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

Sponsor

Universitätsklinikum Hamburg-Eppendorf (Other)

Overall Status

Recruiting

CT.gov ID

NCT05842759

Collaborator

(none)

120

Enrollment

Location

Arm

10.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypotension Anesthesia Hypotension on Induction	Procedure: Monitoring Procedure: Norepinephrine preparation Procedure: Propofol administration Procedure: Alarm adjustment Procedure: Intervention threshold	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a prospective, single center, clinical interventional proof-of-concept study in 120 patients scheduled for elective major non-cardiac surgery at the University Medical Center Hamburg-Eppendorf.This is a prospective, single center, clinical interventional proof-of-concept study in 120 patients scheduled for elective major non-cardiac surgery at the University Medical Center Hamburg-Eppendorf.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 7, 2023

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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