What is the proper interval before we should give another dose of opioid to patients who still have significant pain?
The authors of this study suggest that 3 to 5 minutes would be ideal, but that the ED (Emergency Department) is not a setting where that is practical.
Administration of small doses of intravenous opioids every 3 to 5 minutes until pain relief is achieved, as typically practiced in postoperative care settings, is highly appealing. However, this is simply not feasible in most EDs because of ubiquitous and progressive crowding.18,19
Taking into consideration the heightened risk of adverse effects associated with administration of too large or too rapid a dose of intravenous opioid, we wished to develop a modiﬁed titration strategy appropriate to the constraints of the ED.
This would seem to make EMS the right people to administer opioids at theat ideal frequent rate of every 3 to 5 minutes. The main problem with having EMS do this seems to be the continuing refusal of many medical directors to do what is best for the patient.
Because of the staffing limitations of the ED, something that does not apply to EMS, the authors chose 15 minutes as the Do you want more pain medication? interval for their ED study.
The primary efﬁcacy outcome was the difference in the proportion of patients in each arm who, when asked, declined additional pain medication at 60 minutes after receiving their ﬁrst dose of intravenous hydromorphone. The primary safety outcome was use of naloxone as a reversal agent.
One group received 2 mg hydromorphone intially and appears to have been asked an hour later if they wanted more pain medicine. The other group received 21 mg hydromorphone intially, was asked at 15 minutes if they want any more pain medicine and only appears to have been asked again an hour later if they wanted more pain medicine.
The outcome showed no statistically significant difference between the groups.
There was never any need for naloxone for any patient, but that should not be a surprise to anyone who has treated severe pain more aggressively than was treated in this study.
Only one patient had an oxygen saturation that dropped below 95%, but that was in the 1+1 group. It is not documented whether this was after the initial 1 mg, after a repeat dose of 1 mg, or after doses beyond the protocol (it is not clear if any doses were administered beyond the protocol).
All patients received supplemental 2 L nasal cannula oxygen in response to a greater-than-expected incidence of oxygen desaturation in a previous study of the safety and efﬁcacy of the 2 mg intravenous hydromorphone protocol.26 
This is not unreasonable in an ED that is busy, but EMS should be able to more closely assess the oxygenation and avoid this medical intervention. In EMS, since we are usually with the patient at all times, it is easy to just get the patient to talk if the oxygen saturation drops below 94%, or the heart rate drops to something undesirable, or if hypotension develops (usually just a reaction to histamine when using morphine). When the patient talks, the patient ventilates and oxygenates. Problem solved. If the patient takes a nap, that is not a problem.
Do you want more pain medication? as the primary efﬁcacy endpoint. This measure has a number of advantages and limitations. It is a simple, patient-centered index, with an immediate and unambiguous treatment strategy embedded within it. It invites the patient to take into account not only severity of pain but also other clinically relevant considerations, such as common opioid adverse effects that patients may ﬁnd more unpleasant than partially attenuated pain.
As much as we may think we know the patient’s pain level better than the patient, or the authenticity of the patient’s pain better than the patient, it is unlikely that we are right. Feel free to provide some research to contradict me, if you disagree.
Even after receiving the approximate equivalent of 14 mg morphine either all at once or in 2 equally divided doses, one third of patients still wanted additional analgesia. This is consistent with the work of other investigators, demonstrating similar and substantial interindividual variation in opioid requirement.10-12,35 
We are sometimes discouraged from providing good patient care because of numbers that we might think are too much.
The problem is when not some numbers are too much.
The problem is when the patient’s pain is too much.
The mean level of pain was clearly lower at all times in the study.
With more attention to the patient’s pain and to the possible side effects, we can prove more aggressive pain management that is just as safe, if not more safe, than less aggressive dosing with opioids.
The difference between the conclusions we would have drawn according to a retrospective analysis indirectly comparing studies that appeared to constitute a valid comparison versus what we have concluded according to the current randomized clinical trial is a useful reminder of the hazards of using historical comparison groups, even if they are samples from the same population. Had we not performed a randomized trial to confirm our previous findings, we would have concluded that the 2 mg hydromorphone bolus protocol was superior to the 1+1 titration protocol.
An initial 2 mg bolus does not appears to increase the benefits to the patients in this ED study.
In EMS our goal is usually to manage the pain before we move the patient.
In EMS an initial 1 mg hydromorphone, with 5 minute repeat doses would not appear to delay benefits, but the study’s end point was the need for more medicine at 1 hour, not the ability to adequately control the patient’s pain before moving the patient.
 Randomized Clinical Trial of the 2 mg Hydromorphone Bolus Protocol Versus the “1+1″ Hydromorphone Titration Protocol in Treatment of Acute, Severe Pain in the First Hour of Emergency Department Presentation.
Chang AK, Bijur PE, Lupow JB, Gallagher EJ.
Ann Emerg Med. 2013 May 16. doi:pii: S0196-0644(13)00201-1. 10.1016/j.annemergmed.2013.02.023. [Epub ahead of print]
PMID: 23694801 [PubMed - as supplied by publisher]
Chang AK, Bijur PE, Lupow JB, & Gallagher EJ (2013). Randomized Clinical Trial of the 2 mg Hydromorphone Bolus Protocol Versus the “1+1″ Hydromorphone Titration Protocol in Treatment of Acute, Severe Pain in the First Hour of Emergency Department Presentation. Annals of emergency medicine PMID: 23694801