To Örebro University

BACKGROUND: Anastomotic leakage is the most serious and unwelcome complication in rectal surgery. It has a great impact on postoperative morbidity and mortality. In this pilot study, changes of mRNA expression in blood were analyzed in an animal model designed to imitate anastomotic leakage.

MATERIALS AND METHODS: Twelve pigs were randomized into two groups: A sham-operated control group and an experimental group in which iatrogenic rectal perforation was performed. The changes in the mRNA expression at 4 hours after creating the perforation were studied. Microarray analysis was performed using Gene Chip whole porcine genome array. mRNA expression of 19,124 genes was investigated.

RESULTS: Significantly increased levels of genes with a fold change greater than 2 were found, including 276 coding for unknown proteins and 48 coding for known proteins. Eleven of those which coded for known proteins were up-regulated with a fold change >4.

CONCLUSION: Eleven known genes were highly up-regulated after rectal perforation. These genes were mainly involved in inflammatory response, intracellular signaling and cell membrane regulation. Their corresponding proteins might potentially be clinical biomarkers of anastomotic leakage and should be evaluated in further clinical studies.

Background: Partial resuscitative endovascular balloon occlusion of the aorta (REBOA) is a concept of aortic occlusion to reduce ischemic organ injuries below the occlusion level. It is, however, difficult to determine when the occlusion is partial in clinical settings. End-tidal carbon dioxide (ETCO2) is an aerobic metabolite and its production is reduced during ischemia. The aim of this study was to investigate if ETCO2 can be used as an estimate of the degree of aortic occlusion and distal organ metabolism during normovolemia and hemorrhagic shock in a porcine model.

Methods: Nine pigs (25-32 kg) were anesthetized and surgically prepared. Zone 1 aortic occlusion by 33%, 66% and 100% of aortic blood flow was induced during normovolemia and controlled hemorrhagic grade IV shock. Hemodynamic and respiratory variables including ETCO2, aortic and mesenteric blood flow, femoral arterial blood pressure and blood gases were measured. Oxygen consumption and carbon dioxide production were correlated to measures of partial occlusion used in previous studies.

Results: Aortic occlusion gradually lowered distal blood flow and pressure, whereas ETCO2, oxygen consumption and carbon dioxide production decreased at 66 % and 100 % of aortic occlusion. End-tidal carbon dioxide, and blood flow of the superior mesenteric artery and abdominal aorta, strongly correlated to oxygen consumption and carbon dioxide production, whereas femoral blood pressure did not.

Conclusion: End-tidal carbon dioxide may be used as an estimator of partial REBOA and distal organ metabolism in both normovolemia and hemorrhagic shock.

EndoVascular and Hybrid Trauma Management (EVTM) is an emerging concept for the early treatment of trauma patients using aortic balloon occlusion (ABO), embolization agents and stent grafts to stop ongoing traumatic bleeding. These techniques have previously been implemented successfully in the treatment of ruptured aortic aneurysm.

We describe our very recent experience of EVTM using ABO in bleeding patients and lessons learned over the last 20 years from the endovascular treatment of ruptured abdominal aortic aneurysms (rAAA). We also briefly describe current knowledge of ABO usage in trauma.

A small series of educational cases in our hospital is described, where endovascular techniques were used to gain temporary hemorrhage control. The methods used for rAAA and their applicability to EVTM with a multidisciplinary approach are presented.

Establishing femoral arterial access immediately on arrival at the emergency room and use of an angiography table in the surgical suite may facilitate EVTM at an early stage. ABO may be an effective method for the temporary stabilization of severely hemodynamically unstable patients with hemorrhagic shock, and may be useful as a bridge to definitive treatment of the bleeding patients.

EVTM, including the usage of ABO, can be initiated on patient arrival and is feasible. Further data need to be collected to investigate proper indications for ABO, best clinical usage, results and potential complications. Accordingly, the ABOTrauma Registry has recently been set up. Existing experiences of EVTM and lessons from the endovascular treatment of rAAA may be useful in trauma management.

Purpose: The radiocephalic arteriovenous fistula (RC-AVF) has significant failure rates due to occlusions and failure to mature. The size and quality of the veins are considerable limiting factors for the procedure. The aim of this pilot study was to describe the No-Touch technique (NTT) to create RC-AVF and present the results up to 1 year of follow-up.

Methods: Thirty-one consecutive patients who were referred for surgery for a RC-AVF were included (17 men, mean age 63 years, range 35-84) and operated by NTT where the vein and artery were dissected with a tissue cushion around it. Twenty-two patients had small veins or arteries (<= 2 mm), 12 patients had a small cephalic vein (<= 2 mm), and the mean distal cephalic vein diameter was 2.4 mm (range 1.0-4.1 mm).

Results: Technical surgical success and immediate patency were obtained in all patients. Clinical success was achieved in 23 of the 27 (85%) patients who required hemodialysis. The proportion of primary patency at 30 days and 6 months was 84% and 64%, respectively. Secondary patency at 30 days and 6 months was 97% and 83%, respectively. At 1-year follow-up, primary patency was 54% and secondary patency was 80%. There was no major difference in patency due to preoperative vein diameter.

Conclusions: The results of this study indicate that NTT can be used for primary radio-cephalic fistula surgery with very good results. This method offers the potential to create a RC-AVF in patients who are not usually considered appropriate for a distal arm fistula due to a small cephalic vein.

Objective: This study aims to investigate the abdominal metabolic response and circulatory changes after decompression of intra-abdominal hypertension in a porcine model. Design: Prospective study with controls. Setting: University hospital research laboratory.

Subjects: Three-months old domestic pigs of both sexes. Interventions: The animals were anesthetised and ventilated. Nine animals had a pneumoperitoneum-induced intra-abdominal hypertension of 30 mmHg for six hours. Twelve animals had corresponding intra-abdominal hypertension for four hours followed by decompression and were monitored for another two hours.

Measurements and Main Results: Hemodynamics, urine output and arterial blood samples were analysed. Laserdoppler measured mucosal blood flow and urine output decreased with pressure induction and showed a statistically significant restitution after decompression. Glucose, glycerol, lactate and pyruvate concentrations and lactate-pyruvate (l/p) ratio were measured by microdialysis. Both groups developed distinct metabolic changes intraperitoneally at pressure induction including an increased l/p ratio as signs of organ hypoperfusion. In the decompression group the intraperitoneal l/p ratio normalised during the second decompression hour, indicating partially restored perfusion.

Conclusions: Decompression after four hours of intra-abdominal hypertension results in restoration of intestinal blood flow and normalised intraperitoneal metabolism.

Background: To investigate the effects of supraceliac aortic balloon occlusion (ABO) and superior mesenteric artery (SMA) occlusion on abdominal visceral metabolism in an animal model using intraperitoneal microdialysis (IPM) and laser Doppler flowmetry.

Methods: A total of 9 pigs were subjected to ABO and 7 animals were subjected to SMA occlusion for 1 hour followed by 3 hours of reperfusion. Seven animals served as controls. Hemodynamic data, arterial blood samples, urinary output, and intestinal mucosal blood flow (IBF) were followed hourly. Intraperitoneal (i.p) glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (lip) ratio were measured using IPM.

Results: Compared with the baseline, ABO reduced IBF by 76% and decreased urinary output. SMA occlusion reduced IBF by 75% without affecting urinary output. ABO increased the i.p lip ratio from 18 at baseline, peaking at 46 in early reperfusion. SMA occlusion and reperfusion tended to increase the i.p lip ratio, peaking at 36 in early reperfusion. ABO increased the i.p glycerol concentration from 87 mu M at baseline to 579 p,M after 3 hours of reperfusion. SMA occlusion and reperfusion increased The i.p glycerol concentration but to a lesser degree.

Conclusions: Supraceliac ABO caused severe hemodynamic, renal, and systemic metabolic disturbances compared with SMA occlusion, most likely because of the more extensive ischemia-reperfusion injury. The intra-abdominal metabolism, measured by microdialysis, was affected by both ABO and SMA occlusion but the most severe disturbances were caused by ABO. The i.p lip ratios and the glycerol concentrations increased during ischemia and reperfusion and may serve as markers of these events and indicate anaerobic metabolism and cell damages respectively.

Objective: To study the splanchnic metabolism and intestinal circulation in a porcine model with increased abdominal pressure.

Methods: In an experimental porcine study, performed under intravenous anaesthesia, five animals were subjected to gradually increasing intra-abdominal pressure (15 mmHg, 25 mmHg, and 35 mmHg) with pneumoperitoneum. Microdialysis and laser Doppler were the main outcome methods for monitoring the metabolic and circulatory changes.

Results: During stable anaesthesia and gradually increasing intra-abdominal pressure obtained by CO2-pneumoperitoneum, blood flow (microcirculation) was deprived and moderate signs of impaired splanchnic metabolism were recorded.

Conclusions: The model appears usable for studies of splanchnic metabolic consequences of intra-abdominal hypertension.

Objectives: This study aims to evaluate intra-peritoneal (ip) microdialysis after endovascular aortic repair (EVAR) of ruptured abdominal aortic aneurysm (rAAA) in patients developing intra-abdominal hypertension (IAH), requiring abdominal decompression.

Design: Prospective study.

Material and methods: A total of 16 patients with rAAA treated with an emergency EVAR were followed up hourly for intra-abdominal pressure (IAP), urine production and ip lactate, pyruvate, glycerol and glucose by microdialysis, analysed only at the end of the study. Abdominal decompression was performed on clinical criteria, and decompressed (D) and non-decompressed (ND) patients were compared.

Results: The ip lactate/pyruvate (l/p) ratio was higher in the D group than in the ND group during the first five postoperative hours (mean 20 vs. 12), p = 0.005 and at 1 h prior to decompression compared to the fifth hour in the ND group (24 vs. 13), p = 0.016. Glycerol levels were higher in the D group during the first postoperative hours (mean 274.6 vs. 121.7 mu M), p = 0.022. The IAP was higher only at 1 h prior to decompression in the D group compared to the ND group at the fifth hour (mean 19 vs. 14 mmHg).

Conclusions: lp l/p ratio and glycerol levels are elevated immediately postoperatively in patients developing IAH leading to organ failure and subsequent abdominal decompression.

Intra-abdominal hypertension (IAH) and the progression to abdominal compartment syndrome (ACS) are known complications of vascular and abdominal surgery, trauma, sepsis, and burns. ACS is associated with high mortality. In ACS, hypoperfusion, hypoxia, onset of inflammatory pathways and increased levels of oxygen reactive species are believed to cause tissue damage and initiate organ failure. Early detection of IAH is central in order to stop the pathological processes. Microdialysis is a method to determine extracellular metabolic changes through analysis of glucose, pyruvate, lactate and glycerol. Microdialysis is known to be feasible in the abdomen to detect early signs of postoperative complications. The ratio of lactate and pyruvate (l/p ratio) reflects the intracellular relationship between aerobic and anaerobic metabolism. Glycerol is elevated when cells have increased energy needs and in cell damage. Our hypothesis was that IAH and ACS cause early metabolic changes in the abdomen which could be determined by microdialysis, and possibly serve as clinical markers for organ failure due to IAH. In Paper I methodology was established using a porcine model with CO2 pneumoperitoneum. Using the model in Paper II and III, we showed that metabolic changes (elevated l/p ratio and glycerol) occurred early in the abdomen as IAH was induced and also restituted after decompression. Decrease in urine output, circulatory changes and impaired mucosal circulation indicated that the model mimicked ACS well. In a clinical study (Paper IV), patients that underwent endovascular surgery for rAAA and later needed decompression due to IAH with organ failure, had more pronounced early metabolic alterations than patients without severe IAH. In conclusion, early abdominal metabolic changes due to IAH are seen experimentally in a model and in patients after rAAA. These changes can be measured with microdialysis and they could, if the results are verified in further studies,be used as clinical markers for IAH and ACS.