Circulation Of Cirrhotic Patients Research Articles

No Differences in Rotational Thromboelastometry Measurements between Portal and Peripheral Circulation in Cirrhotic Patients Undergoing TIPS

In patients with liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) is considered a standardized treatment of refractory ascites or variceal bleeding. TIPS thrombosis (TT) and/or portal vein thrombosis (PVT) are possible complications during/after TIPS placement. Previous studies suggested increased clotting activity in portal circulation (PORC). This pilot study aimed to evaluate alterations and differences of coagulation function in PORC and in peripheral circulation (PERC) via rotational thromboelastometry during TIPS. Blood samples were collected from cirrhotic patients (n = 13; median Model of End Stage Liver Disease, MELD Score: 12; median age: 60 years) undergoing TIPS (10/13 TIPSs were elective procedures due to refractory ascites) as follows: median cubital vein (MCV; PERC)-confluence of the three hepatic veins to the inferior cava vein (HV/ICV; PORC)-portal vein (PV; PORC)-TIPS (PORC). This research utilized four variables of the extrinsic test EXTEM, i.e., clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum lysis (ML). EXTEM results [mean, M (range) ± standard deviation, SD (range)] showed no significant differences for CT [M (70-73) ± SD (9-13); p = 0.93] or CFT [M (137-155) ± SD (75-112); p = 0.97] or MCF [M (51-54) ± SD (9-10); p = 0.90] or ML [M (9-10) ± SD (4-5); p = 0.89] between the compartments, i.e., MCV vs. HV/ICV vs. PV vs. TIPS. Overall, we detected no differences in coagulation function between PERC and PORC. These results are in contrast to previous reports suggesting increased clotting activity in PORC vs. PERC in association with liver cirrhosis. Rotational thromboelastometry-based evaluation of coagulation function in PERC appears to reliably reflect coagulation function in PORC with respect to risk estimation for TT and/or PVT in cirrhotic patients undergoing TIPS.

Can the Computed Tomographic Aspect of Porto-Systemic Circulation in Cirrhotic Patients be Associated with the Presence of Variceal Hemorrhage?

Background and objectives: Variceal bleeding is a serious complication caused by portal hypertension, frequently encountered among cirrhotic patients. The purpose of this study was to determine whether the aspect of the collateral, porto-systemic circulation, as detected by CT are associated with the presence variceal hemorrhage (VH). Materials and Methods: 81 cirrhotic patients who underwent a contrast-enhanced CT examination were retrospectively included in the study. Patients were divided into two groups: Cirrhotic patients with variceal hemorrhage during the hospital admission concomitant, with the CT examination (n = 33) and group 2-cirrhotic patients, without any variceal hemorrhage in their medical history (n = 48). The diameter of the left gastric vein, the presence or absence and dimensions of oesophageal and gastric varices, paraumbilical veins and splenorenal shunts were the indicators assessed on CT. Results: The univariate analysis showed a significant association between the presence of upper GI bleeding and the diameters of paraoesophageal veins, paragastric veins and left gastric vein respectively, all of these CT parameters being higher in patients with variceal bleeding. In the multivariate logistic regression analysis, only the diameter of the left gastric vein was independently associated with the presence of variceal hemorrhage (OR = 1.6 (95% CI: 1.17–2.19), p = 0.003). We found an optimal cut-off value of 3 mm for the diameter of the left gastric vein useful to discriminate among patients with variceal hemorrhage from the ones without it, with a good diagnostic performance (AUC = 0.78, Se = 97%, Sp = 45.8%, PPV = 55.2%, NPV = 95.7%). Conclusions: Our observations point out that an objective CT quantification of porto-systemic circulation can be correlated with the presence of variceal hemorrhage and the diameter of the left gastric vein can be a reliable parameter associated with this condition.

Randomized Open Label Clinical Study on Assessment of Effect of Liquid and Solid Meal Intake in Cirrhotic Patients

Portal hypertension is almost unavoidable complication of cirrhosis. The physiological stimuli like food intake will affect the splanchnic circulation in cirrhotic patients. Hence the present study has been designed to measure the portal blood flow pressure after ingestion of solid and liquid meal in normal and cirrhotic patients. It is a randomized open label clinical study. The study included 32 male healthy volunteers (52 to 74 years) and 10 clinically proven cirrhotic patients (54-76years). The portal blood flow velocity was measured by Doppler method. The portal flow velocity in the fasting and in post prandial period was measured at the time interval of 15,30,45,60 and 90 minutesafter either solid or liquid meal ingestion. Solid meals include 4 idli’s each weighing 50 gmswith dhal and chutney. The liquid meal includes Ensure healthy mix in 270ml of water. Both the liquid and solid meals’ calorific value is 405. The results indicate that, the basal blood flow velocity in cirrhotic patients is on higher sidein comparison to normal subjects. Intake of solid as well as liquid meals increased the portal velocity in both normal as well as cirrhotic patients and it was found to be high at 45 minutes. In cirrhotic patients the liquid meal itself is able to increase the portal pressure in comparison to normal volunteers. The study can be concluded that being cirrhotic patients are more susceptible to vein puncture through increase in blood flow velocity low food load or liquid food might help them to control the velocity induced blood vessel rupturing. The observation has direct clinical implications and first time we are reporting with such a study in Indian population.

Hemodynamic Profile of Portopulmonary Hypertension

Portopulmonary hypertension (PPHTN) refers to the development of pulmonary arterial hypertension in the setting of portal hypertension with or without chronic hepatic failure. This syndrome is characterized by marked alternations of pulmonary vascular tone and obstruction of pulmonary arterial blood flow. An increased pulmonary blood flow, which is a hallmark of the hyperdynamic circulation of cirrhotic patients, seems to be present in almost all patients who develop PPHTN. The elevations of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) along with the transpulmonary gradient (TPG) have been considered in diagnosing PPHTN. Only a high TPG reflects the severity of obstruction to pulmonary blood flow and differentiates an elevated PAP with concomitant elevated PVR from the situation where the increase in PAP is due only to the hyperdynamic flow and elevated volume. A considerable risk for cardiovascular death arises when PAP increases significantly; this may occur in rapidly evolving syndromes, in very advanced disease, or during a complicated liver transplantation. The distinction between PPHTN and elevated PAP in the context of a hyperdynamic state is of great importance; a PAP increase of hyperkinetic origin, as opposed to PPHTN, is apparently not associated with a high risk for adverse effects during and following liver transplantation.

Prostaglandin production in cirrhosis and portal hypertension—Experimental and clinical study

Disease-related changes in prostaglandin (PG) levels may contribute to a bleeding tendency and local vasodilation in the portal circulation in patients with liver cirrhosis. We measured the plasma and tissue PG metabolite levels (6-keto PGF1 α and thromboxane TXB 2) in the systemic and portal circulation in 12 rats with CCl 4-induced liver cirrhosis (LC rats) and ten with portal hypertension induced by 2 weeks of partial portal ligation (PH rats) and compared them with normal control rats ( n=10). We also compared the plasma PG metabolite levels in the systemic and portal circulations in 11 cirrhotic patients with hepatocellular carcinoma (HCC) and five patient controls without liver disease. In the animal study, LC rats had significantly higher portal blood 6-keto PGF1 α ( P<0.01) and TXB 2 ( P<0.05) levels than the control rats; and significantly higher systemic blood TXB 2 level than PH rats ( P<0.05) and control rats ( P<0.05), but the systemic blood 6-keto PGF1 α levels were not significantly different among the three groups. PH and LC rats had significantly higher portal vein tissue 6-keto PGF1 α levels than the control rats ( P<0.01 and P<0.05), and the level in PH rats was higher than that in LC rats ( P<0.05). LC rats had significantly higher portal vein tissue TXB 2 level than control rats ( P<0.05). The liver tissue levels of both metabolites did not differ among the three groups. Compared with control rats, LC rats had significantly higher 6-keto PGF1 α/TXB 2 ratios in the portal circulation ( P<0.01) and liver tissue ( P<0.05); and PH rats had significantly higher ratios in the portal vein ( P<0.01), systemic circulation ( P<0.05) and liver tissue ( P<0.05). In the clinical study, both PG metabolite levels were significantly higher in the portal circulation than in the systemic circulation in cirrhotic patients with HCC, whereas the levels were only slightly higher in the portal circulation in control patient without liver disease. The PG metabolite ratio was significantly higher in the portal circulation than in the systemic circulation in cirrhotic patients (2.0±0.1 vs. 1.5±0.1, P<0.05), but the ratios were not significantly different in patient controls (1.8±0.3 vs. 1.3±0.1). These results suggest that the production of PG, especially of prostacycline, may be enhanced in the portal system in cirrhosis and may in part evoke portal pressure increase and other vascular alterations.

Decreased right heart blood volume determined by magnetic resonance imaging: evidence of central underfilling in cirrhosis

Whether the central blood volume is reduced or expanded in cirrhosis is still under debate. Accordingly, the current study was undertaken to assess the volume of the heart cavities. Ten cirrhotic patients and matched controls had their right and left ventricular end-diastolic volumes (RVDV and LVDV), and end-systolic volumes (RVSV and LVSV) determined by magnetic resonance imaging (MRI). RVDV (122 vs. control 166 mL, P < .02), RVSV (41 vs. 80 mL, P < .02) and right atrial volume (47 vs. 64 mL, P < .05) were significantly reduced in the patients. In contrast, LVDV (134 vs. 129 mL, NS), LVSV (54 vs. 40 mL, NS), and left atrial volume (70 vs. 57 mL, P = .08) were normal or slightly increased. The right ejection fraction (68% vs. 53%, P < .05) was significantly increased, but the left ejection fraction was slightly reduced (61% vs. 69%, NS). The central and arterial blood volume (CBV), assessed as the cardiac output (CO) multiplied by the central circulation time, was significantly decreased (1.47 vs. 1.81 L, P < .05). The noncentral blood volume (4.43 vs. 3.64 L, P < .02), plasma volume (4.05 vs. 3.27 L, P < .02), and CO (7.11 vs. control 5.22 L/ min, P < .01) were significantly increased in the patients. CCT (13.1 vs. 20.0 sec, P < .005) and the right ventricular transit time (0.79 vs. 1.35 sec, P < .005) were significantly reduced, but the left ventricular transit time was normal (0.91 vs. 0.88 sec, NS). Systemic vascular resistance was reduced (991 vs. 1,490 dyn-sec/cm 5, P < .01). Our results are in keeping with a hyperkinetic circulation in cirrhotic patients with central vascular underfilling with reduced right heart blood volume and central and arterial blood volume. The normal or slightly increased left heart blood volume suggests a complex pattern with a relatively decreased left ventricular function. The results support the concept of an abnormal distribution of the blood volume, with central and arterial underfilling (consequent on the combination of decreased systemic vascular resistance and left ventricular dysfunction) as major elements in the abnormal fluid homeostasis in cirrhosis.

Cardiovascular effects of octreotide in patients with hepatic cirrhosis

Octreotide is thought to reduce splanchnic and variceal blood flow with minimal effects on the systemic circulation in cirrhotic patients with portal hypertension. However, we noticed significant bradycardia in some patients immediately after administration of bolus doses of octreotide. Therefore, we investigated the effect of intravenous octreotide on systemic hemodynamics in 59 patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32 patients received a 25-micrograms bolus and 20 patients received an infusion of 50-micrograms/hr of octreotide/placebo. Immediately after the bolus dose of octreotide was administered, there were significant reductions in pulse rate (77 +/- 3 vs. 65 +/- 3 beats per minute, P < .01) and cardiac output (9.2 +/- 0.8 vs. 7.9 +/- 0.8 L/min; P < .01) and significant increases in mean arterial pressure (81 +/- 3 vs. 87 +/- 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 +/- 1.0 vs. 16.6 +/- 1.5 mm Hg; P < .01), right atrial pressure (3.8 +/- 0.8 vs. 6.6 +/- 1.0 mm Hg; P < .01), right ventricular pressure (7.1 +/- 0.6 vs. 12.5 +/- 1.3 mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 +/- 0.8 vs. 11.2 +/- 1.4 mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance. Thirty minutes after the start of the infusion, there were significant increases in mean right atrial pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. This study suggests that intravenous octreotide has significant effects on the systemic circulation in patients with cirrhosis and that these effects appear to be more marked after administration of bolus doses.

Cardiovascular effects of octreotide in patients with hepatic cirrhosis

Octreotide is thought to reduce splanchnic and variceal blood flow with minimal effects on the systemic circulation in cirrhotic patients with portal hypertension. However, we noticed significant bradycardia in some patients immediately after administration of bolus doses of octreotide. Therefore, we investigated the effect of intravenous octreotide on systemic hemodynamics in 59 patients with cirrhosis. In two double-blind, placebo-controlled protocols, 32 patients received a 25-μg bolus and 20 patients received an infusion of 50-μg/hr of octreotide/placebo. Immediately after the bolus dose of octreotide was administered, there were significant reductions in pulse rate (77 ± 3 vs. 65 ± 3 beats per minute, P < .01) and cardiac output (9.2 ± 0.8 vs. 7.9 ± 0.8 L/min; P < .01) and significant increases in mean arterial pressure (81 ± 3 vs. 87 ± 3 mm Hg; P < .05), mean pulmonary artery pressure (9.1 ± 1.0 vs. 16.6 ± 1.5 mm Hg; P < .01), right atrial pressure (3.8 ± 0.8 vs. 6.6 ± 1.0 mm Hg; P < .01), right ventricular pressure (7.1 ± 0.6 vs. 12.5 ± 1.3 mm Hg; P < .01), pulmonary capillary wedge pressure (4.8 ± 0.8 vs. 11.2 ± 1.4 mm Hg; P < .01), systemic vascular resistance, and pulmonary vascular resistance. Thirty minutes after the start of the infusion, there were significant increases in mean right atrial pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. This study suggests that intravenous octreotide has significant effects on the systemic circulation in patients with cirrhosis and that these effects appear to be more marked after administration of bolus doses.

Increased blood flow in the stomach of cirrhotic patients as assessed by radionuclide angiography.

To assess the gastric hemodynamics of patients with cirrhosis of the liver, radionuclide angiography of the left gastric artery, using technetium-99m-labeled human serum albumin (99mTc-HSA), was performed in 13 cirrhotics and 4 control subjects. The half-life (T1/2) of radioactivity of the stomach was significantly shorter in cirrhotics than in controls, 7.1 +/- 2.2 s (+/- SD, n = 13) and 14.1 +/- 3.4 s (+/- SD, n = 4), respectively (p less than 0.001). Accordingly, the calculated blood flow per unit plasma volume of the stomach of cirrhotics was significantly increased compared with that of controls, 6.4 +/- 1.9 ml/min (+/- SD, n = 13) and 3.1 +/- 0.8 ml/min (+/- SD, n = 4), respectively (p less than 0.01). These results provide direct evidence that a hyperdynamic state exists in the gastric circulation of cirrhotic patients.

A New Method for Evaluation of Portasystemic Shunting: The rectal octanoate tolerance test

Hepatic clearance of a small dose of a medium chain fatty acid was used to estimate portasystemic shunting in patients with cirrhosis. Sodium octanoate dissolved in isotonic saline was administered by rectum (11.4 mg per kg of lean body mass) in three groups of 10 patients with cirrhosis and in 10 noncirrhotic controls. Two groups of patients were classified as mild and severe cirrhotics on the basis of a clinical evaluation. The third group of cirrhotic patients had a surgical portacaval shunt. Serum octanoate levels were measured in each subject for a 1-hr period following the administration of sodium octanoate by rectum. A highly significant difference (P less than 0.001) was demonstrated between all four groups of subjects with highest levels occurring in the shunted cirrhotics and the lowest levels in the control group. Serum levels obtained in 2 patients before and after a portacaval shunt increased by a factor of 2 following the operation. Two patients with proven occlusion of a surgical shunt fell well within the range of the nonoperated cirrhotic patients. The results suggest that the rectal octanoate tolerance test can probably be used for evaluation of collateral circulation in cirrhotic patients and for testing the patency of surgical shunts.