Kassiani Theodoraki

Anesthetic and perioperative management of adult transplant recipients in nontransplant surgery.

E ach year, .16,000 patients receive whole organ transplants in the United States alone, and this number is expected to increase yearly (1). Because the 1-yr survival rate for most transplant recipients is approaching 80%–90% and continues to improve annually, an increasing number of patients who received a transplant present for either elective or emergency nontransplant surgery (2–4). Therefore, anesthesiologists and surgeons are often required to manage transplant recipients in hospitals that are not otherwise involved in transplantation procedures. The general considerations related to any transplant recipient are the physiological and pharmacological problems of allograft denervation, the side effects of immunosuppression, the risk of infection, and the potential for rejection.

Global Consequences of Liver Ischemia/Reperfusion Injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organs post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion.

Effect of mesocaval shunt on survival of small-for-size liver grafts: Experimental study in pigs

Segmental liver grafts with a calculated ideal liver weight (CILW) less than 40% may be associated with portal flow-related injuries and primary dysfunction. This study evaluated the effect of mesocaval shunts on the survival of grafts with a CILW less than 20%. Sixteen pigs underwent orthotopic transplantation of segmental liver grafts with a CILW less than 20%. In eight animals (study group), transplantation was combined with a mesocaval shunt, and eight animals served as controls without a mesocaval shunt. Liver function, systemic hemodynamics, portal vein pressure, intracranial pressure, and cerebral perfusion pressure were assessed postoperatively. The controls showed a rapid impairment of liver function reflected by a significant elevation in aspartate aminotransferase, international normalized ratio, bilirubin, and intracranial pressure and a decrease in cerebral perfusion pressure compared with the study group (P <0.05). Mesocaval shunts showed protective effects on grafts with CILW less than 20% and may have a clinical role in the salvage of small-for-size liver grafts.

IRON CHELATION FOR AMELIORATION OF LIVER ISCHEMIA-REPERFUSION INJURY

Liver resections are frequently associated with significant ischemia-reperfusion (I-R) injury of the liver remnant. The aim of this study was to investigate whether deferoxamine (DFO) can ameliorate I-R injury during major hepatectomies performed under vascular exclusion of the liver in a porcine model. Twelve female domestic pigs were divided into control (n = 6) and DFO treatment (n = 6) groups and subjected to 150 min. liver ischemia followed by 70% hepatectomy and 24 hours reperfusion. Pigs in the DFO group received a continuous intravenous infusion of 100 mg/kg DFO. Liver remnant injury was evaluated by liver function tests, hepatic histology as well as serum and liver tissue malondialdehyde (MDA) concentrations. Deferoxamine-treated animals had reduced total bilirubin, γ-glutamyl transferase and ammonia levels as well as hepatocyte necrosis and oxidative injury. In a subsequent randomized clinical trial using DFO for I-R protection during major liver surgery, preliminary results revealed amelioration of hepatocellular damage, oxidative and inflammatory serum markers and apoptotic response in liver remnant biopsies.

Anesthetic Considerations in Hepatectomies under Hepatic Vascular Control

Background. Hazards of liver surgery have been attenuated by the evolution in methods of hepatic vascular control and the anesthetic management. In this paper, the anesthetic considerations during hepatic vascular occlusion techniques were reviewed. Methods. A Medline literature search using the terms “anesthetic,” “anesthesia,” “liver,” “hepatectomy,” “inflow,” “outflow occlusion,” “Pringle,” “hemodynamic,” “air embolism,” “blood loss,” “transfusion,” “ischemia-reperfusion,” “preconditioning,” was performed. Results. Task-orientated anesthetic management, according to the performed method of hepatic vascular occlusion, ameliorates the surgical outcome and improves the morbidity and mortality rates, following liver surgery. Conclusions. Hepatic vascular occlusion techniques share common anesthetic considerations in terms of preoperative assessment, monitoring, induction, and maintenance of anesthesia. On the other hand, the hemodynamic management, the prevention of vascular air embolism, blood transfusion, and liver injury are plausible when the anesthetic plan is scheduled according to the method of hepatic vascular occlusion performed.

Ischemia as a possible effect of increased intra-abdominal pressure on central nervous system cytokines, lactate and perfusion pressures.

IntroductionThe aims of our study were to evaluate the impact of increased intra-abdominal pressure (IAP) on central nervous system (CNS) cytokines (Interleukin 6 and tumor necrosis factor), lactate and perfusion pressures, testing the hypothesis that intra-abdominal hypertension (IAH) may possibly lead to CNS ischemia.MethodsFifteen pigs were studied. Helium pneumoperitoneum was established and IAP was increased initially at 20 mmHg and subsequently at 45 mmHg, which was finally followed by abdominal desufflation. Interleukin 6 (IL-6), tumor necrosis factor alpha (TNFa) and lactate were measured in the cerebrospinal fluid (CSF) and intracranial (ICP), intraspinal (ISP), cerebral perfusion (CPP) and spinal perfusion (SPP) pressures recorded.ResultsIncreased IAP (20 mmHg) was followed by a statistically significant increase in IL-6 (p = 0.028), lactate (p = 0.017), ICP (p < 0.001) and ISP (p = 0.001) and a significant decrease in CPP (p = 0.013) and SPP (p = 0.002). However, further increase of IAP (45 mmHg) was accompanied by an increase in mean arterial pressure due to compensatory tachycardia, followed by an increase in CPP and SPP and a decrease of cytokines and lactate.ConclusionsIAH resulted in a decrease of CPP and SPP lower than 60 mmHg and an increase of all ischemic mediators, indicating CNS ischemia; on the other hand, restoration of perfusion pressures above this threshold decreased all ischemic indicators, irrespective of the level of IAH.

Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms.

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect.

Association between biliary complications and technique of hilar division (extrahepatic vs. intrahepatic) in major liver resections.

BackgroundDivision of major vascular and biliary structures during major hepatectomies can be carried out either extrahepatically at the porta hepatic or intrahepatically during the parenchymal transection. In this retrospective study we test the hypothesis that the intrahepatic technique is associated with less early biliary complications.Methods150 patients who underwent major hepatectomies were retrospectively allocated into an intrahepatic group (n = 100) and an extrahepatic group (n = 50) based on the technique of hilar division. The two groups were operated by two different surgical teams, each one favoring one of the two approaches for hilar dissection. Operative data (warm ischemic time, operative time, blood loss), biliary complications, morbidity and mortality rates were analyzed.ResultsIn extrahepatic patients, operative time was longer (245 ± 50 vs 214 ± 38 min, p < 0.05) while the overall complication rate (55% vs 52%), hospital stay (13 ± 7 vs 12 ± 4 days), bile leak rate (22% vs 20%) and mortality (2% vs 2%) were similar compared to intrahepatic patients. However, most (57%) bile leaks in extrahepatic patients were grade II (leaks that required non-operative interventional treatment, while most (70%) leaks in the intrahepatic group were grade I (leaks that resolved and presented two injuries (4%) of the remaining bile ducts (p < 0.05).ConclusionIntrahepatic hilar division is as safe as extrahepatic hilar division in terms of intraoperative blood requirements, morbidity and mortality. The extrahepatic technique is associated with more severe bile leaks and biliary injuries.

The introduction of a simple maneuver to reduce the risk of postoperative bleeding after major hepatectomies

BACKGROUND/PURPOSE In major hepatectomies, postoperative increases in central venous pressure (CVP) may cause suture failure and massive bleeding. The aim of our study is to test the application of an intraoperative maneuver to reduce the risk of postoperative bleeding. METHODS Our study included 172 consecutive patients who had major liver resection with selective hepatic vascular exclusion and sharp transection of the liver parenchyma. An intraoperative maneuver (5 s occlusion of the hepatic vein) was applied in an alternating way, and the patients were assigned to two groups: Cohort A (n = 86), that was granted the maneuver, and Cohort B (n = 86), that was used as a control group. RESULTS In Cohort A, application of the maneuver was successful in demonstrating bleeders under low CVP levels. Cohort A had lower rate of massive bleeding requiring emergency reoperation (2.3 vs 5.8%, P = 0.049), less postoperative blood transfusions (13 vs 24%, P = 0.042), lower morbidity (20 vs 35%, P < 0.045) and shorter hospital stay compared to Cohort B. CONCLUSIONS Hepatectomies conducted under low CVP are prone to postoperative hemorrhage which can be prevented if the final bleeding control is performed under high pressure in the hepatic veins. Application of our testing maneuver effectively unmasked previously undetectable bleeding veins.