Pharmacologic methods to minimise coughing during extubation in the era of COVID-19.

BACKGROUND/AIM: Given the current severe acute respiratory syndrome coronavirus 2 pandemic, coughing at the time of extubation is at risk of creating aerosolisation. This may place health care workers at risk of nosocomial infection during the perioperative period. This study aims to summarise the current pharmacologic methods to minimise cough at the time of extubation, and to determine whether some strategies could be more beneficial than others. METHODS: This is a summary of systematic reviews. A comprehensive search through MEDLINE was performed. Thirty-three publications were screened for eligibility. Only the manuscripts discussing pharmacologic methods to minimise coughing on extubation were included in this review. FINDINGS: Many pharmacological agents have been proposed to decrease the incidence of cough at the time of extubation. Of these, intravenous administration of dexmedetomidine (relative risk 0.4; 95% CI: 0.4-0.5) or remifentanil (RR 0.4; 95% CI: 0.4-0.5) seems to have the largest effect to reduce cough on extubation. CONCLUSION: The available data in the current literature is sparse. Yet, dexmedetomidine and remifentanil seem to be the most efficient agents to decrease the incidence of emergence coughing.

Tracheotomy in ventilator-dependent patients with COVID-19: a cross-sectional study of analgesia and sedative requirements.

OBJECTIVE: During March 2020 in the United States, demand for sedatives increased by 91%, that for analgesics rose by 79%, and demand for neuromuscular blockers increased by 105%, all owing to the number of COVID-19 cases requiring invasive mechanical ventilation (MV). We hypothesize that analgesic and sedative requirements decrease following tracheotomy in this patient population. METHODS: In this cross-sectional study, we conducted a retrospective chart review to identify patients with COVID-19 who underwent tracheotomy (T) at an academic medical center between March 2020 and January 2021. We used a paired Student t-test to compare total oral morphine equivalents (OMEs), total lorazepam equivalents, 24-hour average dexmedetomidine dosage in µg/kg/hour, and 24-hour average propofol dosage in µg/kg/minute on days T-1 and T+2 for each patient. RESULTS: Of 50 patients, 46 required opioids before and after tracheotomy (mean decrease of 49.4 mg OMEs). Eight patients required benzodiazepine infusion (mean decrease of 45.1 mg lorazepam equivalents. Fifteen patients required dexmedetomidine infusion (mean decrease 0.34 µg/kg/hour). Seventeen patients required propofol (mean decrease 20.5 µg/kg/minute). CONCLUSIONS: When appropriate personal protective equipment is available, use of tracheotomy in patients with COVID-19 who require MV may help to conserve medication supplies in times of extreme shortages.

Physical Compatibility of Nafamostat with Analgesics, Sedatives, and Muscle Relaxants for Treatment of Coronavirus Disease 2019.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) may require continuous administration of analgesics, sedatives, and muscle relaxants. Nafamostat has recently been reported as a therapeutic agent for COVID-19. However, there is a lack of information on the compatibility of nafamostat with the aforementioned drug classes. This study evaluated the physical compatibility of nafamostat with these drug classes. METHODS: Nafamostat was combined with 1-3 target drugs (fentanyl, morphine, midazolam, dexmedetomidine, and rocuronium). Fifteen physical compatibility tests were conducted. Nafamostat was dissolved in 5% glucose solution; the final concentration was 10 mg/mL. All other medications were diluted in 0.9% sodium chloride to obtain clinically relevant concentrations. The power of hydrogen (pH) of all medications was measured during each test. Compatibility tests were conducted with 4 test solutions in which nafamostat and the target drugs were compounded at equal volume ratios (1:1, 1:1:1, or 1:1:1:1). Visual appearance, turbidity, and pH were evaluated immediately after mixing and at 1 and 3 hours. Physical incompatibilities were defined as gross precipitation, cloudiness, appearance of the Tyndall effect, or a turbidity change of ≥0.5 nephelometric turbidity units (NTU) based on nafamostat. RESULTS: The mean pH of nafamostat was 3.13 ± 0.03. The combination of nafamostat, fentanyl, and dexmedetomidine had the highest pH (3.39 ± 0.01; 3 hours after mixing). All drugs were compatible with nafamostat until 3 hours after admixture, with a mean turbidity value of ≤0.03 NTU. CONCLUSIONS: Infusions combining nafamostat with the tested sedatives, analgesics, and muscle relaxants could be safely administered.

Successful Emergency Treatment of Refractory Neuroleptic Malignant Syndrome With Electroconvulsive Therapy and a Novel Use of Dexmedetomidine: A Case Report From California in the Era of COVID-19.

ABSTRACT: We describe the case of a patient, hospitalized in a California community medical ICU for over a month, with severe neuroleptic malignant syndrome (NMS), unresponsive to medical management, but responsive to electroconvulsive therapy (ECT). We discuss the medical, logistical, and legal challenges in providing ECT in this setting. We also describe a previously unpublished use of dexmedetomidine, which aided in the safe and rapid reduction of benzodiazepines and permitted a successful ECT course. The rapid delivery and efficacy of ECT were essential because of the burgeoning coronavirus pandemic. The patient's treatment required exemplary efforts by providers across multiple disciplines, ongoing medicolegal consultation with the county mental health medical director, as well as consultation with expert members of the International Society for ECT and Neurostimulation. We conclude with a discussion of the unique challenges of providing emergency ECT to patients in California, including during a serious pandemic, when courts are closed. This case illustrates the importance of cultivating and maintaining high-quality ECT expertise in community hospitals and keeping ECT services available even during pandemics. Also, this case demonstrates that ECT is not "merely an elective procedure" but a vital, life-saving treatment, even during the era of COVID-19. To our knowledge, this is the first such published case of emergency ECT performed in California.

Weaning From Exogenous Sedation in the Era of COVID-19 Infection: Recommendations for Sedation and Its Discontinuation.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

[A comparative study on clinical effects of dexmedetomidine and midazolam on patients with severe coronavirus disease 2019 on non-invasive ventilation].

OBJECTIVE: To compare the therapeutic effects and safety of dexmedetomidine and midazolam on patients with severe coronavirus disease 2019 (COVID-19) who received non-invasive ventilation. METHODS: Patients with COVID-19 who needed non-invasive ventilation in one critical care medicine ward of Wuhan Jinyintan Hospital during the team support period from the department of critical care medicine of Renmin Hospital of Wuhan University from January 23rd to February 15th in 2020 were investigated retrospectively. Ramsay score, mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), arterial oxygen partial pressure (PaO2) before sedation and at 1, 12, 24 hours after sedation, sleep time were collected, and the side effects such as excessive sedation, fall of tongue, abdominal distension, aspiration, bradycardia, escalation to invasive mechanical ventilation during 24 hours were also collected. According to different sedative drugs, patients were divided into the control group (without sedative drugs), dexmedetomidine group and midazolam group. The changes of indicators among the three groups were compared. RESULTS: Fourteen patients were injected with dexmedetomidine (loading dose of 1 µg/kg for 10 minutes, maintained at 0.2-0.7 µg×kg-1×h-1); 9 patients were injected with midazolam (loading dose of 0.05 mg/kg for 2 minutes, maintained at 0.02-0.10 mg×kg-1×h-1); 12 patients didn't use sedative drugs due to limitations of previous hospital or patients' rejection. In dexmedetomidine group and midazolam group, the Ramsay score was maintained at 2-3 points after sedation, which were higher than those of control group at different time points after sedation, and there was no significant difference between dexmedetomidine group and midazolam group. MAP of dexmedetomidine group and midazolam group decreased gradually after sedation. MAP after 1-hour sedation was significantly lower than that before sedation, and MAP after 24 hours sedation was significantly lower than that in the control group [mmHg (1 mmHg = 0.133 kPa): 109.7±11.5, 107.1±12.3 vs. 121.1±13.3, both P < 0.05]. HR decreased gradually after sedation treatment, which was significantly lower after 12 hours of sedation than that before sedation, and HR in dexmedetomidine group was significantly lower than that in control group after 12 hours of sedation (bpm: 84.0±13.9 vs. 92.8±15.4 at 12 hours; 81.0±16.7 vs 92.6±12.7 at 24 hours, both P < 0.05). PaO2 increased and RR decreased in all three groups after ventilation. PaO2 in dexmedetomidine group and midazolam group were significantly higher than that in the control group after 12 hours of sedation [cmH2O (1 cmH2O = 0.098 kPa): 79.0±6.5, 79.0±8.9 vs. 70.0±7.8, both P < 0.05]; the decreases of RR in dexmedetomidine group and midazolam group were significant than that in control group after 1 hour of sedation (bpm: 34.0±3.9, 33.8±4.6 vs. 39.0±3.6, both P < 0.05). There were no differences of MAP, HR, PaO2 and RR between dexmedetomidine group and midazolam group at different time points. The sleep duration in dexmedetomidine group and midazolam group were significantly longer than that in the control group (hours: 4.9±1.9, 5.8±2.4 vs. 3.0±1.8, both P < 0.05), but there was no difference between dexmedetomidine group and midazolam group (P > 0.05). Adverse events occurred in all three groups. In midazolam group, there were 2 cases of excessive sedation with fall of tongue and abdominal distension, including 1 case of aspiration, 1 case receiving intubation due to refractory hypoxemia and 1 case due to unconsciousness. In dexmedetomidine group, there were 2 cases of bradycardia, 1 case of intubation due to refractory hypoxemia. In control group, 4 cases underwent intubation due to refractory hypoxemia. CONCLUSIONS: Non-invasive mechanical ventilation is an important respiratory support technology for patients with severe COVID-19. Appropriate sedation can increase the efficiency of non-invasive mechanical ventilation. Dexmedetomidine is more effective and safer than midazolam in these patients, but attention should be paid to HR and blood pressure monitoring.