Effects of Beta-blockade on Cardiopulmonary Exercise Testing

NCT02106286 | Completed Early Phase 1

• 1 other identifier: 11/NW/0810
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

A major determinant of perioperative mortality is the inability of the heart to increase its output in response to surgical stress. This is termed perioperative cardiac failure (PCF), and may only be apparent postoperatively when oxygen demand is increased. The risk of perioperative cardiac complications is the summation of the individual patient's risk and cardiac stress related to the surgical procedure1. The functional capacity of the patient determines their ability to support the postoperative demand of increased oxygen consumption, and therefore of cardiac output. Exercise capacity is one of the most powerful predictors of cardiovascular and all cause mortality2. Cardiopulmonary exercise test (CPET) is an established investigation used, among other applications, in the preoperative assessment of patient fitness for surgery3. CPET involves monitoring the electrocardiographic trace and the exhaled gas mixture (particularly CO2, whose production depends on aerobic metabolism), during incremental exercise (usually on an exercise bike), on room air. Several parameters can be measured during CPET, including maximal systemic oxygen delivery, the anaerobic threshold (the oxygen delivery value at which anaerobic metabolism begins), maximum workload, and ST segment depression/elevation (as in a standard exercise tolerance test). The cardiopulmonary "performance" during CPET has been correlated with postoperative outcome3. Pulmonary function tests will be performed in order to assess lung function. It is well known that therapy with beta-blockers in patients with ischaemic heart disease and cardiac failure reduces perioperative morbidity and mortality4-7. However, beta blockers reduce myocardial contractility and the heart rate response to adrenergic stimulation, thus blunting the physiological response to stress/surgery/exercise. Whilst this mechanism may protect the heart perioperatively, it may decrease the ability of some patients to withstand other complications. This potential decrease in "performance" has never been quantified. There is no agreement on whether preoperative CPET should be performed on or off beta-blockers and, at Aintree in particular, it is standard procedure to take patients off beta-blockers prior to their CPET. Some argue that, as beta-blockade should be maintained in the perioperative period, CPET should be performed on medications, even if these could mask the presence significant ischaemic heart disease (a significant, modifiable, risk factor for surgery by beta blockade), and even if it is not always possible to maintain beta-blockade throughout the whole postoperative period. For these reasons, other clinicians prefer to perform CPET off beta-blockers, thus, potentially, overestimating the perioperative cardiorespiratory "performance", which may be diminished once the medications are resumed. Patients on long-term beta blockade may develop some tolerance to the medications, so the effect of acute and chronic beta blockade on cardiorespiratory performance may also be different. Aim To compare cardiopulmonary performances on and off beta blockers as objectively assessed by cardiopulmonary exercise testing.

Conditions

Abdominal Aortic Aneurysm Patients Under Surveillance

Keywords

Cardiopulmonary exercise test; surgery; abdominal aortic aneurysm; anaerobic threshold; fitness; beta-blockers

Outcome Measures

Primary Outcomes (1)

• Change in oxygen uptake

  Baseline and 72hours post beta-blockade

Study Arms (2)

Bisoprolol

ACTIVE COMPARATOR

Patients not betablocked at baseline receive an acute 72hr dose of beta blocker therapy before CPET

Drug: Bisoprolol

No Bisoprolol

NO INTERVENTION

No beta blocker given

Interventions

Bisoprolol DRUG

Bisoprolol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years of age inclusive, undergoing major surgery who are already on therapy with beta blockers
• \>18 years of age, undergoing major surgery who are not on beta blockers
• Patient able to consent to study protocol
• Ability to perform CPET on an exercise bike
• AAA patients under surveillance.

You may not qualify if:

• Known contraindication to bisoprolol (known intolerance, asthma or history of bronchospasm, II or III degree heart block, treatment with verapamil or ivrabadine, sinus bradycardia, Prinzmetal's angina),
• Severe ischaemic heart disease (including acute coronary syndrome within 3 months of recruitment),
• Inability to use an exercise bike
• Stage IV and V chronic kidney disease
• Uncontrolled hypertension
• Patients withholding informed consent
• Patients unable to give informed consent due to mental incapacity
• Patients who find uncomfortable and anxiety provoking performing an exercise test
• Patients who present contraindications (relative/absolute) to their first initial CPET based on the American Thoracic Society (ATS) exercise testing guidelines.

Sponsors & Collaborators

• Michelle Mossa: lead

Study Sites (1)

Aintree University Hospitals

Liverpool, L97AL, United Kingdom

Location

Related Publications (2)

• Key A, Parry M, West MA, Asher R, Jack S, Duffy N, Torella F, Walker PP. Effect of beta-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD. BMJ Open Respir Res. 2017 Apr 5;4(1):e000164. doi: 10.1136/bmjresp-2016-000164. eCollection 2017.

  PMID: 28409004 DERIVED

• West MA, Parry M, Asher R, Key A, Walker P, Loughney L, Pintus S, Duffy N, Jack S, Torella F. The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study. Br J Anaesth. 2015 Jun;114(6):878-85. doi: 10.1093/bja/aev026. Epub 2015 Feb 24.

  PMID: 25716221 DERIVED

MeSH Terms

Conditions

Aortic Aneurysm, Abdominal

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research and Development Deputy Director

Study Record Dates

• First Submitted: March 31, 2014
• First Posted: April 8, 2014
• Study Start: February 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 8, 2014

Record last verified: 2014-04

Locations

GB (1)