Preoperative Ephedrine Attenuates the Hemodynamic Responses of Propofol During Valve Surgery: A Dose Dependent Study
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Purpose
The prophylactic use of small doses of ephedrine may be effective in obtunding of the hypotension responses to propofol with minimal hemodynamic and ST segment changes. The investigators aimed to evaluate the effects of small doses of ephedrine on hemodynamic responses of propofol anesthesia for valve surgery.
There is widespread interest in the use of propofol for the induction and maintenance of anesthesia for fast track cardiac surgery. However, its use for induction of anesthesia is often associated with a significant rate related transient hypotension for 5-10 minutes. This is mainly mediated with decrease in sympathetic activity with minor contribution of its direct vascular smooth muscle relaxation and direct negative inotropic effects.
Ephedrine has demonstrated as a vasopressor drug for the treatment of hypotension in association with spinal and general anesthesia. Prophylactic use of high doses of ephedrine [10-30 mg] was effective in obtunding the hypotensive response to propofol with associated marked tachycardia. However, the use of smaller doses (0.1-0.2 mg/kg) was successfully attenuated, but not abolished, the decrease in blood pressure with transient increase in heart rate. This vasopressor effect is mostly mediated by β-stimulation rather than α-stimulation and also indirectly by releasing endogenous norepinephrine from sympathetic nerves.
Because the effect of decreasing the dose of ephedrine from 0.1 to 0.07 mg/kg may be clinically insignificant, the investigators postulated that the prophylactic use of small dose of ephedrine may prevent propofol-induced hypotension after induction of anesthesia for valve surgery with minimal in hemodynamic, ST segment, and troponin I changes.
The aim of the present study was to investigate the effects of pre-induction administration of 0.07, 0.1, 0.15 mg/kg of ephedrine on heart rate (HR), mean arterial blood pressure (MAP), central venous and pulmonary artery occlusion pressures (CVP and PAOP, respectively), cardiac (CI), stroke volume (SVI), systemic and pulmonary vascular resistance (SVRI and PVRI, respectively), left and right ventricular stroke work (LVSWI and RVSWI, respectively) indices, ST segment, and cardiac troponin I (cTnI) changes in the patients anesthetized with propofol-fentanyl for valve surgery.
| Condition | Intervention | Phase |
|---|---|---|
|
Hypotension Valve Surgery |
Drug: Ephedrine Drug: Placebo Drug: Phenylephrine |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Caregiver, Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | Preoperative Ephedrine Attenuates the Hemodynamic Responses of Propofol During Valve Surgery: A Dose Dependent Study |
- Primary outcome variables include the changes in hemodynamic variables namely; MAP, SVRI, CI, HR, LVSWI, and ST segment changes. [ Time Frame: before (baseline), and 5 min after induction, 5, 10, 15, and 30 min after endotracheal intubation; and 15 min after sternotomy. ] [ Designated as safety issue: Yes ]
- Secondary outcome variables were outcome data, troponin I changes, and the need for vasoactive drugs. [ Time Frame: cardiac troponin I. measured at before, 3, 12, 24, and 48 hours after CPB ] [ Designated as safety issue: Yes ]
| Enrollment: | 150 |
| Study Start Date: | March 2004 |
| Study Completion Date: | March 2010 |
| Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Ephedrine 0.15 mg/kg
received intravenous injection of 0.1 mL/kg of a study solution containing 1.5 mg/kg of ephedrine
|
Drug: Ephedrine
Subjects were allocated randomly to five groups by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code. The subjects received intravenous injection of 0.1 mL/kg of a study solution containing either saline 0.9% solution [group 1 (n=30)], ephedrine 0.7 mg/mL [group 2 (n=30)], ephedrine 1 mg/mL [group 3 (n=30)] or ephedrine 1.5 mg/mL [group 4 (n=30)]or phenylephrine 15 mcg/mL [group 5 (n=30)]. All study solutions were injected over 1 min at 1 min before induction of anesthesia. The placebo and the ephedrine solutions were prepared in identical syringes labeled 'study drug' by the local pharmacy department before induction of anesthesia.
|
|
Active Comparator: Ephedrine 0.1 mg/kg
received intravenous injection of 0.1 mL/kg of a study solution containing 1 mg/kg of ephedrine
|
Drug: Ephedrine
Subjects were allocated randomly to five groups by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code. The subjects received intravenous injection of 0.1 mL/kg of a study solution containing either saline 0.9% solution [group 1 (n=30)], ephedrine 0.7 mg/mL [group 2 (n=30)], ephedrine 1 mg/mL [group 3 (n=30)] or ephedrine 1.5 mg/mL [group 4 (n=30)]or phenylephrine 15 mcg/mL [group 5 (n=30)]. All study solutions were injected over 1 min at 1 min before induction of anesthesia. The placebo and the ephedrine solutions were prepared in identical syringes labeled 'study drug' by the local pharmacy department before induction of anesthesia.
|
|
Active Comparator: Ephedrine 0.07 mg/kg
received intravenous injection of 0.1 mL/kg of a study solution containing 0.7 mg/kg of ephedrine
|
Drug: Ephedrine
Subjects were allocated randomly to five groups by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code. The subjects received intravenous injection of 0.1 mL/kg of a study solution containing either saline 0.9% solution [group 1 (n=30)], ephedrine 0.7 mg/mL [group 2 (n=30)], ephedrine 1 mg/mL [group 3 (n=30)] or ephedrine 1.5 mg/mL [group 4 (n=30)]or phenylephrine 15 mcg/mL [group 5 (n=30)]. All study solutions were injected over 1 min at 1 min before induction of anesthesia. The placebo and the ephedrine solutions were prepared in identical syringes labeled 'study drug' by the local pharmacy department before induction of anesthesia.
|
|
Placebo Comparator: Placebo
received intravenous injection of 0.1 mL/kg of a study solution containing either saline 0.9% solution
|
Drug: Placebo
Subjects were allocated randomly to five groups by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code. The subjects received intravenous injection of 0.1 mL/kg of a study solution containing either saline 0.9% solution [group 1 (n=30)], ephedrine 0.7 mg/mL [group 2 (n=30)], ephedrine 1 mg/mL [group 3 (n=30)] or ephedrine 1.5 mg/mL [group 4 (n=30)]or phenylephrine 15 mcg/mL [group 5 (n=30)]. All study solutions were injected over 1 min at 1 min before induction of anesthesia. The placebo and the ephedrine solutions were prepared in identical syringes labeled 'study drug' by the local pharmacy department before induction of anesthesia.
|
|
Active Comparator: Phenylephrine
received intravenous injection of 0.1 mL/kg of a study solution containing 15 mcg/kg of phenylephrine
|
Drug: Phenylephrine
Subjects were allocated randomly to five groups by drawing sequentially numbered sealed opaque envelopes containing a computer-generated randomization code. The subjects received intravenous injection of 0.1 mL/kg of a study solution containing 15 mcg/ml of phenylephrine [group 5 (n=30)] All study solutions were injected over 1 min at 1 min before induction of anesthesia. The placebo, the ephedrine, and the phenylephrine solutions were prepared in identical syringes labeled 'study drug' by the local pharmacy department before induction of anesthesia.
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- One hundred fifty ASA III-IV patients
- aged 18-55 years
- scheduled for elective valve surgery
Exclusion Criteria:
- Patients with documented un-controlled hypertension -ischemic heart disease-
- left ventricular ejection fraction less than 45%
- peripheral vascular disease
- thyrotoxicosis
- neurological
- hepatic
- renal diseases
- pregnancy
- re-do or emergency surgery
- allergy to the study medications
- those requiring preoperative inotropic, vasopressor or mechanical circulatory or ventilatory support
- those who had electrocardiograph (ECG) characteristics that would interfere with ST segment monitoring, included baseline ST segment depression, left bundle-branch block, atrial fibrillation, left ventricular hypertrophy, digitalis effect, QRS duration >0.12 s, as well as pacemaker-dependent rhythms,
Contacts and Locations| Egypt | |
| Mansoura University Hospitals | |
| Mansoura, DK, Egypt | |
| Saudi Arabia | |
| King Fahd Hospital of the University | |
| Al Khubar, Eastern, Saudi Arabia | |
| Principal Investigator: | Mohamed R El Tahan, M.D | King Faisal University |
More Information
No publications provided
| Responsible Party: | Dr. Mohamed R. El-Tahan, Anesthesiology Department, King Faisal University |
| ClinicalTrials.gov Identifier: | NCT01006863 History of Changes |
| Other Study ID Numbers: | 28/2004 |
| Study First Received: | October 30, 2009 |
| Last Updated: | May 26, 2010 |
| Health Authority: | Egypt: Institutional Review Board |
Keywords provided by King Faisal University:
|
Ephedrine phenylephrine hypotension |
propofol anesthesia cardiac valve surgery |
Additional relevant MeSH terms:
|
Hypotension Vascular Diseases Cardiovascular Diseases Ephedrine Phenylephrine Oxymetazoline Pseudoephedrine Propofol Central Nervous System Stimulants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Sympathomimetics Autonomic Agents |
Peripheral Nervous System Agents Vasoconstrictor Agents Cardiovascular Agents Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Nasal Decongestants Respiratory System Agents Bronchodilator Agents Anti-Asthmatic Agents Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-Agonists Adrenergic Agonists Cardiotonic Agents Mydriatics |
ClinicalTrials.gov processed this record on June 18, 2013