Der septische Schock geht bis heute mit einer hohen Mortalität einher und stellt für die Intensivmedizin ein schwer beherrschbares Krankheitsbild dar. Er ist die häufigste Todesursache auf nicht kardiologischen Intensivstationen und es wird davon ausgegangen, dass der Anteil septischer Patienten relativ wie absolut zunehmen wird. Das Ziel der vorliegenden Arbeit war, den Einfluss von Hydrokortison auf die Schockdauer und die Wirkung von Hydrokortison in Abhängigkeit der Nebennierenrindenfunktion sowie den Einfluss auf die Morbidität, gemessen am SOFA-Score zu untersuchen. Es wurden 41 Patienten mit frühem septischem Schock in eine doppelblinde, placebokontrollierte, randomisierte Studie eingeschlossen. Zur Beurteilung der Nebennierenfunktion wurde vor Beginn der Studie ein ACTH-Test durchgeführt und je nach Anstieg wurden die Patienten in „Non-Responder“ und „Responder“ unterteilt. Es zeigte sich, dass Hydrokortison zu einer signifikanten Verkürzung der Schockdauer führte. Die Frage nach dem unterschiedlichen Effekt von Hydrokortison bei „Respondern“ und „Non-Respondern“ konnte nicht abschließend geklärt werden; es zeigte sich bei den „Respondern“ und „Non-Respondern“, die Hydrokortison erhalten hatten, ein Trend zu einer kürzeren Schockdauer, der aber keine statistische Signifikanz erreichte, vermutlich weil die Gruppengröße durch die Aufteilung zu klein wurde. Die vorliegenden Ergebnisse sind insofern mit anderen Studien kongruent, bedürfen aber noch der weiteren Abklärung in Studien mit größeren Patientenkollektiven. Der SOFA-Score war unter Hydrokortison in den ersten 48 Stunden signifikant reduziert. In anderen Studien war dies mit einer geringeren Mortalität assoziiert. Die Behandlung mit Hydrokortison reduziert also die Schockdauer und stellt eine wichtige Therapierationale zur Vorbeugung des sepsis-induzierten Organversagens dar. / Up to the present day septic shock is often accompanied with high mortality. For the medical intensive care field it is a hardly controllable disease pattern. Septic shock is the most frequent cause of death at non-cardiological intensive care units. It is believed that the number of septic patients will increase relatively as well as absolutely. The aim of this paper was to examine the influence of hydrocortisone on shock duration, the effect of hydrocortisone dependent on the adrenal function and the influence on morbidity, measured with SOFA score. 41 patients with early septic shock participated in a double-blind, placebo-controlled, randomised study. In the beginning of the study an ACTH-test was conducted in order to assess the adrenal function. Dependent on the increase of ACTH, the patients were classified into "non-responder" and "responder". It became apparent that hydrocortisone leads to a significant reduction of shock duration. The question about the different effect of hydrocortisone on “responder“ and “non-responder“ could not cleared up conclusively. “Responder“ and „non-responder“ who received hydrocortisone showed a trend towards shorter shock duration. There was, however, no statistic significance, probably because the groups became too small because of the division. The present results are insofar congruent with other studies, but they need further clarification through studies with bigger patient groups. For those using hydrocortisone the SOFA score was significantly reduced during the first 48 hours. In other studies this fact was associated with less mortality. The treatment with hydrocortisone therefore reduces the shock duration and is an important therapy rationale for the prevention of septic induced multi-organ failure.

Sammanfattning Sedan sjukdomen Covid-19s uppdykande i början av 2020 har forskning pågått för att karaktärisera sjukdomen ur alla tänkbara vinklar för att på kortast möjliga tid bereda väg för ett fungerande botemedel. Effektiva läkemedel som kan minska risken för allvarligt sjuka patienter att avlida i sjukdomen behövs; många preparat har föreslagits och testats och i Sverige har hittills två läkemedel godkänts för Covid-19. Ett av dessa är kortikosteroiden dexametason som godkänts för Covid-19-patienter i behov av syrgas eller respirator. Syftet med detta arbete var att undersöka hur effektiv kortikosteroidbehandling av svårt sjuka Covid-19-patienter var i jämförelse med standardbehandling utan kortikosteroider. En litteratursökning gjordes i PubMed och i covid-nma efter randomiserade kliniska studier av kortikosteroider jämfört med standardbehandling till patienter med Covid-19. Ur resultatet som inkluderade 7 kontrollerade studier med 7784 svårt sjuka patienter från 11 länder och fem kontinenter, gjordes en sammanvägning av den primära utfallsvariabeln mortalitet 28 dagar efter randomisering varpå relativ risk (RR) räknades ut individuellt per studie och sammanvägt för alla studier. Analysen gjordes också med den mest dominanta studien borträknad. Vidare utforskades möjliga samband mellan sjukdomsgrad och effektstorlek, dels genom ett försök till metaregression av studiemortalitet och andningshjälpsnivå mot RR som var inkonklusivt, men också genom att leta efter speciellt sjuka undergrupper i studierna. 3 studier rapporterade mortalitet efter 28 dagar, 1 studie rapporterade mortalitet efter 21 dagar, 2 studier rapporterade död på sjukhus och en studie rapporterade död efter 15 dagar. Testade preparat var dexametason, hydrokortison och metylprednisolon. Av 2885 patienter som randomiserats till någon kortikosteroid, dog 739, medan det av de 4899 som randomiserats till standardbehandling dog 1347 patienter vilket gav en icke signifikant RR på 0,93 (95% CI 0,86–1,01). Vid borträkning av den största studien som bestod av relativt friskare patienter erhölls en starkare och signifikant effekt med RR 0,80 (95% CI 0,70–0,92) baserat på 257 av 781 döda i steroidgrupperna jämfört med 237av 578 döda i någon kontrollgrupp med standardbehandling. Resultatet var även i linje med analysen av olika sjuka undergrupper från största studien som visade bäst effekt hos de med invasiv mekanisk andningshjälp (absolut riskreduktion 12,1%) samt en icke signifikant försämring hos de friskaste patienterna utan syrgasbehov. Sammantaget tyder dessa resultat på att behandling av svårt sjuka Covid-19-patienter med kortikosteroider minskar mortaliteten efter 28 dagar. Dessutom ger studien en stark indikation på att bästa effekten fås om kortikosteroiderna ges till patienter där den systemiska inflammationen i lungorna nått en gasutbyteshämmande nivå / ABSTRACT Since the emergence of the new corona virus disease, Covid-19, much research effort has gone into characterising every possible angle of the disease to pave the way for a possible cure in the shortest possible time. Effective therapies are needed that will reduce the risk of dying for severely to critically ill Covid-19 patients. Many existing therapies have been suggested, tested and repurposed for the treatment of Covid-19 but so far only two drugs have been approved in Sweden for this indication, namely the antiviral drug remdesivir and the corticosteroid dexamethasone. Corticosteroids are both immunosuppressive and anti-inflammatory and when they were administered previously for severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and influenza they were found to increase the time to rid the body of virus. The purpose of this study was to investigate evidence found in the research literature of how effective corticosteroids are in reducing the risk of dying as compared to standard treatment with no corticosteroids when administered to hospitalised patients with severe Covid-19. A literature search was made in the PubMed and covid-nma databases for randomized clinical studies of corticosteroids versus standard treatment to patients with Covid-19. The result included 7 studies with 7784 patients from 11 countries and 5 continents which all reported death as an outcome in groups that were receiving corticosteroids compared to groups that were receiving standard care. The studies used one of the following corticosteroids as intervention: dexamethasone, methylprednisolone and hydrocortisone in different doses. In the groups receiving standard care, 1347 patients out of 4899 died while in the corticosteroid groups 739 of 2885 patients died. When doing a statistical calculation these figures indicated that the risk of dying when getting corticosteroids was 93% of the risk when not getting corticosteroids, however the difference was not statistically significant. After omitting the largest study from the material, that contributed the absolute majority of total participants, who were deemed relatively healthy or well taken care of, the results were instead that 257 out of 781 died in the steroid groups and 237 of 578 died in the control groups. This later comparison among supposedly sicker patients, gave a statistically significant 8,1% lower absolute risk of dying in the corticosteroid groups; an effect that could also be expressed as for every 25 patients treated, 2 more lives would be saved. A further control of a more severely sick subgroup of patients from the largest study, in need of invasive mechanical ventilation, revealed an absolute reduction of the risk of dying when given corticosteroids of 12,1%. This group showed the most effectful response to the administered corticosteroids in this study which could also be expressed as 1 more life saved for every 8 patients treated. Another sub group analysis of the patients from the largest study that were not in need of any type of oxygen support, indicated on the other hand a possible harm of corticosteroids. This potentially harmful effect was however not statistically significant. In summary, the results of this study imply that administration of corticosteroids to patients with severe Covid-19 will reduce the risk of dying. The greatest effect is seen in those patients that has reached a level of illness were the gas exchange in the lungs is impaired by the inflammation. Furthermore, caution must be taken not to introduce harm by giving corticosteroids to patients with milder disease in which the immunosuppressive properties of the drug could lead to unintended worsening of the illness.