Cimetidine inhibits the hypoxia-induced increase in cerebral blood flow in dogs

Cimetidine is an H2 receptor-blocking drug frequently given to ICU patients for the prevention of stress ulcers. However, histamine causes potent cerebral vasodilation through the H2 receptors. This study tested the hypothesis that cimetidine, by blocking the H2 receptors, could blunt the increase of cerebral blood flow induced by hypoxia. We induced isocapnic hypoxia in 12 conscious dogs that were randomly divided into two groups. Six dogs received no treatment (control group), and the other six received iv cimetidine (4 mg/kg) to block the H2 receptors. Cerebral blood flow (CBF) was measured with the radioactive microsphere technique before, and 2 and 4 h after hypoxia was induced. In the control group, CBF significantly increased with hypoxia in all the regions of the brain. Cimetidine blunted this increase in all the regions of the brain except the pons and bulb. As a result of the reduced flow, cimetidine significantly decreased the oxygen supply to the brain compared to the control group. We conclude that cimetidine blunts the increase in CBF during hypoxia and might reduce oxygen supply to the brain in hypoxic patients.     

Effect of propranolol on hepatic blood flow in patients with cirrhosis

The effect of propranolol on systemic and hepatic hemodynamics was studied in patients with cirrhosis. One hour after 40 mg propranolol by mouth as well as during continuous oral dosing at doses that reduced heart rate 25%, cardiac output and the hepatic venous pressure gradient fell significantly, whereas arterial pressure and hepatic blood flow did not change significantly. In six patients with cirrhosis and surgical end-to-side portacaval shunts, cardiac output and the hepatic venous pressure gradient also decreased 15 minutes after intravenous propranolol (5 mg), whereas hepatic blood flow did not change significantly. In the patients with surgical shunts, systemic vascular resistance rose significantly but hepatic arterial vascular resistance fell. Our data show that in patients with cirrhosis, propranolol induces an increase in the fraction of cardiac output reaching the liver.     

Sepsis biomarkers in polytrauma patients

Despite continual advances in medical care and injury prevention efforts, traumatic injury remains a leading cause of death of Americans with these deaths occurring in a tri-modal pattern. The early phases of this pattern are characterized by immune activation whereas the last phase is marked by profound immune dysfunction. It is during this last phase that many trauma patients die of septic complications pointing to a dire need for a specific biomarker for post-traumatic infection. This article discusses several biomarkers, including emerging ones, for infection and sepsis following trauma including inflammatory cytokines, intracellular proteins, and cellular biomarkers.     

Relationship between portal blood flow measured by image-directed doppler ultrasonography and hepatic blood flow measured by indocyanine green constant infusion in patients with cirrhosis

The validity of portal blood flow measurement in image-directed Doppler ultrasound (PBF-IDU) is still under debate. In this study PBF-IDU has been compared with hepatic blood flow measured by the indocyanine green constant infusion technique (HBF-ICG), which is the reference invasive method with which to measure total hepatic blood flow in man (ie, the sum of hepatic artery and portal vein blood flow). In 27 cirrhotic patients with hepatopetal portal blood flow, PBF-IDU was measured by multiplying the portal vein cross-sectional area by the averaged mean velocity of blood in the vessel. About 1 hour later HBF-ICG was measured during hepatic vein catheterization performed to evaluate portal hypertension. In 19 of 27 patients, intra-hepatic arterial resistance indices were also measured. PBF-IDU and HBF-ICG were 1.010 ± 0.555 L/min (M ± SD) and 1.496 ± 0.731 L/min, respectively. Blood flow measured by the two methods showed a close correlation (r = 0.80, p < 0.001). The regression line showed that HBF-ICG was systematically higher than PBF-IDU (mean difference + 29 ± 30%). The hepatic artery component of HBF-ICG probably accounted for the difference. An inverse correlation was found between the differences between the two procedures and intrahepatic arterial resistance indices (r = ?0.52, p = 0.04), which may be considered indirect parameters of arterial supply. It can be concluded that image-directed Doppler ultrasound is a sufficiently accurate method to measure portal blood flow in cirrhotics. © 1995 John Wiley & Sons, Inc.     

Real-time assessment of hepatic function is related to clinical outcome in critically ill patients after polytrauma

OBJECTIVES: The aim was to investigate the outcome MODS/MOF in critically ill patients with regard to early hepatic dysfunction. METHODS: Thirty adult polytrauma patients admitted to the ICU, with ISS >or=16 were prospectively investigated. Real-time liver function was assessed using the MEGX test and arterial ketone body ratio (AKBR) 12-24 h after admittance to ICU, and on days 3, 5, 8, 12. RESULTS: Six patients (19%) died between days 4 and 29. Non-survivors were older (64.2 vs. 31.5 years), had a significantly higher ISS (40.5 vs. 30; p=0.002) and MODS score (9.5 vs. 5; p=0.001) on admittance to the ICU than survivors. On day 3 MEGX values (31 vs. 71.3 microg/L; p=0.001) and the AKBRs (0.6 vs. 1.3; p=0.001) were significantly lower in non-survivors than in survivors whereas IL-6 levels were significantly higher in the former group (519 vs. 61 microg/L; p=0.05). CONCLUSIONS: The MEGX test and AKBR are sensitive early indicators of hepatic dysfunction in severely injured polytrauma patients at risk for developing MODS/MOF.     

Doppler ultrasonographic evaluation of hepatic blood flow in clinical sepsis

The aim of this study was to determine the hemodynamic response of the liver to sepsis by measuring hepatic blood flow. Thirty patients with sepsis were examined using Doppler ultrasonography and measurements of portal venous blood flow, hepatic arterial blood flow and total hepatic blood flow were recorded. Data were retrospectively reviewed and compared with findings for a control group of 12 healthy subjects. Significantly increased values of hepatic blood flow (p<0.01) and portal venous blood flow (p<0.001) were observed in patients during early sepsis (5 h). In contrast, hepatic arterial blood flow was not significantly different from controls. During late sepsis (24 h), no significant differences were observed between patients and healthy controls. Our results support the concept that hepatic blood flow is significantly increased in patients with early sepsis due to increased portal venous blood flow; however, during late sepsis, hepatic blood flow is similar to that in controls.     

Induction of anaesthesia by propofol and hepatic blood flow in the rabbit

Summary. Effects of propofol (12.5 mg kg^-1, i.v. bolus injection) or 0.9% sodium chloride on arterial blood pressure, arterial blood gases and hepatic circulation (radio-labelled microsphere technique) were studied in 15 conscious and unpremedicated rabbits. No significant changes were observed after sodium chloride. Propofol resulted in anaesthesia, respiratory depression (-49±14% decrease in PaO₂; mean±SD) and hypotension (-49±13% decrease in mean arterial pressure; mean±SD), but no changes in hepatic arterial and portal venous blood flows. We conclude that propofol does not affect the liver circulation despite marked depression of mean arterial pressure and respiration.     

Effect of enteral versus parenteral feeding on hepatic blood flow and steady state propofol pharmacokinetics in ICU patients

Objective: The main objective of this study was to evaluate the effect of switching from parenteral to enteral feeding on liver blood flow and propofol steady-state blood concentrations in patients in the intensive care unit (ICU). Design and patients: Steady-state blood concentrations of propofol were measured in eight ICU patients before (on days D –3, D –2, and D –1) and after (on days D + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day D0). All patients received a continuous intravenous infusion of propofol (4.5 mg · kg^–1· h^–1) from several days before the start of the study, continuing throughout the experimental period. Hepatic blood flow was estimated by measuring steady-state D-sorbitol hepatic clearance. Results: Hepatic blood flow was high and was not affected by switching from parenteral to enteral feeding: 33 ± 8 ml · min^–1· kg^–1 (mean ± SD) and 33 ± 10 ml · min^–1· kg^–1 on D-3 and D –1, respectively, as compared to 37 ± 11 ml · min^–1· kg^–1 and 34 ± 8 ml · min^–1· kg^–1 on days D + l and D + 3, respectively. Systemic clearance of propofol was much higher than liver blood flow with average values on the six observation days ranging from 74.0 to 81.2 ml · min^–1· kg^–1 and was not affected by switching from parenteral to enteral feeding. Conclusions: Liver blood flow and systemic clearance of propofol were not affected by switching from parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic clearance accounted for at least two thirds of the overall systemic clearance of propofol. Received: 18 July 1997 Accepted: 1 April 1998     

The effects of oral nifedipine on hepatic blood flow in humans

Duplex ultrasonography was used to measure changes in hepatic blood flow in 13 healthy volunteers after they received single doses of 10 mg oral nifedipine and placebo. Blood flow was measured in the hepatic artery and branches of the portal and hepatic veins at baseline and 0.3, 0.6, 1, 1.5, 2, 3, 4, and 5 hours after drug administration. Cardiac output was also measured at baseline and 1, 2, and 3 hours after dosing. Blood flow initially increased in all three vessels 0.6 hour after administration of nifedipine (29%, 56%, and 31% in the hepatic artery, hepatic vein, and portal vein, respectively) compared with placebo. Flow rapidly returned to baseline in the hepatic artery and hepatic vein, whereas it appeared to remain elevated through 3 hours in the portal vein. Nifedipine administration resulted in an increase in cardiac output of 26%, 22%, and 14% above placebo at 1, 2, and 3 hours, respectively. No significant differences were detected in the systolic, diastolic, or mean arterial blood pressures after nifedipine or placebo. This study demonstrates that nifedipine increases hepatic blood flow in a transient nature and systemic hemodynamic parameters do not necessarily reflect specific organ responses. The nifedipine-induced change in blood flow should be considered when nifedipine is coadministered with high-clearance drugs, because systemic availability may be increased.