Metalloporphyrins, used for HO-1 inhibition, themselves affect hepatic microcirculation, liver function, and hepatocellular integrity.

BACKGROUND: Metalloporphyrins (MPs) are broadly used in the studies of the role of the heme oxygenase (HO)-1 system in different stress models. However, possible side effects of the MP administration itself have to be further investigated. METHODS: Sin IV mesoporpyhrin IX (SnMP; 10 micromol/kg body weight), tin protoporpyhrin IX (SnPP; 50 micromol/kg body weight), or chromium mesoporpyhrin IX (CrMP; 40 micromol/kg body weight) were administered to Sprague-Dawley rats (each group, n=5). The hepatic microcirculation was assessed by intravital microscopy (IVM). Blood samples were taken and the activity of HO-1 inhibition was measured by the determination of bilirubin accumulation after bile duct ligation. RESULTS: CrMP administration led to a decrease in mean arterial pressure. CrMP induced a marked hemolysis, a significant decrease of sinusoidal diameter and blood flow, and a marked inflammatory response. SnMP decreased sinusoidal diameters; however, this was compensated by an increase of sinusoidal red blood cell velocity. SnPP, but not SnMP, led to an increase of the number of nonperfused sinusoids. SnPP and CrMP revealed a two-fold increase in aspartite aminotransferase values after the completion of the IVM. The administration of MPs led to a 40%-50% decrease in the levels of conjugated bilirubin therapy, indicating that they actually inhibit HO-1 activity. CONCLUSIONS: The administration of MPs affects both the systemic macrohemodynamics and the hepatic microcirculation. As SnMP displayed the smallest number of side effects, this MP can be recommended for the studies of the HO-1 action on the liver microcirculation.

Indocyanine green disappearance rate is the most useful marker for liver resection.

BACKGROUND/AIMS: Non-invasive measurement of indocyanine green plasma disappearance rate (PDR(ICG)) is supposed to be an accurate liver function parameter. However, its value compared to conventional markers like bilirubin and prothrombin time (PT) is unclear. The authors therefore prospectively determined PDR(ICG) and bilirubin and PT and recorded the clinical course after liver resection. METHODOLOGY: Ninety-six patients underwent liver resection. Three patients died due to liver failure. Twenty patients (21%) developed signs of liver dysfunction. Receiver operating curve (ROC) analysis was performed to assess the value of each parameter to detect postoperative liver failure and dysfunction. RESULTS: PDR(ICG) and PT but not bilirubin preoperatively differentiated between patients with and without cirrhosis. In cirrhosis, PDR(ICG) patients did not recover to preoperative baseline values. ROC analysis revealed that PDR(ICG) [area under the curve (AUC): 0.867] did significantly better indicate postoperative liver dysfunction than bilirubin (AUC: 0.633) and PT (AUC: 0.570). CONCLUSIONS: PDR(ICG) should be measured preoperatively and daily after liver resection in patients at risk (underlying liver disease, resections > 30% standard liver volume).

Central venous oxygen saturation does not correlate with the venous oxygen saturation at the surgical site during abdominal surgery.

INTRODUCTION: Measurement of central venous oxygen saturation has become a surrogate parameter for fluid administration, blood transfusions and treatment with catecholamines in (early) goal directed therapy in the treatment of acute septic patients. These strategies are not easily transferred to the postoperative management of abdominal surgery due to the different conditions in surgical patients. MATERIALS AND METHODS: A study population of 15 patients (8 females/7 males) underwent elective major abdominal surgery: 6 gastrectomies, 5 major liver resections and 4 lower anterior rectum resections. Surgery was performed for primary or secondary malignancy. The patients' age was 65.4+/-12.7 (mean+/-standard deviation, range 44-84, median 62) years. Blood samples were taken intraoperatively from indwelling central venous lines as well as from draining veins at the surgical site. Blood gas analyses to determine the oxygen saturations were performed immediately. All patients were operated in standardized general anesthesia including epidural analgesia and in a balanced volume status. RESULTS: Central venous oxygen saturations and oxygen saturations in blood from the draining veins of the surgical site showed a wide range with high intra- and interindividual differences intraoperatively. Overall, at most time points no correlation between the two oxygen saturations could be detected in three operation types. A significant correlation was only observed at one time point during liver resections. CONCLUSION: Our results show a lack of correlation between central venous oxygen saturations and oxygen saturations in the draining veins of the surgical site during major abdominal surgery. Measurement of central venous oxygen saturations does not seem to be a good surrogate for the local oxygen supply in the field of interest in major abdominal surgery even under standardized conditions.

Indocyanine green elimination but not bilirubin indicates improvement of graft function during MARS therapy.

Measurement of indocyanine green plasma disappearance rate (PDR(ICG)) has been suggested as a meaningful liver function parameter. However, there are only very limited data concerning its value in the monitoring of graft dysfunction (GDF) and primary non-function (PNF) especially during molecular absorbent recirculating system (MARS) therapy. This study was therefore performed to evaluate the diagnostic accuracy to detect and monitor GDF with the measurement of the PDR(ICG) in direct comparison with conventional markers like bilirubin and prothrombin time (PT). Of the 19 liver recipients, four patients with GDF and two patients with PNF were treated with 38 MARS cycles. Only PDR(ICG) did reliably indicate liver function between patients with GDF/PNF and patients with sufficient graft function who served as controls. Moreover, receiver operating characteristic analysis showed the highest areas under the curve (AUC) for PDR(ICG) (AUC(PDRICG max): 0.840, AUC(PDRICG max): 0.822), followed by bilirubin (AUC(bilirubin): 0.528) and PT (AUC(PT): 0.546). In contrast to the decrease of the serum bilirubin concentration due to MARS, a noticeable improvement of PDR(ICG) was evident only in patients with GDF. Patients with acute fulminant failure and PNF had significantly lower PDR(ICG) values, which did not improve even during continuous MARS treatments. Conclusively, monitoring of PDR(ICG) is superior to bilirubin and PT measurements to determine the graft function especially in patients with PNF and GDF undergoing MARS therapy.

The standardized surgical approach improves outcome of gallbladder cancer.

BACKGROUND: The objective of this study was to examine the extent of surgical procedures, pathological findings, complications and outcome of patients treated in the last 12 years for gallbladder cancer. METHODS: The impact of a standardized more aggressive approach compared with historical controls of our center with an individual approach was examined. Of 53 patients, 21 underwent resection for cure and 32 for palliation. RESULTS: Overall hospital mortality was 9% and procedure related mortality was 4%. The standardized approach in UICC stage IIa, IIb and III led to a significantly improved outcome compared to patients with an individual approach (Median survival: 14 vs. 7 months, mean+/-SEM: 26+/-7 vs. 17+/-5 months, p = 0.014). The main differences between the standardized and the individual approach were anatomical vs. atypical liver resection, performance of systematic lymph dissection of the hepaticoduodenal ligament and the resection of the common bile duct. CONCLUSION: Anatomical liver resection, proof for bile duct infiltration and, in case of tumor invasion, radical resection and lymph dissection of the hepaticoduodenal ligament are essential to improve outcome of locally advanced gallbladder cancer.

Liver tissue concentrations of levofloxacin after single intravenous administration of 500 mg for antibiotic prophylaxis in liver surgery.

High concentrations of levofloxacin in soft tissues and body fluids, including gallbladder and bile, have been repeatedly reported, but no study on its penetration into human liver tissue after single-shot application has yet been published. Levofloxacin 500 mg was administered intravenously to 28 patients scheduled for liver resection. Blood samples were taken after the end of infusion and at the time of liver resection; concomitantly, a tissue specimen was also obtained. Serum concentrations (mean+/-standard deviation) 10 min after the end of infusion were 6.59+/-1.72 microg/mL and decreased only slightly throughout the operation. At the time of liver resection, levofloxacin concentrations in liver tissue were 18.14+/-5.44 microg/g with corresponding serum concentrations of 4.84+/-1.37 microg/mL. The tissue/serum ratio (3.72+/-0.73 at the time of resection) was nearly constant over the sampling period ranging from 0.4 h to 3.8 h after the end of infusion, indicating a fast distribution of levofloxacin into the liver tissue. The tissue concentrations showed a significant correlation with serum concentrations and an inverse correlation with the grade of steatosis but not cirrhosis. Infectious post-operative complications were not observed. Levofloxacin penetrates into liver tissue exceptionally well and fast and is therefore a good candidate for antibiotic prophylaxis before invasive hepatobiliary procedures such as liver surgery as well as for treatment of biliary tract infections caused by levofloxacin-susceptible microorganisms.

Gender-specific differences in sex hormones and cytokines in patients undergoing major abdominal surgery.

PURPOSE: Experimental and clinical evidence suggests that gender has a profound influence on outcome after inflammatory hits caused by such events as trauma. We conducted this prospective clinical study to evaluate the influence of gender on the release of pro- and anti-inflammatory cytokines in the circulation and after lipopolysaccharide (LPS) ex vivo stimulation. We also measured the course of sex hormones in the acute phase response after surgery and assessed their correlation with cytokine release. METHODS: We measured the serum concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), testosterone, estradiol, prolactin, procalcitonin, and sex hormone-binding globulin, as well as the release of IL-6, TNF-alpha, and IL-10 after LPS ex vivo stimulation of whole blood in 26 patients without complications after major or minor abdominal surgery. RESULTS: There was a gender-specific pattern of decreasing testosterone concentrations in men and increasing testosterone concentrations in women. Increasing estradiol concentrations were seen in both men and women. The ex vivo-stimulated and systemic IL-6, IL-8, IL-10, and TNF-alpha cytokine release was not gender specific. There was a marked prolactin peak after the induction of anesthesia before the commencement of surgery. CONCLUSION: In contrast to the release of pro- and anti-inflammatory cytokines, sex hormones show a gender-specific pattern during the acute phase response 1 week after abdominal surgery.

Comparison between a general and a disease-specific health-related quality-of-life questionnaire in patients after pancreatic surgery.

BACKGROUND/PURPOSE: The aim of this study was to compare the short-form (SF-) 36 as a general instrument and the gastrointestinal quality of life index (GIQLI) as a disease-specific instrument in patients after pancreatic surgery. METHODS: The questionnaires were sent to patients receiving pancreatic surgery over a time period of three years. Patients were compared with a normal population completing the SF-36 or reported normal-population values for the GIQLI. Agreement between the instruments was analyzed using Bland Altman plots. RESULTS: A total of 98 patients were included, most of them undergoing a Whipple procedure (86%). The most frequent complaints were meteorism, obstipation, stool urgency, and stress incontinence in 9% of the patients. Whereas in almost every domain of the SF-36 the HRQL was impaired in comparison to the normal population, the GIQLI showed differences in only the domain emotions. Neither the SF-36 nor the GIQLI was different between patients with early and advanced cancer stages. The SF-36 had no agreement with the GIQLI. CONCLUSIONS: The results of HRQL studies depend on the instruments which were used. Whereas a general instrument may detect factors such as comorbidity more accurately, disease-specific instruments have the advantage of better clinical interpretability.

Changes in acid-base balance following bolus infusion of 20% albumin solution in humans.

OBJECTIVE: To evaluate changes in acid-base balance following bolus infusions of a 20% albumin solution. DESIGN AND SETTING: Randomized prospective study in a university hospital. PATIENTS AND PARTICIPANTS: Two groups of eight patients each undergoing gynecological surgery. INTERVENTIONS: Patients were randomly assigned to receive either 0.9% saline or lactated Ringer's solution. At the end of surgery two boluses of 0.5 g/kg body weight of a 20% albumin solution were administered. Arterial blood gases, electrolytes, and total protein were measured. The strong ion difference and the amount of weak plasma acid were calculated. pH and titratable acidity of the 20% albumin solution were determined. MEASUREMENTS AND RESULTS: The infusion of a 20% albumin solution resulted in a significant decrease in pH from 7.284 to 7.262 in the saline group and from 7.422 to 7.394 in the Ringer's group. In both groups the 20% albumin solution caused an increase in strong ion difference and an increase in the amount of weak plasma acid. The observed changes in serum bicarbonate concentration were in good agreement with the changes in strong ion difference and the amount of weak plasma acid. The 20% albumin solution possessed a pH of 6.95 and a titratable acidity of 8.5 [corrected] mEq/l. CONCLUSIONS: According to the Stewart approach, the observed changes in acid-base balance are the net result of the two opposing effects of the strong ion difference and the amount of weak plasma acid. Alternatively, the acidifying effect of the 20% albumin solution may stem from the titratable acid content of the solution.

Change remains--paradigm shifts in modern surgery.

This article aims to describe underlying principles of paradigm shifts in clinical medicine by means of analysis of typical examples. Retrospectively, profound shifts of ruling paradigms can be shown in diverse fields such as outcome research, in the redefining of patients' and doctor's autonomies, in the challenges presented by consumer medicine and the free market economy. This has provoked controversy between doctors, patients and the community. The judgement on whether recent shifts in paradigms in medicine have improved the health care delivered today is by no means uncontroversial. Aiming to demonstrate how shifts of paradigms in medicine occur and what consequences can result from such shifts we reflect on the works of Thomas S. Kuhn, the eminent philosopher of science. An analysis of his theories lends important insight into the observed shifts in paradigms.

Short- and long-term outcome and health-related quality of life after severe peritonitis.

The short-form survey 36 (SF-36) is a useful and qualified instrument for measurement of health-related quality of life (HRQL) in critically ill patients. In this study we determined hospital mortality, hospital discharge mortality, and HRQL of 136 patients with severe peritonitis admitted to our hospital between January 1996 and May 1999. Hospital mortality was 46% and hospital discharge mortality 10%. The HRQL-questionnaire was answered completely by 97% of the patients who where still alive during the study period. Age significantly reduced physical functions in these patients. Patients with cancer had significant impaired physical functions in the first year, followed by significant impairment in emotion. Generally, patients who survived peritonitis and had no malignancy had an acceptable outcome when compared to individuals from a large normal population. Health-related quality of life measurements in peritonitis patients justify the high efforts in the treatment of these patients, but they do not provide a useful tool in the outcome prediction for individual patients.