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

NCT01006863 | Completed Phase 2

• 1 other identifier: 28/2004
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Hypotension; Valve Surgery

Keywords

Ephedrine; phenylephrine; hypotension; propofol; anesthesia; cardiac valve surgery

Outcome Measures

Primary Outcomes (1)

• Primary outcome variables include the changes in hemodynamic variables namely; MAP, SVRI, CI, HR, LVSWI, and ST segment changes.

  before (baseline), and 5 min after induction, 5, 10, 15, and 30 min after endotracheal intubation; and 15 min after sternotomy.

Secondary Outcomes (1)

• Secondary outcome variables were outcome data, troponin I changes, and the need for vasoactive drugs.

  cardiac troponin I. measured at before, 3, 12, 24, and 48 hours after CPB

Study Arms (5)

Ephedrine 0.15 mg/kg

ACTIVE COMPARATOR

received intravenous injection of 0.1 mL/kg of a study solution containing 1.5 mg/kg of ephedrine

Drug: Ephedrine

Ephedrine 0.1 mg/kg

ACTIVE COMPARATOR

received intravenous injection of 0.1 mL/kg of a study solution containing 1 mg/kg of ephedrine

Drug: Ephedrine

Ephedrine 0.07 mg/kg

ACTIVE COMPARATOR

received intravenous injection of 0.1 mL/kg of a study solution containing 0.7 mg/kg of ephedrine

Drug: Ephedrine

Placebo

PLACEBO COMPARATOR

received intravenous injection of 0.1 mL/kg of a study solution containing either saline 0.9% solution

Drug: Placebo

Phenylephrine

ACTIVE COMPARATOR

received intravenous injection of 0.1 mL/kg of a study solution containing 15 mcg/kg of phenylephrine

Drug: Phenylephrine

Interventions

Ephedrine DRUG

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.

Ephedrine 0.07 mg/kg; Ephedrine 0.1 mg/kg; Ephedrine 0.15 mg/kg

Placebo DRUG

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

Phenylephrine DRUG

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.

Phenylephrine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• One hundred fifty ASA III-IV patients
• aged 18-55 years
• scheduled for elective valve surgery

You may not qualify if:

• 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,

Sponsors & Collaborators

• King Faisal University: lead
• Mansoura University: collaborator

Study Sites (2)

Mansoura University Hospitals

Al Mansurah, DK, Egypt

Location

King Fahd Hospital of the University

Dammam, Eastern Province, Saudi Arabia

Location

MeSH Terms

Conditions

Hypotension

Interventions

Ephedrine; Phenylephrine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines; Ethanolamines

Study Officials

• Mohamed R El Tahan, M.D

  King Faisal University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 3, 2009
• Study Start: March 1, 2004
• Primary Completion: June 1, 2009
• Study Completion: March 1, 2010
• Last Updated: September 2, 2020

Record last verified: 2020-08

Locations

EG (1); SA (1)