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Biomedical subjects

V Gülberg

Publications and source records attributed to V Gülberg.

At least 19 recordsLinked to original sources

A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.

BACKGROUND: In patients with cirrhosis and ascites, creation of a transjugular intrahepatic portosystemic shunt may reduce the ascites and improve renal function. However, the benefit of this procedure as compared with that of large-volume paracentesis is uncertain. METHODS: We randomly assigned 60 patients with cirrhosis and refractory or recurrent ascites (Child-Pugh class B in 42 patients and class C in 18 patients) to treatment with a transjugular shunt (29 patients) or large-volume paracentesis (31 patients). The mean (+/-SD) duration of follow-up was 45+/-16 months among those assigned to shunting and 44+/-18 months among those assigned to paracentesis. The primary outcome was survival without liver transplantation. RESULTS: Among the patients in the shunt group, 15 died and 1 underwent liver transplantation during the study period, as compared with 23 patients and 2 patients, respectively, in the paracentesis group. The probability of survival without liver transplantation was 69 percent at one year and 58 percent at two years in the shunt group, as compared with 52 percent and 32 percent in the paracentesis group (P=0.11 for the overall comparison, by the log-rank test). In a multivariate analysis, treatment with transjugular shunting was independently associated with survival without the need for transplantation (P=0.02). At three months, 61 percent of the patients in the shunt group and 18 percent of those in the paracentesis group had no ascites (P=0.006). The frequency of hepatic encephalopathy was similar in the two groups. Of the patients assigned to paracentesis in whom this procedure was unsuccessful, 10 received a transjugular shunt a mean of 5.5+/-4 months after randomization; 4 had a response to this rescue treatment. CONCLUSIONS: In comparison with large-volume paracentesis, the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites.

Adult↗

Successful treatment of chronic Budd-Chiari syndrome with a transjugular intrahepatic portosystemic shunt.

Budd-Chiari syndrome is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for chronic Budd-Chiari syndrome are limited. We report the case of a 28-year-old woman who presented with recurrence of chronic Budd-Chiari syndrome with total obstruction of all major hepatic veins. Due to worsening liver function over the course of 1 year, she had to be listed for liver transplantation. Because of therapy-refractory ascites, declining renal function and severe esophageal varices, a transjugular intrahepatic portosystemic shunt (TIPS) was placed, planned as a bridge to transplantation. Following TIPS, a marked recovery of liver function could be observed, accompanied by disappearance of ascites, esophageal varices, and normalization of kidney function. Therefore, the patient could be removed from the waiting list for liver transplantation. This case demonstrates for the first time that the use of TIPS in chronic Budd-Chiari syndrome may result in marked recovery of liver function.

Adult↗

High-frequency oscillatory ventilation does not decrease endothelin release in lung-lavaged rabbits.

UNLABELLED: High-frequency oscillatory ventilation (HFO) has been shown to reduce lung injury and pulmonary arterial pressure (PAP). We hypothesized that HFO leads to decreased endothelin 1 (ET-1) and endothelin 3 (ET-3) release when compared to conventional mechanical ventilation (CMV) in lung-lavaged rabbits. DESIGN: Prospective, randomized, controlled animal study. In 26 adult New Zealand White Rabbits ventilated by CMV or HFO under hypoxemic and normoxemic conditions after lung lavage (CMV-hypo: n = 5; CMV-normo: n = 8; HFO-hypo: n = 7; HFO-normo: n = 6) we recorded systemic and PAP, measured blood gases, ET-1 and ET-3 and calculated intrapulmonary venous admixture during a 4-h experiment. ET-1 was significantly increased after lavage (p < 0.05) with no further increase until the end of the experiment. Neither pulmonary arterial nor systemic arterial ET-1 differed between CMV and HFO or between hypoxemia and normoxemia. Systemic arterial ET-3, however, was significantly higher in HFO-hypo than in the other two groups ventilated under normoxemic conditions at the end of the experiment (HFO-hypo vs. CMV-normo, p < 0.05; HFO-hypo vs. HFO-normo, p < 0.05). PAP showed a continuous increase in all groups (p < 0.05). We did not find any correlation between PAP and ET-1 or ET-3. Intrapulmonary venous admixture increased in animals ventilated under hypoxemic conditions, whereas it decreased after lung lavage in those ventilated under normoxemic conditions until the end of the experiment (HFO-normo, p < 0.05). CONCLUSIONS: This study suggests that HFO does not decrease ET-1 and ET-3 release compared to CMV in lung-lavaged rabbits. Hypoxemia, however, may increase ET-3 release from the lungs, leading to an increased intrapulmonary shunt.

Animals↗

Transjugular intrahepatic portosystemic shunt for cirrhosis and ascites: Effects in patients with organic or functional renal failure.

BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is increasingly being used for treatment of patients with refractory ascites and functional renal failure. In contrast, organic renal disease is commonly considered a relative contraindication for TIPS placement. The aim of this pilot study was to investigate the effects of TIPS in patients with refractory ascites and organic or functional renal impairment. METHODS: A TIPS was placed for refractory or intractable ascites in 10 consecutive patients with liver cirrhosis and impaired renal function (serum creatinine > 1.5 mg/100 ml). Four of them had organic kidney disorders. Of these patients, three had moderate renal impairment, and one had end-stage renal disease and needed hemodialysis every other day. The other six patients had functional renal impairment due to the underlying liver disease. RESULTS: TIPS was effective in reducing ascites in 8 of 10 patients, including all patients with organic renal disease. Furthermore, after TIPS the renal function improved in all patients. Serum creatinine and serum urea levels decreased significantly from 1.8 +/- 0.1 to 1.5 +/- 0.1 mg/100 ml (P < 0.05) and from 107 +/- 13 to 78 +/- 14 mg/100 ml (P < 0.05), respectively. The renal function of the three patients with organic renal failure improved similarly, as observed in the six patients with functional renal failure. In the patient on hemodialysis, TIPS was effective in reducing the frequency of paracenteses. CONCLUSION: TIPS may be useful in patients with functional and in patients with organic renal disease, resulting in improvement of ascites and renal function.

Aged↗

Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure.

BACKGROUND/AIMS: C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. RESULTS: Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p<0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=-0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v. 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours. CONCLUSIONS: Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.

Analysis of Variance↗

Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis.

Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more. Measurements were repeated after high-volume plasmapheresis (HVP) with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant infusion of D-sorbitol and calculated according to Fick's principle from peripheral artery and hepatic vein concentrations. In 14 patients with acute liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min) were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3 mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36 L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32 to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2 L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm-5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD, neither systemic nor splanchnic vascular resistance was affected by HVP, but as cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more blood was directed to the splanchnic region. In all liver failure patients treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP. Changes of ET-1 were positively correlated with changes in HBF (P <.005) and VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and oxygenation. ET-3 was negatively correlated with systemic vascular resistance index before HVP (P <.05) but changes during HVP did not correlate. Our data suggest that liver failure is associated with increased HBF and VO2, sp. HVP further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that splanchnic hypoxia was not present.

Acute Disease↗

Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine.

Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 +/- 1 mL/min, UNaV 7 +/- 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 microgram/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 +/- 4 mL/min, UNaV 47 +/- 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 +/- 10 mL/min, UNaV 8 +/- 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation.

Dopamine↗

Renal effects of transjugular intrahepatic portosystemic shunt in cirrhosis: comparison of patients with ascites, with refractory ascites, or without ascites.

Renal effects of the transjugular intrahepatic portosystemic shunt (TIPS) were compared in 6 patients without ascites (group 1), 11 patients with ascites responding to diuretic treatment (group 2), and 6 patients with refractory ascites (group 3). Seven days after insertion of TIPS, 24-hour urinary sodium excretion had increased in patients with ascites: 113 +/- 16 mmol to 170 +/- 30 mmol (P = .012) in group 2, and 22 +/- 8 mmol to 77 +/- 27 mmol (P = .050) in group 3. In group 3, fractional sodium excretion tended to increase from 0.26% +/- 0.14% to 0.62% +/- 18% (P = .081). The relative increase of urinary sodium excretion (to 444% +/- 122%) and fractional sodium excretion (to 413% +/- 127%) in group 3 was significantly (P < .05) higher than in group 1 and group 2, respectively. Creatinine clearance and 24-hour urinary volume were not significantly changed in either group. Patients with Child-Pugh class C had a more pronounced effect of TIPS on urinary sodium excretion (increase to 396% +/- 115% vs. 139% +/- 15%; P = .066) and on fractional sodium excretion (increase to 415% +/- 103% vs. 94% +/- 15%; P = .020) than patients with less-severe liver disease. Fractional sodium excretion of less than 0.35% before TIPS was found to be an indicator of renal response to TIPS. The effect of TIPS on urinary sodium excretion and on fractional sodium excretion was related to the patients' Child-Pugh score (r = .55; P = .007 and r = .68; P = .001, respectively) and inversely to their fractional sodium excretion (r = -.44; P = .047 and r = -.54; P = .012, respectively) before TIPS. These data demonstrate that TIPS affects renal sodium handling in patients with ascites, particularly in patients with refractory ascites. Severity of liver disease and fractional sodium excretion before TIPS are parameters to predict the extent of the renal response.

Adult↗

Transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding in portal hypertension: comparison of emergency and elective interventions.

Nonsurgical reduction of portal hypertension by transjugular intrahepatic portosystemic shunt (TIPS) is widely used for prevention of variceal rebleeding (elective TIPS). Information is limited about the value of emergency TIPS for acute variceal bleeding unresponsive to endoscopic and drug therapy. The aim of the present study was therefore to determine whether the effects and complications differ between emergency and elective TIPS in patients with cirrhosis of the liver. TIPS was performed in 11 patients with acute variceal bleeding unresponsive to endoscopic treatment and 22 patients in stable condition after an episode of variceal bleeding. Clinical examination, blood sampling, Doppler sonography of TIPS flow, and upper gastrointestinal endoscopy were performed at days 1, 7, and 30 and at three-month intervals after TIPS. Mean follow-up was 549 (1-987) days. Bleeding was controlled by emergency TIPS in 10/11 patients. Probability of survival was not different after emergency and elective TIPS (0.73 vs 0.84 at one year). Early rebleeding (< or =2 weeks) occurred more often after emergency TIPS (3/11 vs 0/22 patients; P = 0.03), but there was no significant difference in late rebleeding. Occlusion of TIPS was more frequent after emergency TIPS. Occurrence of TIPS stenoses was identical in both groups (4/11 vs 8/22). De novo or deterioration of preexisting hepatic encephalopathy was similar (18% vs 24%; NS). It is concluded that TIPS is effective for control of acute variceal bleeding unresponsive to endoscopic and drug treatment. Early rebleeding and stent occlusion occurred more often after emergency TIPS. Late rebleeding, complications, and long-term survival did not differ from elective TIPS.

Acute Disease↗

[Successful conservative therapy of hepatorenal syndrome with vasopressin-1-receptor antagonist ornipressin].

A 47-year-old male patient with alcoholic cirrhosis Child-Pugh grade C was admitted to our center for evaluation of liver transplantation. Serum creatinine had increased from 1.6 to 4.3 mg/100 ml within the previous two weeks, creatinine clearance was 12 ml/min, and urinary sodium 12 mmol/24 h. The diagnosis of HRS type I was established. Diuretic treatment was discontinued. Following albumin infusion, central venous pressure was increased to above 10 cm H2O and dopamine (2 micrograms/kg/min) infusion was started. However, renal function did not improve. An i.v. infusion of ornipressin (POR8, Sandoz; 6 IU/h) was started and dopamine infusion continued. During a four-hour interval, urinary volume and sodium excretion doubled. Therefore treatment was continued for three weeks. After 22 days, renal function had normalized (creatinine 1.2 mg/100 ml, creatinine clearance 65 ml/min, urinary sodium 62 mmol/24 h) and diuretic therapy was resumed. No adverse effects were observed. Ornipressin/dopamine infusion was discontinued and renal function remained normal. Three weeks later, the patient underwent liver transplantation with normal renal function. Ornipressin infusion had no effect on circulating endothelin, but decreased the activation of the renin-aldosterone system and of the sympathetic activity. So far, no noninvasive therapy of hepatorenal syndrome has been established. This is the first report of successful medical treatment of HRS type I with a three-week infusion of the vasopressin-l-receptor agonist ornipressin.

Dose-Response Relationship, Drug↗

Experiences with novel techniques for reduction of stent flow in transjugular intrahepatic portosystemic shunts.

The transjugular intrahepatic portosystemic shunt (TIPS) may deteriorate liver function and can cause encephalopathy in patients with cirrhosis of the liver. Then reduction of TIPS flow may be required. We here report several attempts to reduce shunt flow in TIPS-induced encephalopathy or liver function impairment with novel techniques. Three patients with cirrhosis of the liver were investigated: Two with severe recurrent encephalopathy and one with impaired liver function following TIPS insertion. Insertion of a reducing stent was ineffective to decrease shunt flow velocity in one patient with severe coagulopathy. Sufficient reduction of shunt flow was achieved by embolizing the space around the hourglass waist of the reducing stent with an occlusion emulsion. Insertion of a conventional stent within the preexisting TIPS with or without additional embolization reduced TIPS flow in the other patients. After reduction of shunt flow encephalopathy improved and liver function returned to the level before TIPS, respectively. During follow-up no occlusion of TIPS was observed. Thus, reduction of shunt flow velocity can be achieved by insertion of an additional stent into a curve-shaped TIPS. Embolization can be helpful to decrease TIPS flow, particularly in patients with severe coagulopathy. Reduction of TIPS flow can correct TIPS-induced complications.

Blood Flow Velocity↗

Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function.

BACKGROUND/AIMS: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis. METHODS: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period. RESULTS: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups. CONCLUSIONS: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.

Adult↗