BACKGROUND: Dyspnea is common in interstitial lung disease (ILD) patients and often refractory to conventional treatment. Little is known regarding the safety of systemic morphine in ILD patients.
OBJECTIVE: The objective of this study is to evaluate the safety of a single subcutaneous morphine injection and to determine the recommended dose of morphine for alleviating dyspnea in ILD patients.
DESIGN: We conducted a dose-escalation Phase I study for investigating the recommended dose of a single subcutaneous morphine injection to alleviate dyspnea in ILD patients.
SETTING/SUBJECTS: Eligible subjects were ILD inpatients with dyspnea at rest who were refractory to conventional dyspnea treatment. The morphine doses used were 1 mg and 2 mg in cohort 1 and cohort 2, respectively. The primary endpoint was dose-limiting toxicity, which was defined as (1) respiratory depression, that is, 30% reduction of respiratory rate and 10 Torr increase of PaCO2 compared with baseline; (2) hypotension, that is, 20% reduction of systemic blood pressure compared with baseline and presentation of hypotension-related symptoms; or (3) grade 3, 4, or 5 treatment-emergent adverse events graded by Common Terminology Criteria for Adverse Events (version 4).
RESULTS: A total of six patients were enrolled, with three patients each in cohorts 1 and 2. No dose-limiting toxicities were observed; three patients experienced worsened somnolence, but no patients experienced sedation.
CONCLUSION: We conclude that 2 mg of morphine has a tolerable safety profile in ILD patients with dyspnea, and can be tested in further clinical trials.
PURPOSE: This study investigated the effect of two types of palliative sedation defined using intervention protocols: proportional and deep sedation.
METHODS: We retrospectively analyzed prospectively recorded data of consecutive cancer patients who received the continuous infusion of midazolam in a palliative care unit. Attending physicians chose the sedation protocol based on each patient’s wish, symptom severity, prognosis, and refractoriness of suffering. The primary endpoint was a treatment goal achievement at 4 h: in proportional sedation, the achievement of symptom relief (Support Team Assessment Schedule (STAS) = 1) and absence of agitation (modified Richmond Agitation-Sedation Scale (RASS) = 0) and in deep sedation, the achievement of deep sedation (RASS = - 4). Secondary endpoints included mean scores of STAS and RASS, deep sedation as a result, and adverse events.
Among 398 patients who died during the period, 32 received proportional and 18 received deep sedation. The treatment goal achievement rate was 68.8% (22/32, 95% confidence interval 52.7–84.9) in the proportional sedation group vs. 83.3% (15/18, 66.1–100) in the deep sedation group. STAS decreased from 3.8 to 0.8 with proportional sedation at 4 h vs. 3.7 to 0.3 with deep sedation; RASS decreased from + 1.2 to - 1.7 vs. + 1.4 to - 3.7, respectively. Deep sedation was needed as a result in 31.3% (10/32) of the proportional sedation group. No fatal events that were considered as probably or definitely related to the intervention occurred.
CONCLUSION: The two types of intervention protocol well reflected the treatment intention and expected outcomes. Further, large-scale cohort studies are promising.