Serum alanine transaminase total bilirubin concentrations predict CYP3A activity as measured by midazolam and 1'-hydroxylation.

BACKGROUND: Microsomal enzyme P450 (CYP450) plays an important role in metabolism of most xenobiotics. The activity of CYP3A decreases in patients with liver dysfunction. However, whether serum concentrations of liver enzymes reflect the activity of CYP3A is unclear. We aimed to search for a new clue to predict the activity of CYP3A and guide clinical medication. MATERIAL AND METHODS: Forty-five patients undergoing surgery under general anesthesia were enrolled in the study, including 15 cases with normal liver function (Group N), 15 cases with moderate fatty liver according to both the results of ultrasonic diagnosis of moderate fatty liver and the laboratory results of elevated alanine transaminase less than 3 times the normal (Group M), and 15 cases with end-stage liver disease (Group S). Each patient received a single dose of 5 mg midazolam intravenously. CYP3A activity was measured by plasma 1'hydroxymidsazolam/midazolam (1'-OH-MDZ/MDZ) ratio at 2 h after administration of midazolam. RESULTS: They was no significant difference in CYP3A activity between the patients with normal liver function and moderate fatty liver (P=0.332). The activity of CYP3A in Group S was lower than in Group N and Group M (P=0.000). Multiple linear regression analysis showed a statistically significant linear relationship between the activity of CYP3A and alanine transaminase (ALT, R2=0.682, P=0.000), and total bilirubin (TB, R2=0.519, P=0.002). There were no other factors, including albumin (ALB, P=0.881) and alkaline phosphatase (ALP, P=0.497), correlated with the activity of CYP3A. CONCLUSIONS: We conclude that the activity of CYP3A in patients with end-stage liver disease decreased. The decrease in the activity of CYP3A was determined by the increase in the serum concentration of ALT and TB and not by patient's age or body weight. ALT and TB therefore might have predictive value for the activity of CYP3A. An abnormal liver function test likely gives the clinician a hint about dosage adjustment.

Inferior thyroid artery pseudoaneurysm associated with internal jugular vein puncture: a case report.

BACKGROUND: Central venous catheter placement is an important aspect of patient care for the administration of fluids and medications and for monitoring purposes. However, it is still associated with significant morbidity and mortality. CASE PRESENTATION: We report a case of iatrogenic inferior thyroid artery pseudoaneurysm during the central line placement due to internal jugular vein puncture. This is a rare complication of central venous cannulation. Fortunately the pseudoaneurysm was monitored closely, diagnosed promptly and obliterated by using radiological intervention. We discuss the risk factors and management of the unintended artery puncture. CONCLUSION: The pathway of the management post arterial puncture depends on the size of the needle or catheter, which is direct related to the consequence of arterial injuries. Identifying risk factors is very important to avoid the complications. However, the use of ultrasound guided venipuncture is the most important method to avoid mechanical complications.

Effect of hepatic function on the EC50 of midazolam and the BIS50 at the time of loss of consciousness.

OBJECTIVE: To explore the effect of hepatic function on loss of consciousness (LOC) and bispectral index (BIS) during sedation with midazolam (MDZ). METHODS: Forty-five patients were assigned to three groups according to their liver function. Thirty of these patients with diagnoses of cholelithiasis were scheduled laparoscopic cholecystectomy, including 15 patients with normal liver function (normal group), and 15 patients with moderately abnormal liver function based on the results of ultrasonic diagnosis of a moderately fatty liver and elevated alanine transaminase levels of less than three times normal (moderate group). The other 15 patients with end-stage liver disease (severe group) underwent liver transplantation. Each patient was administered MDZ by way of target-controlled infusion to increase the concentration gradually. At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ. The concentration of MDZ (EC50) and the BIS value (BIS50) at which 50% of patients lose consciousness were calculated using logistic regression. RESULTS: At the time of LOC, the EC50 of MDZ and the BIS50 were similar in the normal and moderate groups (P>0.05). LOC occurred at a lower EC50 of MDZ and at a higher BIS50 in the severe group, compared with the normal and moderate groups (P<0.01). CONCLUSIONS: Patients with end-stage liver disease were more sensitive to MDZ and this affected the prediction of their time of LOC following MDZ administration. There were no changes in response in patients with moderately abnormal hepatic function.