Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery.

INTRODUCTION: Parenteral opioids are the standard of care for treating moderate to severe postsurgical pain. This randomized, double-blind, dose-ranging study compared the safety and efficacy of intranasal (IN) morphine with intravenous (IV) morphine and placebo.

METHODS: In total, 187 postbunionectomy patients with moderate to severe pain were randomized to receive IN morphine 3.75 mg, 7.5 mg, 15 mg, or 30 mg, IV morphine 7.5 mg, or placebo in the single-dose phase and IN morphine 7.5 mg or 15 mg thereafter. The primary outcome was a dose-response assessment for total pain relief based upon visual analog scales. Secondary endpoints included pain intensity, pain relief, patient global evaluation, and time to rescue medication. Safety assessments included adverse events and nasal examination.

RESULTS: A statistically significant linear dose response was observed over the IN morphine dose range for 4-hour total pain relief. Patients reported statistically significant pain relief and pain intensity differences following IV morphine and IN morphine at doses of 7.5 mg and greater within 30 minutes postdose, compared with placebo. Median times to rescue medication were 124 and 140 minutes for IN morphine 7.5 mg and 15 mg dosage groups, respectively, and 130 minutes for IV morphine. Local adverse events associated with IN morphine were transient and mostly mild (bad taste, nasal congestion, throat irritation, and sneezing). Systemic adverse events, regardless of route of administration, were dose-related and consistent with expected opioid effects.

CONCLUSIONS: By multiple measures of pain intensity and pain relief, IN morphine provides sustained analgesia in postsurgical patients and thus may offer a safe and less invasive alternative to IV morphine.