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

Hypotension on Induction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05497700
• Other study ID #: VASO_IRC
• Status: Recruiting
• Phase: Phase 3
• Start date: September 15, 2022
• Est. completion date: October 30, 2023

Study information

• Verified date: September 2022
• Source: Brugmann University Hospital
• Contact: Denis Schmartz, MD
• Phone: +3224773996
• Email: denis.schmartz[@]chu-brugmann.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypotension
• Hypotension on Induction

Intervention

Drug:
• Ephedrine
Bolus injection of 6 mg ephedrine to keep mean arterial blood pressure above 65 mm Hg
• Norepinephrine
Bolus injection of either 6 mcg norepinephrine to keep mean arterial blood pressure above 65 mm Hg

Locations

Country	Name	City	State
Belgium	CHU Brugmann	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (17)

Ahuja S, Mascha EJ, Yang D, Maheshwari K, Cohen B, Khanna AK, Ruetzler K, Turan A, Sessler DI. Associations of Intraoperative Radial Arterial Systolic, Diastolic, Mean, and Pulse Pressures with Myocardial and Acute Kidney Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2020 Feb;132(2):291-306. doi: 10.1097/ALN.0000000000003048. — View Citation

Ali Elnabtity AM, Selim MF. Norepinephrine versus Ephedrine to Maintain Arterial Blood Pressure during Spinal Anesthesia for Cesarean Delivery: A Prospective Double-blinded Trial. Anesth Essays Res. 2018 Jan-Mar;12(1):92-97. doi: 10.4103/aer.AER_204_17. — View Citation

Beierwaltes WH, Carretero OA, Scicli AG. Renal hemodynamics in response to a kinin analogue antagonist. Am J Physiol. 1988 Sep;255(3 Pt 2):F408-14. — View Citation

Camilleri JF, Barragan P, Massonat J, Moyal C, Jouve B, Durand C, Collet F, Gérard R. [Acute occlusion of the renal artery caused by an embolism of cardiac origin. Treatment by in situ thrombolysis]. Arch Mal Coeur Vaiss. 1989 Jul-Aug;82(8):1473-6. French. — View Citation

Chooi C, Cox JJ, Lumb RS, Middleton P, Chemali M, Emmett RS, Simmons SW, Cyna AM. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev. 2017 Aug 4;8:CD002251. doi: 10.1002/14651858.CD002251.pub3. [Epub ahead of print] Review. Update in: Cochrane Database Syst Rev. 2020 Jul 1;7:CD002251. — View Citation

Cockwell P, Fisher LA. The global burden of chronic kidney disease. Lancet. 2020 Feb 29;395(10225):662-664. doi: 10.1016/S0140-6736(19)32977-0. Epub 2020 Feb 13. — View Citation

Converse RL Jr, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, Victor RG. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992 Dec 31;327(27):1912-8. — View Citation

Deng J, Lenart J, Applegate RL. General anesthesia soon after dialysis may increase postoperative hypotension - A pilot study. Heart Lung Vessel. 2014;6(1):52-9. — View Citation

Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, Matsushita K, Wen CP. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013 Jul 27;382(9889):339-52. doi: 10.1016/S0140-6736(13)60595-4. Epub 2013 May 31. Review. — View Citation

Grassi G, Quarti-Trevano F, Seravalle G, Arenare F, Volpe M, Furiani S, Dell'Oro R, Mancia G. Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension. 2011 Apr;57(4):846-51. doi: 10.1161/HYPERTENSIONAHA.110.164780. Epub 2011 Feb 7. — View Citation

Hassani V, Movaseghi G, Safaeeyan R, Masghati S, Ghorbani Yekta B, Farahmand Rad R. Comparison of Ephedrine vs. Norepinephrine in Treating Anesthesia-Induced Hypotension in Hypertensive Patients: Randomized Double-Blinded Study. Anesth Pain Med. 2018 Aug 26;8(4):e79626. doi: 10.5812/aapm.79626. eCollection 2018 Aug. — View Citation

Mathis MR, Naik BI, Freundlich RE, Shanks AM, Heung M, Kim M, Burns ML, Colquhoun DA, Rangrass G, Janda A, Engoren MC, Saager L, Tremper KK, Kheterpal S, Aziz MF, Coffman T, Durieux ME, Levy WJ, Schonberger RB, Soto R, Wilczak J, Berman MF, Berris J, Biggs DA, Coles P, Craft RM, Cummings KC, Ellis TA 2nd, Fleishut PM, Helsten DL, Jameson LC, van Klei WA, Kooij F, LaGorio J, Lins S, Miller SA, Molina S, Nair B, Paganelli WC, Peterson W, Tom S, Wanderer JP, Wedeven C; Multicenter Perioperative Outcomes Group Investigators. Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury. Anesthesiology. 2020 Mar;132(3):461-475. doi: 10.1097/ALN.0000000000003063. Erratum in: Anesthesiology. 2020 Jan 6;:. — View Citation

Schmidt IM, Hübner S, Nadal J, Titze S, Schmid M, Bärthlein B, Schlieper G, Dienemann T, Schultheiss UT, Meiselbach H, Köttgen A, Flöge J, Busch M, Kreutz R, Kielstein JT, Eckardt KU. Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study. Clin Kidney J. 2019 May 24;12(5):663-672. doi: 10.1093/ckj/sfz046. eCollection 2019 Oct. — View Citation

Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, Youngs EJ. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998 May;88(5):1170-82. — View Citation

Südfeld S, Brechnitz S, Wagner JY, Reese PC, Pinnschmidt HO, Reuter DA, Saugel B. Post-induction hypotension and early intraoperative hypotension associated with general anaesthesia. Br J Anaesth. 2017 Jul 1;119(1):57-64. doi: 10.1093/bja/aex127. — View Citation

Xu S, Mao M, Zhang S, Qian R, Shen X, Shen J, Wang X. A randomized double-blind study comparing prophylactic norepinephrine and ephedrine infusion for preventing maternal spinal hypotension during elective cesarean section under spinal anesthesia: A CONSORT-compliant article. Medicine (Baltimore). 2019 Dec;98(51):e18311. doi: 10.1097/MD.0000000000018311. — View Citation

Zoccali C, Mallamaci F, Parlongo S, Cutrupi S, Benedetto FA, Tripepi G, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Cataliotti A, Stancanelli B, Malatino LS. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation. 2002 Mar 19;105(11):1354-9. Erratum in: Circulation 2002 May 7;105(18):2230. Cateliotti A [corrected to Cataliotti A]. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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