NSAIDs, local anesthetics, NMDA antagonists, and the gabapentenoids to name a few.4 Regional anesthetic techniques and non pharmacologic techniques like using virtual reality are also invaluable tools.5 Unquestionably, acetaminophen (paracetamol) is the most commonly used adjuvant in pediatric multimodal analgesia.6 In today’s PAAD, Mahon et al.1 discovered that in their practice (Akron Children’s Hospital), “acetaminophen was mostly an afterthought in the perioperative MMA regimen with many barriers to prescribing oral acetaminophen and IV acetaminophen and was given only to the surgical cases thought to be more painful.”1 They wondered how they could increase both the enteral and parenteral use of acetaminophen perioperatively using quality improvement methodology.
Like many other QI projects previously discussed in the PAAD, they assembled a multidisciplinary team of stakeholders and were guided by the Model for Improvement methodology.7,8 Their goal was to achieve a 50% acetaminophen administration rate within 24 months of instituting their new process. We wonder why so low and not strive for > 90%? “Multiple interventions were conducted, including education, increasing the availability of acetaminophen, and optimizing the electronic medical record (EMR). Monthly data was collected using an automated re-port in the EMR.”1 They far exceeded their modest goals and “the use of acetaminophen increased from 39.5% to 70% within four months. Despite some fluctuations, by the end of 24 months, they not only met but surpassed their goal, with 63% of patients receiving perioperative acetaminophen. Similarly, the usage of oral acetaminophen increased from a baseline of 10% to 78%. Average maximum PACU pain scores and the percentage of patients receiving rescue opioids were essentially unchanged.
Standardizing oral acetaminophen dosing was accomplished by the development of a simple table by the institution’s pharmacists.
We are reproducing this table to enable many of you to institute a similar one in your practice. Finally, and not surprisingly, the cost savings by switching to oral acetaminophen in the preop area to IV administration intraoperatively were substantial. “Our baseline overall acetaminophen cost estimates were $53 718–$58 898 per month. Post-implementation overall acetaminophen cost estimates were $15 767–$24 627 per month. The monthly cost savings for acetaminophen post-implementation were $29 338–$43 131.”1 Unfortunately, how the authors presented their cost analysis was confusing. We wish they had presented the actual number (or percentage) of patients who received IV vs preoperative oral acetaminophen through the period of the study.
To be honest, we were amazed that at the start of this project, the PACU did not have ready availability of acetaminophen. In our own practices, acetaminophen alone or combined with oral midazolam have been routinely given to patients preoperatively in the PACU for decades. Additionally, the authors did not mention (or have the perioperative availability) of rectal acetaminophen. For young children, Patrick Birmingham and his colleagues demonstrated more than 2 decades ago that rectal acetaminophen (30 mg/kg/dose) given intraoperatively was a wonderful alternative to oral administration preoperatively.9,10And like the oral formulation, the rectal suppository is extremely inexpensive.
We think that routine oral acetaminophen administration on arrival to the PACU (after weigh in) with a glass of water is an idea whose time has come. Using the weight based chart, standing orders, and easy availability in the PACU makes this a “no brainer” quality improvement process for all of you.
Let us know what you think and send your comments to Myron who will post in a Friday readers response.
References
1. Mahon RM, Rajbhandari P, Brown TA, Engler LJ, Bhalla T. Improving perioperative acetaminophen administration for safer and cost-effective multimodal analgesia in pediatric surgery: A QI initiative. Paediatric anaesthesia 2024 (In eng). DOI: 10.1111/pan.14893.
2. Lammers CR, Schwinghammer AJ, Hall B, et al. Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. Anesthesia and analgesia 2021;133(6):1568-1576. (In eng). DOI: 10.1213/ane.0000000000005678.
3. Chisholm AG, Sathyamoorthy M, Seals SR, Carron JD. Does intravenous acetaminophen reduce perioperative opioid use in pediatric tonsillectomy? Am J Otolaryngol 2019;40(6):102294. (In eng). DOI: 10.1016/j.amjoto.2019.102294.
4. O'Neill A, Lirk P. Multimodal Analgesia. Anesthesiology clinics 2022;40(3):455-468. (In eng). DOI: 10.1016/j.anclin.2022.04.002.
5. Heydinger G, Karthic A, Olbrecht VA. Paediatric pain management: from regional to virtual. Current opinion in anaesthesiology 2023;36(3):347-353. (In eng). DOI: 10.1097/aco.0000000000001247.
6. Doleman B, Read D, Lund JN, Williams JP. Preventive Acetaminophen Reduces Postoperative Opioid Consumption, Vomiting, and Pain Scores After Surgery: Systematic Review and Meta-Analysis. Regional anesthesia and pain medicine 2015;40(6):706-12. (In eng). DOI: 10.1097/aap.0000000000000311.
7. Courtlandt CD, Noonan L, Feld LG. Model for improvement - Part 1: A framework for health care quality. Pediatric clinics of North America 2009;56(4):757-78. (In eng). DOI: 10.1016/j.pcl.2009.06.002.
8. Franz AM, Dahl JP, Huang H, et al. The development of an opioid sparing anesthesia protocol for pediatric ambulatory tonsillectomy and adenotonsillectomy surgery-A quality improvement project. Paediatric anaesthesia 2019;29(7):682-689. (In eng). DOI: 10.1111/pan.13662.
9. Birmingham PK, Tobin MJ, Henthorn TK, et al. Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations. Anesthesiology 1997;87(2):244-252.
10. Birmingham PK, Tobin MJ, Fisher DM, Henthorn TK, Hall SC, Cote CJ. Initial and subsequent dosing of rectal acetaminophen in children: a 24-hour pharmacokinetic study of new dose recommendations. Anesthesiology 2001;94(3):385-389.