Diphenhydramine as an adjunct to sedation for colonoscopy: a double-blind randomized, placebo-controlled study.

BACKGROUND: Intravenous benzodiazepines in combination with opiates are used to achieve moderate sedation for colonoscopy. Although effective, these agents have potential adverse effects, such as respiratory depression and hypotension. Diphenhydramine hydrochloride possesses central nervous system depressant effects that theoretically could provide a synergistic effect for sedating patients. OBJECTIVE: The objective was to assess the efficacy of adding diphenhydramine hydrochloride as an adjunct to improve sedation and to reduce the amount of standard sedatives used during colonoscopy. DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled study. SETTING: The study was conducted in a university hospital with an active GI fellowship training program. PATIENTS: The study group comprised 270 patients undergoing screening/diagnostic/therapeutic colonoscopy were enrolled. INTERVENTIONS: Patients were randomized to receive either 50 mg of diphenhydramine or placebo, given intravenously 3 minutes before starting conscious sedation with intravenous midazolam and meperidine. MAIN OUTCOME MEASUREMENTS: The main outcome measure was anesthetic effect as assessed by the endoscopy team and by the patient; quantity of adjunctive sedatives to achieve adequate sedation. RESULTS: Of 270 patients, data were analyzed for 258 patients, with 130 patients in the diphenhydramine group and 128 patients in the placebo group. There was a 10.1% reduction in meperidine usage and 13.7% reduction in midazolam usage in favor of the diphenhydramine group. The mean evaluation scores as judged by the faculty, the fellows, and the nurses were statistically significant in favor of the diphenhydramine group. In addition, patient scores for overall sedation and pain level favored the group that received diphenhydramine. CONCLUSIONS: Intravenous diphenhydramine given before initiation of standard sedation offers a significant benefit to conscious sedation for patients undergoing colonoscopy.

The biology of TNF blockade.

Rheumatoid arthritis and Crohn's disease are costly diseases that result in significant long-term patient disability. They are chronic inflammatory diseases that are associated with increased production of Tumor Necrosis Factor (TNF). Blockage of this cytokine with bio-engineered compounds has significantly changed therapy of these diseases and has ushered in the era of biological therapy. The pro-inflammatory role of TNF is mediated by its essential respiratory burst function that is effectively inhibited by anti-TNF therapy. Anti-TNF therapy is effective in approximately two-thirds of patients to whom it is administered, but the effect is temporary. Lack of response to anti-TNF therapy stems from interplay of host-factors including: host cytokine response, disease phenotype, and antibody response to the anti-TNF agents. NOD 2, a defect present in approximately 50% of Crohn's disease patients, bears no relationship to non-response. Additionally, TNF promoter gene polymorphisms and TNF receptor gene heterogeneity play a significant role in non-response and disease course/severity. Adverse effects of anti-TNF therapy include early and delayed hypersensitivity reactions, cell-mediated infections, lupus-like syndrome, demyelinating diseases, and exacerbation of CHF.