Opioids for Dyspnea End of Life Review

Objective: The objective of this systematic review is to consolidate the existing evidence on opioid use, including administration, dosing and efficacy, for the relief of dyspnea at end-of-life. The overarching goal is to optimize clinical management of dyspnea by identifying patterns in opioid use, improving opioid management of dyspnea, and to prioritize future research. Background: Opioids are commonly used in the management of dyspnea at end of life; yet specific administration guidelines are limited. A greater understanding of the effectiveness of opioids in relieving end-of-life dyspnea with consideration of study design, patients, and opioids, including dyspnea evaluation tools and outcomes, will leverage development of standardized administration and dosing. Methods: A PRISMA guided systematic review using six databases identified quality studies of opioid management for patients with dyspnea at end of life. Results: Twenty-three references met review inclusion criteria which included terminally ill cancer and non-cancer patients with various diagnoses. Studies included two randomized controlled trials, three non-randomized experimental, three prospective observational, one cross-sectional, and one case series. Thirteen retrospective chart reviews were also included due to the limited rigorous studies rendered by the search. Thirteen studies evaluated morphine, followed by fentanyl (6), oxycodone (5), general opioid use (4), and hydromorphone (2). Routes of administration were parenteral, oral, combination, and nebulization. Dyspnea was evaluated using self-reporting and non-self-reporting evaluation tools. Sedation was the most reported opioid related adverse effect. Discussion: Challenges persist in conducting end of life research preventing consensus on standardization of opioid treatment for dyspnea within this specific palliative timeframe. Future robust prospective trials using specific, accurate assessment with re-assessment of dyspnea/respiratory distress, and consideration of opioid tolerance, polypharmacy, and comorbidities are require

Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children

To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single‐blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m 2 or ranitidine 60 mg/m 2 when gastric pH 1 hour with serial blood sampling following first dose. Twenty‐four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty‐four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p  = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours ( p  > 0.2). No difference between drugs in clearance, volume of distribution and half‐life ( p  > 0.05). Ratio of AUC pH to AUC drug concentration 0–12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p  < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102678/1/jcph219.pd