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

Study Overview
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Brief Summary
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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.

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

Conditions
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Intraoperative Hypotension

Intervention / Treatment
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* Procedure: Continuous norepinephrine administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous norepinephrine administration<br> | Procedure: Continuous norepinephrine administration<br>* 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.<br>|
| No Intervention: Bolus norepinephrine administration<br> | |

What is the study measuring?
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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 |