Tuesday, January 14, 2014

ICU: No Harm Seen With Shortage-Fueled Switch

SAN FRANCISCO -- When fentanyl was in short supply, switching to hydromorphone did not adversely affect critically ill patients on mechanical ventilation, researchers reported here.

The median time on ventilation -- a co-primary endpoint -- was 8 days among the patients treated with hydromorphone versus 7 days for those treated with fentanyl (P=0.69), said Alison Vo, PharmD, a clinical care pharmacist at St. Luke's Medical Center, Houston.

For the other primary endpoint, the rate of performing tracheostomies was 14% among those patients on hydromorphone and 19% among those patients treated with fentanyl (P=0.52), Vo reported in her poster presentation at the annual meeting of the Society of Critical Care Medicine.

Additionally, Vo told MedPage Today that there was no statistical difference in the number of days on opioid therapy -- 6 days with hydromorphone and 4 days with fentanyl (P=0.18), and there was no difference in cumulative opioid dose, a median of 430 mg of morphine equivalents among the patients receiving hydromorphone and a median of 464 mg of morphine equivalents among the patients treated with fentanyl (P=0.25).

"We were specifically looking to see if there were any negative outcomes," she said. "We also did look at hospital length of stay, and there were no differences there either. Numerically there appears to be greater use of rescue medication in the patients on hydromorphone, but when you group the need for rescue medication together there are no statistical differences," she said.

"There were no differences in our clinical endpoints and that was something we were hoping to see -- that we were not doing any harm to our patients," Vo said.

During the poster discussion session, moderator Steven Blau, MD, critical care surgeon at Good Samaritan Hospital Medical Center, West Islip, New York, asked, "If there was no shortage of fentanyl, which drug would you prefer?" Vo said she would still opt to use fentanyl. Blau persisted, "Under what circumstances would you use hydromorphone instead of fentanyl?" Vo said that if a patient had several organ dysfunctions, she might consider hydromorphone instead of fentanyl.

According the FDA, shortages of fentanyl persist in some dosing formats from two of three manufacturers, although the companies are accelerating delivery

In commenting on the study, Joel Zivot, MD, assistant professor of anesthesiology and surgery at Emory University School of Medicine, Atlanta, told MedPage Today, "Hydromorphone and fentanyl have different pharmacokinetics so I would not routinely use one instead of the other in critically ill patients.

"This study's findings that show little negative differences in these outcomes are reassuring if substitution of hydromorphone is needed due to shortages of fentanyl," he said.

Noting that the study's design was a limiting factor, Vo said that switching to hydromorphone "is not something we would recommend for routine care. This is a retrospective study. It is interesting because there are no data on this comparison. Hydromorphone (Dilaudid) has been around for a long time, but it has not been used in this setting before."

She said "sedatives and analgesics are frequently used in the intensive care unit as part of standard care to provide comfort and safety to critically ill patients on mechanical ventilation. The choice of sedative depends on clinical implications, patient specific factors, and opioids. The mainstays of sedation therapy in the intensive care unit include propofol, benzodiazepines, dexmedetomidine, and opioids. However, only opioids and dexmedetomidine provide both analgesic and sedative effects.

"The concept of providing analgesia first, supplemented by sedation when necessary, has been shown to be effective and is currently recommended by the American College of Clinical Care Medicine. The most frequently used opioids in the intensive care unit include fentanyl, morphine, and hydromorphone, but only fentanyl has been used for both intermittent and continuous administration."

Vo said her study was prompted by ongoing drug shortage situations, resulting in the use of alternative therapies. "For example, the fentanyl shortage led to an alternative use of continuous intravenous hydromorphone for sedation in critically ill patients on mechanical ventilation at this institution," she said. "Despite several differences in pharmacokinetics, hydromorphone was chosen due to similar characteristics to fentanyl compared with other opioids such as morphine, which has a longer duration of action and potential side effects from the release of histamine."

Using the hospital's electronic database to conduct the retrospective study, Vo and colleagues identified 363 patients treated between March 2012 and June 2012 who received either hydromorphone or fentanyl therapy.

After applying inclusion and exclusion criteria, the researchers were left with 170 patients, 58 of whom were treated with hydromorphone and 112 who were on fentanyl. All the patients included in the analyses had to have been on mechanical ventilation for at least 24 hours. Most of the patients included in the study were in critical care due to noncardiac related medical illnesses.

"Most of the patients in the study were on light sedation. There were only a few patients who required heavy sedation," Vo said.

http://www.medpagetoday.com/MeetingCoverage/SCCM/43778

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