Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics

Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics? - A Pilot Study. Optional Deoxyribo-Nucleic Acid Donation for the Study of Hypertension.

It is controversial whether or not patients whose Renin Angiotensin System is blocked for the treatment of hypertension suffer increased risk when undergoing surgery and anaesthesia. The investigators wish to test the hypothesis: Blockade of the Renin Angiotensin System causes altered dose response under general anaesthesia in a dose dependant manner. The investigators wish to look for altered responses across the usual anaesthetic dosing range as measured by blood pressure and heart responses.

There has been mixed results in retrospective studies examining the effects of renin angiotensin blockade for the treatment of cardiovascular disease and post operative outcomes. Studies done in high risk patients have shown increased risk of death if patients are exposed to angiotensin converting enzyme inhibitors and angiotensin blocking agents. The hypothesis is that patients exposed to medications that block the renin angiotensin system have altered dose response (a type of adverse drug reaction) to inhaled anaesthetic agents in a dose dependant manner as measured by cardiovascular response, specifically systemic vascular resistance index. This is a pilot study of hypertensive patients undergoing anaesthesia and composite head and neck surgery. The patients will be separated into three groups: Angiotensin converting enzyme inhibitor exposed, Angiotensin Receptor Blocking Agent exposed, and any other treated hypertension. Following separation into groups based upon preoperative medication exposures each group will be randomized to determine the order in which two types of inhaled anaesthetics are administered. Each subject will be randomized to receive either Sevoflurane/air/oxygen first or Sevoflurane/50 per cent nitrous oxide/oxygen second or vice versa. The dose of the anaesthetic will be adjusted across the dosing range from 0.8 MAC (minimum alveolar concentration) to 1.6 MAC in steps of 0.2 MAC. Each subject will have hemodynamic parameters measured at each dose of anaesthetic at each MAC. Five measurements of hemodynamic parameters will be recorded to minimize the effects of surgery on each measurement. The hemodynamic variables will be measured using a Flotrak and Vigeleo monitor and the quantities to be measured are: heart rate, blood pressure, systemic vascular resistance, systemic vascular resistance index, cardiac output, cardiac index, central venous pressure, stroke volume variation. The subjects are offered the opportunity to donate DNA for future study of hypertension.

Hypertension, Sevoflurane, Inhaled Anesthetic, Angiotensin Converting Enzyme Inhibitor, Angiotensin II Receptor Blocking Agent

Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients exposed to Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)will make up this arm. Preoperative Exposure to any of the following Angiotensin Converting Enzyme Inhibitors Enalapril (Vasotec/Renitec) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace) Quinapril (Accupril) Perindopril (Coversyl/Aceon) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril) Benazepril (Lotensin) Imidapril (Tanatril) Zofenopril (Zofecard) Trandolapril (Mavik/Odrik/Gopten) Fosinopril (Fositen/Monopril)

Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients exposed to Angiotensin Receptor Blocking Agents (ARBs). Preoperative Exposure to any of the following Angiotensin II Receptor Blocking Agents Losartan(Cozaar) Candesartan (Atacand) Valsartan (Diovan) Irbesartan (Avapro) Telmisartan (Micardis) Eprosartan (Teveten) Olemisartan (Benicar) Azilsartan (Edarbi)

Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients not exposed to angiotensin converting enzyme inhibitors or Angiotensin receptor blocking agents will be put into this arm.

Sevoflurane (Sevorane, Ultane, Sojourn), 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane, fluoromethyl hexafluoroisopropyl ether, Nitrous oxide, oxgyen, air, nitrogen

Patients in each arm will be randomized to receive either: 50 per cent oxygen, air, and sevoflurane or 50% nitrous oxide, oxygen and sevoflurane. They will then cross over to the other gas mixture. The depth of each the anesthetic will be varied from 0.8 MAC (minimum alveolar concentration) to 1.6 MAC in 0.2 MAC steps. Hemodyamic variables will be measured at each anesthetic concentration (average of five measurements). Time will be allowed for anesthetic agent equilibration. Paralysis and analgesia using rocuronium and fentanyl will be provided to ensure patients do not move at low (less than 1.0 MAC. It is estimated the time for the cross over experiment will be approximately six hours.

A calculated hemodyamic parameter that assesses the resistance the heart faces to the forward flow of blood. Corrected for body surface area. SVRI = (cardiac output/blood pressure)/body surface area.

Calculated volume of blood flow in Litres per minute(measured in mmHg). Cardiac Output = mean arterial pressure/systemic vascular resistance.

Calculated volume of blood flow in Litres per minute(measured in mmHg/m2), corrected for body surface area. Cardiac Output = (mean arterial pressure/systemic vascular resistance)/body surface area.

Calculated variation in stroke volume between heart beats (blood pressure = stroke volume x rate x systemic vascular resisitance).measured in real time throughout experiment, and at each anesthetic concentration

A calculated parameter reflecting the resistance the heart faces to the forward flow of blood. Not corrected for body surface area. SVR = cardiac ouptut / blood pressure. Measured at each concentraion of inhaled anesthetic

Inclusion Criteria: age over 40 composite head and neck tumor resection treated hypertension hypertension medications taken on morning of surgery (except diuretics) Exclusion Criteria: patient refusal age less than 40 or over 80 years combined surgical procedures emergency surgery Left ventricular ejection fraction less than 50 per cent calculated creatinine clearance less than 60 mL per minute