Pathophysiologic Hemodynamics After Primary Unilateral Total Hip Arthroplasty (THA)

Pathophysiologic Hemodynamics After Primary Unilateral Total Hip Arthroplasty

Incidence and pathophysiologic hemodynamics of orthostatic intolerance and orthostatic hypotension in patients undergoing unilateral THA

Study Overview

• Status: Unknown
• Conditions: Postoperative Complications; Orthostatic Hypotension; Orthostatic Intolerance

Detailed Description

Early postoperative mobilization is a cornerstone in the so-called fast track multimodal perioperative approach and is essential in preventing postoperative morbidity and reducing hospital length-of-stay. Intact orthostatic blood pressure regulation is essential for early postoperative mobilization. However, early postoperative mobilization can be delayed due to postoperative orthostatic hypotension (POH) defined as a fall in systolic pressure > 20 mmHg and/or diastolic pressure > 10 mmHg or due to postoperative orthostatic intolerance (POI), characterized by dizziness, nausea, vomiting, blurred vision or syncope during mobilization. Although these conditions are well-known clinical problems that can delay early mobilization, relatively few data are available on pathophysiological mechanisms and possible treatments.

Several prospective studies with standardized mobilization procedures have already established that the incidence of POI and POH after THA is 38-42% at 6 hours after surgery.

Previous studies on patients undergoing prostatectomy and THA have also demonstrated that attenuated vasopressor response and a concomitant reduction in cardiac output (CO) and cerebral perfusion during postural changes after surgery contributes to POI and POH. Strategies aiming to reduce the incidence of POI and POH by pain management, vasoconstrictive treatment with alpha-1 receptor agonist, optimized fluid management with goal-directed fluid therapy and reduction of surgical stress-response with pre-operative high-dose glucocorticoid did not solve the problem.

The precise pathophysiological mechanisms of POI and POH remain to be elucidated and this is therefore the aim of the current prospective observational study.

• Study Type: Observational
• Enrollment (Anticipated): 26

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Hvidovre Hospital
    • Contact: Ana-Marija Hristovska, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients undergoing primary unilateral total hip arthroplasty in spinal anesthesia in standardized fast-track setting

Description

Inclusion Criteria:

• Age 18-65
• Written informed consent
• Patients that speak and understand Danish
• Patients undergoing primary unilateral total hip arthroplasty in spinal anesthesia in standardized fast-track setting

Exclusion Criteria:

• Alcohol and drug abuse
• Cognitive dysfunction
• History of orthostatic hypotension
• Use of anxiolytic or antipsychotic drugs
• Use of opioids
• Use of following vasodilator antihypertensive drugs: beta-blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin 2 receptor blockers (ARBs), calcium channel blockers
• Use of loop diuretics, thiazid diuretics and potassium-sparing diuretics
• Use of Gabapentin
• Arrhythmias or heart failure
• Diabetes mellitus type I
• Diabetes mellitus type II
• History of following diseases in the autonomic nervous system: Parkinson disease, multiple sclerosis, autonomic neuropathies
• History of cerebral apoplexy or transitory cerebral ischemia
• Dementia
• American Society of Anesthesiologists (ASA) score ≥ 4

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Orthostatic intolerant (OI); 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
Orthostatic tolerant (OT); 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

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	Preoperatively, 6 and 24 hours postoperatively
Changes in diastolic arterial pressure (DAP) during mobilization	Measured in mmHg	Preoperatively, 6 and 24 hours postoperatively
Changes in mean arterial pressure (MAP) during mobilization	Measured in mmHg	Preoperatively, 6 and 24 hours postoperatively
Changes in systemic vascular resistance (SVR) during mobilization	Measured in mmHg⋅min⋅mL-1	Preoperatively, 6 and 24 hours postoperatively
Changes in cardiac output (CO) during mobilization	Measured in mL/min	Preoperatively, 6 and 24 hours postoperatively
Changes in stroke volume (SV) during mobilization	Measured in mL	Preoperatively, 6 and 24 hours postoperatively
Changes in hematocrit	Measured in %	Preoperatively, 6 and 24 hours postoperatively
Changes in C-Reactive Protein	Measured in mg/L	Preoperatively, 6 and 24 hours postoperatively
Changes in haemoglobin (Hgb) concentration	Measured in millimoles/L	Preoperatively, 6 and 24 hours postoperatively
Changes in heart rate variability (HRV) during mobilization	Measured in ms	Preoperatively, 6 and 24 hours postoperatively
Changes in baroreflex sensitivity (BRS) during mobilization	Measured in ms/mmHg	Preoperatively, 6 and 24 hours postoperatively
Changes in peripheral perfusion index (PPI) during mobilization	Measured in arbitrary units (AU)	Preoperatively, 6 and 24 hours postoperatively
Changes in cerebral perfusion (ScO2) during mobilization	Measured in %	Preoperatively, 6 and 24 hours postoperatively
Changes in muscular perfusion (SmO2) during mobilization	Measured in %	Preoperatively, 6 and 24 hours postoperatively
Changes in total blood volume (TBV)	Measured in mL	Preoperatively, 6 and 24 hours postoperatively
Changes in erythrocyte volume (ECV)	Measured in mL	Preoperatively, 6 and 24 hours postoperatively
Changes in plasma volume (PV)	Measured in mL	Preoperatively, 6 and 24 hours postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score	Measured by verbal rating scale (VRS) from 0 to 10 (0 = no pain, 10 = worse pain imaginable)	Preoperatively, 6 and 24 hours postoperatively
Estimated bleeding	Measured in mL	Intraoperatively, 6 and 24 hours postoperatively
Opioid use	Measured in mg	6 and 24 hours postoperatively
Cumulative fluid administration and losses	Measured in mg	Intraoperatively, 6 and 24 hours 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.
• Lindberg-Larsen V, Petersen PB, Jans O, Beck T, Kehlet H. Effect of pre-operative methylprednisolone on orthostatic hypotension during early mobilization after total hip arthroplasty. Acta Anaesthesiol Scand. 2018 Aug;62(7):882-892. doi: 10.1111/aas.13108. Epub 2018 Mar 24.
• Jans O, Mehlsen J, Kjaersgaard-Andersen P, Husted H, Solgaard S, Josiassen J, Lunn TH, Kehlet H. Oral Midodrine Hydrochloride for Prevention of Orthostatic Hypotension during Early Mobilization after Hip Arthroplasty: A Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology. 2015 Dec;123(6):1292-300. doi: 10.1097/ALN.0000000000000890.
• Bundgaard-Nielsen M, Jans O, Muller RG, Korshin A, Ruhnau B, Bie P, Secher NH, Kehlet H. Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial. Anesthesiology. 2013 Oct;119(4):813-23. doi: 10.1097/ALN.0b013e31829ce4ea.
• 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): March 18, 2019
• Primary Completion (ANTICIPATED): January 1, 2021
• Study Completion (ANTICIPATED): May 15, 2021

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (ACTUAL): November 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Orthostatic Intolerance; Orthostatic Hypotension
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Postoperative Complications; Hypotension, Orthostatic; Orthostatic Intolerance
• Other Study ID Numbers: H-18052195

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