A prospective, randomized, double blind, comparative study of intramuscular nalbuphine hydrochloride, butorphanol tartrate and pentazocine lactate for post-operative pain relief following abdominal hysterectomy

Background: This study aimed to compare the efficacy and safety of intramuscularly administered nalbuphine, butorphanol and pentazocine for post-operative pain relief after abdominal hysterectomy.Methods: Seventy-five adult female patients, aged between 20-50 years, belonging to American Society of Anaesthesiologists (ASA) class 1 and 2, posted for abdominal hysterectomy under spinal anesthesia were included in the study. The subjects were randomly divided into 3 groups (n=25 each) and given – Group A: pentazocine lactate (30 mg, 1mL), Group B: butorphanol tartarate (2 mg, 1 ml) and Group C: nalbuphine hydrochloride (10 mg, 1 mL) when post-operative pain intensity reached ≥4 mm on the Visual analogue scale (VAS). The onset, duration, time to peak effect and adverse events were recorded at regular intervals for 24 hours, postoperatively.Results: The mean time to onset of anesthesia was significantly faster (P<0.05 each) in the nalbuphine (10.2±2.2 minutes) and butorphanol (11.3±2 minutes) groups when compared to the pentazocine group (14±2.7 minutes). Duration of analgesic action was significantly longer (P<0.05 each) in the nalbuphine (236.4±75.1 minutes) and butorphanol (202±59.2 minutes) groups when compared to the pentazocine group (177.4±55.3 minutes). No significant differences in respiratory and cardiovascular parameters were noted between the groups. Nausea and vomiting was seen significantly higher in the pentazocine group (36%) when compared to butorphanol (20%) and nalbuphine (8%) groups (p<0.05 each).Conclusions: Intramuscular nalbuphine and butorphanol provided effective analgesia with rapid onset and longer duration of action, with lower incidence of nausea and vomiting when compared to pentazocine. In particular, nalbuphine can be a suitable agent to provide post-operative pain relief in gynecologic lower abdominal surgery

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society