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.
试验速览
- 阶段
- 4 期
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Systemic Vascular Resistance Index (SVRI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age over 40
- •composite head and neck tumor resection
- •treated hypertension
- •hypertension medications taken on morning of surgery (except diuretics)
排除标准
- •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
研究组 & 干预措施
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)
干预措施: 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)
干预措施: 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.
干预措施: Sevoflurane/oxygen/air/nitrous oxide (Other)
结局指标
主要结局
Systemic Vascular Resistance Index (SVRI)
时间窗: 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.
次要结局
- Stroke Volume Varriation(approximately every 5 minutes for 6 hours)
- Systolic Blood Pressure(approximately every 5 minutes for 6 hours)
- Cardiac Output (CO)(approximately every 5 minutes for 6 hours)
- Cardiac Index (CI)(approximately every 5 minutes for 6 hours)
- Diastolic Blood Pressure(approximately every 5 minutes for 6 hours)
- Central Venous 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)
研究者
Craig Railton
Assistant Professor
Lawson Health Research Institute