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Review Article http://doi.org/10.18231/j.ijirm.2020.022

Ether therapy in SARS-CoV-2: Prophylactic, therapeutic and mass elimination

S. S. Jha

Director and Head, Dept. of Orthopaedics & Joint Replacement , Mahavir Vaatsalya Aspatal, Patna, Bihar, India

*Corresponding Author: S. S. Jha Email: [email protected]

Abstract No specific therapeutic has been found. In the absence of any specific therapy and non-availability of vaccine, anaesthetic () is recommended to be used as a prophylactic and therapeutic intervention in the management of COVID-19 disease. Strong evidence based property of ether as lipid has provided the impetus for this approach. The lipid content of the outer envelope of the virus is the weak-link to get dissolved ether and thus leading to disintegration of the single-stranded RNA. The viruses present inside the blood stream are bound to be killed by the presence of ether in the blood circulation.

Keywords: , Lipid solvent, Oxygenation, Recreational, , Ether.

Coronaviruses are RNA virus and some of the viruses dropping directly over an anaesthesia mask) or by a close (RNA / DNA) are enveloped whereas some of them are circuit (on an anaesthesia workstation). naked viruses. The envelopes of these viruses have a fat The COVID-19 outbreak causes pneumonia, failure membrane. This fat membrane is a self assembled nano of multiple organs and systems, and death. The World particle with lipid bilayer, which is the weakest link. Health Organization has indicated that COVID-19 Compared to non-enveloped (naked) viruses, the fat viruses can be killed by ether solvent. One can ask membrane enveloped viruses are more sensitive to whether ether can be used to treat patients with COVID- neutralizing agents like chemical antiseptics and changes 19, especially in the case in the light of the fact that no in pH / temperature. specific therapeutic intervention is available against this There is extensive proof that on exposure of the virus virus, it is definitely plausible that ether can be used to to soap, the semi-rigid envelope of the corona virus prevent and treat patients with COVID-19. opens up at the lipid weak-link and the virus gets The usefulness of Ether in management of COVID annihilated. All coronaviruses including SARS-CoV-2 patient is strongly recommended. This is in conformity possess this fat layer as a component of the viral with previous evidence based concept of the virus fat envelope. envelope dissolving in ether and this has been further Anaesthetic ether vapour works as a lipid solvent and testified in the recent article in BMJ (19 February, 2020) ether has a traditional heritage of having the lipid by Deng (February 2020) clearly mentions “ether, 75% dissolving quality and is extensively used in labs for this , chlorine disinfectant, peracetic acid, and purpose. Liquid is used similarly to dissolve the can effectively inactivate the virus, but not fat content. This anaesthetic ether vapour will dissolve chlorhexidine”.7 Cascella (April 2020) similarly the lipid bilayer in the viral envelope and subsequently emphatically mentions “These viruses can be effectively the viral RNA gets disintegrated. inactivated by lipid including ether (75%), The outer surface of the virus has an overcoat / ethanol, chlorine-containing disinfectant, peroxyacetic envelope of lipid with protein. The presence of lipid acid and chloroform except for chlorhexidine”.5 makes it vulnerable to fat solvents like Ether, Ethanol Fortunately, the progress in research has helped to prove and Chloroform, of which Ether is most easily available this path-breaking invention. During this pandemic and cheap and can be safely administered through oral period, unfortunately attention has not been drawn inhalation as vapour on a sugar crystal vehicle in small towards the use of Ether in prevention and management dose (few drops) otherwise it can be administered as an protocol. inhalation anaesthetic agent either by open method (by

Covid-19 Special Issue, April, 2020;1(2):28-31 28 S. S. Jha Ether therapy in SARS-CoV-2: Prophylactic, therapeutic and mass elimination

Deng (February 2020) and Cascella (April 2020) Apart from this, all the viruses circulating in the blood have separately written along with their colleagues and gets disintegrated-most unique feature of Ether. have reconfirmed the sensitivity of COVID virus to With use of volatile anaesthetic, diethyl ether for Ether. In spite of this fat dissolving property, Ether has , blood concentration is 24% or never been considered for being included in the higher. These concentrations could be higher enough to management protocol of SARS-COVID-2 at various kill COVID-19 viruses. In clinical practice volatile stages. This is strongly being recommended for in current use are , and consideration by ICMR, Union Ministry of Health and . These newer volatile anesthetics reach a Prime Minister Office for permitting to implement the much lower blood concentrations during general use of Ether in prevention and management of SARS- . Volatile anesthetics can induce vascular COVID disease. dilation and improve ventilation. Those lung segments Anaesthetic Ether can be used in three phases in the capable of ventilation, will contain inhaled volatile following ways:- anesthetics to dilate their vasculature. These agents including ether may improve oxygenation of patients First Phase Prophylactic and Therapeutic use with pneumonia. Thus, these agents could have role in Ether should never be consumed as such, rather it should treating patients with COVID-19. In this regard, diethyl be used as vapour after sucking ten drops of Ether, ether or its like could be very useful for its potential of soaked on to a lump of sugar and put over the tongue and “viral killing effects”. A watch is to be kept on liver inhale the fumes. The residual saliva-sugar mixture is enzymes. It also increases oxidative stress and may then allowed to be sucked down the throat. It kills the modulate immune functions. corona virus lodged in the throat. This is noteworthy, that Apart from hepatic functions, patients should be this virus is lodged in throat for initial four days after carefully monitored for blood changes, acidosis and getting infected from other corona patients. If this hemodynamics. The use of diethyl ether should be used procedure is conducted in similar way as “mass via a closed circuit system. It may be ideal to combine its immunization by polio drops”, REVOLUTIONARY use and immunoglobulin or other immune function success to prevent the pandemic of corona can be modulators to maintain or enhance the immune functions achieved. These viruses, still present in upper respiratory of the patients. tract of the patient, brought in contact with the vaporized Ether, will get eliminated. It should preferably be Third Phase administered once on a single day to each family member The continuation of corona pandemic beyond few of the hotspot affected areas. The oral administration of months, there is a possibility of spread of the disease into Ether should be initiated in similar way as “Two Drops the frontline health workers including doctors. Despite of Pulse Polio” programme to eradicate corona virus. The the negative test for corona in all routine or emergency family members of marked households of positive operations, it should be assumed that they can be corona patients in the hotspot areas, should be administered oral positive in subsequent few days. The government is ether daily for continuous five days. The quarantined requested to recommend the use of Ether as an people should also be administered with immediate agent for patient undergoing surgery wherever indicated. effect. It should also used for prevention in frontline By doing this, the corona viruses will disintegrate in the warriors. system following ether inhalation anaesthesia.

Second Phase of Critical Management Diethyl Ether Elimination of Virus - It is recommended to administer History of anaesthetic ether ether inhalation in small quantity through anaesthesia The compound may have been synthesised by either Jābir machine to the patients suffering from inflammation of ibn Hayyān in the 8th century8 or Ramon Llull in 1275.4, lungs by corona viruses. It is also indicated for the 20 It was synthesized in 1540 by Valerius Cordus, who patients waiting for intubation for undergoing ventilatory called it "sweet oil of vitriol" (oleum dulce vitrioli)—the support. Ether expands the vessels of alveoli which are name reflects the fact that it is obtained by distilling a inflamed providing more blood and better oxygenation. mixture of ethanol and (then known as oil of

Covid-19 Special Issue, April, 2020;1(2):28-31 29 S. S. Jha Ether therapy in SARS-CoV-2: Prophylactic, therapeutic and mass elimination vitriol)—and noted some of its medicinal properties.8 At climates, help with cold starting an engine at sub-zero about the same time, discovered the temperatures. properties of the molecule in dogs.8 The name ether was 3. Laboratory uses given to the substance in 1729 by August Sigmund Diethyl ether is a common laboratory aprotic solvent. It Frobenius.20 is ideal for use as the non-polar solvent in liquid-liquid William T. G. Morton participated in a public extraction. When used with an , the demonstration of ether anesthesia on October 16, 1846 at diethyl ether layer is on top as it has a lower than the in Boston, Massachusetts. British doctors the water. Due to its application in the manufacturing of were aware of the anesthetic properties of ether as early illicit substances, it is listed in the Table II precursor as 1840 where it was widely prescribed in conjunction under the United Nations Convention Against Illicit with .3 Diethyl ether largely supplanted the use of Traffic in and Psychotropic Substances.17 chloroform as a general anesthetic due to ether's more 4. Anaesthetic use favorable , that is, a greater difference Diethyl ether does not depress the myocardium but rather between an effective dose and a potentially toxic dose.1 it stimulates the sympathetic nervous system leading to It was considered to be a sulfur compound until the hypertension and tachycardia. It is safely used in patients idea was disproved in about 1800.2 with shock as it preserves the baroreceptor reflex.15 Its Diethyl ether, or simply ether, is an of minimal effect myocardial depression, respiratory drive, with the formula (C2H5)2O, sometimes low cost, and high therapeutic index allows it to see 13,16 abbreviated as Et2O. It is a colorless, highly volatile continued use in developing countries. Diethyl ether flammable liquid. It is commonly used as a solvent in could also be mixed with other anesthetic agents such as laboratories and as a starting fluid for some engines. It chloroform to make C.E. mixture, or chloroform and was formerly used as a general anesthetic, until non- alcohol to make A.C.E. mixture. In the 21st century, ether flammable drugs were developed, such as halothane. It is rarely used. The use of flammable ether was displaced has unfortunately been used as a recreational drug to by nonflammable fluorinated hydrocarbon anesthetics. cause intoxication. Prior to 2005 it was on the World Health Organization's List of Essential Medicines for use as an anesthetic.10,11 Production 5. History of Medical use Most diethyl ether is produced as a byproduct of the Ether was once used before in treatment of pneumonitis vapor-phase hydration of to make ethanol. This and scurvy. A mixture of alcohol and ether, one part of process uses solid-supported catalysts.12 diethyl ether and three parts of ethanol, was known as A nucleophilic atom of unprotonated ethanol "Spirit of ether", Hoffman's Anodyne or Hoffman's displaces a water molecule from the protonated Drops. In the United States this concoction was removed (electrophilic) ethanol molecule, producing water, a from the Pharmacopeia at some point prior to June ion and diethyl ether. 1917,19 as a study published by William Procter, Jr. in the Getting a good yield of ether requires that ether be American Journal of Pharmacy as early as 1852 showed distilled out of the reaction mixture before it reverts to that there were differences in formulation to be found ethanol. between commercial manufacturers, between international pharmacopoeia, and from Hoffman's Uses original recipe.6 It's also used to treat Hiccups through 1. It is particularly important as a solvent in the instillation into nasal cavity.18 production of cellulose plastics such as cellulose 6. Recreational use acetate.12 The anesthetic and intoxicating effects of ether have 2. Fuel made it a recreational drug. Diethyl ether in anesthetic Diethyl ether has a high cetane number of 85–96 and is dosage is an which has a long history of used as a starting fluid, in combination with petroleum recreational use. One advantage is a well-defined margin distillates for and Diesel engines.14 Ether between therapeutic and toxic doses, which means one starting fluid is sold and used in countries with cold would lose consciousness before dangerous levels of dissolved ether in blood would be reached. In the 19th

Covid-19 Special Issue, April, 2020;1(2):28-31 30 S. S. Jha Ether therapy in SARS-CoV-2: Prophylactic, therapeutic and mass elimination century and early 20th century ether drinking was popular 2019 Outbreak in China. J. Clin. Med. 2020, 9, 575; among Polish peasants.9 doi:10.3390/jcm9020575 Ether is advocated to be used as an effective tool in 8. Toski, Judith A; Bacon, Douglas R; Calverley, Rod K (2001). The history of . In: Barash, Paul G; prevention and management protocol of COVID-19 Cullen, Bruce F; Stoelting, Robert K. Clinical Anesthesia disease. Mass elimination of COVID-19 like polio, (4 ed.). Lippincott Williams & Wilkins. p. 3. ISBN 978-0- though it is not a vaccine can be achieved if the whole 7817-2268-1. nation undergoes one day mass elimination drive. 9. Zandberg, Adrian. "Short Article "Villages … Reek of Ether Vapours": Ether Drinking in Silesia before 1939". Medical History. 2010;54(3):387-96. Summary 10. "Essential Medicines WHO Model List (revised April Earliest use of ether in cases of pneumonitis and later use 2003)" (PDF). apps.who.int (13th ed.). Geneva, in inducting inhalation general anaesthesia. Switzerland: World Health Organization. April 2003. Unfortunately, the use of ether as a recreational drug is a Retrieved 6 September 2017. matter of concern. It is only the vapourised ether which 11. "Essential Medicines WHO Model List (revised March provides the desired result of annihilation of the viruses 2005)" (PDF). apps.who.int (14th ed.). Geneva, Switzerland: World Health Organization. March 2005. in throat during the early intubation period. For these Archived from the original (PDF) on 5 August 2005. reasons, it is advocated to be used as preventive and Retrieved 6 September 2017. therapeutic protocol. Mass elimination of COVID-19 like 12. ", by Lawrence Karas and W. J. Piel". Kirk‑Othmer polio, though it is not a vaccine can be achieved if the Encyclopedia of Chemical Technology. John Wiley & whole nation undergoes one day mass elimination drive. Sons, Inc. 2004. 13. "Ether and its effects in Anesthesia". 2010-10-31. 14. "Extra Strength Starting Fluid: How it Works". Valvovine. Source of Funding Archived from the original on 2007-09-27. Retrieved 2007- None. 09-05. 15. https://anesthesiageneral.com/ether-effects/ Conflict of Interest 16. https://www.sciencedirect.com/topics/neuroscience/diethyl- None. ether 17. Microsoft Word – RedListE2007.doc Archived February 27, 2008, at the Wayback Machine References 18. NCBI, Treatment of hiccups with instillation of ether into 1. Calderone FA. "Studies on ether dosage after pre-anesthetic nasal cavity. medication with (, 19. The National druggist, Volume 47, June 1917, pp.220 Sulphate and )" (PDF). J Pharmacol Exp 20. "VIII. An account of a spiritus vini aethereus, together with Therapeutics. 1935;55(1):24-39. several experiments tried therewith". Philosophical 2. Chisholm, Hugh, ed. (1911). "Ether". Encyclopædia Transactions of the Royal Society of London. 36(413):283- Britannica. 9 (11th ed.). Cambridge University Press. p. 9. 806. 3. Grattan, N. "Treatment of Uterine Haemorrhage". Provincial Medicine and Surgical Journal. Vol. 1, No. 6 (Nov. 7, 1840), p. 107 4. Hademenos, George J.; Murphree, Shaun; Zahler, Kathy; Warner, Jennifer M. (2008-11-12). McGraw-Hill's PCAT. McGraw-Hill. p. 39. ISBN 978-0-07-160045-3. Retrieved 2011-05-25. 5. Marco Cascella; Michael Rajnik; Arturo Cuomo; Scott C. Dulebohn; Raffaela Di Napoli. Features, Evaluation and Treatment Coronavirus (COVID-19). StatPearls Publishing LLC. April 6, 2020. https://www.ncbi.nlm.nih.gov/books/NBK554776/ 6. Procter, Jr., William (1852). "On Hoffman's Anodyne Liquor". American Journal of Pharmacy. 28. 7. Sheng-Qun Deng and Hong-Juan Peng. Characteristics of and Public Health Responses to the Coronavirus Disease

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