Incidence of Delirium Tremens in Acute Poisoning by Psychopharmacological Drugs or Corrosive Substances and Its Prevention Using Intestinal Lavage: on the Pathogenesis of Delirium Tremens

RELEVANCE. In patients suffering from alcohol dependence admitted to hospital with an intercurrent disease, the probability of delirium tremens (DT) is high, so the search for means of its prevention is relevant.

THE AIM OF STUDY. To study the incidence of DT in patients with poisoning by psychopharmacological drugs and corrosive substances, and to evaluate the effectiveness of intestinal lavage as its prevention.

MATERIAL AND METHODS. We conducted a prospective study that followed 287 patients (observation group). Of these, 162 patients had psychopharmacological drug poisoning (PPDP) and 125 patients had corrosive substance poisoning (CSP), who underwent intestinal lavage (IL) for the purpose of detoxification and correction of metabolic disorders.

A retrospective analysis of the examination results of 211 patients with PPDP and 102 with CSP (a total of 313 patients — comparison group) who did not receive IL was conducted. The patients in the groups were comparable in terms of gender, age, and severity of the same poisonings.

The severity of PPDP corresponded to stage 2b, and the severity of CSP corresponded to 2nd-3rd degree chemical burn of the upper gastrointestinal tract, including the stomach. All the patients had metabolic disorders that required correction.

The study endpoints were the incidence of DT, and the duration of treatment in the intensive care unit (ICU).

RESULTS. In the comparison group, DT in PPDP and CSP developed in 57.8% and 56.9%, respectively. In the observation group, with the same nosological forms of poisoning, DT developed in 6.8% and 12% of cases, respectively. The intergroup differences in the incidence of DT in the same types of poisoning were statistically significant (p<0.05; U curve).

The ICU stay of patients with DT in CSP who had previously underwent IL was 10 days shorter than in the comparison group, and in PPDP — 11 days shorter than in the comparison group. This difference was statistically significant (p<0.05; U curve).

CONCLUSION. The obtained results showed the effectiveness of intestinal lavage as a method for preventing delirium tremens in individuals with alcohol dependence. The observed phenomenon of decreased risk of delirium tremens development in patients who underwent intestinal lavage suggests that the pathogenesis of delirium tremens is associated with morphological and functional disorders of the gastrointestinal tract, the key link of which is the excess proliferation of microflora, for the vital activity of which ethanol is necessary. The decreased risk of delirium tremens in the group of patients who underwent intestinal lavage in the complex treatment is obviously associated with the therapeutic mechanisms of the latter — detoxification of the body and correction of homeostasis disorders, including intestinal microbiota, by eliminating ethanol-dependent microflora and its toxins.

FINDINGS. 1. In individuals suffering from alcoholism with poisoning by psychopharmacological drugs and corrosive substances, delirium tremens occurs in 57.8% and 56.9% of cases, respectively.

2. When using intestinal lavage in complex treatment for the same poisonings, the incidence of delirium tremens is 6.8% and 12.0%, respectively, which is 8.5 and 4.7 times less than in case of standard treatment. This difference is statistically significant (p<0.05).

3. The use of intestinal lavage in acute poisoning by psychopharmacological drugs and corrosive substances reduces the stay of patients with delirium tremens in the intensive care unit by 2.6 and 2.7 times, respectively. This difference is statistically significant (p<0.05).

LIMITATIONS OF THE STUDY: age from 28 to 55 years, clinical diagnosis of “Alcohol related disorders” (ICD-10 code F10) in patients with poisoning by psychopharmacological drugs or corrosive substances, intestinal lavage in a volume of at least 12 (9; 15) l.

1. Luzhnikov EA (ed.). Neotlozhnaya klinicheskaya toksikologiya. Moscow: Medpraktika Publ., 2007. (In Russ.)

2. Ostapenko YuN. (ed.) Toksicheskoe deystvie raz”edayushchikh veshchestv. Toksicheskoe deystvie myl i detergentov. Federal’nye klinicheskie rekomendatsii. Moscow, 2014. (In Russ.)

3. Zaikovskiy VV, Luzhnikov YeA, Sukhodolova GN, Petrov SI, Klychnikova YeV, Alexandrovskiy VN, et al. Use of Sodium Hypochlorite in the Therapy of Alcoholic Abstinent Syndrome at Acute Intoxication by Ethano. Toxicological Review. 2010; 2:10–16. (In Russ.)

4. Muronov AY. Delirium tremens: early diagnosis and intensive care guidelines. Review. Annals of Critical Care. 2020;(1):53–65. (In Russ.). https://doi.org/10.21320/1818-474X-2020-1-53-65

5. Grover S, Ghosh A. Delirium Tremens: Assessment and Management. J Clin Exp Hepatol. 2018;8(4):460–470. PMID: 30564004. https://doi.org/10.1016/j.jceh.2018.04.012

6. Mennecier D, Thomas M, Arvers P, Corberand D, Sinayoko L, Bonnefoy S, et al. Factors predictive of complicated or severe alcohol withdrawal in alcohol dependent inpatients. Gastroenterol Clin Biol. 2008;32(8–9):792–797. PMID: 18757147. https://doi.org/10.1016/j.gcb.2008.06.004

7. Chan GM, Hoffman RS, Gold JA, Whiteman PJ, Goldfrank LR, Nelson LS. Racial variations in the incidence of severe alcohol withdrawal. J Med Toxicol. 2009;5(1):8–14. PMID: 19191209. https://doi.org/10.1007/BF03160974

8. Skrobik Y. Delirium prevention and treatment. Anesthesiol Clin. 2011;29(4):721–727. PMID: 22078919. https://doi.org/10.1016/j.anclin.2011.09.010

9. Salottolo K, McGuire E, Mains CW, van Doorn EC, Bar-Or D. Occurrence, Predictors, and Prognosis of Alcohol Withdrawal Syndrome and Delirium Tremens Following Traumatic Injury. Crit Care Med. 2017;45(5):867–874. PMID: 28266937. https://doi.org/10.1097/CCM.0000000000002371

10. Kekelidze ZI, Zemskov AP, Filimonov BA. Tyazhelyy alkogol’nyy deliriy. RMJ. 1998;(2):103–108. (In Russ.)

11. Matkevich VA. Kishechnyy lavazh. In: Luzhnikov EA. (ed.). Meditsinskaya toksikologiya. Moscow: GEOTAR-Meditsina Publ., 2012. Ch. 4. pp. 162–186. (In Russ.)

12. Jang SH, Woo YS, Lee SY, Bahk WM. The Brain-Gut-Microbiome Axis in Psychiatry. Int J Mol Sci. 2020;21(19):7122. PMID: 32992484. https://doi.org/10.3390/ijms21197122

13. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018;1693(Pt B):128–133. PMID: 29903615. https://doi.org/0.1016/j.brainres.2018.03.015

14. Hamamah S, Aghazarian A, Nazaryan A, Hajnal A, Covasa M. Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling. Biomedicines. 2022;10(2):436. PMID: 35203645. https://doi.org/10.3390/biomedicines10020436

15. Breit S, Kupferberg A, Rogler G, Hasler G. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018;9:44. PMID: 29593576. https://doi.org/10.3389/fpsyt.2018.00044

16. Reigstad CS, Salmonson CE, Rainey JF 3rd, Szurszewski JH, Linden DR, Sonnenburg JL, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2015;29(4):1395–1403. PMID: 25550456. https://doi.org/10.1096/fj.14-259598

17. Borre YE, O’Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20(9):509–518. PMID: 24956966. https://doi.org/10.1016/j.molmed.2014.05.002

18. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145–155. PMID: 28092661. https://doi.org/10.1038/nn.4476

19. Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16(8):461–478. PMID: 31123355. https://doi.org/10.1038/s41575-019-0157-3.

20. Lal S, Kirkup AJ, Brunsden AM, Thompson DG, Grundy D. Vagal afferent responses to fatty acids of different chain length in the rat. Am J Physiol Gastrointest Liver Physiol. 2001;281(4):G907–G915. PMID: 11557510. https://doi.org/10.1152/ajpgi.2001.281.4.G907.

21. Matkevich VA, Luzhnikov EA, Belova MV, Yevdokimova NV, Syromyatnikova ED, Kurilkin YuA. The Role of Intestinal Translocation in the Origin of Endotoxemia in Acute Poisoning and Detoxification Effect of Intestinal Lavage. Russian Sklifosovsky Journal Emergency Medical Care. 2015;(4):16–21.

22. Matkevich VA, Tkeshelashvili TT, Vorobyova AG, Stolbova NE, Potskhveriya MM, Goldfarb YuS. The Role of Intestinal Translocation in the Pathogenesis of Pneumonia in Acute Poisoning and the Contribution of Intestinal Lavage to Its Prevention and Resolution. Russian Sklifosovsky Journal Emergency Medical Care. 2024;13(2):212–225. https://doi.org/10.23934/2223-9022-2024-13-2-212-225

23. Matkevich VA, Potskhveriya MM, Simonova AYu, Sukhodolova GN, Belova MV, Bitkova EE. Management of Disorders of Homeostasis With Saline Enteral Solution in Acute Poisoning With Psychopharmacological Drugs. Russian Sklifosovsky Journal Emergency Medical Care. 2020;9(4):551–563. https://doi.org/10.23934/2223-9022-2020-9-4-551-563

24. Matkevich VA, Potskhveriya MM, Simonova AYu, Vasina TA, Petrikov SS. Intestinal Microbiocenosis Disorders Correction With Intestinal Lavage in Patients With Acute Poisoning. Russian Sklifosovsky Journal Emergency Medical Care. 2021;10(2):285–292. https://doi.org/10.23934/2223-9022-2021-10-2-285-292

25. Wiatrak B, Balon K, Jawień P, Bednarz D, Jęśkowiak I, Szeląg A. The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease. Int J Mol Sci. 2022;23(9):4862. PMID: 35563253. https://doi.org/10.3390/ijms23094862

26. Bondarenko VM, Gracheva NM, Matsulevich TV. Disbakteriozy kishechnika u vzroslykh. Moscow: KMK Scientific Press, 2003. (In Russ.)

27. Dzgoeva FKh, Egshatyan LV. Intestinal microbiota and type 2 diabetes mellitus. Endocrinology: News, Opinions, Training. 2018;7(3):55–63. (In Russ.) https://doi.org/10.24411/2304-9529-2018-13005

28. Akhmedov VA, Goloktionova AA, Isaeva AS. Ozhirenie i mikrobiota kishechnika. Lechaschi vrach. 2019;(7):68–71. (In Russ.)

29. Miliukhina IV, Ermolenko EI, Ivanova AS, Suvorov AN. Role of Gut Microbiota in Pathogenesis of Parkinson’s Disease. Nevrologicheskiy zhurnal. 2017;22(6):280–286. https://doi.org/10.18821/1560-9545-2017-22-6-280-286

30. Afineevskaya AYu, Mal’kov OА, Govorukhina AA. The Role of Intestinal Microbiota in the Pathogenesis of Atherosclerosis and Promising Preventive Measures (Review). Journal of Medical and Biological Research. 2020;8(2):184–193. (In Russ.) https://doi.org/10.37482/2542-1298-Z009

31. Shenderov BA. Meditsinskaya mikrobnaya ekologiya i funktsional’noe pitanie: In 3 vol. Vol. I. Mikroflora cheloveka i zhivotnykh i ee funktsii. Moscow: ”GRANT” Publ., 1998. (In Russ.)

32. Sonnenburg JL, Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64. PMID: 27383980. https://doi.org/10.1038/nature18846

33. Kiprushkina EI, Kolodyaznaya VS, Fillippov VI, Shestopalova IA, Broyko YuV, Andrukhova KO, et al. The Importance of Nutrition in The Forming of Intestinal Microbiome. Journal of International Academy of Refrigeration. 2020;(2):52–59. (In Russ.) https://doi.org/10.17586/1606-4313-2020-19-2-52-59

34. Tkachenko EI, Uspenskiy YuP. Pitanie, mikrobiotsenoz i intellekt cheloveka. Saint Petersburg: SpetsLit Publ., 2006. (In Russ.)

35. Bogdanova YeA, Fetisov RN, Nesvizhsky YuV, Korolyov AA, Zverev VV. The role of food factor in the forming of the variety of the characteristics of fecal microbiocenosis in rats. Annals of the Russian Academy of Medical Sciences. 2008;(1):23–26. (In Russ.) PMID: 18318152.

36. Dubinkina VB, Tyakht AV, Odintsova VY, Yarygin KS, Kovarsky BA, Pavlenko AV, et al. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease. Microbiome. 2017;5(1):141. PMID: 29041989. https://doi.org/10.1186/s40168-017-0359-2

37. Queipo-Ortuño MI, Boto-Ordóñez M, Murri M, Gomez-Zumaquero JM, Clemente-Postigo M, Estruch R, et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. Am J Clin Nutr. 2012;95(6):1323–1334. PMID: 22552027. https://doi.org/10.3945/ajcn.111.027847.

38. Bakulin IG, Shalikiani NV. Alcohol and Changes in Intestinal Flora: Current Understanding. Doctor.Ru. 2016;1(118):38–42. (In Russ.)

39. Silva-Gomes S, Decout A, Nigou J. Pathogen-Associated Molecular Patterns (PAMPs). In: Parnham M. (ed.) Encyclopedia of Inflammatory Diseases. Birkhäuser, Basel; 2014. https://doi.org/10.1007/978-3-0348-0620-6_35-1

40. Nikitenko VI, Zakharov VV, Borodin AV, Simonenko EV, Kopylov VA, Fomina MV. Rol’ translokatsii bakteriy v patogeneze khirurgicheskoy infektsii. Pirogov Russian Journal of Surgery. 2001;(2):63–66. (In Russ.)

41. Tret’yakov EV, Varganov MV, Nifontova EE. Sovremennyy vzglyad na kishechnuyu translokatsiyu bakteriy kak osnovnuyu prichinu gnoyno-septicheskikh oslozhneniy pri destruktivnom pankreatite. Advances in current natural sciences. 2013;(9):78–80. (In Russ.)

42. Trukhan DI, Chusova NA. Syndrome of Increased Epithelial Permeability of the Intestine in Real Clinical Practice. Therapy. 2020;6(8):174–185. https://doi.org/10.18565/therapy.2020.8.174-185

43. Gorky J, Schwaber J. The role of the gut-brain axis in alcohol use disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65:234–241. PMID: 26188287. https://doi.org/10.1016/j.pnpbp.2015.06.013