Continuous Versus Bolus Administration of Norepinephrine to Treat Hypotension During Anesthetic Induction (INDUCT)

Continuous Versus Bolus Administration of Norepinephrine to Treat Hypotension During Anesthetic Induction - the INDUCT Randomized Trial

Intraoperative hypotension is common in patients having non-cardiac surgery with general anesthesia and is associated with organ injury and death. The timely treatment of intraoperative hypotension is thus important to avoid postoperative complications. About one third of intraoperative hypotension occurs during anesthetic induction - i.e., between the start of anesthetic induction and surgical incision. Hypotension during anesthetic induction is associated with postoperative acute kidney injury.

Unmodifiable risk factors for hypotension during anesthetic induction include age, male sex, and a high American Society of Anesthesiologists physical status class. However, hypotension during anesthetic induction is mainly driven by modifiable factors - specifically, anesthetic drugs that cause vasodilation.

In most German hospitals, norepinephrine is the first-line vasopressor to treat hypotension during anesthetic induction. Norepinephrine is usually given as repeated manual boluses of 5, 10, or 20 μg. The continuous administration of norepinephrine via a perfusion pump is usually started only later. It remains unknown whether giving norepinephrine continuously - compared to giving it as repeated manual boluses - reduces hypotension during anesthetic induction.

We thus propose to investigate whether giving norepinephrine continuously - compared to giving it as repeated manual boluses - reduces hypotension during anesthetic induction in non-cardiac surgery patients.

Study Overview

• Status: Completed
• Conditions: Intraoperative Hypotension
• Intervention / Treatment: Procedure: Continuous norepinephrine administration

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20251
    • University Medical Center Hamburg-Eppendorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• non-cardiac surgery
• >45 years of age
• American Society of Anesthesiologists physical status classification II, III, and IV.

Exclusion Criteria:

• Planned intraarterial blood pressure monitoring during anesthetic induction with an arterial catheter
• Emergency surgery
• Transplant surgery
• History of organ transplant
• Pregnancy
• Heart rhythms other than sinus rhythm
• Impossible Finger-cuff blood pressure monitoring
• Rapid sequence induction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous norepinephrine administration	Procedure: Continuous norepinephrine administration; In patients randomized to continuous norepinephrine administration, hypotension (= mean arterial pressure < 65mmHg) will be treated with continuous norepinephrine infusion. The norepinephrine perfusion line will be connected to the saline infusion line using a three-way valve. Treating anesthesiologists will be free to reduce or increase the norepinephrine infusion rate anytime.
No Intervention: Bolus norepinephrine administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypotension during anesthetic induction	Area under a MAP of 65 mmHg [mmHg x min]	First 15 minutes of anesthetic induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypotension during anesthetic induction	Area under a MAP of 60, 50, and 40 mmHg [mmHg x min]	First 15 minutes of anesthetic induction
Hypotension during anesthetic induction	Duration of a MAP <65, <60, <50, and <40 mmHg [min]	First 15 minutes of anesthetic induction
Hypertension during anesthetic induction	Duration of a MAP >100, >110, >120, and >140 mmHg [min]	First 15 minutes of anesthetic induction
Hypertension during anesthetic induction	Area above a MAP of 100, 110, 120, and 140 mmHg [mmHg x min]	First 15 minutes of anesthetic induction
Hypertension during anesthetic induction	Absolute [n] and relative [%] number of patients with any MAP measurement >100, >110, >120 and >140 mmHg	First 15 minutes of anesthetic induction
Hypotension during anesthetic induction	Absolute [n] and relative [%] number of patients with any MAP measurement <65, <60, <50, and <40 mmHg	First 15 minutes of anesthetic induction
Hypotension during anesthetic induction	Absolute [n] and relative [%] number of patients with at least one 1-minute episode of a MAP <65, <60, <50, and <40 mmHg	First 15 minutes of anesthetic induction
Hypotension during anesthetic induction	Cumulative dose of norepinephrine indexed to body weight [μg kg-1]	First 15 minutes of anesthetic induction

Collaborators and Investigators

• Sponsor: Kristen Thomsen

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Actual): June 6, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: July 4, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypotension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: 2023-100999-BO-ff

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No