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Am Fam Physician. 2016;94(3):216-217

Author disclosure: No relevant financial affiliations.

Clinical Question

Is acetaminophen an effective treatment for neonates with pain caused by medical procedures?

Evidence-Based Answer

Acetaminophen does not significantly reduce pain associated with heel lance, eye examinations, or assisted vaginal births in newborns. Acetaminophen may reduce the total amount of morphine a newborn needs in the first 48 hours following major abdominal or thoracic surgery. (Strength of Recommendation: B, based on inconsistent or limited quality patient-oriented evidence.)

Practice Pointers

Neonates are often exposed to painful interventions during routine newborn care or complicated neonatal intensive care unit hospitalizations. Pharmacologic therapies for pain relief include opiates, benzodiazepines, anesthetics, nonsteroidal anti-inflammatory drugs, and acetaminophen, and nonpharmacologic therapies include oral sweet solutions, sucking, swaddling, and kangaroo care.13 Despite increased awareness of the importance of pain prevention, the effectiveness and safety of these modalities remain controversial, and they may be underused for the treatment of pain in neonates.3

The authors of this Cochrane review identified eight studies evaluating the effectiveness of acetaminophen for the treatment of pain in 614 neonates (30 days or younger). Pain was measured by validated tools examining newborn facial actions, body movements, cry, heart rate, and/or oxygen saturation. The painful procedures included heel lance, assisted vaginal birth, eye examination for retinopathy of prematurity, and postoperative care following abdominal or thoracic surgery.

In infants undergoing heel lance, oral acetaminophen (20 mg per kg) did not significantly reduce pain compared with sterile water, lidocaine/prilocaine (EMLA) cream, or cherry elixir. At higher doses of 40 mg per kg, oral acetaminophen was no more effective than sterile water at reducing pain. Oral glucose solution appeared to be more effective than oral acetaminophen (20 mg per kg) at reducing pain scores following heel lance (Premature Infant Pain Profile [PIPP] score, range = 0 to 21 points; mean difference [MD] = 2.21; 95% confidence interval [CI], 0.72 to 3.70). For eye examinations performed to evaluate retinopathy of prematurity, oral acetaminophen (15 mg per kg) did not reduce pain compared with sterile water; and PIPP scores were significantly higher in infants who received oral acetaminophen (15 mg per kg) compared with infants who received sucrose (approximately 25% solution; MD = 3.90; 95% CI, 2.92 to 4.88).

Acetaminophen suppositories (doses ranging from 50 to 70 mg based on infant weight) did not decrease pain in infants born via assisted vaginal delivery (vacuum extraction or forceps). When infants exposed to assisted vaginal births underwent a heel lance at two to three days of life, pain scores and time spent crying were increased in the acetaminophen suppository group (doses ranging from 60 to 100 mg based on weight) vs. the placebo group (MD = 19 seconds; 95% CI, 14 to 24). In a separate study examining infants undergoing major thoracic or abdominal surgery, the total morphine rescue dose in the 48-hour postoperative period did not differ significantly between infants randomized to intravenous acetaminophen and those randomized to continuous morphine.

No two trials used the same assessment tool for the outcome of pain; therefore, a meta-analysis could not be conducted and tests for heterogeneity were not applicable. Despite the small sample sizes of the individual trials, the risk of bias was considered low and the quality of evidence considered good. The authors did not identify any studies on the use of acetaminophen for the prevention of pain. No adverse effects were noted, but no studies assessed the long-term effects of acetaminophen use, so there was insufficient evidence to comment on its safety.

The American Academy of Pediatrics recommends that caregivers routinely implement effective strategies for the prevention and treatment of pain associated with medical procedures in newborns. It also suggests that acetaminophen not be used alone but as an adjunct for severe pain, after minor procedures, or in the later postoperative period.3 This Cochrane review supports these guarded recommendations. Further study is warranted to determine the benefit of acetaminophen in reducing postoperative pain and pain associated with other procedures in neonates.

SOURCE: OhlssonAShahPSParacetamol (acetaminophen) for prevention or treatment of pain in newborns. Cochrane Database Syst Rev2015;(6):CD011219.

The practice recommendations in this activity are available at

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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