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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Hypotension, Anesthesia, Hypotension on Induction

Intervention / Treatment
-----------------
* Procedure: Monitoring
* Procedure: Norepinephrine preparation
* Procedure: Propofol administration
* Procedure: Alarm adjustment
* Procedure: Intervention threshold


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hypotension Avoidance Strategy<br>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<br>* Continuous blood pressure monitoring<br>Procedure: Norepinephrine preparation<br>* Norepinephrine infusion will be prepared and connected to peripheral or central venous catheter (infusion will not be started)<br>Procedure: Propofol administration<br>* 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<br>Procedure: Alarm adjustment<br>* Lower mean arterial pressure alarm threshold will be set to 75 mmHg<br>Procedure: Intervention threshold<br>* Lower mean arterial pressure intervention threshold will be 75 mmHg: continuous norepinephrine infusion will be started when mean arterial blood decreases below 75 mmHg<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypotension, Low Blood Pressure, Anesthesia Induction, Surgery