A Sensitive Method for Measuring Plasma Catecholamines and Its Application on the Study of the Effect of Alfentanil and Esmolol on Intra-Operative Hypertension

This dissertation, "A Sensitive Method for Measuring Plasma Catecholamines and Its Application on the Study of the Effect of Alfentanil and Esmolol on Intra-operative Hypertension" by 蕭德成, Tak-shing, Siu, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled 'A Sensitive Method for Measuring Plasma Catecholamines and Its Application on The Study of The Effect of Alfentanil and Esmolol on Intra-operative Hypertension' Submitted by Siu Tak-shing for the degree of Master of Philosophy at the University of Hong Kong in September 1998. Hypertension and tachycardia often occur during laryngoscopy and endotracheal intubation (LETI) following induction of anaesthesia. These responses to LETI can be profound and associated with serious cardiovascular and cerebral side effects. Because elevation of plasma catecholamine levels is often associated with hypertension, the haemodynamic changes are probably related to sympathetic stimulation. A simple and sensitive method was developed for the analysis of catecholamines in plasma, using alumina extraction followed by high performance liquid chromatography with coulometric detection. The three catecholamines [norepinephrine (NE), epinephrine (EP) and dopamine (DA)] as well as 3,4-dihydroxybenzylamine [the internal standard], were adsorbed on alumina at pH 8.6. The catechols were desorbed by eluting with 0.1 mol/L phosphoric acid, and 50 L was injected into HPLC. Separation of the compounds was achieved isocratically with a C18 5m column (150x4mm) at 45 C. The mobile phase consisted of 12 mmol/L phosphate buffer at pH 2.8 containing 24 mmol/L heptanesulfonate with a methanol content of 22%. At a flow rate of 1.0 mL/min, the chromatography was completed in 12 minutes. The analytes were detected at an oxidation potential of 350 mV. The lower limit of detection was 0.1, 0.1 and 0.2 nmol/L for NE, EP and DA irespectively. The day-to-day precision was less than 10%. There were no endogenous interferences in plasma. In addition, presence of diuretics, β-adrenoceptor blockers, calcium channel blockers and other vasodilators; and drugs for induction of anaesthesia did not interfere with the assay. To illustrate the validity of the method, forty-five patients, ASA physical status I or II, scheduled for elective abdominal surgery, were randomly assigned in a double-blind, placebo-controlled manner to receive, after induction of anaesthesia and before LETI, an intravenous dose of one of the three study drugs, saline, 30 g/kg alfentanil, or 2 mg/kg esmolol. Patients receiving saline showed significant increases in systolic, diastolic and mean blood pressure, heart rate, plasma NE and EP concentrations in response to LETI. The haemodynamic responses were positively correlated with the catecholamines responses. Alfentanil 30 g/kg prevented any increase in heart rate and blood pressures (BP), and was associated with a decrease in plasma NE and EP after LETI. Esmolol 2 mg/kg attenuated tachycardia, but did not prevent the increased BP in response to LETI. Esmolol did not lower the increases in plasma NE and EP that associated with LETI. The described analytical method has demonstrated a positive correlation of plasma catecholamines and cardiovascular parameters during the episodes of anaesthetic induction and LETI. In the future, with more careful, unbiased patient selection and more directed hypotheses, the analytical procedure could be reliable and sensitive enough in the clinical study of other forms of hypertension such as essential hypertension. ii DOI: 10.5353/th_b3016257 Subject