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Covid-19: a puzzle with many missing pieces

BMJ 2020; 368 doi: (Published 19 February 2020) Cite this as: BMJ 2020;368:m627

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Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2)

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Re: Covid-19: a puzzle with many missing pieces. "Diethyl ether and COVID-19"

Dear Editor;

The coronavirus disease 2019 (COVID-19) outbreak initially occurred in Wuhan, China, and has now spread to many countries. It causes pneumonia, failure of multiple organs and systems, and death. [1,2] The World Health Organization has indicated that COVID-19 viruses can be killed by ether solvent. One can ask whether ether can be used to treat patients with COVID-19, especially in the case that no specific therapeutic intervention is available for this virus.

Diethyl ether is a volatile anesthetic that was used to induce general anesthesia. Its minimum alveolar concentration (MAC) is 2.0% in humans and its blood:gas partition coefficient is 12. [3] Thus, the concentrations reached in the blood may be 24% or higher if ether is used for general anesthesia. These concentrations could be higher enough to kill COVID-19 viruses. Volatile anesthetics that are currently used in clinical practice in the United States are isoflurane, sevoflurane and desflurane. Their MACs are 1.15%, 2.0% and 6.0%, respectively. The corresponding blood:gas partition coefficients are 1.4, 0.68 and 0.4. [4] Thus, these newer volatile anesthetics reach a much lower blood concentrations during general anesthesia. Since volatile anesthetics can induce vascular dilation and may improve ventilation:perfusion mismatch in patients with pneumonia (those lung segments that have ventilation will contain inhaled volatile anesthetics to dilate their vasculature), [5] these agents may improve oxygenation of patients with pneumonia. Thus, these agents could have role in treating patients with COVID-19, especially for those patients with pneumonia requiring endotracheal intubation and mechanical ventilation. In this regard, diethyl ether or its like could be very useful for its potential of viral killing effects. However, diethyl ether is highly explosive and inflammable, can inhibit liver enzymes and has other side-effects. It also increases oxidative stress and may modulate immune functions. [6,7] Thus, caution needs to be applied when using diethyl ether in patients with COVID-19.

I would suggest the following steps to test the potential of using volatile anesthetics in fighting COVID-19.

First, we will need to test the effective concentrations of volatile anesthetics to kill or inhibit COVID-19 viruses in vitro. If these concentrations are reachable in the blood during general anesthesia, ethical approval is needed before any clinical testing. The potential of diethyl ether or other volatile anesthetics can be tested in those patients with respiratory failure who require mechanical ventilation or mechanical support for their cardiac and pulmonary functions. Patients should be carefully monitored for their haptic functions, blood gas changes, acidosis and hemodynamics. The use of diethyl ether shall be in a well-ventilated room and applied via a close circuit system. It may be ideal to combine its use and immunoglobulin or other immune function modulators to maintain or enhance the immune functions of the patients. If diethyl ether is proved to be effective in helping patients with COVID 19, one can speculate that diethyl ether or its like could be used to fight other coronaviruses.

1. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020. 10.1056/NEJMoa2001316

2. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020. 10.1001/jama.2020.1585

3. Das BB. Minimum blood concentration--a universal concept of anaesthetic potency. Br J Anaesth 1975;47:881-4.

4. Khan SK, Hayes I, Buggy DJ. Pharmacology of anesthetic agents II Continuing Education in Anesthesia Critical Care & Pain. 2014;14:106-11.

5. Sykes MK, Davies DM, Chakrabarti MK, Loh L. The effects of halothane, trichloroethylene and ether on the hypoxic pressor response and pulmonary vascular resistance in the isolated, perfused cat lung. Br J Anaesth 1973;45:655-63.

6. Normann PT, Ripel A, Morland J. Diethyl ether inhibits ethanol metabolism in vivo by interaction with alcohol dehydrogenase. Alcohol Clin Exp Res 1987;11:163-6.

7. Keefer LK, Garland WA, Oldfield NF, Swagzdis JE, Mico BA. Inhibition of N-nitrosodimethylamine metabolism in rats by ether anesthesia. Cancer Res 1985;45:5457-60.

Competing interests: No competing interests

26 February 2020
Zhiyi Zuo
Physician and Researcher
Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, Virginia 22908-0710, U.S.A.