Orthostatic Intolerance and Hypotension After Administration of Morphine in Patients Prior to Hip or Knee Arthroplasty

Incidence of Orthostatic Intolerance and Orthostatic Hypotension After Administration of Intravenous Morphine in Patients Prior to Hip or Knee Arthroplasty

Incidence of orthostatic intolerance and orthostatic hypotension after intravenous administration of morphine in patients prior to hip or knee arthroplasty.

Study Overview

• Status: Recruiting
• Conditions: Orthostatic Hypotension; Orthostatic Intolerance
• Intervention / Treatment: Drug: Morphine

Detailed Description

Early postoperative mobilization is crucial for recovery of patients undergoing surgery in the multimodal fast-track approach to perioperative care, since physical immobilization is highly associated with increased risk of postoperative complications and prolonged hospital length of stay. Postoperative mobilization is often delayed due to patients experiencing orthostatic hypotension (OH), defined as a drop in systolic blood pressure > 20 mmHg or diastolic blood pressure > 10 mmHg, or orthostatic intolerance (OI), characterized by dizziness, blurred vision, nausea, vomiting, sensation of heat or syncope.

Previous studies have found a high incidence of postoperative OI (> 40 %) among patients undergoing total hip arthroplasty.

A possible causative factor to the high occurrence of OH and OI after surgery could be postoperative pain management by administration of morphine. Morphine is known to have many side-effects including nausea, vomiting, dizziness and orthostatic hypotension.

The object of this study is to isolate and estimate the effect of intravenous morphine on the incidence of OH and OI.

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

Contacts and Locations

• Study Contact: Name: Bodil Uldall-Hansen, BA Medicine; Phone Number: +4528342057; Email: bodil.uldall-hansen@regionh.dk
• Study Contact Backup: Name: Ana-Marija Hristovska, Resident; Phone Number: +4538621508; Email: anamarijahristovska@gmail.com

Study Locations

• Denmark
  • Hvidovre, Denmark, 2960
    • Recruiting
    • Hvidovre University Hospital
    • Contact: Bodil Uldall-Hansen, BA Medicine; Phone Number: +4528342057; Email: bodil.uldall-hansen@regionh.dk
    • Contact: Ana-Marija Hristovska, Resident; Phone Number: +4538621508; Email: anamarijahristovska@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients undergoing primary unilateral total hip arthroplasty, total knee arthroplasty or unicompartmental knee arthroplasty

Description

Inclusion Criteria:

• Patients undergoing primary unilateral total hip arthroplasty (THA), total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA)
• Patients > 18
• Patients that understand and speak Danish
• Patients that have provided written informed consent

Exclusion Criteria:

• Alcohol or substance abuse
• Habitual use of opioids
• Habitual use of anxiolytic, antidepressant and/or antipsychotic drugs
• History of previous orthostatic intolerance or hypotension
• Cognitive dysfunction
• Glomerular filtration rate (GFR) < 30 ml/min
• Cardiac arrhythmia

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients undergoing primary hip or knee arthroplasty	Drug: Morphine; Administration of 0.1 mg/kg (IBW) intravenous morphine; Other Names: opioid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of orthostatic hypotension	Orthostatic hypotension is defined as a fall in systolic pressure > 20 mmHg and/or diastolic pressure > 10 mmHg during mobilization	30 minutes after morphine administration

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	Before and 30 minutes after morphine administration
Changes in diastolic arterial pressure (DAP) during mobilization	Measured in mmHg by non-invasive LiDCO	Before and 30 minutes after morphine administration
Changes in mean arterial pressure (MAP) during mobilization	Measured in mmHg by non-invasive LiDCO	Before and 30 minutes after morphine administration
Changes in heart rate (HR) during mobilization	Measured in beats min-1 by non-invasive LiDCO	Before and 30 minutes after morphine administration
Changes in stroke volume (SV) during mobilization	Measured in mL by non-invasive LiDCO	Before and 30 minutes after morphine administration
Changes in cardiac output (CO) during mobilization	Measured in L/min by non-invasive LiDCO	Before and 30 minutes after morphine administration
Changes in systemic vascular resistance (SVR) during mobilization	Measured in dynes s cm-5 by non-invasive LiDCO	Before and 30 minutes after morphine administration
Changes in peripheral perfusion index (PPI) during mobilization	Measured in % by Root Masimo	Before and 30 minutes after morphine administration
Changes in cerebral perfusion (ScO2) during mobilization	Measured in % by Root Masimo	Before and 30 minutes after morphine administration
Changes in muscular perfusion (SmO2) during mobilization	Measured in % by Root Masimo	Before and 30 minutes after morphine administration
Changes in baroreflex sensitivity - vagal (BRSv) during Valsalva manoeuvre	Measured in ms	Before and 30 minutes after morphine administration
Changes in heart rate variability (HRV) during Valsalva manoeuvre	Measured in ms	Before and 30 minutes after morphine administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain score during mobilisation	Measured by verbal rating scale (VRS) from 0 to 10 (0 = no pain, 10 = worse pain imaginable)	Before and 30 minutes after morphine administration
Occurence of side-effects to morphine administration	Occurrence of following side-effects to morphine administration: nausea, vomiting, pruritus, headache or dizziness	30 minutes after morphine administration

Collaborators and Investigators

• Sponsor: Copenhagen University Hospital, Hvidovre
• Collaborators: Kehlet, Henrik, M.D., Ph.D.
• Investigators: Study Director: Nicolai Bang Foss, Dr. Med., Copenhagen University Hospital, Hvidovre

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Morphine; Orthostatic Intolerance; Orthostatic Hypotension; Autonomic Dysfunction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neurologic Manifestations; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Hypotension, Orthostatic; Orthostatic Intolerance; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: H-20071567

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