The “1+1” Protocol: Risks, Benefits, and Alternatives

Article Outline

• References
• Copyright

To the Editor:

Chang and colleagues continue to improve our understanding of emergency department (ED) pain management with their study of the “1+1” protocol,¹ but further consideration of the benefits, risks, and alternatives to this protocol are warranted prior to its adoption.

The authors describe the “1+1” protocol as a “compromise” aimed at improving pain management while minimizing the burden on nurses. The potential benefit of the “1+1” protocol over protocols using “individualized” opioid dose titration², ³ is a reduction in the number of opioid bolus dosages required to achieve pain relief. A recent study by Lvovschi and colleagues used a traditional opioid titration strategy (morphine in 2 mg or 3 mg boluses every 5 minutes as needed), finding that it took a median of 3 bolus dosages to achieve pain relief.² Chang and colleagues contrast their findings (median of 1 bolus dose required with the “1+1” protocol) with the results of the Lvovschi study, but the definitions of pain relief were so different in these 2 studies that the number of boluses required is not comparable—from the information provided, it appears that the majority of patients in the “1+1” cohort would not have achieved pain relief using the more stringent definition used by Lvovschi and colleagues.¹, ²

Opioid dose requirement varies substantially between patients,³ so a higher dosing strategy will provide excess opioid to some patients. A sizable proportion of ED patients with severe pain will achieve pain relief with less than 1 mg hydromorphone.², ⁴ These patients are unlikely to benefit from higher dosages but are at increased risk of adverse events than if their dosage had been “individualized.”

Chang and colleagues reported a 5% rate of oxygen desaturation below 95%, and a 1% rate to below 90%.¹ They did not report the rate of central nervous system side effects (eg, sedation), which were the most frequent opioid-induced adverse events in 2 recent ED cohorts.², ⁴ Iatrogenic opioid overdoses, which rarely result in devastating hypoxic encephalopathy or death, can be challenging to diagnose and sometimes occur after appropriate opioid dosages; they almost always present with mental status changes, but often do not have a depressed respiratory rate.⁵ A critical question is whether the widespread application of a protocol that results in a 5% rate of hypoxia is safe outside of a monitored trial. Moreover, if nurses are too busy to “fully individualize treatment” then are they also too busy to adequately monitor patients with a relatively high frequency of respiratory depression?

Are there alternatives to protocols using low or high dose (eg, “1+1”) opioid dose titration? Two possibilities come to mind. First, the combination of opioid and non-opioid analgesics seems to be more effective than either class separately and can reduce opioid dose requirements,³ so protocols employing combination therapy deserve exploration. Second, improved understanding of the factors associated with high versus low opioid dose requirement might allow us to better predict individuals' opioid dose requirement, allowing us to better tailor the opioid dosing strategy to patient needs.

It is unclear how we should value the competing interests of pain relief, patient safety, and nursing care requirements. The authors allude to an ongoing trial comparing the “1+1” protocol with routine care, the results of which are eagerly awaited. However, prior to adopting strategies like the “1+1” protocol, we will need further research defining the risks, benefits, and alternatives to higher dose opioid titration protocols.

Back to Article Outline

References 

1. Chang AK, Bijur PE, Campbell CM, et al. Safety and efficacy of using 1 mg doses of intravenous hydromorphone in emergency department patients with acute severe pain: the “1 + 1” protocol. Ann Emer Med. 2009;54:221–225
   • View In Article
2. Lvovschi V, Aubrun F, Bonnet P, et al. Intravenous morphine titration to treat severe pain in the ED. Am J Emerg Med. 2008;26:676–678
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (136 KB)
   • CrossRef
3. American Pain Society. In: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. Sixth Edition. 2008;p. 22–29Glenview, IL
   • View In Article
4. O'Connor AB, Zwemer FL, Hays DP, et al. Outcomes after intravenous opioids in emergency patients: A prospective cohort analysis. Acad Emerg Med. 2009;16:477–487
   • View In Article
   • CrossRef
5. Whipple JK, Quebbeman EJ, Lewis KS, et al. Difficulties in diagnosing narcotic overdoses in hospitalized patients. Ann Pharmacother. 1994;28:446–450
   • View In Article
   • MEDLINE