Opioid-Induced Respiratory Depression: Is Hydromorphone Safer Than Morphine?

To the Editor In their excellent articles concerning postoperative respiratory depression, Prielipp et al1 and Khanna et al2 did not present data to assess whether one particular opioid posed more risk than another. The difference in pharmacokinetics between morphine and hydromorphone suggests patient-controlled analgesia (PCA)–administered hydromorphone is inherently safer than PCA-administered morphine. Ideally, when using PCA, the previously administered dose will have reached peak analgesia and peak respiratory depression before the next dose is administered. Unfortunately, that is not accomplished with morphine and hydromorphone, but it is more closely accomplished with hydromorphone. Even though the peak plasma concentrations for both morphine and hydromorphone are about 20 minutes, the peak effect of morphine, as assessed by miosis, may be an hour after the peak plasma concentration.3 Thus, peak analgesic and respiratory depression may be delayed. There seems to be an effect site concentration versus a plasma concentration issue with morphine (hysteresis) that we may not have with hydromorphone. Because of the delay until peak analgesic effect, another dose may be administered before the previous dose has achieved full effect. This stacking will result in an overshoot. The pharmacokinetics suggest that a larger overshoot (ie, overdose) is more likely with morphine. For example, assume a patient needs the full effect of 15 mg of morphine to achieve analgesia. After several boluses by which time 15 mg of morphine has been administered, full effect will not have been achieved as it takes more than an hour to achieve peak effect. More boluses were then administered, and say in this case 25 mg were administered by the time analgesia has been achieved. The effect of morphine continues to increase leading to a respiratory depression event an hour or so later as the patient experienced the full effect of 25 mg. It would seem this scenario would be less likely and less severe with hydromorphone. Is there any data to suggest hydromorphone PCA is inherently safer than morphine PCA? Jonathan V. Roth, MDAlbert Einstein Medical CenterDepartment of AnesthesiologyPhiladelphia, Pennsylvania[email protected]