Fibrinogen and albumin synthesis rates in major upper abdominal surgery.

Plasma fibrinogen and albumin concentrations initially decrease after abdominal surgery. On postoperative days 3-5 fibrinogen concentration returns to the preoperative level or even higher, while albumin stays low. It is not known if these altered plasma concentrations reflect changes in synthesis rate, utilization, or both. In particular a low albumin plasma concentration has often been attributed to a low synthesis rate, which is not always the case. The objective of this study was to determine fibrinogen and albumin quantitative synthesis rates in patients undergoing major upper abdominal surgery with and without intact liver size. Patients undergoing liver or pancreatic resection (n = 9+6) were studied preoperatively, on postoperative days 1 and 3-5. De novo synthesis of fibrinogen and albumin was determined; in addition, several biomarkers indicative of fibrinogen utilization were monitored. After hemihepatectomy, fibrinogen synthesis was 2-3-fold higher on postoperative day 1 than preoperatively. On postoperative days 3-5 the synthesis level was still higher than preoperatively. Following major liver resections albumin synthesis was not altered postoperatively compared to preoperative values. After pancreatic resection, on postoperative day 1 fibrinogen synthesis was 5-6-fold higher than preoperatively and albumin synthesis 1.5-fold higher. On postoperative days 3-5, synthesis levels returned to preoperative levels. Despite decreases in plasma concentrations, de novo synthesis of fibrinogen was markedly stimulated on postoperative day 1 after both hemihepatectomies and pancreatectomies, while de novo albumin synthesis remained grossly unchanged. The less pronounced changes seen following hepatectomies were possibly related to the loss of liver tissue.

Association of post-reperfusion syndrome and ischemia-reperfusion injury with acute kidney injury after liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is frequently observed after orthotopic liver transplantation (OLT) even in patients with previously normal renal function. In this study, we investigated the impact of factors such graft steatosis, post-reperfusion syndrome (PRS), and hepatic ischemia reperfusion injury (HIRI) on the development of AKI after OLT in adult patients. METHODS: We retrospectively examined consecutive adult patients who underwent OLT at our institution between July 2011 and June 2017. AKI was diagnosed based on the criteria proposed by the International Kidney Disease Improving Global Outcomes (KDIGO) workgroup. Peak aspartate aminotransferase (AST) level within 72 hours after OLT was used as a surrogate marker for HIRI. Graft steatosis was diagnosed by histopathological examination using specimens biopsied intraoperatively at the end of transplantation procedure and categorized as <10%, 10%-20%, 20%-30%, and ≥30% of hepatic steatosis. RESULTS: Out of 386 patients, 141 (37%) developed AKI (KDIGO stage 1:71 patients; stage 2:29 patients; stage 3:41 patients). Multivariable logistic regression analysis revealed that cold ischemic time (P = .012) and HIRI (P = .007) were independent risk factors for post-OLT AKI. Multivariable analysis also revealed that graft steatosis was associated with HIRI but not directly with AKI. PRS was not associated with HIRI or AKI in the multivariable analyses. CONCLUSION: Our results indicate that greater severity of liver graft injury during transplantation negatively affects renal function after OLT. As expected, the severity of liver graft steatosis contributes to accelerated liver injury occurring during the transplantation procedure.

Albumin mass balance and kinetics in liver transplantation.

BACKGROUND: In major abdominal surgery albumin is shifted from the circulation, presumably leaking into the interstitial space, contributing to a 30-40% decrease in plasma albumin concentration. During and after liver transplantation exogenous albumin is infused for volume substitution and to maintain plasma albumin concentration. Here we used liver transplantation as a model procedure for the study of albumin mass balance and kinetics during major abdominal surgery with albumin substitution. METHODS: Patients were studied during liver transplantation (n = 16), and until postoperative day 3 (POD 3) (n = 11). Cumulative perioperative albumin shift was assessed by mass balance of albumin and hemoglobin. Synthesis rates of albumin and fibrinogen were estimated by the flooding technique using deuterium-labeled phenylalanine. Albumin distribution was assessed by radioiodinated human serum albumin. RESULTS: At the end of surgery, 37 ± 17 g of albumin (p < 0.0001) had shifted from plasma, and this amount was stable until POD 3 (48 ± 33 g, p = 0.0017 versus baseline). There was 91 ± 37 g exogenous albumin infused peroperatively and another 47 ± 35 g was infused postoperatively until POD 3. Absolute synthesis rates of albumin and fibrinogen on POD 3 were 239 ± 84 mg/kg body weight/day and 33 mg/kg body weight/day (range 5-161), respectively. CONCLUSIONS: Albumin net leakage from plasma progressed until the end of surgery, and was then unaltered until POD 3. This is in contrast with the normalization of the cumulative albumin shift identified at day 3 after non-transplant major abdominal surgery. Liver synthesis of export proteins was high compared to reference values at the third postoperative day, suggesting rapid recovery of synthesis capacity. TRIAL REGISTRATION: Swedish Medical Product Agency, EudraCT 2015-002568-18. Registered on 15 July 2015.

Thromboelastometry: Relation to the severity of liver cirrhosis in patients considered for liver transplantation.

The severity of liver disease is assessed by scoring systems, which include the conventional coagulation test prothrombin time-the international normalized ratio (PT-INR). However, PT-INR is not predictive of bleeding in liver disease and thromboelastometry (ROTEM) has been suggested to give a better overview of the coagulation system in these patients. It has now been suggested that coagulation as reflected by tromboelastomety may also be used for prognostic purposes. The objective of our study was to investigate whether thrombelastometry may discriminate the degree of liver insufficiency according to the scoring systems Child Pugh and Model for End-stage Liver Disease (MELD).Forty patients with chronic liver disease of different etiologies and stages were included in this observational cross-sectional study. The severity of liver disease was evaluated using the Child-Pugh score and the MELD score, and blood samples for biochemistry, conventional coagulation tests, and ROTEM were collected at the time of the final assessment for liver transplantation. Statistical comparisons for the studied parameters with scores of severity were made using Spearman correlation test and receiver-operating characteristic (ROC) curves.Spearman correlation coefficients indicated that the thromboelastometric parameters did not correlate with Child-Pugh or MELD scores. The ROC curves of the thromboelastometric parameters could not differentiate advanced stages from early stages of liver cirrhosis.Standard ROTEM cannot discriminate the stage of chronic liver disease in patients with severe chronic liver disease.

The temporal pattern of postoperative coagulation status in patients undergoing major liver surgery.

INTRODUCTION: After major liver surgery, there are risks of both postoperative bleeding and thrombosis. Routine coagulation monitoring is indicated, but may not provide adequate clinical guidance. Thus, we described the clotting status in a pilot study using broader coagulation testing. We analysed the temporal pattern of coagulation tests to assess whether thromboelastometry (ROTEM®) would improve the quality of the postoperative monitoring of the coagulation status in patients undergoing major hepatic resections. MATERIAL AND METHODS: Sixteen patients undergoing major liver resections were examined prior to surgery, on postoperative day 1, and subsequently, every three postoperative days during hospitalization. At the same time, the clinical signs of bleeding and thrombotic complications were monitored. RESULTS: On postoperative day 1, increases in bilirubin, PT-INR, APTT, and D-dimers were observed, together with concomitant decreases in fibrinogen, platelet count, antithrombin (AT), protein C and protein S compared to preoperative values. On postoperative days 4 and 7, all of the variables had returned to the normal range except for D-dimers, AT and protein C. The ROTEM® median values remained within the normal range. There were no significant episodes of postoperative bleeding. Two patients were diagnosed with a pulmonary embolism. CONCLUSION: Despite the abnormalities observed in routine coagulation monitoring, thromboelastometry indicated a balanced coagulation status following major hepatic surgery. The levels of both pro- and anticoagulant proteins changed over time during this period. The exact clinical role for thromboelastometry in major hepatic surgery remains to be established.

Uvulopalatopharyngoplasty in 158 OSAS patients failing non-surgical treatment.

CONCLUSIONS: Uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep apnoea syndrome (OSAS) who had failed treatment with continuous positive airway pressure (CPAP) and mandibular retaining device (MRD) was effective and safe. The satisfaction rate was high. We recommend UPPP in selected OSAS patients, especially younger patients. OBJECTIVES: To evaluate the efficacy and complication rate of UPPP. PATIENTS AND METHODS: This was a non-randomized prospective study of 139 men and 19 women, median age 45 years (range 20-75), median body mass index (BMI) 29 (range 20-48), who underwent UPPP. One year follow-up comprised ambulant sleep apnoea recordings and questionnaires with the Epworth Sleepiness Scale (ESS). RESULTS: In all, 76% of the patients underwent sleep recordings preoperatively and postoperatively. The oxygen desaturation index (ODI(4)) decreased from median 23 (range 6-100) to 8 (range 0-60), p<0.001. Criteria of success (>50% reduction and ODI<20), was 64%. The ESS value decreased from median 12 (range 0-21) to 6 (0-22), p<0.001. In all, 88% of the patients were satisfied. Four of 158 patients (2.5%) had serious postoperative complications. There was neither sequel of complications nor mortality.

Enhanced in vivo protein synthesis in circulating immune cells of ICU patients.

Insufficient function of the immune system contributes to a poor prognosis in intensive care unit (ICU) patients. However, the immune system function is not easily monitored and evaluated. In vivo protein synthesis determination in immune competent cells offers a possibility to quantify immunological activation. The aim of this descriptive study was to determine the in vivo fractional protein synthesis rate (FSR) in immune cells of ICU patients during the initial phase of the critical illness. Patients (n = 20) on ventilator treatment in the general ICU were studied during their first week of ICU stay. FSR was determined in circulating T lymphocytes, mononuclear cells, the whole population of blood leukocytes, and in stationary immune cells of palatine tonsils during a 90-min period by a flooding technique. Healthy, adult subjects (n = 11), scheduled for elective ear, nose, and throat surgery served as a control group. The FSR in leukocytes and mononuclear cells of ICU patients was higher compared with the control group. In contrast, the FSR of circulating T lymphocytes and of tonsillar cells was not different from that in the healthy subjects. In summary, the ICU patients showed a distinct polarization of metabolic responses during the initial phase of the critical illness. The in vivo rate of protein synthesis was high in the circulating mononuclear cells and leukocytes, reflecting enhanced metabolic activity in these cell populations. Determination of the in vivo protein synthesis rate may be used as a tool to obtain additional information on activation of the immune system.

Determination of in vivo protein synthesis in human palatine tonsil.

The palatine tonsils are constantly exposed to ingested or inhaled antigens which, in turn, lead to a permanent activation of tonsillar immune cells, even in a basic physiological state. The aim of the present study was to investigate if the immunological activation of the human palatine tonsil is reflected by a high metabolic activity, as determined by in vivo measurement of protein synthesis. The protein synthesis rate of the tonsil was also compared with that of the circulating T-lymphocytes, the total blood mononuclear cells and the whole population of blood leucocytes. Phenotypic characterization of immune-competent cells in tonsil tissue and blood was performed by flow cytometry. Pinch tonsil biopsies were taken after induction of anaesthesia in healthy adult patients (n=12) scheduled for ear surgery, uvulopalatopharyngoplasty or nose surgery. Protein synthesis was quantitatively determined during a 90-min period by a flooding-dose technique. The in vivo protein synthesis rate in the palatine tonsils was 22.8+/-5.7%/24 h (mean+/-S.D.), whereas protein synthesis in the circulating T-lymphocytes was 10.7+/-3.4%/24 h, in mononuclear cells was 10.8+/-2.8%/24 h and in leucocytes was 3.2+/-1.2%/24 h. CD3+ lymphocytes were the most abundant cell population in the tonsil. The in vivo protein synthesis rate in human tonsils was higher compared with the circulating immune cells. This high metabolic rate may reflect the permanent immunological activity present in human tonsils, although cell phenotypes and activity markers do not explain the differences.

Albumin synthesis in humans increases immediately following the administration of endotoxin.

In order to investigate the immediate (i.e. within 3 h) response of albumin synthesis to the administration of endotoxin, as a model of a moderate and well controlled catabolic insult, two measurements employing L-[(2)H(5)]phenylalanine were performed in 16 volunteers. One group ( n =8) received an intravenous injection of endotoxin (4 ng/kg; lot EC-6) immediately after the first measurement of albumin synthesis, whereas the other group received saline. A second measurement was initiated 1 h later. In the endotoxin group, the fractional synthesis rate of albumin was 6.9+/-0.6%/day (mean+/-S.D.) in the first measurement. In the second measurement, a significant increase was observed (9.6+/-1.2%/day; P <0.001). The corresponding values in the control group were were 6.6+/-0.6%/day and 7.0+/-0.6%/day respectively (not significant compared with first measurement and P <0.001 compared with the second measurement in the endotoxin group). The absolute synthesis rates of albumin were 148+/-35 and 201+/-49 mg x kg(-1) x day(-1) before and after endotoxin ( P <0.01). In the control group, the corresponding values were 131+/-21 and 132+/-20 mg x kg(-1) x day(-1) (not significant compared with the first measurement and P <0.01 compared with the second measurement in the endotoxin group). In conclusion, these results indicate that albumin synthesis increases in the very early phase after a catabolic insult, as represented by the administration of endotoxin.