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- Jansson, Kjell, 1958-
(författare)
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Intraperitoneal microdialysis : technique and results
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microdialysis has recently developed from a laboratory research method of animals to a useful clinical tool to evaluate parameters suggesting tissue ischemia. It is now used in neurosurgery, plastic surgery and liver transplantation.Shock and multiple organ failure after surgery are rare but serious complications with a high mortality rate and splanchnic ischemia is an early and important step in this development. Splanchnic ischemia is leading to increased permeability of the intestinal mucosa and to activation of macrophages. Subsequent release of inflammatory mediators like cytokines initiates shock, which may result in multiple organ failure and death. The importance of splanchnic hypoxia/ischemia is investigated in these five studies in relation to activation of cytokines (intraperitoneal and systemic) during a normal recovery and in case of surgical complications after major gastrointestinal surgery.Postoperatively the metabolic substances, glucose, pyruvate, lactate and glycerol were analysed and the LP ratio was calculated using microdialysis intraperitoneally and subcutaneously. Two studies are focused on the activation of the immunologic system by measurement of the cytokines TNF-, IL-6 and IL-10 and the relationship between LP ratio and the cytokines. Three studies are describing the performance of intraperitoneal microdialysis, different responses depending on the site of measurement, the difference between intraperitoneal and subcutaneous measurements and normal values in postoperative gastrointestinal surgery. Patients with clinical complications are described separately.No adverse effects of the intraperitoneal measurement technique were seen. An increase of the intraperitoneal LP ratio and decrease of glucose were in several cases preceding clinical complications. Intraperitoneal LP ratio, glucose and cytokines were higher in the abdominal cavity compared to subcutaneous and systemic measurements in a normal postoperative recovery. An intraperitoneal correlation between TNF-a and the LP ratio was found. Intraperitoneal concentrations of the cytokines and the LP ratio were decreasing in parallel during a normal postoperative recovery.The intraperitoneal inflammatory response is higher, during a normal postoperative recovery as well as in patients suffering from complications, compared to systemic findings, emphazising the importance of the gastrointestinal tract as the source of early immunological reactions postoperatively. IPM enables safe and sensitive analysis of glucose, pyruvate, lactate and glycerol from the intraperitoneal organs measured in the intraperitoneal fluid.Measurement of the LP ratio with microdialysis seems to detect early splanchnic hypoxia/ischemia that correlates to the intraperitoneal inflammation. IPM may have a future as an important clinical tool for monitoring patients at risk of developing postoperative surgical complications.
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| 2. |
- Oikonomakis, Ioannis, 1977-
(författare)
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Anastomotic leakage in colorectal surgery : early diagnosis and treatment with stent
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year inn Sweden more than 6000 individuals are diagnosed with colorectal cancer and more than 5000 operations are performed. Anastomotic leakage (AL) is the most dreaded complication in colorectal surgery and has a great impact on postoperative morbidity and mortality. In Study I, an iatrogenic rectal perforation was performed on an experimental group of pigs, in order to imitate AL and compared with a control group which had a sham operation over a 10-hours follow-up with intraperitoneal microdialysis (IPM) and cytokines. Glucose levels were lower in the experimental group at 4 hours and lactate and lactate/pyruvate ratios (L/P) were higher in the experimental group at 7 hours. Intraperitoneal (IP) Interleukine 6 (IL6) and Interleukine 10 (IL10) were higher in the experimental group at 10 hours and blood IL6 was higher in the experimental group at 4 hours. IPM and cytokines thus seem to react early after rectal perforation. Study II was a prospective observational study in which 7 patients with AL after surgery were compared with 13 patients without complications during the first 7 postoperative days with IPM, and intravenous and IP cytokines. In patients who later developed AL, IP lactate and L/P were higher immediately after surgery, while glycerol levels were lower. At the anastomosis higher L/P in AL patients were found after the fifth postoperative day. Intravenous and IP IL6 was higher in the leakage group. In Study III, mRNA expression in blood was analyzed in an animal model designed to imitate AL. Significantly increased levels of 276 genes were found and 11 of the 48 genes which coded for a known protein were highly up-regulated.In Study IV, the metabolic effects of a fully covered self-expandable metal stent (FCSEMS) over a colorectal anastomosis were investigated with IPM, after laparotomy, colon resection and anastomosis with stent. Lactate and L/P rise at the oral part of the anastomosis were significantly higher, while glucose showed a small tendency toward numerically declining values. At the distal part of the anastomosis glucose decreased significantly after the resection but did not reach zero. Lactate increased significantly while L/P slightly increased. This suggest that hypermetabolism occurs in the intestinal ends next to the resectate, but even a start of hypoxemia cannot be excluded after the placement of a FCSEMS.
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| 3. |
- Sadeghi, Mitra, 1982-
(författare)
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Resuscitative endovascular balloon occlusion of the aorta : Physiology and clinical aspects of an emerging technique
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic hemorrhagic shock is a major cause of death worldwide. Patients enter the fatal triad of hypothermia, acidosis and coagulopathy and die quickly due to cardiovascular collapse. Ideally, procedures should be performed at the injury scene to prevent this fatal event. Unfortunately, intervention cannot be performed as soon as is needed and time to intervention becomes the enemy of survival. Hemorrhage control until definitive repair can possibly save lives. Hemorrhage from the extremities can be controlled by external pressure but severe hemorrhage from thoracic, abdominal or pelvic cavities, called non-compressible torso hemorrhage, requires internal hemorrhage control. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) uses an endovascular balloon that is inserted into the aorta using minimally invasive methods and is inflated to increase perfusion pressure and avoid cardiovascular collapse, providing a bridge to intervention. REBOA is hypothetised to increase central blood pressure but cause ischemia reperfusion injury below the occlusion level. The purpose of this thesis was to investigate the general impact of REBOA on physiology, metabolism, inflammatory response in normovolemia and hemorrhage. Investigation was conducted through clinical and experimental models.Study I was a multicentre cohort study of patients with traumatic hemorrhagic shock who received REBOA. Ninety-six patients were included, with an overall mortality of 56% and with no major complications from REBOA use. REBOA was used in a continuous and non-continuous fashion depending on the patients’ level of hypovolemia.Study II and the following three studies were animal experimental studies. Study II was a randomized control study in pigs to evaluate physiological, metabolic, inflammatory and end-organ function in a normovolemic state. It was demonstrated that REBOA increased central blood pressure but caused ischemic insult.Study III, a randomised controlled experimental model in pigs. Investigation was made to examine the possibility of titrating blood pressure with partial occlusion and investigate if partial occlusion reduced the ischemic insult. Partial REBOA could be achieved in this study and the ischemia reperfusion injury was less pronounced in partial occlusion than total. However, the difficulty regarding how to determine partial occlusion in a clinical setting remained.Study IV was therefore an experimental study conducted to compare the different methods of determining partial occlusion and detect the best correlation to organ perfusion. The following variables were compared to oxygen consumption: end-tidal carbon dioxide, aortic blood flow, superior mesenteric blood flow and femoral mean pressure. The study revealed that end-tidal carbon dioxide correlates best to organ perfusion.
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| 4. |
- Seilitz, Jenny, 1978-
(författare)
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The gastrointestinal tract in cardiac anaesthesia and intensive care : Clinical and experimental studies
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastrointestinal (GI) complications after cardiac surgery have a substantial impact on outcome. The aims were to investigate the frequency of, and methods for detecting, GI dysfunction after cardiac surgery and its relation to outcome, and the impact of vasoactive drugs on the GI tract in experimental cardiogenic shock. Paper I investigated the intraabdominal metabolism, using intraperitoneal microdialysis, during and after routine cardiac surgery in six patients. The results imply that, even during a normal perioperative course, the GI tract may be subjected to a subclinical anaerobic state. In Paper II the impact of stepwise reductions of cardiac output (CO) on the metabolism and circulation in the GI tract was studied in anaesthetised pigs using cardiac tamponade (n=6) or partial inflation of a caval vein balloon (n=6). The two models had similar haemodynamic effects and the intraabdominal metabolism became increasingly anaerobic when the CO was reduced by 50%. In Paper III the caval vein balloon model was utilised to examine the GI effects of two inodilators (levosimendan and milrinone) and two vasoconstrictors (vasopressin and norepinephrine) at 40% CO reduction (n=7/group). Negligible splanchnic vasodilation by the inodilators in fixed low CO, and possible GI specific side effects of high dose vasopressors, were demonstrated. Paper IV included 501 cardiac surgery patients assessed using the Acute Gastrointestinal Injury (AGI) grade. Only 32.7% were asymptomatic during the first three postoperative days. At least GI dysfunction, i.e. AGI grade ≥2, developed in 2.2% and was associated with more complex surgeries and higher postoperative frequencies of GI complications and mortality. In Paper V a biomarker for enterocyte damage, intestinal fatty acid-binding protein (IFABP), was investigated in relation to AGI grade. The group with AGI ≥2 (n=11) was compared to a matched group without GI symptoms (n=22). An I-FABP concentration in the fourth quartile on day one was associated with higher frequencies of organ dysfunction and 365-day mortality. In conclusion, this thesis provides evidence for an association between intraoperative GI injury, postoperative GI dysfunction and manifest complications, and that the effects of inodilators and vasoconstrictors must be considered.
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| 5. |
- Skoog, Per, 1975-
(författare)
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On the metabolic consequenses of abdominal compartment syndrome
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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