Comparative Efficacity of Ephedrine Versus Norepinephrine to Correct Anesthesia Induction Related Hypotension

Study Overview
=================
Brief Summary
-----------------
Hypotension occurs frequently after anesthesia induction and is more frequent in patients with chronic renal insufficiency. This hypotension occurs most frequently during the 20 minutes after anesthesia induction. Hypotension is commonly corrected by ephedrine bolus injection. However, presynaptic noradrenaline reserve may be lower in patients with chronic renal insufficiency rendering this treatment less effective. Another drug commonly used is norepinephrine, which action is independent of presynaptic noradrenaline storage. The primary hypothesis is that in patients with chronic renal insufficiency, bolus injection of norepinephrine will be more effective then ephedrine injections to correct hypotension after anesthesia induction. 60 patients with a glomerular filtration rate less than 45 mL/min/m2 (KDIGO classification less than grade 3b) will be included in this prospective double blind trial. All patients will be anesthetized by target-controlled infusion of propofol adjusted to a patient state index (Measured by Sedline, Masimo) of 25-50. Sufentanil injection will be based on noxious stimuli according to the attending anesthesiologist's judgement. Non-invasive blood pressure will be measured at the pre-anesthesia clinic, before induction and every minute up to 20 minutes post anesthesia induction. Episodes of hypotension, defined as a mean arterial blood pressure less than 65 mm Hg, will be treated either by a bolus injection of 6 mg ephedrine or a bolus injection of 6 mcg norepinephrine, which are equipotent doses. Seringues containing either ephedrine 3 mg/mL or norepinephrine 3 mcg/mL will be prepared by an anesthesia nurse not involved in the care of the patient and labeled as VASO-IRC-inclusion number. Randomization will be done by a computer generated list in a block randomization of 5. Primary outcome is the number of boluses needed to maintain arterial blood pressure above a mean of 65 mm Hg.

Official Title
-----------------
Comparison of Ephedrine Versus Norepinephrine Efficacity to Correct Anesthesia Induction Related Hypotension in Chronic Renal Insufficiency Patients

Conditions
-----------------
Hypotension on Induction

Intervention / Treatment
-----------------
* Drug: Ephedrine
* Drug: Norepinephrine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: elective non-cardiac surgery general anesthesia chronic renal insufficiency defined as a glomerular filtration rate < 45 mL/min/m2 Exclusion Criteria: cardiac insufficiency with a left ventricular ejection fraction < 50% severe cardiomyopathy severe cardiac valvular disease use of enzyme converting inhibitors or sartans less than 24h before surgery use of alpha2 antihypertension medication chronic treatment by: noradrenaline or dopamine recapture inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ephedrine group<br>In this group, any hypotension less than 65 mm Hg will be corrected by bolus injection of 6 mg ephedrine. Bolus injection will be repeated every 3 minutes, as needed, to keep mean arterial pressure above 65 mm Hg. | Drug: Ephedrine<br>* Bolus injection of 6 mg ephedrine to keep mean arterial blood pressure above 65 mm Hg<br>|
| Experimental: Norepinephrine group<br>In this group, any hypotension less than 65 mm Hg will be corrected by bolus injection of 6 mcg norepinephrine. Bolus injection will be repeated every 3 minutes, as needed, to keep mean arterial pressure above 65 mm Hg. | Drug: Norepinephrine<br>* Bolus injection of either 6 mcg norepinephrine to keep mean arterial blood pressure above 65 mm Hg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of boluses | Primary outcome is the number of boluses of either ephedrine or norepinephrine needed to keep mean arterial blood pressure above 65 mm Hg | 20 minutes after anesthesia induction |