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.
Trial Snapshot
- Phase
- Phase 4
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Systemic Vascular Resistance Index (SVRI)
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Angiotensin Converting Enzyme Exposed
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)
Intervention: Sevoflurane/oxygen/air/nitrous oxide (Other)
Angiotensin Receptor Blocker Exposed
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)
Intervention: Sevoflurane/oxygen/air/nitrous oxide (Other)
Non ACE/ARB Exposed
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.
Intervention: Sevoflurane/oxygen/air/nitrous oxide (Other)
Outcomes
Primary Outcomes
Systemic Vascular Resistance Index (SVRI)
Time Frame: approximately every 5 minutes for 6 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.
Secondary Outcomes
- Cardiac Output (CO)(approximately every 5 minutes for 6 hours)
- Cardiac Index (CI)(approximately every 5 minutes for 6 hours)
- Central Venous Pressure(approximately every 5 minutes for 6 hours)
- Stroke Volume Varriation(approximately every 5 minutes for 6 hours)
- Systolic Blood Pressure(approximately every 5 minutes for 6 hours)
- Diastolic Blood Pressure(approximately every 5 minutes for 6 hours)
- Heart Rate(approximately every 5 minutes for 6 hours)
- Systemic Vascular Resistance(approximately every 5 minutes for 6 hours)
Investigators
Craig Railton
Assistant Professor
Lawson Health Research Institute