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Efficacy of Hyaluronidase Preceding Subcutaneous Opioid Infusions for the Treatment of Pain among Hospice Patients

Ronald S. Schonwetter, Sehwan Kim, Mary J. Quinn, Dee Boehm, Dipesh Patel, Cathy Emmett, Beverly Douglas, Teresa Kirkland, Stephen Leedy, Deidra Woods and Anna K. Westmoreland

Background: Morphine or hydromorphone are often administered by the subcutaneous (SC) route when oral and/or venous access is difficult to achieve or higher doses of opiates are needed. Human recombinant hyaluronidase is believed to increase the permeability of SC connective tissues by degrading hyaluronan and increasing the dispersion and absorption of coadministered molecules.

Objectives:To determine whether hyaluronidase coadministered with SC morphine or hydromorphone to hospice patients results in 1) faster reduction in pain level; 2) self-perceived pain relief, 3) improved pain-related distress, 4) reduction in the frequency of opiate bolus attempts utilized, and 5) more favorable outcomes on these measures over an eight-hour period.

Methods:This double blind, randomized, placebo-controlled study compared patients given SC hyaluronidase (n=25) and those receiving normal saline (n=29) both immediately prior to SC infusions with morphine or hydromorphone.

Results:Hyaluronidase was found to facilitate reduced pain level (p=0.059) and augmented pain relief (p=0.047) during the first 15 minutes following co-infusion of hyaluronidase when compared to patients in the control group who received usual pain control medication involving SC morphine or hydromorphone. In subsequent periods of observation up to eight hours, the intensity of pain level and the magnitude of pain relief realized showed no difference between the groups. There were no differences between the groups in pain-related distress (p≥0.657) and in the frequency of nfusion bolus attempts during the entire period under observation (p=0.173).

Conclusion: Hyaluronidase may be an effective adjunct during the first 15 minutes of drug administration in reducing pain intensity and enhancing pain relief when administered at the onset of a subcutaneous opioid infusion among hospice patients.

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