Pathophysiologic Hemodynamics After Primary Unilateral Total Hip Arthroplasty in Patients Receiving ACEIs and ARBs

Pathophysiologic Hemodynamics After Primary Unilateral Total Hip Arthroplasty in Patients Receiving Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs)

Incidence and pathophysiologic hemodynamics of postoperative orthostatic intolerance and orthostatic hypotension in patients receiving antihypertensives

Study Overview

• Status: Recruiting
• Conditions: Orthostatic Hypotension; Orthostatic Intolerance
• Intervention / Treatment: Other: Mobilisation procedure

Detailed Description

Early postoperative mobilization is essential for rapid functional recovery after surgery and it is considered a cornerstone in the so-called fast track multimodal perioperative approach, which includes early ambulation, oral nutrition, multimodal opioid-sparing analgesia and optimized fluid therapy. This strategy has improved patient outcome after surgery and reduced hospital length of stay. Immobilization after surgery is associated with increased risk of complications including venous thromboembolism (deep venous thrombosis, pulmonary embolism), muscle wasting, pneumonia and atelectasis, thereby impending convalescence.

However, early postoperative mobilization can be delayed due to failed orthostatic cardiovascular regulation, resulting in postoperative orthostatic hypotension (OH), defined as a decrease in systolic blood pressure > 20 mmHg or diastolic blood pressure > 10 mmHg or postoperative orthostatic intolerance (OI), characterized by dizziness, nausea, vomiting, visual disturbances or syncope.

Previous studies investigating the incidence and pathophysiology of postoperative OI and OH included mixed patient populations. Hitherto no studies have been performed looking into the incidence and pathophysiologic hemodynamics of postoperative OI and OH specifically in patients receiving angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), antihypertensive agents with potential effects on cardiovascular compensatory functions.

The current study aims therefore to estimate the incidence and gain knowledge on pathophysiological hemodynamics of postoperative OI and OH in patients receiving ACEIs and ARBs.

• Study Type: Observational
• Enrollment (Anticipated): 24

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2960
    • Recruiting
    • Hvidovre University Hospital
    • Contact: Ana-Marija Hristovska; Phone Number: 38621508; Email: anamarijahristovska@gmail.com
    • Contact: Nicolai Foss

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients receiving antuhypertensives (ACEIs, ARBs) and undergoing primary unilateral total hip arthroplasty in spinal anesthesia in standardized fast-track setting

Description

Inclusion Criteria:

• Patients undergoing primary unilateral total hip arthroplasty (THA) in spinal anaesthesia in standardized fast-track setting
• Habitual use of angiontensin-Converting Enzyme Inhibitors (ACEIs) and/or angiotensin 2 receptor blockers (ARBs) on any indication
• Patients > 18
• Patients that understand and speak Danish
• Patients that have provided written informed consent

Exclusion Criteria:

• Alcohol abuse
• Any type of substance abuse
• Chronic pain treated by habitual use of opioids
• Habitual use of anxiolytic, antidepressant and/or antipsychotic drugs
• History of cerebral apoplexy or transitory cerebral ischemia
• History of previous orthostatic intolerance or hypotension
• History of diabetes mellitus
• History of following diseases of the autonomic nervous system: Parkinson disease, multiple sclerosis, multiple system atrophy, autonomic neuropathies
• Cognitive dysfunction
• Dementia
• American Society of Anesthesiologists (ASA) > 3

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Orthostatic tolerant patients (OT); Patients that experience symptoms of orthostatic intolerance (dizziness, nausea, vomiting, blurry vision or syncope) or orthostatic hypotension (fall in systolic pressure > 20 mmHg and/or diastolic pressure > 10 mmHg) during mobilisation	Other: Mobilisation procedure; A standardized mobilization procedure was performed preoperatively ~ 1h before surgery and was repeated 6h and 24h after surgery. The mobilization procedure included patient supine rest (5 minutes), followed by 45° passive leg raise (PLR) (3 minutes), supine rest (5 minutes), sitting on the edge of the bed with feet resting on the floor (3 minutes) followed by standing using a walker while the patient was encouraged verbally to stand on toes and shift body weight from one leg to the other (3 minutes) and finally rest in supine position (5 minutes). The procedure was terminated prematurely in any position if patients experienced unbearable symptoms of OI or upon a decrease of systolic arterial pressure (SAP) > 30 mmHg.
Orthostatic intolerant patients (OI); Patients that do not experience symptoms of orthostatic intolerance (dizziness, nausea, vomiting, blurry vision or syncope) or orthostatic hypotension (fall in systolic pressure > 20 mmHg and/or diastolic pressure > 10 mmHg) during mobilisation	Other: Mobilisation procedure; A standardized mobilization procedure was performed preoperatively ~ 1h before surgery and was repeated 6h and 24h after surgery. The mobilization procedure included patient supine rest (5 minutes), followed by 45° passive leg raise (PLR) (3 minutes), supine rest (5 minutes), sitting on the edge of the bed with feet resting on the floor (3 minutes) followed by standing using a walker while the patient was encouraged verbally to stand on toes and shift body weight from one leg to the other (3 minutes) and finally rest in supine position (5 minutes). The procedure was terminated prematurely in any position if patients experienced unbearable symptoms of OI or upon a decrease of systolic arterial pressure (SAP) > 30 mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of orthostatic intolerance	Symptoms of orthostatic intolerance: dizziness, nausea, vomiting, blurry vision or syncope during mobilization	6 hours postoperatively
Incidence of orthostatic hypotension	Orthostatic hypotension is defined as a fall in systolic pressure > 20 mmHg and/or diastolic pressure > 10 mmHg during mobilization	6 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in systolic arterial pressure (SAP) during mobilization	Measured in mmHg by non-invasive Lithium Dilution Cardiac Output (LiDCO) measurement	Preoperatively, 6 and 24 hours postoperatively
Changes in diastolic arterial pressure (DAP) during mobilization	Measured in mmHg by non-invasive LiDCO	Preoperatively, 6 and 24 hours postoperatively
Changes in mean arterial pressure (MAP) during mobilization	Measured in mmHg by non-invasive LiDCO	Preoperatively, 6 and 24 hours postoperatively
Changes in systemic vascular resistance (SVR) during mobilization	Measured in dynes s cm-5 by non-invasive LiDCO	Preoperatively, 6 and 24 hours postoperatively
Changes in cardiac output (CO) during mobilization	Measured in L/min by non-invasive LiDCO	Preoperatively, 6 and 24 hours postoperatively
Changes in stroke volume (SV) during mobilization	Measured in mL by non-invasive LiDCO	Preoperatively, 6 and 24 hours postoperatively
Changes in heart rate (HR) during mobilization	Measured in beats min-1 by non-invasive LiDCO	Preoperatively, 6 and 24 hours postoperatively
Changes in pulse pressure (PP) during mobilization	Measured in mmHg	Preoperatively, 6 and 24 hours postoperatively
Changes in cerebral perfusion (ScO2) during mobilization	Measured in % by Root Masimo	Preoperatively, 6 and 24 hours postoperatively
Changes in muscular perfusion (SmO2) during mobilization	Measured in % by Root Masimo	Preoperatively, 6 and 24 hours postoperatively
Changes in peripheral perfusion index (PPI) during mobilization	Measured in % by Root Masimo	Preoperatively, 6 and 24 hours postoperatively
Changes in total blood volume (TBV)	Measured in mL by Carbon Monoxide - rebreathing technique	Preoperatively, 6 and 24 hours postoperatively
Changes in red blood cell volume (RBCV)	Measured in mL by Carbon Monoxide - rebreathing technique	Preoperatively, 6 and 24 hours postoperatively
Changes in plasma volume (PV)	Measured in mL by Carbon Monoxide - rebreathing technique	Preoperatively, 6 and 24 hours postoperatively
Changes in hematocrit	Measured in %	Preoperatively, 6 and 24 hours postoperatively
Changes in total mass of hemoglobin	Measured in grams	Preoperatively, 6 and 24 hours postoperatively
Changes in hemoglobin concentration	Measured in gr/L	Preoperatively, 6 and 24 hours postoperatively
Changes in C-Reactive Protein	Measured in mg/L	Preoperatively, 6 and 24 hours postoperatively
Changes in heart rate variability (HRV) during Valsalva manoeuvre	Measured in ms	Preoperatively, 6 and 24 hours postoperatively
Changes in baroreflex sensitivity - vagal (BRSv) during Valsalva manoeuvre	Measured in ms	Preoperatively, 6 and 24 hours postoperatively
Changes in Valsalva ratio (VR) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Systolic Sympathetic Index 1 (SSI1) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Systolic Sympathetic Index 2 (SSI2) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Systolic Sympathetic Index 3 (SSI3) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Diastolic Sympathetic Index 1 (DSI1) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Diastolic Sympathetic Index 2 (DSI2) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Diastolic Sympathetic Index 3 (DSI3) during Valsalva manoeuvre	Measured as index	Preoperatively, 6 and 24 hours postoperatively
Changes in Pressure Recovery Time (PRT) during Valsalva manoeuvre	Measured in seconds	Preoperatively, 6 and 24 hours postoperatively
Changes in Baroreceptor Reflex Sensitivity-adrenergic (BRS-a) during Valsalva manoeuvre	Measured in seconds	Preoperatively, 6 and 24 hours postoperatively
Changes in systolic latency during Valsalva manoeuvre	Measured in seconds	Preoperatively, 6 and 24 hours postoperatively
Changes in diastolic latency during Valsalva manoeuvre	Measured in seconds	Preoperatively, 6 and 24 hours postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgery duration	Minutes	Intraoperative
Pain score during mobilisation	Measured by verbal rating scale (VRS) from 0 to 10 (0 = no pain, 10 = worse pain imaginable)	Preoperatively, 6 and 24 hours postoperatively
Estimated intraoperative bleeding	Measured in mL	During surgery
Intraoperative fluid balance	Measured in mL	Intraoperative
Intraoperative propofol usage	Mg	Intraoperative
Usage of cumulated opioids prior to mobilisation	mg	Postoperatively
Usage of Chlorzoxazone prior to mobilisation	mg	Postoperatively
Preoperative use of antihypertensives	Type, dose and time of administration	Preoperatively
Postoperative use of antihypertensives	Type, dose and time of administration	Postoperatively

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Kehlet, Henrik, M.D., Ph.D.

Publications and helpful links

General Publications

• Jans O, Bundgaard-Nielsen M, Solgaard S, Johansson PI, Kehlet H. Orthostatic intolerance during early mobilization after fast-track hip arthroplasty. Br J Anaesth. 2012 Mar;108(3):436-43. doi: 10.1093/bja/aer403. Epub 2011 Dec 15.
• Jans O, Kehlet H. Postoperative orthostatic intolerance: a common perioperative problem with few available solutions. Can J Anaesth. 2017 Jan;64(1):10-15. doi: 10.1007/s12630-016-0734-7. Epub 2016 Sep 14. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (Actual): April 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Postoperative period; Orthostatic Intolerance; Autonomic dysfunction; Orthostatic Hypotension; Antihypertensives
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Hypotension, Orthostatic; Orthostatic Intolerance
• Other Study ID Numbers: H-20017723

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