To Örebro University

OBJECTIVE: Open repair of ruptured abdominal aortic aneurysms (rAAA) has been increasingly replaced by endovascular aortic repair (EVAR) in many centers. Despite being a minimally invasive procedure, EVAR is associated with a risk of abdominal compartment syndrome (ACS), which can lead to significant morbidity and mortality. This study examines the incidence and clinical manifestation of ACS in a consecutive cohort of rAAA patients treated exclusively with EVAR at Örebro University Hospital over a 12-year period.

METHODS: This is a retrospective analysis of prospectively collected data. We identified 139 patients who had presented to Örebro University Hospital with rAAA between October 2009 and September 2021. Patients with isolated iliac artery, thoracic and thoracoabdominal aortic ruptures, previous aortic interventions (open or endovascular), and patients receiving palliative treatment were excluded. Patients developing ACS after rAAA were compared with those who did not develop ACS.

RESULTS: A total of 100 patients treated using EVAR were included in this study. ACS was identified in 17 patients, and these were compared with 83 patients who did not develop ACS. Mortality at 30 days was 53% in the ACS group (9/17) and 22% in the No-ACS group (18/83, p = 0.015). Regression analysis showed that advanced age and ACS were independent risk factors for death, with ACS increasing the hazard 4-fold (HR 4.26, CI 1.99-9.10, p < 0.001) and age increasing the hazard by 6% for every year (HR 1.06, CI 1.06-1.1, p = 0.004). The use of aortic balloon occlusion was not independently associated with the development of ACS.

CONCLUSIONS: ACS is a life-threatening complication of rAAA treated using EVAR and a significant number of patients developed ACS with high mortality and complication rates. All rAAA patients treated using EVAR should be monitored closely for ACS and treatment with decompressive laparotomy should be initiated without delay.Clinical ImpactOpen repair of ruptured abdominal aortic aneurysms (rAAA) has been increasingly replaced by endovascular aortic repair (EVAR). Despite being a minimally invasive procedure, EVAR is associated with a risk of abdominal compartment syndrome (ACS), which can lead to significant morbidity and mortality This article investigates abdominal compartment syndrome (ACS) in a cohort of total endovascular treated rAAA in a single centre and the treatment as well as the results, and gives insight on ACS in this patient group and might contribute to better understanding how to treat them and avoid this life-threatening complication.

OBJECTIVES: Optimal antibiotic treatment is important in the treatment of sepsis. However, patients with sepsis are at risk of suboptimal antibiotic concentrations. This study aimed to evaluate β-lactam antibiotic concentrations during the first 48 h in patients with community-acquired sepsis admitted to the ICU, and to identify variables associated with antibiotic concentrations that were too low or too high.

METHODS: This prospective, observational, single-centre study included patients aged ≥18 years with a high likelihood of infection, a SOFA score of ≥2p, planned β-lactam antibiotic treatment, and ICU admission. The exclusion criteria were ongoing antibiotic treatment and/or nosocomial infections. β-Lactam concentrations were measured up to seven times during the first 48 h. The estimated trough concentrations were divided by the predetermined MIC to generate MIC-multiples for comparison. Patients were allocated to three groups based on the MIC-multiple (MIC× < 1, 1-8 or >8).

RESULTS: Fifty patients were included, with a median of seven samples per patient (257 samples). The group with MIC-multiples of <1 (n = 16) was associated with younger age, lower Charlson comorbidity index, Simplified Acute Physiology Score 3, creatinine concentration, and need for noradrenaline. The group with MIC-multiples of >8 (n = 15) had higher creatinine and noradrenaline levels.

CONCLUSIONS: ICU patients with sepsis are at risk of either too low or too high antibiotic concentrations, and specific patient characteristics may be predictable. Therapeutic drug monitoring in combination with model-informed precision dosing may also help to optimize antibiotic dosing in the early phase of community-acquired sepsis to prevent treatment failure and toxicity.

OBJECTIVE: Induced hypothermia improves outcome in aortic arch surgery, neonatal neurointensive care, and transplant surgery for example. In contrast, spontaneous hypothermia has been associated with worse outcomes in patients suffering from hemorrhagic shock, mostly explained by its adverse effects on the coagulation system. We investigated if induced hypothermia would impair short-term survival in experimental aortic rupture with retroperitoneal bleeding.

METHODS: Anesthetized pigs were randomized into 2 groups: hypothermia by peritoneal lavage of ice-cold Ringer's acetate and external cooling (n = 10) and normothermia (n = 10). Aortic rupture with retroperitoneal bleeding was induced by endovascular means creating a 6 mm hole in the retroperitoneal portion of abdominal aorta. Survival (primary outcome), hemodynamics, and arterial blood gases including lactate were collected and analyzed up to 180 min after aortic rupture.

RESULTS: The body temperature (mean ± standard deviation) in the hypothermic group was 31.5 ± 1.0 °C and 38.7 ± 0.4 °C in the normothermic group at the time for aortic rupture. Survival up to 180 min after the retroperitoneal bleeding was significantly higher in the hypothermic compared with the normothermic group (P = 0.023).

CONCLUSIONS: Induced hypothermia did not impair survival in this experimental retroperitoneal aortic bleeding model in anesthetized pigs. This finding may indicate a minor role for the coagulation system in this type of bleeding.

OBJECTIVE: This study aimed to investigate the association between intestinal fatty acid-binding protein, acute gastrointestinal injury grade, and gastrointestinal complications after fenestrated or branched endovascular aortic aneurysm repair.

METHODS: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for intestinal fatty acid-binding protein with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the acute gastrointestinal injury grade every day during postoperative intensive care.

RESULTS: Higher concentrations of intestinal fatty acid-binding protein at 24 h and 48 h correlated to higher acute gastrointestinal injury grade on postoperative days 1, 2 and 3 (p=0.032 and p=0.048, p=0.040 and p=0.018, and p=0.012 and p=0.016, respectively). Patients who developed a gastrointestinal complication within 90 days postoperatively had a higher overall acute gastrointestinal injury grade than those who did not develop a gastrointestinal complication (p<0.001), as well as higher concentrations of intestinal fatty acid-binding protein at 48 h (p=0.019). Patients developing gastrointestinal dysfunction (acute gastrointestinal injury grade ≥2) had a higher frequency of complications (p=0.009) and longer length of stay in the intensive care unit (p=0.008).

CONCLUSIONS: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma intestinal fatty acid-binding protein concentrations and postoperative gastrointestinal dysfunction, evaluated using the acute gastrointestinal injury grade, were associated with gastrointestinal complications, indicating that these measures may be useful in the postoperative management of these patients.

BACKGROUND: Intra-aortic balloon pump (IABP) and resuscitative endovascular balloon occlusion of the aorta (REBOA) are two endovascular intervention methods for circulatory support. The aim of this study was to compare the hemodynamic effects of simultaneous mechanical chest compressions (MCC) with IABP, REBOA and those with only MCC (overall and detailed in the MCC cycle) and return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR) in experimental non-traumatic cardiac arrests (CA).

METHOD: CA was electrically induced (ventricular fibrillation) in 24 anesthetized pigs, which then were randomized to MCC synchronized IABP (n = 8), total occluded REBOA (n = 8), or control (n = 8). After 10 min of CA, CPR with MCC was started followed by one of the interventions after one minute of CPR. Every other minute after MCC start, the pigs were defibrillated with 200 J if VF/ventricular tachycardia, and after six minutes, adrenaline was administered and repeated every four minutes. The proportions of ROSC were calculated. Hemodynamic variables, including systemic blood and coronary perfusion pressures (CPP), and carotid and iliac blood flows, were collected and analyzed with 0.02 s resolution.

RESULTS: In both the IABP and REBOA groups, 7 of 8 animals (87.5 %) achieved ROSC, in contrast with 2 of 8 (25 %) in the control group (P = 0.04). IABP and REBOA significantly increased systemic arterial pressure (P = 0.002 and P = 0.015, respectively), and REBOA also increased CPP and carotid blood flow when compared to controls (P = 0.007 and P = 0.03, respectively). Animals with IABP had a preserved blood flow in the iliac artery during CPR. No differences were detected after ROSC in hemodynamic, metabolic, and organ injury variables between the REBOA and IABP groups.

CONCLUSION: Both IABP and REBOA increased the proportion of ROSC compared to controls. However, REBOA occluded distal blood flow, while IABP maintained it. This study suggests that MCC synchronized IABP could be an adjunct in the treatment of non-traumatic CA.

PURPOSE: Combining resuscitative endovascular balloon occlusion of the aorta (REBOA) and the inferior vena cava (REBOVC) with open surgery is a new hybrid approach for treating retrohepatic vena caval injuries. We compared endovascular total hepatic isolation with supraceliac REBOA ± suprahepatic REBOVC and no occlusion in experimental retrohepatic vena cava bleeding regarding survival, bleeding volume, hemodynamic stability, and arterial collateral blood flow.

METHODS: Twenty-five anesthetized pigs (n = 6-7/group) were randomized to REBOA; REBOA + REBOVC; REBOA + infra and suprahepatic REBOVC + portal vein occlusion (endovascular Heaney maneuver, four-balloon-occlusion, 4BO) or no occlusion. After balloon inflation, free bleeding was initiated from an open sheath in the retrohepatic vena cava. Bleeding volume, right internal thoracic artery (RITA) blood flow, hemodynamics, and arterial blood variables were measured until death or up to 90 min.

RESULTS: The REBOA group had a longer median survival time (63 min) compared with the 4BO (24 min, P = 0.02) and no occlusion (30 min, P = 0.02) groups, not versus the REBOA + REBOVC group (49 min, P > 0.05). The first 15 min accumulated bleeding was comparable in all groups (P > 0.05); Thereafter, bleeding volume was higher in the REBOA group versus the 4BO group (P < 0.05), not versus the other groups. RITA blood flow and MAP were higher in the REBOA group versus the other groups after 10 min of bleeding (P < 0.05).

CONCLUSIONS: Endovascular Heaney maneuver was not beneficial for survival or hemodynamic stability in this porcine model, whereas supraceliac REBOA was. Anatomical differences in thoracoabdominal collaterals between pigs and humans must be considered when interpreting these results.

Objective: Endovascular aneurysm repair (EVAR) has been increasingly performed for ruptured abdominal aortic aneurysms (rAAAs). However, multiple randomized trials have failed to demonstrate a survival benefit compared with open aortic surgery. During a 12-year period, 100% of patients without a history of aneurysm surgery had undergone EVAR for a rAAA at orebro University Hospital, with no emergent open aortic surgery performed. In the present study, we evaluated the mortality and technical success during this "EVAR-only" period.

Methods: A single-center, retrospective observational study was conducted. We identified all patients who had presented to Orebro University Hospital with a rAAA between October 2009 and September 2021. Patients with isolated iliac artery, thoracic, and thoracoabdominal aortic ruptures were not included. Patients who had received previous aortic interventions (open or endovascular) and patients who had received palliative treatment instead of surgical intervention were also excluded. The patient characteristics, perioperative and postoperative data, and mortality rate were investigated.

Results: EVAR had been performed in 100 patients. Preoperative hemodynamic instability had been present in 54 patients (54%), and 18 (18%) had undergone aortic balloon occlusion. The aneurysm location was infrarenal in 89 patients (89%). Bifurcated stent grafts had been used in 97 patients (97%), and adjunct endovascular techniques had been used for 27 patients (27%). Of 98 patients, EVAR had been performed with the patient under local anesthesia for 62 patients (63%). Peri-and postoperative complications at 30 days had occurred in 20 of 100 patients (20%) and 22 of 79 patients (28%), respectively. The overall mortality at 30 days was 27% (27 of 100 patients), and the mortality for those with an isolated infrarenal rAAA was 24% (21 of 89 patients). The overall mortality at 1 year was 39% (39 of 100 patients) and for those with an isolated infrarenal rAAA was 37% (33 of 89 patients). The presence of preoperative hemodynamic instability and the use of ABO were statistically significantly and independently associated with increased 30-day mortality on multivariate logistic regression analysis.

Conclusions: All 100 patients who had undergone surgery for a rAAA had been treated using EVAR and endovascular adjuncts, with a relatively low mortality rate, thus continuing the "EVAR-only" approach. A low proportion of rAAA patients were considered surgically unsuitable. These findings support the applicability of EVAR for the treatment of all rAAAs at suitable centers.

OBJECTIVES: In fluoroscopy-free settings, alternative safe and quick methods for placing resuscitative endovascular balloon occlusion of the aorta (REBOA) and resuscitative endovascular balloon occlusion of the inferior vena cava (REBOVC) are needed. Ultrasound is being increasingly used to guide the placement of REBOA in the absence of fluoroscopy. Our hypothesis was that ultrasound could be used to adequately visualize the suprahepatic vena cava and guide REBOVC positioning, without significant time-delay, when compared with fluoroscopic guidance, and compared with the corresponding REBOA placement.

METHODS: Nine anesthetized pigs were used to compare ultrasound-guided placement of supraceliac REBOA and suprahepatic REBOVC with corresponding fluoroscopic guidance, in terms of correct placement and speed. Accuracy was controlled by fluoroscopy. Four intervention groups: (1) fluoroscopy REBOA, (2) fluoroscopy REBOVC, (3) ultrasound REBOA and (4) ultrasound REBOVC. The aim was to carry out the four interventions in all animals. Randomization was performed to either fluoroscopic or ultrasound guidance being used first. The time required to position the balloons in the supraceliac aorta or in the suprahepatic inferior vena cava was recorded and compared between the four intervention groups.

RESULTS: Ultrasound-guided REBOA and REBOVC placement was completed in eight animals, respectively. All eight had correctly positioned REBOA and REBOVC on fluoroscopic verification. Fluoroscopy-guided REBOA placement was slightly faster (median 14 s, IQR 13-17 s) than ultrasound-guided REBOA (median 22 s, IQR 21-25 s, p=0.024). The corresponding comparisons of the REBOVC groups were not statistically significant, with fluoroscopy-guided REBOVC taking 19 s, median (IQR 11-22 s) and ultrasound-guided REBOVC taking 28 s, median (IQR 20-34 s, p=0.19).

CONCLUSION: Ultrasound adequately and quickly guide the placement of supraceliac REBOA and suprahepatic REBOVC in a porcine laboratory model, however, safety issues must be considered before use in trauma patients.

LEVEL OF EVIDENCE: Prospective, experimental, animal study. Basic science study.

BACKGROUND: The definition of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is not yet determined and clinical markers of the degree of occlusion, metabolic effects and end-organ injury that are clinically monitored in real time are lacking. The aim of the study was to test the hypothesis that end-tidal carbon dioxide (ETCO2) targeted pREBOA causes less metabolic disturbance compared to proximal systolic blood pressure (SBP) targeted pREBOA in a porcine model of hemorrhagic shock.

MATERIALS AND METHODS: Twenty anesthetized pigs (26-35 kg) were randomized to 45 min of either ETCO2 targeted pREBOA (pREBOAETCO2, ETCO2 90-110% of values before start of occlusion, n = 10) or proximal SBP targeted pREBOA (pREBOASBP, SBP 80-100 mmHg, n = 10), during controlled grade IV hemorrhagic shock. Autotransfusion and reperfusion over 3 h followed. Hemodynamic and respiratory parameters, blood samples and jejunal specimens were analyzed.

RESULTS: ETCO2 was significantly higher in the pREBOAETCO2 group during the occlusion compared to the pREBOASBP group, whereas SBP, femoral arterial mean pressure and abdominal aortic blood flow were similar. During reperfusion, arterial and mesenteric lactate, plasma creatinine and plasma troponin concentrations were higher in the pREBOASBP group.

CONCLUSIONS: In a porcine model of hemorrhagic shock, ETCO2 targeted pREBOA caused less metabolic disturbance and end-organ damage compared to proximal SBP targeted pREBOA, with no disadvantageous hemodynamic impact. End-tidal CO2 should be investigated in clinical studies as a complementary clinical tool for mitigating ischemic-reperfusion injury when using pREBOA.

ETHNOPHARMACOLOGICAL RELEVANCE: In Ethiopian traditional medicine the root of Taverniera abyssinica A.Rich is known as a remedy for sudden gastrointestinal cramping and fever. In this study we have isolated and identified the bioactive principle of Taverniera abyssinica that exerts effects on isolated smooth muscle tissues of the rabbit duodenum and guinea-pig ileum.

AIM OF THE STUDY: To isolate and purify the bioactive principle from the root of Taverniera abyssinica A.Rich by bioassay-guided fractionation, HPLC purification and masspectrometry, with further investigation of its bioactivity on isolated smooth muscle strips.

MATERIALS AND METHODS: Roots of Taverniera abyssinica A.Rich extracted in 75% methanol/water were fractioned with a reverse phase column and then subjected to HPLC purification. Each fraction collected from the HPLC was tested for its bioactivity using electric field stimulation-evoked contractions of the rabbit duodenum and guinea-pig ileum. Finally, detailed structural analysis of the fraction displaying significant bioactivity was made by mass spectrometry.

RESULTS: Through bioassay-guided fractionation and HPLC purification the bioactive fractions were identified. These were tested for bioactivity on isolated smooth muscle strips which showed about 50% inhibition of contractions evoked by electric field stimulation. These compounds were identified as formononetin, afrormosin and tectorigenin by using masspectrometry applying relevant standards for detection.

CONCLUSION: The traditionally claimed smooth muscle-relaxing effect of the roots of Taverniera abyssinica A.Rich is essentially due the three isolated and purified the two isoflavones formononetin, afrormosin as well as the metoxyisoflavone tectorigenin, along with possibly other not yet purified bioactive substances, however with similar smooth muscle-relaxing properties.