Non-antibiotic treatment options in patients with sepsis and septic shock syndrome

master's thesis

• Title (croatian): Mogućnosti ne-antibiotskog liječenja bolesnika sa sepsom i sindromom septičkog šoka
• Author: Marian Thomas Hradil
• Mentor: Robert Likić (mentor)
• Committee member: Robert Likić (predsjednik povjerenstva)
• Committee member: Luka Bielen (član povjerenstva)
• Committee member: Boško Skorić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Pharmacology and Toxicology

Abstract

Sepsis, currently defined as dysregulated systemic immune response of the host to an infectious insult with subsequent life-threatening organ dysfunction, is a common multifactorial disease. In conjunction with septic shock, the most severe form of sepsis characterized by profound circulatory and metabolic derangement, the two are one of the leading causes of mortality and critical illness worldwide. Despite improvements in the management of sepsis, including timely administration of antibiotic agents, optimization of intravascular volume status and supportive care, no specific treatment exists as of yet. However, an increased understanding of the pathophysiological mechanisms and the biphasic course consisting of pro and anti-inflammatory states, has paved the way for alternative treatment options. Active research has spawned candidate drugs including extracorporal blood purification, immune modulation with corticosteroids, intravenous immunoglobulins, mesenchymal stem cells, GM-CSF, rhIL-7, thymosin-α1 or nanoparticles. Vasopressin-agonists and beta-blocker are agents regulating the cardiovascular system. Promising strategies targeting other organ systems involve novel agents like alkaline phosphatase, thrombomodulin and the gut microbiome. Finally, micronutrients have been assessed as treatment alternatives. However, investigations on new efficient therapy agents are hampered by the broad spectrum of the syndrome, its definition and the heterogeneity of the patients affected. Lacking identification of sepsis subtypes limits the applicability of research results. The outcomes of studies conducted on alternative treatment agents for sepsis and septic shock distance themselves from one-size-fits-all, to focus on individualized
medicine including careful treatment timing and clinical pheno- and genotyping. In this context, the mentioned agents are currently of particular interest in treatment for sepsis and give a promising outlook. Therefore, the aim should be stratification of disease and patient to identify who benefits most from therapy.

Abstract (croatian)

Sepsa je česta multifaktorna bolest koja se trenutno definira kao neregulirani sustavni imunološki odgovor domaćina na infekciju s naknadnom disfunkcijom organa koja je opasna po život. Najteži oblik sepse je septički šok, kojeg karakterizira poremećaj cirkulacije i metabolizma. Zajedno predstavljaju jedan od vodećih uzroka smrtnosti i kritičnih bolesti u svijetu. Unatoč napretku postignutom u liječenju sepse, uključujući pravovremenu primjenu antibiotskih sredstava, optimizaciju stanja intravaskularnog volumena i potpornu njegu, ne postoji specifično liječenje. Veće razumijevanje patofizioloških mehanizama i dvofaznog tijeka koji se sastoji od pro i protuupalnih stanja, otvorilo je put alternativnim mogućnostima liječenja. Postojeća istraživanja rezultirali su pronalaskom mogućih lijekova, uključujući ekstrakorporalno pročišćavanje krvi, imunološku modulaciju kortikosteroidima, intravenske imunoglobuline, mezenhimske matične stanice, GM-CSF, rhIL-7, timozin-α1 ili nanočestice. Vasopresin agonisti i beta-blokatori su lijekovi koji djeluju na kardiovaskularni sustav. Obećavajuće strategije usmjerene na druge organske sustave uključuju nova terapija poput alkalne fosfataze, trombomodulina i crijevnog mikrobioma. Konačno, mikroelementi su procijenjeni kao alternative liječenju. Međutim, istraživanja novih učinkovitih terapijskih sredstava otežana su širokim spektrom sindroma, njegovom definicijom i heterogenošću pacijenata. Nedostatak identifikacije podtipova sepse ograničava primjenjivost rezultata istraživanja. Rezultati studija provedenih alternativnim terapijama za liječenje sepse i septičnog šoka, ukazuju na veću uspješnost individualnog pristupa pacijentu od univerzalnog. Takav pristup uključuje pažljivo određivanje vremena liječenja te kliničko feno- i genotipiziranje. Upravo zbog prethodno navedenog, spomenuta sredstva trenutno su od posebnog interesa za liječenje sepse i daju obećavajuće izglede stoga bi cilj trebao biti raslojavanje bolesti i pacijenta kako bi se utvrdilo tko će najvjerojatnije imati koristi od terapije.

• Keywords: sepsis; septic shock; critically ill; therapy
• Keywords (croatian): sepsa; septički šok; kritično bolestan; terapija
• Language: english
• URN:NBN: urn:nbn:hr:105:133789
• Study programme: Title: Medicine (in English language); Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-12-21 10:46:32