Preoperative Ephedrine Attenuates the Hemodynamic Responses of Propofol During Valve Surgery: A Dose Dependent Study

This study has been completed.
Sponsor:
Collaborator:
Mansoura University
Information provided by:
King Faisal University
ClinicalTrials.gov Identifier:
NCT01006863
First received: October 30, 2009
Last updated: May 26, 2010
Last verified: May 2010
  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

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Further study details as provided by King Faisal University:

Primary Outcome Measures:
  • 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 Measures:
  • 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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01006863

Locations
Egypt
Mansoura University Hospitals
Mansoura, DK, Egypt
Saudi Arabia
King Fahd Hospital of the University
Al Khubar, Eastern, Saudi Arabia
Sponsors and Collaborators
King Faisal University
Mansoura University
Investigators
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 April 14, 2014