Norepinephrine Weaning Guided by the Hypotension Prediction Index in Vasoplegic Shock After Cardiac Surgery (NORAHPI)

In postoperative cardiac surgery under extracorporeal circulation, the patient may develop a vasoplegic syndrome, characterized by arterial hypotension (mean arterial pressure (MAP) < 65 mmHg); a decrease in vascular resistance and a cardiac output that may be normal or increased, and increased postoperative mortality/ International recommendations recommend the prescription of noradrenaline as a first-line treatment to reduce morbidity and mortality. However, excess norepinephrine or duration of exposure is also deleterious. The Acumen IQ device (Edwards Lifesciences) allows the calculation of a predictive index of arterial hypotension episodes (predictive hypotension index, HPI). HPI could improve norepinephrine weaning by preventing episodes of arterial hypotension or detecting preload dependence, thus avoiding the transient increase in norepinephrine during hypotension.

This is a single-center, prospective, open-label, randomized, controlled, 2-group, parallel, intention-to-treat study. The aim was to evaluate the superiority of a new decision algorithm, based on the HPI delivered by the Acumen IQ device, to reduce the duration of norepinephrine administration in post-cardiac surgery vasoplegic shock.

The duration of the interventional protocol is 72 hours. To evaluate the clinical impact of the protocol, the time of the study will be 30 days. Several follow-up visits will be performed (end-of-protocol day, discharge day, and at D30 of inclusion) to collect clinical, biological, and HPI monitoring data.

Study Overview

• Status: Recruiting
• Conditions: Shock; Surgery; Vasoplegia; Norepinephrine
• Intervention / Treatment: Drug: norepinephrine weaning protocol; Drug: norepinephrine weaning protocol and guided by the HPI

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christophe Beyls, MD; Phone Number: 0322087866; Email: Beyls.Christophe@chu-amiens.fr

Study Locations

• France
  • Amiens, France
    • Recruiting
    • CHU Amiens Picardie
    • Sub-Investigator: Osama Abou Arab, MD
    • Contact: Christophe Beyls, MD; Phone Number: 0322087866; Email: Beyls.Christophe@chu-amiens.fr
    • Sub-Investigator: Yazine Mahjoub, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 18 years
• The patient was hospitalized in the cardiothoracic-vascular and respiratory intensive care unit of Amiens-Picardy University Hospital.
• Patient scheduled for on-pomp cardiac surgery [coronary artery bypass grafting, valve replacement, ascending aorta replacement, or combined surgery (valve and bypass grafting)].
• Introduction of norepinephrine post-surgery for the treatment of vasoplegic syndrome.
• On-pomp cardiac surgery in less than 48 hours.
• Hemodynamically stable patient with MAP > 65 mmHg for more than 4 hours on noradrenaline
• Monitoring of MAP with a radial or femoral arterial catheter
• Social security beneficiary
• Signature of the consent to participate in the study by the patient, preoperatively

Exclusion Criteria:

• Permanent arrhythmia (atrial fibrillation, flutter, or frequent atrial extrasystoles).
• Treatment with dobutamine, epinephrine, or vasopressin analog
• Patients with preoperative chronic end-stage renal failure require postoperative extra-renal purification.
• Pregnant woman
• The patient is dependent on an internal or external pacemaker.
• Hypothermia < 36°.
• Patient under mechanical circulatory assistance after cardiac surgery.
• Hemorrhagic shock
• Patient under guardianship or curators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard care arm; MAP-based (MAP > 65 mmHg) norepinephrine weaning protocol	Drug: norepinephrine weaning protocol; MAP-based (MAP > 65 mmHg) norepinephrine weaning protocol
Experimental: Experimental arm (HPI-guided); MAP-based (MAP > 65 mmHg) norepinephrine weaning protocol and guided by the HPI (HPI<80) delivered by the Acumen IQ medical device.	Drug: norepinephrine weaning protocol and guided by the HPI; MAP-based (MAP > 65 mmHg) norepinephrine weaning protocol and guided by the HPI (HPI<80) delivered by the Acumen IQ medical device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the duration of norepinephrine administration between both groups	The duration will be defined as the difference in time between the beginning of the study (day 0) and the end of the study protocol (day 3).	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of norepinephrine protocol weaning failures	Number of norepinephrine protocol weaning failures, defined as persistent norepinephrine delivery 72 hours after the start of inclusion	2 years
Prevalence of hypotensive episodes monitored by the Acumen IQ® device	Hypotension is defined by the presence of a mean arterial pressure < 65 mmHg for a minimum duration of 30 seconds. Blood pressure must be invasive and monitored on the HemoSphere® monitor.	72 hours
Frequency of hypotensive episodes monitored by the Acumen IQ® device	Hypotension is defined by the presence of a mean arterial pressure < 65 mmHg for a minimum duration of 30 seconds. Blood pressure must be invasive and monitored on the HemoSphere® monitor.	72 hours
Duration of hypotensive episodes monitored by the Acumen IQ® device	Hypotension is defined by the presence of a mean arterial pressure < 65 mmHg for a minimum duration of 30 seconds. Blood pressure must be invasive and monitored on the HemoSphere® monitor.	72 hours
NE total dose	The NE (norepinephrine) total dose delivered during the research protocol phase (mg/kg) automatically calculated by the DianeRea® software (BowMedical, France).	72 hours
Cumulative diuresis	The Cumulative diuresis (ml.kg.h) during protocol completion (H0 to H72) or when norepinephrine weaning is considered successful.	72 hours
Volume of administrated fluids	Cumulative volume of administration of crystalloids, colloids, or blood products during protocol or when NE weaning is considered as successful.	72 hours
Total dose of vasoactive drugs	Vaso-active drugs. The total dose of vasoactive drug initiation or reintroduction of NE after the weaning protocol calculated by the NEE and the VIS.	72 hours
Number of stroke	Stroke (Any embolic, thrombotic or haemorrhagic cerebral event with persistent residual motor, sensory or cognitive dysfunction (eg, hemiplegia, hemiparesis, aphasia, sensory deficit, impaired memory) diagnosed on a cerebral scanner)	72 hours
Number of myocardial infarction	Myocardial infarction diagnosed by the clinical presentation, serial changes on 12-lead electrocardiographic suggesting infarction, and rise in cardiac markers (preferably cardiac troponins) with at least one value above the 99th percentile of the upper reference limit.	72 hours
Number of resuscitated cardiac arrest	Cessation of mechanical cardiac activity confirmed by the absence of clinical signs of blood flow	72 hours
Number of acute kidney injury	Increase in serum creatinine of over 27 μmol/L within 48 hours or diuresis lower than 0.5 mL/kg/hour (KDIGO Guidelines).	72 hours
Number of mesenteric ischaemia	Mesenteric ischaemia confirmed by imaging or exploratory laparotomy and/or ischaemic colitis confirmed by gastrointestinal endoscopy or exploratory laparotomy	72 hours
Number of in-hospital mortality.	Mortality from surgery to hospital discharge	72 hours
Number of 30 days hospital mortality	Mortality after surgery until 30 days follow-up	30 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 20, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: surgery; CABG; shock; norepinephrine; vasoplegia; hypotension prediction index; Acumen
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Shock; Hypotension; Vasoplegia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: PI2023_843_0046

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