Evaluation of the effect of perioperative rofecoxib treatment on pain control and clinical outcomes in patients recovering from gynecologic abdominal surgery: a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND AND OBJECTIVES: In this randomized, placebo-controlled, double-blind study, the efficacy and safety of rofecoxib 50 mg was evaluated in patients undergoing major abdominal gynecologic surgery. METHODS: Patients were randomized to receive rofecoxib 50 mg (n = 81) or placebo (n = 83) approximately 2 hours before total abdominal hysterectomy or myomectomy and once daily over the ensuing 4 days. Clinical measurements included average daily opioid use over the 5-day period (primary endpoint), pain intensity on movement, and opioid-related side effects. RESULTS: Patients receiving rofecoxib required 32% less (P = .001) intravenous and oral opioids to relieve their postoperative pain from days 1 to 5 (primary endpoint), used 21% less (P = .011) on day 1, and 42% less (P < .001) from days 2 to 5. The rofecoxib group experienced less pain upon movement (P < .001), less sedation (P = .007), and a 24% reduction in the rate of antiemetic intake (P = .037) over the first 72 hours postsurgery. Earlier mean times to first flatus (-10.1 hours, P = .001), first bowel movement (-14.1 hours, P = .037), and time to hospital discharge (-10.9 hours; 95% confidence interval, -17.1 to -4.7) occurred in the rofecoxib group. There were no significant intergroup differences in blood loss, wound healing, or overall adverse experiences. CONCLUSIONS: Compared with placebo, perioperative administration of rofecoxib 50 mg provided significant opioid sparing, significantly better pain control, improved clinical outcomes, and was well tolerated.

Sleep-disordered breathing associated with long-term opioid therapy.

Three patients are described who illustrate distinctive patterns of sleep-disordered breathing that we have observed in patients who are receiving long-term, sustained-release opioid medications. Polysomnography shows respiratory disturbances occur predominantly during non-rapid eye movement (NREM) sleep and are characterized by ataxic breathing, central apneas, sustained hypoxemia, and unusually prolonged obstructive "hypopneas" secondary to delayed arousal responses. In contrast to what is usually observed in subjects with obstructive sleep apnea (OSA), oxygen desaturation is more severe and respiratory disturbances are longer during NREM sleep compared to rapid eye movement sleep. Further studies are needed regarding the effects of opioids on respiration during sleep as well as the importance of interaction with other medications and associated risk factors for OSA.

Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing.

BACKGROUND: Chronic opioid therapy for pain management has increased dramatically without adequate study of potential deleterious effects on breathing during sleep. METHODS: A retrospective cohort study comparing 60 patients taking chronic opioids matched for age, sex, and body mass index with 60 patients not taking opioids was conducted to determine the effect of morphine dose equivalent on breathing patterns during sleep. RESULTS: The apnea-hypopnea index was greater in the opioid group (43.5/h vs 30.2/h, p < .05) due to increased central apneas (12.8/h vs 2.1/h; p < .001). Arterial oxygen saturation (SpO2) in the opioid group was significantly lower during both wakefulness (difference 2.1%, p < .001) and non-rapid eye movement (NREM) sleep (difference 2.2%, p < .001) but not during rapid eye movement (REM) sleep (difference 1.2%) than in the nonopioid group. Within the opioid group, and after controlling for body mass index, age, and sex, there was a dose-response relationship between morphine dose equivalent and apnea-hypopnea (p < .001), obstructive apnea (p < .001), hypopnea (p < .001), and central apnea indexes (p < .001). Body mass index was inversely related to apnea-hypopnea index severity in the opioid group. Ataxic or irregular breathing during NREM sleep was also more prevalent in patients who chronically used opioids (70% vs 5.0%, p < .001) and more frequent (92%) at a morphine dose equivalent of 200 mg or higher (odds ratio = 15.4, p = .017). CONCLUSIONS: There is a dose-dependent relationship between chronic opioid use and the development of a peculiar pattern of respiration consisting of central sleep apneas and ataxic breathing. Although potentially significant, the clinical relevance of these observations remains to be established.

Etoricoxib provides analgesic efficacy to patients after knee or hip replacement surgery: a randomized, double-blind, placebo-controlled study.

UNLABELLED: In this randomized, double-blind, placebo-controlled, multicenter study we assessed the analgesic effect of etoricoxib (a new cyclooxygenase-2 inhibitor) in patients having had knee or hip replacement surgery. A total of 228 patients with moderate or severe pain were randomly allocated within 72 h after surgery to receive etoricoxib 120 mg, controlled-release naproxen sodium 1100 mg, or placebo (1:1:1) on day 1 followed by etoricoxib and placebo (1:2) on days 2 to 7. Patients reported pain scores, rescue (opioid-combination) medication use, and the response to study drug. On day 1, etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h, the primary end-point; least-squares mean scores were 11.0, 11.5, and 5.6, respectively (P < 0.001 versus placebo). Similarly, a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiving placebo reported good to excellent responses to study drug: 53%, 60%, and 26% respectively. On days 2-7, etoricoxib demonstrated a significant reduction of rescue medication use, 35% (P < 0.001 versus placebo). The clinical relevance of the decrease was confirmed by Patient's Global Evaluation (P < 0.05 versus placebo). Patients receiving etoricoxib also experienced significantly less "worst" and "average" pain than did those on placebo. Etoricoxib was generally well tolerated in this study; the incidence of adverse experiences was infrequent and similar across treatment groups. In summary, etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days. IMPLICATIONS: In a postsurgery setting (knee and hip replacements), etoricoxib 120 mg provided analgesia superior to placebo and similar to controlled-release naproxen sodium 1100 mg. Patients receiving etoricoxib suffered less pain and took less opioid rescue medication compared with patients on placebo.