Postop Oral Surgery Pain: How Effective Is Adding Codeine to Analgesics?

Tuesday, March 6, 2018

R.L. Wynn

Codeine remains a commonly prescribed analgesic after third molar surgery, despite evidence it may not be an effective pain treatment. It would be beneficial to patients and providers if it could be shown that codeine is not necessary to achieve adequate pain relief. To that end, a 2017 report in the Journal of Oral and Maxillofacial Surgery described a lack of effectiveness of codeine in treating postoperative oral surgery pain.

The study, with 131 participants using a randomized, double-blinded, placebo-controlled protocol, showed a lack of any additional pain relief by adding 60 mg of codeine to a combination of acetaminophen and ibuprofen to treat postoperative pain. While the authors recognized that acute postoperative pain remains an important clinical problem after third molar surgery, the use of non-opioids has been emphasized in lieu of opioids in order to mitigate the numbers of opioid prescriptions written by providers and therefore available to the population.

Codeine Study Details

The report can be accessed at: Best AD et al. “Efficacy of codeine when added to paracetamol (acetaminophen) and ibuprofen for relief of postoperative pain after surgical removal of impacted third molars: a double-blinded randomized control trial.” J Oral Maxillofac Surg 2017; 75:2063-2069.

The study was performed at the University of Otago, Dunedin, New Zealand, Department of Oral Diagnosis and Surgical Sciences, Faculty of Dentistry.


The study recruited adults requiring removal of at least one mandibular third molar for which bone removal was expected with or without removal of at least one upper third molar. Participants were randomly assigned to a control group or the intervention group.

Control group subjects received acetaminophen 1,000 mg plus a placebo pill orally every 6 hours and ibuprofen 400 mg orally every 8 hours, beginning immediately postoperatively and continuing for at least 48 hours duration of the study. Intervention group subjects received acetaminophen 1,000 mg plus 60 mg codeine orally every 6 hours and ibuprofen 400 mg orally every 8 hours, beginning immediately postoperatively and continuing for at least 48 hours duration of the study.

All subjects were operated on by the same surgeon using standardized surgical technique. Postoperative pain was measured using a 100 mm visual analog scale (VAS) labeled “no pain” at left end of the scale and “worst pain imaginable” at the right end of scale. Each subject made a baseline preoperative measurement followed by postoperative measurements recorded at home every 3 hours while awake for up to 48 hours after surgery.

Postoperative pain was also assessed using a postoperative questionnaire completed during a review appointment with the surgeon on the third day after surgery. The review consisted of a series of items on the subject’s experience with postoperative pain and whether rescue analgesia or other medical intervention had been necessary. One item on the questionnaire explored the participants’ overall perception of postoperative pain using a verbal rating scale with the response options of “no pain,” “mild pain,” “moderate pain,” “severe pain,” or “agony”.


The study included:

  • 131 patients (36% men) enrolled
  • 67 subjects in the control group; 64 in the intervention group (random allocation). No one was lost in follow up
  • Third molar pain at baseline before surgery (VAS score) was control group 3.6 (SD=8.3) and intervention group 6.3 (SD =14.2)
  • With each 3-hour period, VAS score increased by an average of 0.08

The mean VAS scores over time were as follows:
No codeine (control group)

  • 6 hours: 27
  • 15 hours: 28
  • 21 hours: 25
  • 36 hours: 32
  • 42 hours: 28
  • 48 hours: 31

Codeine 60 mg (intervention group)

  • 6 hours: 27
  • 15 hours: 28
  • 21 hours: 25
  • 36 hours: 32
  • 42 hours: 24
  • 48 hours: 18

According to the authors, there did not appear to be any pattern of response, either increasing or decreasing, or any sort of systematic difference between groups.

From the postoperative questionnaire, the global pain levels during the first 48 hours after third molar surgery by group were the following:

Control -n(%), n = 67

  • None: 6 (9)
  • Mild: 30 (44.8)
  • Moderate: 25 (37.3)
  • Severe: 5 (7.5)
  • Agony: 1 (1.5)

Intervention -n(%), n = 64

  • None: 7 (10.9)
  • Mild: 37 (57.8)
  • Moderate: 16 (25)
  • Severe: 3 (4.7)
  • Agony: 1 (1.6)

From the above data, the authors concluded that there were no significant differences in recorded pain levels between the two groups during the first 48 hours after surgery. Also, the two groups did not differ in their global ratings of postoperative pain.

During the follow-up period, 12 of the 67 control subjects and four of the 64 intervention subjects claimed that their prescribed treatment schedule did not provide sufficient pain relief for the immediate 48-hour period after third molar surgery.


This was the first study to evaluate pain relief after third molar surgery by comparing acetaminophen 1,000 mg and ibuprofen 400 mg coupled with placebo and coupled with codeine 60 mg.

Acetaminophen and codeine combination is a DEA schedule III drug in the U.S. and could become more widely prescribed after oral surgery relative to hydrocodone or oxycodone in combination with acetaminophen, which are both schedule II drugs. Schedule III drugs can be telephoned into the pharmacy and refilled without a new prescription, whereas schedule II agents cannot be called in or refilled without a new prescription. However, the results of this study call into question the efficacy of codeine, since its addition to a regimen of acetaminophen and ibuprofen does not appear to improve analgesia after oral surgery.

The findings of this study are consistent with previous reports showing that codeine-containing regimens have no greater efficacy than selected non-codeine combinations. The authors commented that a movement away from codeine for postoperative pain management in third molar surgery is in the patient’s best interest.

Richard L. Wynn, BS Pharm, PhD, is professor of pharmacology at the Baltimore College of Dental Surgery, Dental School, University of Maryland Baltimore.

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