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Novel Experimental Technique to Create Size-Controlled Retroperitoneal Bleeding in the Infrarenal Aorta of Anesthetized Pigs
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Thoracic and Vascular Surgery.
Hoglandssjukhuset Eksjo, Sweden.
Orebro Univ, Sweden.
Orebro Univ, Sweden.
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2021 (English)In: Innovations (Philadelphia): technology and techniques in cardiothoracic and vascular surgery, ISSN 1556-9845, E-ISSN 1559-0879, Vol. 16, no 4, p. 379-385Article in journal (Refereed) Published
Abstract [en]

Objective: Rupture of abdominal aortic aneurysm (rAAA) with a contained retroperitoneal hematoma is potentially fatal. Physiological studies are difficult to perform in patients suffering from life-threatening conditions such as rAAA. A translational model of the condition is therefore needed. The aim was to develop and validate an endovascular animal model for retroperitoneal bleeding of the abdominal aorta with contained hematoma. Methods: In anesthetized pigs, a puncture hole was made in the posterolateral portion of the infrarenal aorta by an Outback re-entry catheter device. The hole was gradually enlarged using angioplasty balloons to a specific diameter of either 4 mm (n = 6), 6 mm (n = 7), or 8 mm (n = 6). Onset of bleeding was verified by angiography and macroscopically examined on completion of the experiments. Survival up to 180 min was the primary outcome. Hemodynamic and metabolic markers in arterial blood were secondary outcomes. Results: Aortic injury with a contained retroperitoneal hematoma was achieved in all animals. Survival rate at 180 min after onset of bleeding was higher in the 4 mm group compared to the 6 mm (P = 0.021) and 8 mm groups (P = 0.002), but not when comparing the 6 mm and 8 mm groups. Systemic hypotension, arterial acidosis, and lactatemia were provoked in the 6 mm and 8 mm groups but not in the 4 mm group. Conclusions: A porcine model for a controlled contained left posterolateral retroperitoneal bleeding was created using endovascular methods and validated. This model makes it possible to study the pathophysiology of a retroperitoneal hematoma.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC , 2021. Vol. 16, no 4, p. 379-385
Keywords [en]
ruptured abdominal aortic aneurysm; retroperitoneal hematoma; experimental animal model; endovascular surgery; physiology of shock
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-179456DOI: 10.1177/15569845211013803ISI: 000729431000001PubMedID: 34077271OAI: oai:DiVA.org:liu-179456DiVA, id: diva2:1597121
Available from: 2021-09-24 Created: 2021-09-24 Last updated: 2024-05-13
In thesis
1. Experimental and Clinical Studies in Ruptured Abdominal Aortic Aneurysm: Aspects of Hypothermia and Endovascular Treatment
Open this publication in new window or tab >>Experimental and Clinical Studies in Ruptured Abdominal Aortic Aneurysm: Aspects of Hypothermia and Endovascular Treatment
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ruptured Abdominal Aortic Aneurysm (rAAA) is a life-threatening medical condition with historically reported mortality rates of 80%. Open aortic surgery was for the first time performed in 1950s. EndoVscular Aortic Repair (EVAR) was introduced in the 1990s as a minimally invasive treatment alternative because complications after open surgery of rAAA were relatively common. EVAR resulted in substantially lower short-term mortality, but still the life of one in four patients cannot be saved.

The overarching aim of this research project was to study effects of induced hypothermia on survival in hemorrhagic shock caused by bleeding into the retroperitoneal room because of aortic rupture, and the effects of accidental hypothermia and the long-term outcomes of EVAR in treatment of rAAA.

Experimental studies (1 & 2): In absence of a validated model, we created an experimental model, in anesthetized pigs (19 animals), to study size-controlled rupture in the posterolateral aortic wall with retroperitoneal bleeding. This model proved to be accurate and reproducible.

Using this novel model, we studied the effects of moderate induced hypothermia on survival. In a randomized comparison (10 animals in each arm), we found that survival of the experimental animals was not impaired by induced hypothermia.

Clinical studies (3 & 4): Patients treated with an EVAR-only treatment strategy in rAAA, in a single center, between October 2009-, until September 2021 (study 3) and September 2023 (study 4) were included. The retrospective study of outcomes of EVAR, in 100 patients (75 men) with rAAA found an EVAR treatment strategy feasible. Turndown rate was only 3,5%, with patients not suitable for open surgery either. We found a 30-day mortality of 27% and one-year mortality of 37%. After three years, 40% of the patients in the cohort were still alive. Low systemic blood pressure and need for use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) were independently associated with increased 30-day mortality.

In a further retrospective study (EVAR in 86 patients with rAAA), pre-, peri-, and postoperative data with focus on body temperature, blood gas analyses, transfusion needs and presence of multiorgan failure as well as 30-day, 90-day mortality, were studied in three subgroups of body temperature. Accidental hypothermia was found to be associated with deteriorated hemodynamics, with increased need for REBOA and for transfusions. The hypothermic patients suffered multiorgan failure more often. There was a higher mortality, although not statistically significant, in hypothermic patients.

In conclusion, EVAR in rAAA was found to have survival outcomes that are superior to the historically published data.

The favorable outcomes for hypothermia in the experimental study versus worse outcomes in the clinical study suggest that accidental hypothermia and induced hypothermia are two different entities which may set path for future studies in this field.

Abstract [sv]

Rupturerat bukaortaaneurysm (rAAA) är ett livshotande medicinskt tillstånd med historiskt rapporterade dödlighetsnivåer på 80%. Öppen aortakirurgi introducerades på 1950-talet. Endovaskulär aortareparation (EVAR) infördes på 1990-talet som ett minimalinvasivt behandlingsalternativ eftersom komplikationer efter öppen kirurgi vid rAAA var relativt vanliga. EVAR resulterade i betydligt lägre korttidsdödlighet, men ändå kan livet för en av fyra patienter inte räddas.

Det övergripande målet med detta forskningsprojekt var att studera effekterna av inducerad hypotermi på överlevnad vid blödning i retroperitoneala rummet på grund av aortaruptur, samt effekten av accidentell hypotermi och de långsiktiga resultaten av EVAR vid behandling av rAAA.

Experimentella studier (1 & 2): I brist på en validerad modell skapade vi en experimentell modell med sövda grisar (totalt 19 djur) för att studera storlekskontrollerad ruptur i den posterolaterala aortaväggen. Denna modell visade sig vara exakt och reproducerbar. Med denna modell studerade vi effekterna av inducerad måttlig hypotermi på överlevnad. I en randomiserad jämförelse (10 djur i varje arm) fann vi att överlevnaden hos de experimentella djuren inte påverkades negativt av inducerad hypotermi.

Kliniska studier (3 & 4): Patienter som behandlades med en 100%-EVAR-behandlingsstrategi vid rAAA, vid ett enda center, mellan oktober 2009- och september 2021 (studie 3), samt september 2023 (studie 4) inkluderades. Den retrospektiva studien av resultaten av EVAR, med 100 patienter (75 män) med rAAA, visade att en behandlingsstrategi med 100% EVAR var genomförbar. Avvisningsfrekvensen var endast 3,5% och dessa patienter var inte heller lämpliga för öppen kirurgi. Vi fann att 30-dagars-dödlighet var 27% och ettårs-dödligheten var 37%. Efter tre år var 40% av patienterna i kohorten fortfarande i livet. Lågt systemiskt blodtryck under operationen, och behovet av användning av aortaocklusionsballong (REBOA) var, oberoende av varandra, associerade med ökad 30-dagars dödlighet.

I ytterligare en retrospektiv studie (EVAR hos 86 patienter med rAAA) studerades pre-, peri- och postoperativa data med fokus på kroppstemperatur, blodgasanalyser, transfusionsbehov och närvaro av multiorgansvikt, samt 30-dagars och 90-dagars dödlighet i tre undergrupper av kroppstemperatur. Hypotermi visade sig vara associerad med försämrad hemodynamik, med ökat behov av REBOA och transfusioner. De hypotermiska patienterna drabbades oftare av multiorgansvikt. Det fanns en högre dödlighet, även om den inte var statistiskt signifikant, hos hypoterma patienter.

Sammanfattningsvis hade EVAR vid rAAA högre överlevnad än de historiskt publicerade data. De gynnsamma resultaten för hypotermi i den experimentella studien jämfört med sämre resultat i den kliniska studien tyder på att accidentell hypotermi och inducerad hypotermi är två olika entiteter, vilket kan lägga grunden för framtida studier inom detta område.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 69
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1913
Keywords
Ruptured abdominal aortic aneurysm, EVAR, REBOA, Endovascular treatment, Rupturerat bukaortaaneurysm, EVAR, REBOA, Endovaskulär behandlingsmetod
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-203423 (URN)10.3384/9789180756266 (DOI)9789180756259 (ISBN)9789180756266 (ISBN)
Public defence
2024-06-14, Hasselqvistsalen, Building 511, Campus US, Linköping, 09:00 (Swedish)
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Available from: 2024-05-13 Created: 2024-05-13 Last updated: 2024-05-13Bibliographically approved

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