In summary, for patients treated with opioid analgesics to reduce acute abdominal pain:

Benefits in NNT

    Not applicable
    Significant reduction in hospital length-of-stay (NNT not applicable)

Harms in NNT

    Not applicable
    No significant adverse events or morbidity
    No significant difference in physical exam findings
    No significant increase in incorrect diagnosis
    No significant difference in treatment decision errors

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Source: Manterola C, Vial M, Moraga J, Astudillo P. Analgesia in patients with acute abdominal pain. Cochrane Database Syst Rev 2011:CD005660.

Study Population: 922 adult and adolescents (age > 16 years) with acute abdominal pain from 8 trials

Efficacy Endpoints: Rate of accurate management decisions (primary), change in pain intensity and comfort level (secondary)

Harm Endpoints: Physical exam changes, treatment decision errors, incorrect diagnosis, morbidity, hospital length-of-stay

Narrative: Acute abdominal pain (AAP) is the most common reason for U.S. emergency department (ED) visits (6-10%),1, 2 and the incidence is rising.3 Admission rates approach 25%, and the majority (44% - 59%) of patients are treated with an opiate/opioid analgesic, with morphine being administered most commonly (20%).4

Synthetic opiates exert analgesia effects by stimulating pain-inhibitory neurons and inhibiting pain-transmission neurons through interactions with mu receptors in the central nervous system (CNS).5 It was once thought that blocking the somatic efferent fibers conducting messages to the abdominal muscles and skin may alter crucial peritoneal signs (rigidity, guarding, rebound) that may be associated with intra-abdominal pathology requiring surgical intervention.5 Thus, providing opiate analgesia to patients with AAP was historically discouraged until a surgeon had decided to operate for fear of impeding proper diagnosis. This arose from an era when morphine was administered as grains of morphine tartrate, where 1 grain equated 64mg of morphine sulfate, and was famously promoted by the widely read text “Cope’s Early Diagnosis of the Acute Abdomen” (1921). It also led to the common problem of inadequate pain management (oligoanalgesia) for ED patients with AAP. Only 50-66% ED patients with abdominal pain receive analgesia.3, 4, 6, 7, 8 Average analgesia wait times vary considerably and may be longer than the total mean ED length-of-stay for all comers,2, 3 with one study reporting time to analgesia of 4.1 hours (mild), 1.85 hours (moderate), and 1.37 hours for severe AAP.9

The referenced meta-analysis assesses the impact of opioid analgesic administration to patients with AAP on the diagnostic process.10 It includes 8 randomized clinical trials (RCTs; 922 participants). The studied analgesics were morphine sulfate (5-15 mg; 6 studies), tramadol (1 mg/kg; 1 study), and papaveretum (20 mg; 1 study) as compared to saline control. Papaveretum (Omnopon®, Roche Products Ltd, Welwyn Garden City, UK-England) contains a mixture of opium alkaloid salts including phenanthrene groups (morphine, codeine) that exert actions on CNS mu receptors, and anti-spasmodic isoquinoline groups (papaverine). The formulation used in the included study (prior to 1993) also contained noscapine.11 Assessed outcomes included changes in physical examination findings, pain, adverse events, and diagnostic accuracy as determined by concordance of diagnoses by the emergency physician (EP) and discharging physician. Management decision errors were determined by discordance between the EP’s perceived need for surgical vs. medical management versus the treatment administered during hospitalization.

Pre-treatment pain intensity measured by 10 cm visual analogue scale (VAS) was similar between opioid and placebo groups 5.29 ± 2.32 versus 5.18 ± 2.04 (95% confidence interval [CI] -0.01, 0.26; p=0.058).10 Pain intensity was significantly lower in opioid-treated patients in aggregate (mean difference [95%CI]: -2.00 [-2.89, -1.10]), as well as for each agent individually.10 Additionally, when compared to placebo, no change in physical exam findings (5 trials, 328 participants) was observed individually or in aggregate (RR 1.23, 95% CI, 0.69 to 2.20; quality of evidence: high, or by treatment agent (morphine, tramadol).10 Treatment decision errors (3 studies, 488 participants) did not differ between groups in aggregate (RR 0.77, 95% CI, 0.23 to 2.54; quality of evidence: high), or by individual agent (morphine, papveretum).10 Moreover, the likelihood of an incorrect diagnosis (6 studies, 786 participants) did not differ between groups in aggregate (RR 0.86, 95% CI, 0.57 to 1.29; quality of evidence: high), or by individual agent (morphine, papveretum).10 Patient morbidity (nausea or vomiting; 4 studies, 581 participants) did not differ between groups (RR 5.14, 95% CI, 0.26 to 103.37; quality of evidence high). Lastly, hospital length-of-stay in days (1 study, 100 participants) was shorter in the treatment group (mean difference [95%CI]: -1.00 [ -1.52, -0.48]; quality of evidence: high).

Caveats: Despite evidence that the use of opioid analgesics in patients with AAP improves analgesia without changing physical exam findings or increasing treatment decision errors, morbidity, or likelihood of incorrect diagnosis, there are caveats to consider.10 First is the confusion that may arise from applying the number needed to treat (NNT) concept to large absolute risk reductions. For example, the NNT of 5 in this case could be viewed by some to mean that for every five-people treated with opiates one person benefited (more than control), a statement that may seem incongruent with clinical experience. It is possible that everyone in the intervention group had more pain relief than controls, but in aggregate the mean VAS difference between groups was 20%.

Next, significant heterogeneity existed for the variables change in pain intensity (I2 95%) and errors in treatment decisions (I2 55%), which indicate variation pain interpretation between studies, and therefore treatment decision making. The VAS scale is sensitive due to the large number of response categories; however, it may produce unreliable assessments across patient populations owing to variations in scale interpretation. Moreover, the risk-of-bias was high for four studies due to differing research objectives, small sample sizes and inadequate randomization which could invalidate the results.10 Additionally, studies did not report the impact of opioid administration on ED length-of-stay or time to decision for surgery,1 highlighting the need for additional studies. Moreover, studies assessing the impact of other commonly used analgesics (fentanyl, hydromorphone, codeine, hydrocodone, oxycodone) were not identified. Furthermore, the effect of non-intravenous administration routes (intramuscular or oral) remains unknown, as does the impact of pre-existing opiate analgesia taken prior to ED presentation, and the impact of non-opioid analgesic co-administration remains unclear. Lastly, the impact of the common occurrence of mixing different opioid agents in the same patient remains unclear.

A Green color recommendation is based on the evidence of high-quality evidence supporting the benefits that opioid analgesia for patients with AAP improves pain management, without changing physical exam findings or increasing treatment decision errors, patient morbidity, or likelihood of incorrect diagnosis.

Conclusion: Treating patients with acute abdominal pain with opioid analgesics improves analgesia without increasing the risk of diagnosis error or increasing treatment decision errors.

Author: Karissa A. Lambert, MD; Andrew C. Miller, MD

Published/Updated: November 16, 2018

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    • Green: Benefits outweigh risks.
    • Yellow: Unclear risk/benefit profile.
    • Red: Benefits do not outweigh risks.
    • Black: Obvious harms, no clear benefits.
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