Target Hemodynamics and Brain Injury During General Anesthesia in the Elderly

Summary

BACKGROUND: Post-operative cognitive dysfunction (POCD) is a potentially irreversible loss of brain functions observed in elderly patients after surgical operations under general anaesthesia. POCD at 3 post-operative months is observed in up to 15% of patients aged 70 years and more, and the only recognized risk factor for this condition is increasing age. Importantly, the incidence of POCD at 3 months has been associated to an increased disability and mortality.

OBJECTIVES: The present study will evaluate in patients aged 75 years and older undergoing general anaesthesia for non-cardiac surgery, whether an hemodynamic strategy, aiming at maintaining intra-operative arterial blood pressure close to patient's preoperative blood pressure, i.e., to avoid hypotensive episodes, reduces the incidence of POCD at three months.

METHODS: Around 1800 consecutive patients scheduled to undergo general anaesthesia for elective non-cardiac surgery will be enrolled. Each patient's cognitive function will be evaluated preoperatively and at 3 months and 1 year postoperatively, together with the occurrence of hearing loss and vestibular function impairment. Furthermore, the incidence of postoperative delirium and cardiovascular, respiratory and infectious complications will be evaluated.

EXPECTED RESULTS: The primary outcome is a 25% relative reduction in the incidence of POCD at 3 postoperative months. Secondary outcomes are the reduction of POCD incidence at 1 postoperative year, a reduction in postoperative hearing loss and vestibular impairment at 3 months, a reduction in the incidence of delirium. Hospital length of stay and 90 day mortality will also be assessed. This present study could have a high socio-economic impact, reduce healthcare costs and patient morbidity and mortality with a simple not expensive intraoperative intervention.

Conditions

• Post-operative Cognitive Dysfunction

Interventions

PROCEDURE

Hemodynamic target

The anaesthesiologist is requested to maintain intraoperative mean arterial blood pressure of the patient within 10% of the baseline mean arterial blood pressure (recorded during the preoperative evaluation) of that patient. In order to reach this hemodynamic target the anesthesiologist can choose between one or more of the following four sub-interventions: 1. vasoconstrictor agents (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine) 2. intravenous fluids 3. patient's positioning 4. reduction of depth of anesthesia

DRUG

Phenylephrine

Phenylephrine 0.1-0.2 mg intravenous bolus

DRUG

Intravenous fluids

A crystalloid fluid bolus is given intravenously (5-10 ml/kg)

PROCEDURE

Patient's positioning

The operating table is positioned so that the patient's head lies below the level of the patient's feet (Trendelenburg position) in order to increase venous return

PROCEDURE

Reduction of depth of anesthesia

The halogenated anesthetic vapor's inspiratory fraction is decreased in order to reduce the associated peripheral vasodilation

DRUG

Ephedrine

Ephedrine 5-25 mg intravenous bolus

DRUG

Epinephrine

Epinephrine 5-10 mcg intravenous bolus

DRUG

Norepinephrine

Norepinephrine 0.01 - 0.1 mcg/kg/min intravenous continuous infusion

DRUG

Dopamine

Dopamine 5 - 10 mcg/kg/min intravenous continuous infusion

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  lead OTHER

Principal Investigators

• Luciano Gattinoni, MD, FRCP · Dipartimento di anestesiologia terapia intensiva e scienze dermatologiche

• Thomas Langer, MD · Dipartimento di Anestesia, Rianimazione ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy

• Alessandro Santini, MD · Dipartimento di anestesiologia terapia intensiva e scienze dermatologiche

• Michael Quintel, MD, PhD · University of Göttingen, Zentrum Anaesthesiologie-, Rettungs- und Intensivmedizin

• Antonio Pesenti, MD · Dipartimento di Emergenza Urgenza, Azienda Ospedaliera San Gerardo, Monza,Italy

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-10-31

Primary Completion

2018-12-31

Completion

2019-12-31

Countries

• Italy

Study Locations