So often when interpreting the medical literature, success is determined by how you define it. Such is the case with a recent article on the management of pain due to ureteral colic. Published in the Lancet in 2016, Pathan et al examined the efficacy of IM diclofenax, IV acetaminophen, or IV morphine in treating the pain related to urolithiasis. The authors randomized 1644 patients presenting to the Emergency Department with renal colic to receive either IM diclofenax, IV acetaminophen, or IV morphine, each with their respective placebos (1).
Patients randomized to both IM diclofenax and IV acetaminophen achieved moderately more pain relief than patients randomized to receive IV morphine. 61% of the patients randomized to receive IV morphine achieved the authors’ primary outcome, a reduction in pain by greater than 50% at 30 minutes. By comparison, 68% and 66% of the respective patients randomized to IM diclofenax and IV acetaminophen experienced the same reduction in pain. This difference became only more apparent when the per-protocol analysis (the patients with radiographically confirmed renal colic) was examined. In this subset, 50% reduction was achieved in 69%, 68% and 60% in the diclofenax, acetaminophen, and morphine groups respectively. Likewise, more patients randomized to either the IM diclofenax or IV acetaminophen groups had a 3-point or greater drop in their pain scores by 30-minutes. In addition, patients in the IV morphine group more frequently required rescue doses of IV morphine.
Essentially both diclofenax and acetaminophen outperformed morphine in every outcome measure assessed. And so are we to believe that for the treatment of renal colic there is a paradoxical shift in the potency of analgesic medications from what has been our global experience? Is there a physiologic explanation for this singularity? I suspect the answer is far simpler, and is far more likely to be found in the trial’s definition of success.
Patients randomized to receive IV morphine, were given a 0.1 mg/kg bolus. And while this dose is commonly used in clinical trials, it does not consistently provide clinically adequate analgesia. A large portion of patients administered 0.1 mg/kg will require additional doses of IV morphine to reach blood levels required to achieve analgesia. In fact, in most cohorts examining the adequate dose of IV morphine, when administered a dose of 0.1 mg/kg, more than 50% of patients will require further dosing to attain analgesic effects. Bijur et al found when using a dose of 0.1 mg/kg of IV morphine in a cohort of patients presenting to the Emergency Department in severe pain, only 35% would have a reduction in their pain scores by 50% by 30 minutes (2). Birbaum et al found that only 44% of patients receiving a dose of 0.1m/kg achieved a 50% reduction in pain at 30 minutes (3). As such, the 39% of patients requiring additional pain medication observed in the Pathan et al cohort is far from unexpected.
Despite the 0.1 mg/kg dose being commonly utilized, it is an unfair and unrealistic comparison. It is what amounts to a straw man comparator. Allowing for the appearance of sport without truly posing a challenge. To truly obtain fast and adequate analgesia from IV morphine, the dose should be rapidly titrated to effect. In a trial performed by Aubrun et al on post-surgical patients, a protocol of 2-3mg of IV morphine every 5-minutes achieved analgesia in 100% of patients, but the number of doses varied wildly from patient to patient (4). Multiple Emergency Department cohorts have demonstrated that appropriate analgesia is safely and quickly achieved in close to 100% of patients when rapid escalation of opiate pain medication is utilized (5,6). And so what is noted as need for rescue medications in clinical trials, is in reality the appropriate method of achieving adequate analgesia when using IV opiates.
While IM diclofenax and IV acetaminophen may provide superior relief to inadequate doses of IV morphine, this does not translate to appropriate or adequate pain relief for the patient. Although 68% and 66% percent of patients in the diclofenax and acetaminophen groups experienced a 50% reduction in pain at 30 minutes, 32% and 34% did not. 12% and 20% required rescue analgesia. These reductions in pain were achieved at 30-minutes following medication administration. With the appropriately titrated dose of morphine, adequate pain relief can be achieved far earlier. And while this article certainly demonstrates that both NSAIDs and acetaminophen are reasonable options over the course of a patient’s Emergency Department stay, it should not dissuade us from the early and appropriate use of IV opiate analgesics.
- Pathan, SA, Mitra, B, Straney, LD et al.Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial.Lancet. 2016
- Bijur PE, Kenny MK, Gallagher EJ. Intravenous morphine at 0.1 mg/kg is not effective for controlling severe acute pain in the majority of patients. Ann Emerg Med. 2005;46(4):362-7.
- Birnbaum A, Esses D, Bijur PE, Holden L, Gallagher EJ. Randomized double-blind placebo-controlled trial of two intravenous morphine dosages (0.10 mg/kg and 0.15 mg/kg) in emergency department patients with moderate to severe acute pain. Ann Emerg Med. 2007;49(4):445-53, 453.e1-2.
- Coghill RC, Eisenach J. Individual differences in pain sensitivity: implications for treatment decisions. Anesthesiology. 2003;98(6):1312-4.
- Chang AK, Bijur PE, Campbell CM, et al. Safety and efficacy of rapid titration using 1mg doses of intravenous hydromorphone in emergency department patients with acute severe pain: the “1þ1” protocol. Ann Emerg Med. 2009;54:221-225.
- Chang AK, Bijur PE, Holden L, Gallagher EJ. Efficacy of an Acute Pain Titration Protocol Driven by Patient Response to a Simple Query: Do You Want More Pain Medication?. Ann Emerg Med. 2015;