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

Study Overview
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Brief Summary
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Incidence and pathophysiologic hemodynamics of postoperative orthostatic intolerance and orthostatic hypotension in patients receiving antihypertensives

Detailed Description
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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.

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

Conditions
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Orthostatic Intolerance, Orthostatic Hypotension

Intervention / Treatment
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* Other: Mobilisation procedure


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Orthostatic tolerant patients (OT)<br>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<br>* 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.<br>|
| Orthostatic intolerant patients (OI)<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Orthostatic Hypotension, Orthostatic Intolerance, Postoperative period, Antihypertensives, Autonomic dysfunction