Effect of Nebulized Morphine on Dyspnea of Mustard Gas-Exposed Patients: A Double-Blind Randomized Clinical Trial Study

Abstract

Background. Dyspnea is one of the main complaints in a group of COPD patients due to exposure to sulfur mustard (SM) and is refractory to conventional therapies. We designed this study to evaluate effectiveness of nebulized morphine in such patients. Materials and Methods. In a double-blind clinical trial study, 40 patients with documented history of exposure to SM were allocated to two groups: group 1 who received 1 mg morphine sulfate diluted by 4 cc normal saline 0.5% using nebulizer once daily for 5 days and group 2 serving as control who received normal saline as placebo. They were visited by pulmonologist 7 times per day to check symptoms and signs and adverse events. Different parameters including patient-scored peak expiratory flow using pick flow meter, visual analogue scale (VAS) for dyspnea, global quality of life and cough, and number of respiratory rate, night time awaking for dyspnea and cough have been assessed. Results. The scores of VAS for dyspnea, cough and quality of life and also respiratory rate, heart rate, and night time awaking due to dyspnea and night time awaking due to cough improved significantly after morphine nebulization without any major adverse events. Also pick expiratory flow has been improved significantly after nebulization in each day. Conclusion. Our results showed the clinical benefit of nebulized morphine on respiratory complaints of patients due to exposure to SM without significant side effects.

Effects of Opioids on Breathlessness and Exercise Capacity in Chronic Obstructive Pulmonary Disease. A Systematic Review

“…This analysis incorporates data from recent studies, (7)(8)(9) including an adequately powered randomized trial, (7) The present study shows that in a pooled analysis of published trials, there is no evidence that opioids affect the submaximal exercise capacity in severe COPD. Any effect of opioids on quality of life remains unclear.…”

“…(7)(8)(9)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) All included studies were randomized and double-blind, and characteristics are shown in Table 1 and 2. One study was a parallel group trial,(9) and 15 were crossover trials.…”

“…Data on quality of life were reported in three studies. (7,9,25) Poole et al reported that quality of life, measured as the total CRQ score, decreased slightly from baseline, -0.86 (pooled SD, 15.1), after six weeks opioid treatment compared to placebo. (25) Abernethy and colleagues found no significant difference in overall wellbeing (categorical scale: poor, fair, good, or very good) after four days of morphine as compared to placebo (Wilcoxon signed rank test, p = 0.452).…”

“…(6) Jennings et al evaluated effects in COPD in a sub-analysis only and did not assess the quality of the evidence useful for clinical practice. (6) Since then, several studies have been published on the effects of opioids on breathlessness and exercise capacity, (7)(8)(9) including a adequately powered randomized trial. (7) Physicians have reported concerns and reluctance to prescribe opioids in patients with severe COPD for fears of adverse effects including respiratory depression.…”

Opioids for refractory dyspnea

“…Jensen et al found no differences in the intensity or unpleasantness of perceived dyspnea during cycle ergometry with a single dose of nebulized fentanyl citrate (50 µg) compared with saline in patients with COPD [59]. In contrast, Shohrati et al reported that 1 mg of nebulized morphine given daily for 5 days provided a significant reduction in patient-reported dyspnea on a VAS compared with nebulized normal saline in 40 patients who were thought to develop COPD in part due to inhaling sulfur mustard during military conflict [60].…”