Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study.

BACKGROUND: Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. METHODS: In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18-75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. DISCUSSION: To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020.

Specialized Weaning Unit in the Trajectory of SARS-CoV-2 ARDS: Influence of Limb Muscle Strength on Decannulation and Rehabilitation.

BACKGROUND: Patients with ARDS due to COVID-19 may require tracheostomy and transfer to a weaning center. To date, data on the outcome of these patients are scarce. The objectives of this study were to determine the factors associated with time to decannulation and limb-muscle strength recovery. METHODS: This was an observational retrospective study of subjects with COVID-19-related ARDS requiring tracheostomy after prolonged ventilation, who were subsequently transferred to a weaning center from April 4, 2020-May 30, 2020. RESULTS: Forty-three subjects were included. Median age (interquartile range) was 61 (48-66) y; 81% were men, and median body mass index (BMI) was 30 (26-35) kg/m2. Tracheostomy was performed after a median of 19 (12-27) d of mechanical ventilation, and the median ICU length of stay prior to transfer to the weaning center was 30 (21-46) d. On admission to the weaning center, the median Medical Research Council (MRC) score was 36 (27-44). Time to decannulation was 9 (7-18) d after admission to the weaning center. The only factor independently associated with early decannulation was the MRC score on admission to the weaning center (odds ratio 1.16 [95% CI 1.06-1.31], P = .005). Two factors were independently associated with MRC gain ≥ 10: BMI (odds ratio 0.88 [95% CI 0.76-0.99], P = .045) and MRC on admission (odds ratio 0.91 [95% CI 0.82-0.98], P = .03. Three months after admission to the weaning center, 40 subjects (93%) were weaned from mechanical ventilation and 36 (84%) had returned home. CONCLUSIONS: MRC score at weaning center admission predicted both early decannulation and limb-muscle strength recovery.

Health-related quality of life of COVID-19 two and 12 months after intensive care unit admission.

PURPOSE: To describe health-related quality of life (HRQoL) and dyspnea of COVID-19, 2 and 12 months after an intensive care unit (ICU) stay. METHODS: Patients discharged from the ICU between April and June 2020 and subsequently transferred to an inpatient rehabilitation facility were assessed 2 months and 12 months after ICU admission. HRQoL was assessed by the EuroQoL EQ-5D-3L (visual analog scale and time trade-off normalized to the French population algorithm) and dyspnea was assessed by the modified Medical Research Council (mMRC) dyspnea scale. RESULTS: We enrolled 94 patients. Median EQ-5D-3L time trade-off was 0.80 (interquartile range, 0.36-0.91) at 2 months and 0.91 (0.52-1.00) at 12 months (P = 0.12). EQ-5D-3L visual analog scale was 70 (60-85) at 2 months and 70 (60-85) at 12 months (P = 0.07). The mMRC dyspnea scale was 3 (2-4) at ICU discharge, 1 (0-2), P < 0.001 at 2 months and 1 (1-2) at 12 months. At 12 months, 68 (76%) patients reported at least one symptom that was not present prior to ICU admission and 27 (61%) of the 44 patients who were previously working had returned to work. On multiple linear regression, factors associated with EQ-5D-3L were body mass index on ICU admission, tracheostomy, male gender and active smoking. CONCLUSIONS: Twelve months after ICU admission for COVID-19 and subsequent rehabilitation, a substantial proportion of patients reported alterations of HRQoL, dyspnea and symptoms that were not present prior to admission and a substantial proportion of these patients had not returned to work. Factors associated with a risk of poorer 12-month quality of life, may help to identify at-risk patients.

Lifting dyspnoea invisibility: COVID-19 face masks, the experience of breathing discomfort, and improved lung health perception - a French nationwide survey.

QUESTION ADDRESSED: In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health. METHODS: General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered "no" to "treated for a chronic respiratory disease" ("respiratory healthy"), and 152 answered "yes" ("respiratory disease"). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family+ ). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision . RESULTS: Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). "Air hunger" was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family+ (OR 1.85, 95% CI 1.16-2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73-7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25-0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients' experiences. ANSWER TO THE QUESTION: Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions.

Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. METHODS: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. RESULTS: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. CONCLUSION: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.