Does analgesia mask diagnosis of appendicitis among children?

Literature review

Decisions to administer analgesia should be supported by clinical evidence that analgesia does not interfere with accurate diagnosis. In a study from the United Kingdom, 100 consecutive age-controlled patients with clinically significant abdominal pain who were admitted for urgent appendectomies received either intramuscular papaverine or placebo.9 Although abdominal tenderness decreased in the medicated group, localization of pain was unaffected. An incorrect decision to operate or observe was noted in 2 patients who received papaverine compared with 9 patients who received placebo, and there were fewer unnecessary appendectomies in the trial group, showing that diagnosis was not affected.9

In a study among adult patients,10 patient- and examiner-perceived pain scores were lower with analgesia. There were no adverse events or delays in patient care because of analgesia. More recently, 350 patients older than 16 years presenting to the ED with abdominal pain in the right lower quadrant received either intravenous morphine or placebo.11 Diagnostic performance of ultrasound was not altered in the group treated with morphine, suggesting that analgesia did not improve or interfere with the ability to diagnose appendicitis. Decision to operate was not significantly different between the 2 groups, and decision to discharge patients without surgery was appropriate in all cases in both groups.11 In a prospective, double-blind trial from Boston, Mass, patients 18 years and older with undifferentiated abdominal pain received either morphine or placebo.12 No significant changes were noted in either severity or localization of abdominal tenderness or in diagnostic accuracy.

Two other studies examined the use of analgesia for young patients. In a randomized, double-blind, controlled trial from Milwaukee, Wis, 60 children 5 to 18 years old received either intravenous morphine or placebo.13 There was no significant change in the area of tenderness or in diagnostic accuracy. In a Canadian study of 108 children 5 to 16 years old presenting to the ED with acute abdominal pain, morphine administration did not increase the rate of missed appendicitis.14 While the diagnostic accuracy was not affected by giving opioids, morphine was found to decrease pain scores significantly, both statistically and clinically (P < .0001). The rate of perforated appendicitis was unchanged by treatment with morphine.14

Currently, there is no evidence that early analgesia interferes with diagnosis of appendicitis, although a clear positive effect on ease of diagnosis has not been shown. Treating pain is humane, however, and it has been consistently demonstrated that a substantial reduction in perception of pain occurs with analgesia among both pediatric and adult patients.9–13

Limitations of the literature

Reaching a clear resolution to the question is rather complicated, as previous reviews of the literature suggest,7,15,16 owing to design flaws in all the previous trials. Criticisms fall under 3 broad categories. First, although physicians and patients are blinded as to whether patients have received analgesia or placebo, they are aware that they are participating in a study and, therefore, might not react as they would in an uncontrolled setting. Specifically, physicians might be more meticulous in their examinations when they are looking for changes caused by analgesia, and patients might report their pain differently. Also, the studies require that administration of analgesia and examination of patients be done at carefully timed intervals. Second, use of varying doses of different drugs makes it difficult to determine which analgesic is most appropriate. In the United States, opiate drugs are currently the most common choice of both pediatric emergency physicians (64%) and pediatric surgeons (70%) rather than meperidine or fentanyl.4 The ideal drug and dosage, however, are currently unkown.16 Last, there is concern that current studies have not enrolled enough patients to allow a statistical estimate of the adverse outcome rate with analgesia.5,7,12,17 One prospective study followed patients with abdominal pain severe enough to require opioid analgesics.17 Patients were followed up at 3 weeks after treatment and adverse outcomes were recorded, including obstruction, perforation, ischemia, hemorrhage, peritonitis, sepsis, and death. The adverse outcome rate was estimated by logistic regression; based on this rate, the authors suggested that more than 1500 patients would be needed to compare the adverse outcome rates of opioids and placebo.16 Despite these limitations, it seems that analgesia is safe, reasonable, and humane.15,16