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InFocus: Hydromorphone without Side Effects

Roberts, James R. MD

doi: 10.1097/01.EEM.0000434473.06709.0f

Dr. Roberts is the chairman of emergency medicine and the director of the division of toxicology at Mercy Catholic Medical Center, and a professor of emergency medicine and toxicology at the Drexel University College of Medicine, both in Philadelphia.





Emergency physicians regularly administer intravenous opioids to control acute pain. Various treatment protocols utilizing opioid medication have been studied for inpatients, but data are sparse on using opioids for initially controlling acute pain in the ED, and extrapolating that inpatient use to acute care in the ED is not readily applicable.

Emergency clinicians have their favorite analgesic, with morphine being the quintessential choice. Hydromorphone (Dilaudid) is another commonly used opioid that has garnered a reputation for being safe and effective. The proper dose of any IV analgesic is essentially enough to control the pain without causing untoward side effects, but hydromorphone is a particularly potent opioid that must be administered carefully to avoid well known side effects.

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Safety and Efficacy of Rapid Titration Using 1 mg Doses of Intravenous Hydromorphone in ED Patients with Acute Severe Pain: The 1 + 1 Protocol

Chang AK, et al

Ann Emerg Med


These authors from an urban academic ED in New York City emphasize the well-known oligoanalgesia and the often inadequate treatment of acute pain in the ED. This prospective interventional study evaluated the safety and efficacy of an ED protocol where patients with acute pain received an initial 1 mg of IV hydromorphone, followed by an optional second 1 mg IV dose 15 minutes later. The aim was to determine whether this titration protocol would provide effective pain relief without the oxygen desaturation that has been noted when initially higher hydromorphone doses have been used.

Hydromorphone use with this protocol for nonelderly ED patients with acute severe pain was analyzed in 223 individuals, ages 21 to 64. Eligible patients had acute pain, blood pressure above 90 mm Hg, oxygen saturation greater than 95%, and the absence of alcohol or other drug intoxication as an admitting diagnosis. Individuals who had taken opioids within seven days were excluded.

Fifteen minutes following the initial 1 mg of IV hydromorphone, the patients were asked whether they wanted more pain medication. An additional 1 mg of IV hydromorphone was administered if the patient requested more analgesia. Pain scores were obtained using the standard 0-10 pain scale. About 70 percent of the patients had an initial pain scale of 9-10. Forty-four patients declined a second dose, and no patient required naloxone reversal.

A small percentage (5%) experienced oxygen desaturation, defined as a pulse oximetry less than 95%, within 15 minutes of the administration of the first bolus of IV hydromorphone. Three of these patients desaturated to less than 90%, but oxygenation in all patients returned to normal simply by administering four liters of nasal cannula oxygen. No patient required assisted ventilation or intervention other than the supplemental oxygen. About 10 percent were relatively bradycardic without intervention required, and the incidence of nausea and vomiting secondary to drug administration was 13 percent and seven percent, respectively.

About 77 percent of the patients (172/223) decided to forego additional analgesics when it was offered to treat their pain. The authors interpreted the patient's decisions to forgo additional analgesics as an indication of adequate pain control. Overall, 96 percent of patients obtained adequate analgesia within one hour. No clinically important adverse effects were noted.

Comment: Prior data indicated that only about 50 percent of ED patients had at least a two-point reduction of pain on the numerical scale, and 75 percent were discharged with continued moderate to severe pain. (JPain 2007;8[6]:460.) These authors previously found that an initial 2 mg IV hydromorphone resulted in rapid and dramatic pain relief (Acad Emerg Med 2008;15[Supplement 1]:S56), but about one-third of patients experienced oxygen desaturation with this larger dose, prompting the decision to investigate the 1 + 1 protocol. The authors note that prior attempts at using titrated doses of miniscule amounts of morphine (2 mg doses usually), with an individualized nursing intensive protocol, was not totally successful. (Am J Emerg Med 2008;26[6];676.)

Hydromorphone has been traditionally stated to have five- to sevenfold greater potency than morphine, but that has only been studied with the first dose in opioid-naïve patients. The proposed hydromorphone:morphine ratio has not been well studied, and the commonly used ED dose of hydromorphone is usually more than this equivalency would suggest. For some yet-to-be-explained reasons, physicians readily administer 1-2 mg hydromorphone, but are reluctant to administer an estimated equivalent 7-14 mg dose of morphine. It has been my experience that nurses would often question a 15 mg morphine dose, but readily administer an equally potent 2 mg hydromorphone injection. Hydromorphone is supplied in 0.5, 1, and 2 mg vials, and perhaps that packaging is more conducive to administering the larger doses.

Note that elderly patients were excluded, and it is prudent to administer smaller doses of hydromorphone in this subgroup initially. Defining the elderly as greater than 64 years of age is, however, very conservative. One prior study of analgesia in the elderly found that small doses of hydromorphone (0.0075 mg/kg/0.525 mg for 70 kg) and morphine (0.05 mg/kg/3.5 mg for 70 kg) provided similar safe analgesia. (Am J Geriatr Pharmacother 2009;7[1]:1.)

All of these patients were opioid-naïve, and it is a common observation that patients chronically using opioids tolerate much larger doses given more frequently. A common example is opioid-tolerant sickle cell pain, where 2-6 mg IV doses are frequently given every two hours, are well tolerated, and even result in discharge from the ED. The maximum pain relief of any IV opioid is usually achieved after 10-15 minutes, so it appears appropriate to reassess one's use of IV opioids at this juncture. The side effects are usually maximal when the blood levels are highest, so it's generally assumed to be safe to administer additional IV analgesia after 15 minutes.

It is indeed an elusive goal to provide safe and effective analgesia in the ED for treating acute pain. Patients have marked individual variability in pain perception and response to opioids. Administering very small doses of intravenous morphine every three to five minutes until analgesia is achieved is common in the postoperative care setting but impractical in the ED.



No apparent advantage of the initially higher hydromorphone dose was obvious when these authors compared the 1 + 1 titration protocol with an initial 2 mg bolus dose. Most clinicians feel comfortable with an initial 1-2 mg dose of IV hydromorphone. In opioid-naïve patients, 0.5 to 1 mg of IV hydromorphone is often adequate as an initial dose, but conditions such as renal colic or particularly painful fractures often require initially higher and additional dosing. Intravenous opioids are commonly administered for the patient with undiagnosed abdominal pain.

This is indeed an enlightened concept because opioid pain medications were previously eschewed in individuals with abdominal pain for fear that they would mask symptoms or otherwise alter one's clinical evaluation. This analgesic myth has long been known to be meaningless in the ED. Our surgical colleagues have come to generally agree with the initial use of IV opioids to treat abdominal pain to aid an evaluation without altering diagnostic abilities.

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Effective Analgesia with Low-Dose Ketamine and Reduced Dose Hydromorphone in ED Patients with Severe Pain

Ahern TL, et al

Am J Emerg Med


These authors addressed the analgesic effect and feasibility of low-dose ketamine combined with a reduced dose of hydromorphone for ED patients with severe pain. This was an attempt to evaluate the well known potent analgesic effect of low-dose ketamine as an addition to opioid-induced pain relief. The obvious benefit of ketamine is that it has few adverse hemodynamic or respiratory effects. This article is an addition to some others that have shown that ketamine (0.1-0.3 mg/kg) is safe and effective as an analgesic and improves pain management when combined with opioids.

The protocol consisted of 0.5 mg of IV hydromorphone plus 15 mg of IV ketamine, followed by additional 1 mg of hydromorphone at 15 and 30 minutes if required. Pain intensity was measured with a standard 10-point numerical scale, and patients were monitored throughout for adverse effects. The patients had a diverse etiology of the pain, including abdominal pain, back pain, cholecystitis, sickle cell pain, and traumatic or surgical pain.

All 14 of the 30 prospectively enrolled patients with severe pain reported complete pain relief in five minutes, with a mean reduction in the pain scale of 6. Pain relief was adequate at 15 minutes in 67 percent of patients. No significant side effects were noted in any patient, and 90 percent reported that they would have the same medication regimen again. The authors concluded that low-dose ketamine combined with a reduced dose of hydromorphone produced rapid and profound pain relief without significant side effects.

Comment: The side effects of ketamine are minimal with doses less than 0.3 mg/kg, and ketamine because of its ability to augment analgesia in an opioid-sparing milieu, has been used in the ICU, the burn unit, and palliative care settings. Ketamine for analgesia, however, remains largely unstudied in the ED. The reduced initial hydromorphone dose with the addition of ketamine produced analgesia in almost 80 percent of patients who declined additional hydromorphone in 15 minutes. These authors were impressed by the profound pain reduction within five minutes, with almost half of the subjects reporting complete resolution of pain. The rapid and profound analgesia effect was a major strength of the protocol compared with using opioids alone.

Many emergency physicians are familiar with ketamine for ED sedation and intubation, but few have used it in conjunction with opioids to produce potent analgesic effects. One more common side effect was a 25 percent rate of nausea compared with less than 10 percent of this side effect of hydromorphone alone. Nonetheless, the majority of patients reported that they would have ketamine again for similar pain. This was a relatively small unblinded study with no comparison group, but the results are rather impressive. Some minor side effects attributed to ketamine included fatigue, headache, dizziness, and mood changes. The obvious benefit of this combination is the lack of respiratory depression attributed to the lower hydromorphone dose.

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Reader Feedback: Readers are invited to ask specific questions and offer personal experiences, comments, or observations on InFocus topics. Literature references are appreciated. Pertinent responses will be published in a future issue. Please send comments to



Dr. Roberts: I've already used the loop technique on two patients, and am teaching it to others. Thank you! I know this is an elementary question regarding abscess I&D, but what tips can you give on anesthetizing abscesses that already have a small pointed opening, and it seems that 90% of the lidocaine with epi drains right out of the hole no matter how you inject it?

I try redirecting to get in the thin subcutaneous layer, almost like raising a wheal, but frankly it's difficult to achieve anesthesia in these cases. Any tips? — Kendall Thurman, DO, Midlothian, VA

Dr. Roberts responds: If the skin over an abscess is too thin to allow anesthetic injection, it's probably better to do a field block around the entire base of the abscess. That entails a number of needlesticks, but it will give adequate anesthesia.

© 2013 by Lippincott Williams & Wilkins