Clinical trial NCT01715584: Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypertension
Keywords: Hypertension
Sevoflurane
Inhaled Anesthetic
Angiotensin Converting Enzyme Inhibitor
Angiotensin II Receptor Blocking Agent
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2012-10-29
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Systemic Vascular Resistance Index (SVRI)
timeFrame: approximately every 5 minutes for 6 hours
Secondary outcomes:
measure: Heart Rate
timeFrame: approximately every 5 minutes for 6 hours
measure: Systolic Blood Pressure
timeFrame: approximately every 5 minutes for 6 hours
measure: Diastolic Blood Pressure
timeFrame: approximately every 5 minutes for 6 hours
measure: Central Venous Pressure
timeFrame: approximately every 5 minutes for 6 hours
measure: Cardiac Output (CO)
timeFrame: approximately every 5 minutes for 6 hours
measure: Cardiac Index (CI)
timeFrame: approximately every 5 minutes for 6 hours
measure: Stroke Volume Varriation
timeFrame: approximately every 5 minutes for 6 hours
measure: Systemic Vascular Resistance
timeFrame: approximately every 5 minutes for 6 hours
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Campus
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Craig J Railton, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: