Dilaudid-Related Morbidity and Mortality from Respiratory Depression

Howard Marcus, MD, FACP, Chairman, Texas Alliance for Patient Access

The accidental overdose of opioids increased from the early 2000s, escalating to nearly 50,000 opioid-related deaths in 2018.1 Some of these overdoses are iatrogenic. A multiyear study from Ontario, Canada, reports 251 deaths specifically from Dilaudid (HYDROmorphone) due to oral and IV overdose.2 The Doctors Company claims database contains multiple cases of Dilaudid overdose resulting in morbidity and mortality.

These adverse events, specifically related to Dilaudid, are due to multiple reasons—including an erroneous understanding of the conversion ratio between IV Dilaudid and oral Dilaudid and the morphine milligram equivalent (MME) of Dilaudid.

A palliative care study found that 1 mg of IV Dilaudid is equivalent to 2.5 mg of oral Dilaudid and 11.46 mg of oral morphine.3

Conversion tables for commonly used oral opioids, including Dilaudid (HYDROmorphone), are readily available and may be easily referenced when prescribing and/or converting opioid dosage. One example is the oral Opioid Conversion Calculator provided by the Oregon Health Authority. Note that we have found a significant range in the equivalency of IV Dilaudid to morphine ranging from 1:5 to 1:8.

The following are current recommendations from UpToDate Lexicomp for dosing of IV Dilaudid and morphine:

  • Dilaudid IV: Initial, opioid naive—0.2 to 1 mg every 2 to 3 hours as needed.
  • Morphine IV: Initial, opioid naive—2.5 to 5 mg every 3 to 4 hours as needed.

According to the Centers for Disease Control and Prevention, higher dosages of opioids are associated with higher risk of overdose and death, and even relatively low dosages (20–50 MME per day) increase risk. Dosages at 50 MME per day double the risk of overdose compared to 20 MME.4

Appropriate pain management should ensure rapid and effective pain control without placing the patient at risk for harm. However, medical error reporting provides tragic examples of over-aggressive opioid administration as illustrated in the following case example.

A healthy opioid-naive 22-year-old man was admitted to hospital with acute upper back pain. Morphine was initially ordered at 1–5 mg intravenously every two hours as needed and was later increased to 5–10 mg intravenously every two hours as needed. Owing to poor pain control, an order was written in the evening to discontinue morphine and start HYDROmorphone at 5–10 mg intravenously every four hours as needed. The next morning, the patient was found without vital signs. Resuscitation efforts were unsuccessful.5

Alcohol, other opioids, and central nervous system depressants (sedative-hypnotics) can potentiate the respiratory depressant effects of Dilaudid. Seventy-seven percent of morbidity due to opioids occurs in the first postoperative day. Additional risk factors include patients who are over age 65 and those with comorbidities such as chronic obstructive pulmonary disease (COPD), kidney disease, congestive heart failure, and sleep apnea.6

Routine monitoring of vital signs by nursing staff may fail to recognize early signs of respiratory depression. Bradypnea is a poor predictor of desaturation and may be a late or absent finding,7 and pulse oximetry may not be an accurate monitoring tool for patients receiving supplemental oxygen.8 When pain is ameliorated and the patient falls asleep, he or she may slip unnoticed into respiratory depression and apnea.

The following cases from The Doctors Company closed claims files illustrate these points:

  • A 27-year-old male burned his hands after a prolonged period of drinking alcohol and presented to the emergency department with painful second-degree burns. The emergency physician ordered: “titrate HYDROmorphone.” The patient received a total of four 1 mg doses of Dilaudid IV over a period of one hour. He was discharged 30 minutes later fully awake with normal vital signs. He returned home, took Percocet tablets that had been dispensed before discharge, and went to bed at 4:00 AM. He was found dead in bed at 7:45 AM. The postmortem Dilaudid level was 9.2 ng/ml, and the ethanol level was 0.17 gm/dl. (HYDROmorphone concentrations above 75 ng/ml are considered lethal.9) Thus, while Dilaudid levels at autopsy were well below those reported to cause apnea, the combination of alcohol and Dilaudid was the most likely cause of death.
  • A 29-year-old patient admitted with right lower quadrant pain and a history of kidney stones received a total of 11.5 mg of Dilaudid IV (including one single dose of 4 mg), as well as Demerol 50 mg and Valium 5 mg over a period of seven and a half hours. The patient was found dead in the hospital bed. The combination of markedly excessive dosages of Dilaudid (equivalent to a total of 92 mg of morphine) plus additional respiratory depressants resulted in death.
  • A 25-year-old female required a fasciotomy after injuring her leg. She received a total of 14.5 mg of Dilaudid IV over a period of 11 hours and became apneic. She survived but suffered anoxic brain injury with significant neurologic sequelae.
  • An 89-year-old female was admitted with a hip fracture. An initial order of Dilaudid 0.5 mg IV prn resulted in two doses over a period of 90 minutes. The dose of Dilaudid was then increased to 1 mg IV every three hours prn due to the patient’s persistent pain, and she received a total Dilaudid dose of 2 mg over a period of four hours, which resulted in respiratory depression, intubation, and death.

The Institute for Safe Medication Practices has compiled recommendations to help reduce patient harm from Dilaudid. We have added a few recommendations of our own:

  1. Do not confuse HYDROmorphone with morphine. Use tall man lettering to help differentiate between the two.
  2. Because Dilaudid (brand name) is more commonly used and understood than HYDROmorphone, include the brand name when ordering.
  3. Post morphine milligram equivalent charts in patient care areas and ordering systems, and differentiate between oral and parenteral dosages.
  4. Limit initial dose of IV Dilaudid to 0.5 mg, and limit the number of strengths available.
  5. Be aware of adverse risk factors, including obesity, COPD, age, obstructive sleep apnea, and asthma.
  6. Do not rely on pulse oximetry readings alone to detect opioid toxicity. Use capnography to detect respiratory changes caused by opioids, especially for high-risk patients.
  7. Avoid stocking HYDROmorphone prefilled syringes in the same strength as morphine prefilled syringes.

To minimize narcotic-related respiratory depression, one large hospital group simplified narcotic administration by removing meperidine/promethazine from the hospital formulary and making Dilaudid the analgesic of choice but with rigorous controls. Hospital regulations now require an automatic advisory that the recommended Dilaudid dose is 0.2–0.5 mg IV whenever Dilaudid is ordered, a maximum dispensing limit of 1 mg per dose, reassessment of respiratory and pain status 15 to 30 minutes after a Dilaudid dose, and a focused education program for physicians and nurses emphasizing the relative Dilaudid-to-morphine ratio of 7:1.


References

  1. New data show growing complexity of drug overdose deaths in America [news release]. Centers for Disease Control and Prevention Media Relations; December 21, 2018. https://www.cdc.gov/media/releases/2018/p1221-complexity-drug-overdose.html.
  2. Wallage HR, Palmentier JP. Hydromorphone-related fatalities in Ontario. J Anal Toxicol. 2006;30(3):202–209.
  3. Reddy A, Vidal M, Stephen S, et al. The conversion ratio from intravenous hydromorphone to oral opioids in cancer patients. J Pain Symptom Manage. 2017 Sep;54(3):280-288.
  4. New data show growing complexity of drug overdose deaths in America [news release]. Centers for Disease Control and Prevention Media Relations; December 21, 2018. https://www.cdc.gov/media/releases/2018/p1221-complexity-drug-overdose.html.
  5. Lowe A, Hamilton M, Greenall J, Ma J, Dhalla I, Persaud N. Fatal overdoses involving hydromorphone and morphine among inpatients: a case series. CMAJ Open. 2017 Mar 2;5(1):E184-E189.
  6. Taylor S, Kirton OC, Staff I, Kozol RA. Postoperative day one: a high risk period for respiratory events. Am J Surg. 2005;190(5):752.
  7. Overdyk FJ, Carter R, Maddox RR, Callura J, Herrin AE, Henriquez C. Continuous oximetry/capnometry monitoring reveals frequent desaturation and bradypnea during patient-controlled analgesia. Anesth Analg. 2007;105(2).
  8. Fu ES, Downs JB, Schweiger JW, Miguel RV, Smith RA. Supplemental oxygen impairs detection of hypoventilation by pulse oximetry. Chest. 2004;126(5):1552.
  9. Wallage HR, Palmentier JP. Hydromorphone-related fatalities in Ontario. J Anal Toxicol. 2006;30(3):202–209.

The guidelines suggested here are not rules, do not constitute legal advice, and do not ensure a successful outcome. The ultimate decision regarding the appropriateness of any treatment must be made by each healthcare provider considering the circumstances of the individual situation and in accordance with the laws of the jurisdiction in which the care is rendered.

J12231 12/19

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