Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation - a cluster randomized trial with 64,273 participants.

BACKGROUND: Unanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI with usual airway assessment. METHODS: From 01.10.2012 to 31.12.2013, 28 departments were cluster-randomized to apply the SARI model or usual airway assessment. The SARI group implemented the SARI model. The Non-SARI group continued usual airway assessment, thus reflecting a group of anaesthetists' heterogeneous individual airway assessments. Preoperative prediction of difficult intubation and actual intubation difficulties were registered in the Danish Anaesthesia Database for both groups. Patients who were preoperatively scheduled for intubation by advanced techniques (e.g. video laryngoscopy; flexible optic scope) were excluded from the primary analysis. Primary outcomes were the proportions of unanticipated difficult and unanticipated easy intubation. RESULTS: A total of 26 departments (15 SARI and 11 Non-SARI) and 64 273 participants were included. In the primary analyses 29 209 SARI and 30 305 Non-SARI participants were included.In SARI departments 2.4% (696) of the participants had an unanticipated difficult intubation vs 2.4% (723) in Non-SARI departments. Odds ratio (OR) adjusted for design variables was 1.03 (95% CI: 0.77-1.38). The proportion of unanticipated easy intubation was 1.42% (415) in SARI departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68-2.34). CONCLUSIONS: Using the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations. CLINICAL TRIAL REGISTRATION: NCT01718561.

Contrast-enhanced FDG-PET/CT vs. SPIO-enhanced MRI vs. FDG-PET vs. CT in patients with liver metastases from colorectal cancer: a prospective study with intraoperative confirmation.

BACKGROUND: The choice of imaging before liver surgery is debated regarding the use of magnetic resonance (MR) imaging, computed tomography (CT), and positron emission tomography (PET). No studies have compared contrast-enhanced PET/CT with superparamagnetic iron oxide (SPIO)-enhanced MR imaging. PURPOSE: To compare PET/CT with superparamagnetic iron oxide (SPIO)-enhanced MR imaging, PET, and CT in the detection of liver metastases (LM) and extrahepatic tumor from colorectal cancer (CRC). MATERIAL AND METHODS: Thirty-five patients with suspected LM underwent PET/CT with a contrast-enhanced CT protocol and SPIO-enhanced MR imaging. Readers independently analyzed images from MR imaging, PET/CT, and the CT part and PET part of the PET/CT study. Imaging findings were compared with surgical and histological findings. RESULTS: Lesion-by-lesion sensitivity and accuracy for liver lesions was 54% and 77% for PET alone, 66% and 83% for PET/CT, 82% and 82% for SPIO-enhanced MR imaging, and 89% and 77% for CT alone, respectively. CT and SPIO-enhanced MR imaging were less specific but significantly more sensitive than PET (P<0.0001). For extrahepatic tumor, sensitivity and specificity was 83% and 96% for PET/CT and 58% and 87% for CT, respectively. CONCLUSION: CT and SPIO-enhanced MR imaging are more sensitive but less specific than PET in the detection of LM. PET/CT can detect more patients with extrahepatic tumor than CT alone.

Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries.

BACKGROUND: Primary sclerosing cholangitis (PSC) is the most common indication for liver transplantation in the Nordic countries. Because these patients are difficult to evaluate with regard to timing of liver transplantation, it is important to establish predictors of post-transplant survival. METHODS: Data from two groups of patients receiving liver allografts during 1982-2001 were recorded: (a) PSC patients and (b) comparison patients. Outcome following transplantation has been recorded for all patients. Regression analyses have been performed for PSC patients to analyse predictors of patient and graft survival. RESULTS: A total of 245 PSC and 618 comparison patients received a first liver allograft in the period 1982 until the end of the study. The overall 1-, 3- and 5-year patient survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and comparison group, respectively. Survival following transplantation has increased with time in both the PSC and the comparison group. Recent year of transplantation, no previous hepatobiliary surgery and a lower MELD score were predictors of survival following transplantation for PSC patients. PSC patients had a higher rate of re-transplantations (13% versus 8%, P = 0.01). Predictors of re-transplantation in PSC patients were an episode of early rejection and vascular thrombosis. CONCLUSION: In PSC patients, year of transplantation, previous hepatobiliary surgery and MELD score are predictors of survival following transplantation and these patients are more frequently in need of re-transplantation compared to the comparison group.

Highly urgent liver transplantation: possible impact of donor-recipient ABO matching on the outcome after transplantation.

BACKGROUND: Survival after liver transplantation for fulminant hepatic failure has been reported to be less favorable than survival for patients with chronic liver diseases. METHODS: We have studied all patients (n=229) undergoing highly urgent liver transplantation from 1990 to 2001 in the Nordic countries. The impact of patient and donor characteristics, with emphasis on donor-recipient ABO matching (identical, compatible, incompatible), has been studied. RESULTS: One-year and 3-year patient survival rates were 73% and 70% for the total period and 86% and 78% for the last 4-year period. Patients receiving an ABO-compatible liver allograft had significantly lower patient survival rates than those receiving an ABO-identical donor organ (1-year patient survival rates 66% of vs. 79%, P=0.03). Graft survival rates varied less (1-year graft survival rates of 64% vs. 74%, P=0.09). Patients receiving an ABO-incompatible liver allograft had patient survival rates of 70% at 1 year and 60% at 3 years but low graft survival rates (40% and 30% at 1 and 3 years). In a multiple regression analysis, significant independent predictors of poor patient survival were early year of transplantation, ABO-compatible donor, high donor age, and waiting time more than 3 days and less than 9 days. CONCLUSION: Survival after highly urgent liver transplantation has improved and is comparable to that observed in patients receiving a liver allograft because of chronic liver disease. Patients receiving an ABO-identical donor organ had significantly higher patient survival rates compared with those receiving an ABO-compatible donor liver.

Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients.

BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). The erythromycin breath test is an in vivo assay of hepatic CYP3A activity, but the method has never been directly validated. The aim of the study was to investigate whether an early postoperative erythromycin breath test correlated with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients. METHODS: In 18 liver transplant recipients, the erythromycin breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for the CYP3A protein level by Western blotting and for CYP3A activity with erythromycin demethylation and testosterone 6beta- hydroxylation assays. RESULTS: The erythromycin breath test values ranged from 0.14% to 1.65% of carbon 14 per hour, and the CYP3A protein level ranged from 732 to 7822 as measured by optical density. The in vitro catalytic activity determined by the erythromycin demethylation assay ranged from 94 to 902 disintegrations per minute per 5 minutes per milligram of protein, and the activity determined by testosterone 6beta-hydroxylation ranged from 0.030 to 0.627 nmol per minute per milligram of protein. Significant correlation was demonstrated between the erythromycin breath test and both the erythromycin demethylation (Spearman correlation coefficient: R = 0.76, R (2) = 0.57; P =.0004) and the testosterone 6beta-hydroxylation (Spearman correlation coefficient: R = 0.79, R (2) = 0.63; P =.0001) assays. The erythromycin breath test also correlated with the CYP3A protein level (Spearman correlation coefficient: R = 0.60, R (2) = 0.36; P =.01). CONCLUSION: Our data support the erythromycin breath test as a specific in vivo assay of CYP3A activity in humans. The test is applicable in liver transplant recipients in the early postoperative phase. Future studies should evaluate the clinical usefulness of an early postoperative erythromycin breath test as a predictor of cyclosporine-tacrolimus pharmacokinetics in liver transplantation.

Mapping indoor radon-222 in Denmark: design and test of the statistical model used in the second nationwide survey.

In Denmark, a new survey of indoor radon-222 has been carried out, 1-year alpha track measurements (CR-39) have been made in 3019 single-family houses. There are from 3 to 23 house measurements in each of the 275 municipalities. Within each municipality, houses have been selected randomly. One important outcome of the survey is the prediction of the fraction of houses in each municipality with an annual average radon concentration above 200 Bq m(-3). To obtain the most accurate estimate and to assess the associated uncertainties, a statistical model has been developed. The purpose of this paper is to describe the design of this model, and to report results of model tests. The model is based on a transformation of the data to normality and on analytical (conditionally) unbiased estimators of the quantities of interest. Bayesian statistics are used to minimize the effect of small sample size. In each municipality, the correction is dependent on the fraction of area where sand and gravel is a dominating surface geology. The uncertainty analysis is done with a Monte-Carlo technique. It is demonstrated that the weighted sum of all municipality model estimates of fractions above 200 Bq m(-3) (3.9% with 95%-confidence interval = [3.4,4.5]) is consistent with the weighted sum of the observations for Denmark taken as a whole (4.6% with 95%-confidence interval = [3.8,5.6]). The total number of single-family houses within each municipality is used as weight. Model estimates are also found to be consistent with observations at the level of individual counties. These typically include a few hundred house measurements. These tests indicate that the model is well suited for its purpose.

Liver transplantation in patients over 60 years of age.

Liver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990-1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1-year survival was 75% and 3-year survival 62%, which was not significantly lower (P = 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n = 38) did not differ from that of patients 60-65 years of age (n = 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.

Cerebrovascular metabolic autoregulation is impaired during liver transplantation.

BACKGROUND: We determined whether the coupling between cerebral blood flow (CBF) and oxygen metabolism (CMRO2) is preserved during liver transplantation. Because of cerebrovascular dilatation, we hypothesized that cerebral metabolic autoregulation is impaired, because CBF becomes uncoupled from CMRO2 during the reperfusion phase of the operation. MATERIALS AND METHODS: In a prospective study, 13 patients (8 women, median age 46, range 21-6) with liver failure (10 with end-stage chronic liver disease and 3 with acute liver failure) were enrolled. Catheters were placed in a femoral artery and in the internal jugular vein for calculation of the cerebral arteriovenous oxygen content difference (AVDO2). CBF was recorded by the 133Xenon injection technique, and by transcranial Doppler sonography determined mean flow velocity (Vmean) in the middle cerebral artery. The CMRO2 was calculated as the AVDO2 times CBF and the cerebrovascular resistance (CVR) as the mean arterial pressure to CBF ratio. An index of large cerebral artery diameter was expressed by the CBF to Vmean ratio. RESULTS: From induction of anesthesia to the anhepatic period, CBF decreased from a median of 47 (interquartiles 31-55) to 41 (37-48) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged (1.3 [0.9-2.5] vs. 1.7 [0.9-2.3] ml 100 g(-1) min(-1)). In the reperfusion phase, the CBF increased to 51 (45-54) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged at 1.1 (1.0-2.5) ml 100 g(-1) min(-1). The CVR decreased from 2.0 mm Hg (1.4-2.1) to 1.4 (1.1-1.8) mm Hg(-1) min 100 g ml. In the anhepatic phase, mean arterial pressure decreased from 92 mm Hg (84-98) to 85 (80-92) mm Hg and at reperfusion it was 80 (71-105) mm Hg. From the anhepatic to the reperfusion phase, the CBF increased 7% (0 to 26) for each mm Hg concomitant increase in PaCO2. The CBF to Vmean ratio remained stable (1.0 [0.8-1.2] vs. 0.9 [0.7-1.1] ml 100 g(-1) min(-1) cm(-1) sec). CONCLUSION: During the reperfusion phase of liver transplantations, cerebrovascular dilatation uncouples cerebral oxidative metabolism from blood flow. The increase in CBF is beyond what can be explained by changes in arterial carbon dioxide tension and arterial pressure.

Liver transplantation in the Nordic countries, 1982-1998: changes of indications and improving results.

BACKGROUND: Liver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period. METHODS: Data on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry. RESULTS: A total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing. CONCLUSION: Results of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses.

Improved physical performance after orthotopic liver transplantation.

Orthotopic liver transplantation (OLT) has become a frequently used treatment for end-stage liver disease and acute liver failure, and liver function is markedly improved after transplantation. However, no studies have investigated the development in physical capacity after OLT. On this basis, the aim of the present study is to study the influence of OLT on physical fitness during the first postoperative year. Twenty-three men with a mean age of 45.1 years (range, 24 to 62 years) and 15 women with a mean age of 44.6 years (range, 21 to 62 years) were included in the study. Preoperative maximal oxygen uptake (VO2max) during graded ergometer bicycling, isokinetic knee extension/flexion moments, and functional performance (i.e., 6-minute walking distance and standardized transfers and squats) was measured. Preoperative fitness and strength was 40% to 50% less than expected in the age-matched general population. Post-OLT, all patients underwent a supervised exercise program for 8 to 24 weeks. Follow-up data showed a significant increase in all tested physical performance parameters after OLT. Six months post-OLT, VO2max had increased 43%; knee strength, 60% to 100%; and functional performance, 22% to 27%. One year postsurgery, general health was improved and perceived as excellent or good in all patients. All patients were independent in activities of daily living, and the level of physical activity increased after OLT. No further improvement in either physical performance parameters or self-assessed parameters was seen beyond 6 months after OLT. In conclusion, these findings indicate that OLT combined with a supervised post-OLT exercise program improves physical fitness, muscle strength, and functional performance in individuals with chronic liver disease.

Reconstitution of the actin-scavenger system after orthotopic liver transplantation for end-stage liver disease: a prospective and longitudinal study.

Serum levels of the actin scavenger Gc-globulin (group-specific component, vitamin D-binding protein), a member of the albumin multigene family, are decreased in severe liver disease but have not been evaluated in relation to liver transplantation. We measured Gc-globulin and Gc-globulin-actin complex ratio daily for 2 weeks after transplantation in 17 patients with end-stage liver disease. Before transplantation, Gc-globulin levels were significantly less in the patients than in healthy controls (235 +/- 106 v 340 +/- 35 mg/L, respectively; P<.001), whereas complex ratio level was in the normal range. Five patients (group N) had pretransplantation Gc-globulin values within the normal range (mean +/- 2 SD), and 12 patients had subnormal values (group S). In group N, mean Gc-globulin levels posttransplantation remained stable at a lower level than before transplantation but still within normal range. In this group, cold ischemia time correlated inversely with Gc-globulin levels on day 2 (r = -0.88; P <.05). In group S, normal mean levels were reached at a mean of 11 days after transplantation. However, almost half these patients had subnormal Gc-globulin levels at day 14. Complex ratio levels remained normal in the study period in both groups. Prothrombin index levels (plasma coagulation factors II, VII, and X) were identical in both groups and returned to normal 7 days posttransplantation, whereas plasma albumin levels were less than normal in both groups and further decreased after transplantation. In conclusion, the maintenance (group N) or reestablishment (group S) of serum Gc-globulin to normal levels occurred in the early posttransplantation course in the same time frame as the prothrombin index. Gc-globulin synthesis seems unrelated to albumin synthesis. A prolonged cold ischemia time may cause reduced Gc-globulin levels early after transplantation.

Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig.

1. This study examined the extent of liver perfusion and its oxygenation during progressive haemorrhage. We examined hepatic arterial flow and hepatic oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The hepatic surface oxygenation was assessed by near-infrared spectroscopy and the hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy of the hepatic flow. 2. Stepwise haemorrhage until circulatory collapse resulted in proportional reductions in cardiac output and in arterial, central venous and pulmonary wedge pressures. While heart rate increased, pulmonary arterial pressure remained stable. In addition, renal blood flow decreased, renal vascular resistance increased and there was elevated noradrenaline spill-over. Further, renal surface oxygenation was lowered from the onset of haemorrhage. 3. Similarly, the portal blood flow was reduced in response to haemorrhage, and, as for the renal flow, the reduced splanchnic blood flow was associated with an elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was only slightly reduced by haemorrhage, and surface oxygenation did not change. The hepatic oxygen uptake was maintained until the blood loss represented more than 30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic catecholamine uptake was reduced, and the lactate uptake approached zero. 4. Subsequent reduction of cardiac output and portal blood flow elicited a selective dilatation of the hepatic arterial vascular bed. Due to this dilatation liver blood flow and hepatic cell oxygenation and metabolism were preserved prior to circulatory collapse.

Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis.

BACKGROUND: Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. METHODS: Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). RESULTS: Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. CONCLUSION: Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.

Scandiatransplant: organ transplantation in the Nordic countries 1996.

The Nordic collaboration in organ transplantation was initiated nearly 30 years ago in the frame of Scandiatransplant. With a recent formalization of its structure, Scandiatransplant has become a modern organ exchange organization. The increasing activities of Scandiatransplant clearly reflect the continuously growing need for a close and firm Nordic collaboration in the transplantation field, for the benefit of the numerous patients waiting for an organ transplant.

Cerebral oxygen saturation and blood flow during liver transplantation.

After reperfusion of a liver graft, transcranial Doppler determined middle cerebral artery flow velocity, increases more than expected from the arterial carbon dioxide tension (PaCO2). We evaluated if this indication of cerebral hyperperfusion is reflected in the jugular oxygen saturation (SjO2) (n = 31) and oxygen saturation (ScO2) (near-infrared spectrophotometry, n = 22). From the dissection phase to the anhepatic phase SjO2 71.0% (range 62.3%-78.5%), ScO2 70% (range 65%-77%), and PaCO2 34.9 mm Hg (range 30.8-38.3) remained statistically unchanged. In contrast, during the early reperfusion phase, SjO2 increased to 77.0% (71.4%-83.0%) (P < 0.01) and the ScO2 to 75% (68%-80%) (P < 0.05) as PaCO2 increased to 37.5 mm Hg (34.8-41.9) (P < 0.001). Notably, SjO2 also increased at reperfusion from 71.6% (66.5%-78.0% mm Hg) to 80.0% (76.8%-84.8%) in the four patients in whom PaCO2 decreased at reperfusion from 37.6 mm Hg (36.8-39.5) to 34.0 mm Hg (32.3-36.8). If the changes in SjO2 after reperfusion of the grafted liver should be explained as a reflection of changes in cerebral blood flow, in response to PaCO2, it would indicate a highly accentuated CO2 reactivity of 13%/mm Hg. The results support that cerebral blood flow and, in turn, oxygenation increase after reperfusion because the grafted liver liberates a vasodilating substance(s).