Avoiding Postinduction Hypotension: the Clinical ZERO-HYPOTENSION Proof-of-concept Study

In this clinical proof-of-concept study, the aim is to investigate the efficacy of a hypotension avoidance strategy to prevent post-induction hypotension. Specifically, it will be investigate how much postinduction hypotension occurs when using a hypotension avoidance strategy - combining continuous intraarterial blood pressure monitoring, careful administration of anesthetic drugs, and continuous administration of norepinephrine to treat hypotension - in high-risk patients having elective non-cardiac surgery.

Study Overview

• Status: Completed
• Conditions: Hypotension; Anesthesia; Hypotension on Induction
• Intervention / Treatment: Procedure: Monitoring; Procedure: Norepinephrine preparation; Procedure: Propofol administration; Procedure: Alarm adjustment; Procedure: Intervention threshold

Detailed Description

Hypotension is common in patients having non-cardiac surgery with general anesthesia and is associated with organ injury. About one third of hypotension occurs "postinduction" - i.e., after the induction of general anesthesia but before surgical incision. Unmodifiable risk factors for postinduction hypotension include age, male sex, and a high American Society of Anesthesiologists physical status. However, postinduction hypotension is mainly driven by modifiable factors - specifically, anesthetic drugs that cause vasodilation. Vasodilation can be effectively treated with vasopressors, e.g. norepinephrine.

It is reasonable to assume that postinduction hypotension is largely avoidable by careful anesthetic and hemodynamic monitoring and management during anesthetic induction. A hypotension avoidance strategy could include continuous intraarterial blood pressure monitoring, careful administration of anesthetic drugs, and continuous administration of norepinephrine to treat hypotension. However, it remains unknown to which extent a hypotension avoidance strategy actually can avoid postinduction hypotension. Before testing the effectiveness of hypotension avoidance strategies in large-scale randomized trials it is important to investigate their efficacy.

In this clinical proof-of-concept study, the aim is to investigate the efficacy of a hypotension avoidance strategy to prevent post-induction hypotension. Specifically, it will be investigate how much postinduction hypotension occurs when using a hypotension avoidance strategy - combining continuous intraarterial blood pressure monitoring, careful administration of anesthetic drugs, and continuous administration of norepinephrine to treat hypotension - in high-risk patients having elective non-cardiac surgery.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• American Society of Anesthesiologists physical status classification III or higher, and in whom intraarterial blood pressure monitoring is planned for clinical indication

Exclusion Criteria:

• Emergency surgery
• Transplant surgery
• History of organ transplant
• Sepsis
• Pregnancy
• Contraindications for the use of propofol
• Rapid sequence induction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Hypotension Avoidance Strategy; After the patients' arrival in the induction area, routine anesthetic monitoring (electrocardiography and pulse oximetry) will be established. In all patients, the arterial catheter for continuous intraarterial blood pressure monitoring will be inserted before anesthetic induction (after the insertion site has been infiltrated with a local anesthetic). An uncalibrated pulse wave analysis monitor (MostCareUP, Vygon, Aachen, Germany) will be connected to the patient monitor for advanced hemodynamic monitoring of including cardiac output, systemic vascular resistance, stroke volume variation, and pulse pressure variation. Besides continuous intraarterial blood pressure monitoring, the hypotension avoidance strategy will be applied.

Procedure: Monitoring; Continuous blood pressure monitoring; Procedure: Norepinephrine preparation; Norepinephrine infusion will be prepared and connected to peripheral or central venous catheter (infusion will not be started); Procedure: Propofol administration; Propofol infusion will be started only when clinical effects of opioid are noticeable: 1.5 mg/kg propofol in patients less than 55 years old and 1.0 mg/kg propofol in patients 55 years or older over 90 seconds; Procedure: Alarm adjustment; Lower mean arterial pressure alarm threshold will be set to 75 mmHg; Procedure: Intervention threshold; Lower mean arterial pressure intervention threshold will be 75 mmHg: continuous norepinephrine infusion will be started when mean arterial blood decreases below 75 mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under a MAP of 65 mmHg	Area under a mean arterial pressure (MAP) of 65 mmHg within the first 15 minutes of anesthetic induction [mmHg x min].	First 15 minutes of induction of general anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under threshold	Area under a MAP of 60, 50, and 40 mmHg [mmHg x min]	First 15 minutes of induction of general anesthesia
Duration	Duration of MAP <65, <60, <50, and <40 mmHg [min]	First 15 minutes of induction of general anesthesia
Any Hypotension	Absolute [n] and relative [%] number of patients with any MAP measurement <65, <60, <50, and <40 mmHg	First 15 minutes of induction of general anesthesia
1-minute Hypotension	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 induction of general anesthesia
Area above the curve	Area above a MAP of 100, 110, 120, 140 mmHg [mmHg x min]	First 15 minutes of induction of general anesthesia
Norepinephrine	Cumulative dose of norepinephrine indexed to body weight [μg kg-1]	First 15 minutes of induction of general anesthesia

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Output/Index (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia
Stroke Volume/Index (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia
dP/dt (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia
Eadyn (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia
Stroke volume variation (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia
Pulse pressure variation (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia
Systemic vascular resistance (Exploratory Endpoint)	Descriptive analysis including minimum value, duration under threshold, area under threshold, absolute and relative number of patients with at least one episode under threshold.	First 15 minutes of induction of general anesthesia

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Moritz Flick, Universitätsklinikum Hamburg-Eppendorf; Principal Investigator: Kristen Thomsen, Universitätsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2023
• Primary Completion (Actual): August 7, 2023
• Study Completion (Actual): August 7, 2023

Study Registration Dates

• First Submitted: March 5, 2023
• First Submitted That Met QC Criteria: April 22, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; Hypotension; Anesthesia Induction; Low Blood Pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Sympathomimetics; Vasoconstrictor Agents; Propofol; Norepinephrine
• Other Study ID Numbers: 2022-100896-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