Total Intravenous Anesthesia vs Spinal Anesthesia in Patients Undergoing Unilateral Primary Total Knee Arthroplasty

The purpose of this study is to compare same-day discharge rates and recovery outcomes across an adult patient population undergoing elective Total Knee Arthroplasty (TKA), and randomized to receive either spinal block anesthesia or Total IntraVenous Anesthesia (TIVA).

Primary Aim: assess same-day discharge rates between study arms (TIVA vs spinal).

Secondary Aim: Postoperative comparison of recovery during PostOperative Anesthesia Care Unit (PACU) admission, diagnostic assessment scores; outcomes related to cognition, hemodynamic stability, pain, nausea and vomiting; analysis of IntraOperative electroencephalogram (EEG) monitoring metrics, e.g., total suppression time, average Bi-spectral Index monitor (BIS) value, Spectral Edge Frequency (SEF); ability for Physical Therapy (PT) evaluation prior to discharge; longterm-followup (LTFU), hospital readmission, return to surgery, etc.; adverse event (AE) monitoring.

Study Overview

• Status: Recruiting
• Conditions: Total Knee Arthroplasty (TKA)
• Intervention / Treatment: Combination product: Total IntraVenous Anesthesia (TIVA); Device: Electroencephalogram (EEG); Combination product: Spinal-Block

Detailed Description

Same-day discharge after total knee arthroplasty (TKA) has become a central goal within Enhanced Recovery After Surgery (ERAS) protocols, particularly in large academic centers. Spinal anesthesia is widely used in this setting and offers advantages through avoidance of general anesthesia-related risks, including airway instrumentation and systemic anesthetic exposure; however, spinal anesthesia may also be associated with prolonged motor blockade, urinary retention, and delayed mobilization, which can hinder same-day discharge in some patients. Rare risks include headache (sometimes called a spinal headache), back soreness, the numbness spreading too high, or the spinal not working well enough and needing conversion to general anesthesia. Very rare but serious risks include infection, bleeding around the spinal cord, or nerve injury.

Total intravenous anesthesia (TIVA) represents an alternative approach that avoids neuraxial anesthesia and its associated risks, including motor weakness and urinary retention, and may reduce postoperative nausea and vomiting. However, TIVA typically requires airway instrumentation and exposure to general anesthetic agents, which carry risks such as sore throat, airway-related discomfort, dental trauma, and potential concerns regarding anesthetic dosing and recovery, particularly in older adults. Processed EEG-guided anesthesia has been proposed as a strategy to optimize anesthetic depth during general anesthesia and potentially reduce overdosing, though its impact on recovery outcomes within contemporary ERAS pathways remains incompletely defined.

This research will address this knowledge gap through a prospective, randomized trial. By comparing same-day discharge rates as the primary outcome-and examining recovery efficiency, postoperative complications, cognitive outcomes, and patient satisfaction as secondary and exploratory measures-this study will provide foundational evidence to inform anesthetic selection. Ultimately, these findings have the potential to refine perioperative care, optimize recovery, and inform future definitive trials and clinical practice guidelines for TKA, improving outcomes for a growing elderly surgical population.

A study comparison of the two anesthesia techniques (TIVA vs spinal-block) in patients undergoing total knee arthroplasty (TKA) is appropriate because anesthetic choice directly influences perioperative recovery, same-day discharge rates, and patient-centered outcomes. Total Knee Arthroplasty (TKA) represents one of the most common and rapidly increasing elective procedures worldwide, particularly among the elderly population at higher risk for adverse outcomes and longer postoperative recovery. A prospective, randomized study design allows for a controlled comparison of the two widely utilized anesthetic techniques within the context of modern ERAS protocols, while also incorporating standardized follow-up to capture both short-term and 90-day long-term outcomes. Beyond individual patient recovery, this research carries broader public health implications: with an aging population and rising demand for TKA, optimizing perioperative pathways that enhance recovery, reduce complications, and support same-day discharge has the potential to decrease healthcare utilization, lower costs, and improve the sustainability of orthopedic care delivery.

Based on our experience caring of these patients over the years, patients with strong preferences or contradictions to one of the two approaches are relatively small (~10-15%). Most patients defer to their anesthesiologists and surgeons to provide the best care plan for them. In the current practice, both anesthesia approaches are widely acceptable care for most patients undergoing TKA and no clear advantages in risk/benefit ratio in same day discharge between methods of anesthesia.

This is a single-center, prospective, randomized clinical trial. Study enrollment will consist of approximately 150-patients set to undergo elective total joint arthroplasty (TKA), at the University of Chicago Medicine (UCM); with 66-evaluable participants randomly assigned to each study arm (TIVA vs Spinal-block). Most TKA-patients are evaluated at least 1-week prior to their surgery by a member of the anesthesia team in the Anesthesia Pre-Operative Clinic (APMC) in preparation for the anesthetic plan to be administered. Eligible patients must meet initial study criteria regarding 'type of surgery' (TKA) and 'discharge plan' (same-day) to be approached regarding their interest in study participation. Potential patients will be contacted on the day of their preoperative evaluation in APMC or via phone following, by a member of the research team with experience consenting patients. Interested patients will:

• have plain language used to describe study details,
• be given time consider the informed consent material and ask questions,
• affirm their understanding of study details,
• be able to consent for themselves.

Patients showing interest by phone will be approached again on the day of surgery in the UCM-preoperative area, where the informed consent form (paper) can be signed, and baseline study diagnostic assessments can be captured. Only after consent and enrollment is confirmed can a patient be randomized to a study arm (TIVA vs spinal block).

Active study participation can last up to 7-days, following surgery, that includes survey assessment interviews to determine postoperative recovery status; with an additional long-term follow-up (LTFU) planned at day-90 via electronic medical record (EMR). Assessments to determine cognitive and physical function will be conducted at specific timepoints via investigator initiated interview (in-person and phone), using validated diagnostic surveys. Patient response will dictate length of time to complete.

Diagnostic Survey Assessments:

• Short Portable Mental Status Questionnaire (SPMSQ)
• 3-Minute Diagnostic Confusion Assessment Method (3D-CAM)
• Numeric Pain Rating Scale (NPRS)
• Numeric Rating Scale (NRS)

Diagnostic Survey Assessment Schedule

Preoperative Baseline (BL):

• SPMSQ (in-person, 3-minutes)
• 3D-CAM (3-minute)

PostOperative (Day-0):

• SPMSQ (in-person, 3-minutes)
• 3D-CAM (in-person, 3-minutes)
• NPRS (in-person, 1-minute)
• NRS (in-person, 1-minute)

PostOperative Day-1 (POD1):

• SPMSQ (via phone, 3-minutes)
• 3D-CAM (via phone, 3-minutes)
• NPRS (via phone, 1-minute)
• NRS (via phone, 1-minute)

An 'abnormal' 3D-CAM score in PACU will trigger additional assessment survey completion

PostOperative Day-3 (POD3):

• SPMSQ (via phone, 3-minutes)
• 3D-CAM (via phone, 3-minutes)

PostOperative Day-7 (POD7):

• SPMSQ (via phone, 3-minutes)
• 3D-CAM (via phone, 3-minutes)

Active participation will conclude either after, POD1 or POD7 (if triggered). Longterm-Followup (LTFU) will be conducted at PostOperative Day-90 (POD90) via electronic medical record (EMR).

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Frank T Brown Jr, MA; Phone Number: 773-834-5778; Email: ftbrownjr@uchicagomedicine.org
• Study Contact Backup: Name: Zheng Xie, MD, PhD; Phone Number: 773-753-1880; Email: JXie@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Frank T Brown Jr, MA; Phone Number: 773-834-5778; Email: ftbrownjr@uchicagomedicine.org
      • Contact: Zheng (Jimmy) Xie, MD, PhD; Phone Number: 773-753-1880, pager: 1963; Email: JXie@bsd.uchicago.edu
      • Principal Investigator: Zheng (Jimmy) Xie, MD, PhD
      • Sub-Investigator: Robert Fong, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged ≥18 years.
• Scheduled to undergo elective primary total knee arthroplasty (TKA) or robotic total knee arthroplasty (TKA) at the University of Chicago.
• Eligible for same-day discharge (SDD) based on established orthopedic and anesthesia criteria.
• Able to provide written informed consent.
• The ability to comprehend and complete cognitive assessment surveys and questionnaires.
• Consent to receive either Total IntraVenous Anesthesia (TIVA) or Spinal-block Anesthesia in a randomized manner
• No contraindication to either TIVA or spinal anesthesia

Exclusion Criteria:

• Age <18 years.
• Patients undergoing revision TKA or procedures other than elective primary TKA.
• Ineligibility for same-day discharge as determined by the surgical or anesthesia team.
• Contraindications to either anesthetic technique (e.g., spinal block anesthesia contraindicated due to coagulopathy, infection at puncture site, or patient refusal).
• Known allergy or hypersensitivity to study-related medications.
• Significant pre-existing cognitive impairment or dementia that would preclude valid participation in Short Portable Mental Status Questionnaire (SPMSQ), and 3-Minute Diagnostic Assessment for Confusion Assessment Method (3D-CAM) assessments.
• Severe chronic pain syndromes (e.g., fibromyalgia, centrally mediated pain disorders) that could confound perioperative pain assessment.
• Body mass index (BMI) > 40.
• Prisoners or other vulnerable populations unable to provide voluntary consent.
• Unable to give appropriate consent or difficult to comprehend and complete cognitive assessment surveys and questionnaires

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A -Total IntraVenous Anesthesia (TIVA) with Electroencephalogram (EEG); Arm A (TIVA): Induction and maintenance intravenously (propofol, dexmedetomidine, fentanyl, hydromorphone); no volatile agents. Anesthetic depth titration based on clinical responsiveness, hemodynamic and ventilatory parameters, and processed electroencephalogram (EEG) monitoring.	Combination product: Total IntraVenous Anesthesia (TIVA); Total IntraVenous Anesthesia - to achieve deep-sedation via chemical analgesic (propofol, dexmedetomidine, fentanyl, hydromorphone); continuous intravenous infusion.; Other Names: TIVA; General Anesthesia; Systemic Anesthesia; Deep Sedation; Device: Electroencephalogram (EEG); Non-invasive continuous neurological (Neuro) monitoring device, e.g., Bi-spectral (BIS), recording electrical activity of the brain via adhesive scalp electrodes, which transmit neuro-activity during sedation.; Other Names: EEG; BIS; Bi-spectral Index monitor (BIS); Brain Monitoring; Neurological (Neuro) Monitoring
Active Comparator: Arm B - Spinal Block with Electroencephalogram (EEG); Arm B (Spinal): Single-shot intrathecal mepivacaine-2%, 3.0 milliliters (mL) per institutional standard. Light propofol sedation is permitted at clinician discretion, titrated to comfort and clinical responsiveness, hemodynamic and ventilatory parameters, and processed electroencephalogram (EEG) monitoring.	Device: Electroencephalogram (EEG); Non-invasive continuous neurological (Neuro) monitoring device, e.g., Bi-spectral (BIS), recording electrical activity of the brain via adhesive scalp electrodes, which transmit neuro-activity during sedation.; Other Names: EEG; BIS; Bi-spectral Index monitor (BIS); Brain Monitoring; Neurological (Neuro) Monitoring; Combination product: Spinal-Block; Spinal-block (mepivacaine 2%, 3.0 mL) Clinician discretion to administer light-sedation with intravenously infused propofol during surgery.; Other Names: Regional Anesthesia; Local Anesthesia; Nerve-Block; Field-Block; Light Sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Same-Day Discharge (SDD) Rates	Comparison of same-day discharge rates between patients receiving either total intravenous anesthesia (TIVA) or spinal-block anesthesia, during total knee arthroplasty (TKA).	at PostOperative (Day-0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Anesthesia Care Unit (PACU) Length of Admission	PostOperative comparison of post-anesthesia care unit (PACU) length of stay (LOS), between both study arms (TIVA vs Spinal-block). Exact Time Recorded: at PACU admission, physical therapy evaluation, diagnostic survey assessment completion, and at discharge home. Study-arm timepoints range are averaged and compared.	at PostOperative (Day-0)
Changes in Short Portable Mental Status Questionnaire (SPMSQ)	The Short Portable Mental Status Questionnaire (SPMSQ) is an interview based validated diagnostic, evaluating basic orientation, memory, current events, and mathematical capabilities (such as counting backward) to determine if a patient requires further, more extensive neurological evaluation. SPMSQ: 10-question bank SPMSQ Calculation: First - subtract incorrect responses from correct Second - allow for one more error in the scoring if a patient has had a grade school education or less; or one less error if the patient has had education beyond the high school level. Third - calculate outcome associated with number of errors: 0-2 = normal mental functioning 3-4 = mild cognitive impairment 5-7 = moderate cognitive impairment 8 or more errors: severe cognitive impairment	at PreOperative (Baseline), PostOperative (Day-0), PostOperative (Day-1)
Changes in 3-Minute Diagnostic Assessment for Confusion Assessment Method (3D-CAM)	3D-CAM is an interview based bedside tool, screening for, four cardinal features of delirium (i.e., acute changes, inattention, disorganized thinking, altered level of consciousness) 3D-CAM: Patient Interview (10 items): provider asks the patient questions to gauge orientation and attention (e.g., reciting numbers backwards, months of the year backwards, and simple orientation questions) Observer Ratings (10-12 items): provider records clinical observations and asks collateral sources (family members, nurses, or caregivers) about any sudden changes in the patient's mental status from their baseline 0-20 Scale (Total Score): clinician evaluates cognitive and behavioral items, points are assigned for each positive item, resulting in a score between 0 and 20 Severity Bands: a score of 0 to 1 indicates normal/no delirium, while 2 to 20 indicates increasing levels of delirium severity (subsyndromal to severe delirium)	at PreOperative (Baseline), PostOperative (Day-0), PostOperative (Day-1)
Changes in Numeric Rating Scale (NRS) score, Nausea	Nausea, Numeric Rating Scale (NRS), patient-reported diagnostic to evaluate severity of nausea. Patient rating using a single whole integer from 0 to 10 that best reflects the level nausea. Nausea NRS rated on a scale from 0 to 10 (where 0 means no nausea and 10 means the worst possible nausea).	at PostOperative (Day-0) and PostOperative (Day-1)
Monitor changes in Numeric Pain Rating Scale (NPRS) score	Monitoring changes in 'Numeric Pain Rating Scale' (NPRS) diagnostic score to determine effectiveness an anesthesia choice. The NPRS is a validated self-report diagnostic. Patients verbally select a single whole integer from 0 to 10 that best reflects their 'current' pain level. Pain number = severity: 0 = No pain 1-3 = Mild pain 4-6 = Moderate pain 7-10 = Severe pain (worst pain imaginable)	at PostOperative (Day-0) and PostOperative (Day-1)
Satisfaction-Numeric Rating Scale (NRS) score	Satisfaction Numeric Rating Scale (NRS), patient-reported diagnostic to evaluate subjective experiences like pain or distress related to anesthesia care, on a scale from 0 to 10. Satisfaction NRS: 0 (Completely dissatisfied) to 10 (Completely satisfied).	at PostOperative (Day-0) and PostOperative (Day-1)
Changes in IntraOperative electroencephalogram (EEG) monitoring	Compare changes in EEG, i.e., suppression, Bi-Spectral Index (BIS), and Spectral Edge Frequency (SEF), during IntraOperative Total Knee Arthroplasty (TKA), between both groups (TIVA vs Spinal block).	IntraOperative
Adverse Event (AE) monitoring	Monitoring adverse events (AE), such as hemodynamics instability, nausea and vomiting, etc.; or any other events determined probable, possible, or unrelated to the study procedures or protocol. Study patient safety is monitored by investigators with experience in critical care anesthesia and the clinical research team members responsible for monitoring and reporting events.	PeriProcedural to Study Completion
Longterm-Followup (LTFU), Outcomes	Compare PostOperative recovery outcomes between arms at 90-day. Electronic Medical Record capture of information related to longterm recovery from surgery and anesthesia, e.g., infection, hospital readmission, return to surgery, Deep vein thrombosis (DVT), myocardial infarction, etc.	at PostOperative (Day-90)

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Zheng Xie, MD, PhD, University of Chicago, Department of Anesthesia and Critical Care

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Postoperative Recovery; Total IntraVenous Anesthesia (TIVA); Spinal block; Delirium - Postoperative
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Anesthesia and Analgesia; Neurosurgical Procedures; Diagnostic Techniques, Neurological; Electrodiagnosis; Anesthesia; Denervation; Anesthesia, Spinal; Anesthesia, Local; Electroencephalography; Anesthesia, Conduction; Anesthesia, General; Nerve Block; Deep Sedation
• Other Study ID Numbers: IRB25-1483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Per institutional regulation, and at the discretion of Principal Investigator, de-identified data may be shared with researcher(s) at the University of Chicago.
• IPD Sharing Time Frame: De-identified data may be shared adhoc at the discretion of the principal investigator, following completion of study enrollment and data analysis.
• IPD Sharing Access Criteria: Only researchers and statisticians at the University of Chicago may have access to any shared de-identified study data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes