Oral morphine drops for prompt relief of breathlessness in patients with advanced cancer-a randomized, double blinded, crossover trial of morphine sulfate oral drops vs. morphine hydrochloride drops with ethanol (red morphine drops).

PURPOSE: Episodic breathlessness is frequent in palliative cancer patients. Opioids are the only pharmacological agents with sufficient evidence in treatment. In Denmark, the main recommendation is red morphine drops (RMD), an off-label solution of morphine, ethanol, and red color (cochenille) described since 1893 (Pharmacopoea Danica). In 2015, the Danish Medicines Agency increased focus on off-label medicines and recommended registered morphine drops without ethanol instead. However, our palliative patients told us that RMD was better. For that reason, we conducted a clinical trial to clarify any perceived difference between the two types of drops. METHODS: We conducted a randomized, double blinded, crossover trial. Patients were asked to perform standardized activity (2-min walk) aiming to provoke breathlessness. Primary endpoint (breathlessness NRS) and secondary endpoints (saturation, pulse, respiratory frequency) were measured before (t = 0) and after test medicine at t = 1, t = 3, t = 5, t = 10, and t = 20 min. After 2-4 days (washout period), the patients repeated the test, receiving the alternative drops in a blinded setup (crossover). RESULTS: In the first 3 min, the relative drop in breathlessness for morphine drops with ethanol (RMD) was significant more than for morphine drops without ethanol. We found no significant difference in secondary endpoints. CONCLUSIONS: A conclusion could be that ethanol might facilitate morphine absorption in the mouth. Our results needs further research of opioid absorption in the mouth as well as trials, testing morphine vs. more lipophilic opioids. The RMD drops are cheap, easy to use, and noninvasive and keep the patient independent of health care professionals.

Indirect Calorimetry in Mechanically Ventilated Patients: A Prospective, Randomized, Clinical Validation of 2 Devices Against a Gold Standard.

BACKGROUND AND AIMS: The 2 currently available indirect calorimeters, CCM Express Indirect Calorimeter (MedGraphics, St Paul, MN) and Quark RMR ICU Indirect Calorimeter (COSMED, Rome, Italy), have not been validated against a gold standard in mechanically ventilated patients. Our aim was to do so using a gold-standard, modified Tissot bell-spirometer method in mechanically ventilated patients who were hemodynamically, respiratory, and metabolically stable. METHODS: We studied 30 patients undergoing general anesthesia and major gynecological surgery. We measured oxygen consumption ([Formula: see text]O2) and resting energy expenditure (REE) in a randomized, sequential, crossover design with double determination of each device. RESULTS: Compared with the modified Tissot bell-spirometer, the CCM Express Indirect Calorimeter demonstrated a mean Δ-REE of +361 kcal/d, corresponding to a 31% overestimation of energy requirements. Bland-Altman analysis for REE showed a mean (SD) bias of 384 (124) with limits of agreement 142-627 kcal/d. QUARK RMR ICU demonstrated a mean Δ-REE of 81 kcal/d, corresponding to a 7% overestimation of energy requirements. Bland-Altman plot analysis showed a mean (SD) bias of 77 (167) with limits of agreement -249 to 404 kcal/d. CONCLUSIONS: The QUARK RMR ICU Indirect Calorimeter compared better with the gold standard for values of [Formula: see text]O2 and REE than did the CCM Express Indirect Calorimeter in mechanically ventilated patients who were circulatory and respiratory stable. Both indirect calorimeters had low precision.