Your next patient is a 5-year-old boy undergoing tonsillectomy and adenoidectomy. You decide to administer a loading dose of 30 mg/kg of oral acetaminophen. According to a recent trial, which of the following outcomes is MOST likely in this patient compared with a patient who receives a loading dose of 15 mg/kg of intravenous (I.V.) acetaminophen?

  • □ (A) Increased pain scores within the first 24 hours after surgery
  • □ (B) Similar opioid consumption within the first 24 hours after surgery
  • □ (C) Lower plasma acetaminophen level three hours after anesthesia induction
Among pediatric patients, tonsillectomy is one of the most common surgical procedures performed in the United States. Perioperative pain can be substantial. With increasing appreciation of the untoward adverse effects of opioids, the use of a multimodal pain management strategy incorporating acetaminophen, nonsteroidal anti-inflammatory drugs, and intraoperative local anesthetic infiltration of the tonsillar bed has become popular.

In 2010, the U.S. Food and Drug Administration approved I.V. acetaminophen for the treatment of mild to moderate pain in patients aged 2 years and older. Previous research has found no difference between I.V. and oral acetaminophen in pain reduction when a 15 mg/kg dose is administered every four to six hours, although I.V. acetaminophen may have a faster onset. The authors of a recent study hypothesized that if a higher oral loading dose of acetaminophen (30 mg/kg) was administered followed by standard dosing (15 mg/kg), higher plasma acetaminophen concentrations could be achieved faster and pain control effects comparable to I.V. administration could be reached.

The authors conducted a single-center, double-blind, double-dummy, prospective randomized clinical trial of 66 pediatric patients undergoing tonsillectomy and adenoidectomy with or without myringotomy tube placement. Patients were randomized to an oral group (n = 30) or I.V. group (n = 36). Patients in the oral group received 30 mg/kg (maximum, 1,000 mg) of acetaminophen liquid suspension 30 to 60 minutes prior to surgery and a placebo I.V. infusion. Patients in the I.V. group received oral placebo 30 to 60 minutes prior to surgery and 15 mg/kg (maximum, 1,000 mg) of I.V. acetaminophen. Intraoperatively, both groups received 0.5 mg/kg (maximum, 10 mg) of I.V. dexamethasone, 1 μg/kg of fentanyl, and 0.1 mg/kg (maximum, 4 mg) of ondansetron. Surgical technique was standardized and included infiltration of the tonsillar bed with 0.25% bupivacaine with 1:200,000 epinephrine.

All patients had postoperative pain scores measured for 24 hours with age-appropriate scales (Wong-Baker; revised Face, Legs, Activity, Cry, Consolability; or numerical rating scale). Pain was considered moderate with a score of 4 to 6 and severe with a score of 7 to 10. Patients with moderate or severe pain received either 0.25 μg/kg of I.V. fentanyl or 0.025 mg/kg of morphine. A dose of 10 mg/kg of ibuprofen was administered three hours after the I.V. study drug for every six hours, and acetaminophen was administered six hours after the I.V. study drug for every six hours. If pain was not adequately controlled with nonopioid medications, oxycodone was prescribed. Plasma acetaminophen levels were measured at the completion of surgery and at three hours after I.V. study drug administration. The primary outcome was total opioid administration in the first 24 hours postoperatively. Secondary outcomes included pain scores and acetaminophen plasma levels. A difference of 100 μg/kg/d of I.V. morphine was considered clinically important.

The authors did not find a clinically meaningful difference in either postanesthesia care unit (PACU) opioid use or 24-hour cumulative opioid use between the oral and I.V. acetaminophen groups. Likewise, pain scores were similar between the two groups (patients with at least 1 score of severe pain during the study period: oral acetaminophen, 15 [50.0%] versus I.V. acetaminophen, 17 [47.2%]; those with at least 1 score of severe pain after PACU discharge: oral acetaminophen, 2 [6.7%] versus I.V. acetaminophen, 2 [5.6%]). None of the patients required rescue opioids after PACU discharge. Median acetaminophen levels before the end of surgery were 22 mg/L (interquartile range [IQR], 16-28) in the oral group and 20 mg/L (IQR, 17-22) in the I.V. group, with a difference that was not clinically meaningful. Plasma acetaminophen levels were higher in the oral group than in the I.V. group three hours after anesthesia induction, demonstrating a potential advantage of an oral loading dose technique.

In summary, this study illustrates that comparable opioid-sparing effects may be achieved with oral acetaminophen compared with an I.V. formulation. ASA guidelines on postoperative pain management emphasize that there is insufficient evidence to recommend I.V. over oral acetaminophen; thus, this choice may be fiscally irresponsible. Reportedly, the average cost of I.V. acetaminophen in the U.S. is 20 times the cost of the oral preparation.

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