A randomized controlled trial of local injections of hyaluronidase versus placebo in cancer patients receiving subcutaneous hydration

Background: Most cancer patients develop reduced oral intake or dehydration before death. Subcutaneous hydration (SCH) can be safe and effective. SCH is frequently administered using hyaluronidase to improve fluid absorption. The objective of this study was to determine the effects of hyaluronidase on patient comfort during bolus SCH. Patients and methods: Twenty-one cancer patients requiring parenteral hydration were administered a 500 cc bolus of two-thirds dextrose (5%) and one-third normal saline solution subcutaneously at 08:00 and 16:00 hours during day 1 and day 2. On day 1 patients were randomized on a double-blind basis to receive 150 units of hyaluronidase versus placebo as a bolus into the site of infusion immediately before starting each one-hour infusion. During day 2 patients were crossed over to receive the alternate treatment at a new infusion site. Visual analogue scales (0 = best, 100 = worst) for pain and swelling at the infusion site were completed by each patient. In addition, investigators blindly assessed the site of infusion for the presence of edema, rash, and leakage. Results: No significant differences were observed for pain, swelling, edema, rash or leakage between the placebo and the hyaluronidase scores. After completion of the two days of the study, patients blindly chose hyaluronidase in 1 (5%) case, placebo in 5 (24%) cases, and no preference in 15 (71%) cases (P < 0.01). There was no treatment or interaction effect for pain, except for a period effect (P = 0.045) for the morning bolus administration. There were no treatment, period, or interaction effects for any of the other variables. Conclusions: Our results suggest that hyaluronidase is not necessary for routine bolus SCH. It may still be useful for a minority of patients who are not able to tolerate infusion well due to swelling or pain.