Feasibility of Breathwork Intervention With Older Adults After Knee Surgery

A Box Breathing Intervention and the Surgical Stress Response in Older Adults Undergoing Total Knee Arthroplasty: A Randomized Controlled Feasibility Trial

Postoperative complications after surgical procedures, including following total knee arthroplasty (TKA), have a negative impact on the health and well-being of surgical patients. Older adults (≥65 years) are particularly vulnerable to postoperative complications and their associated morbidities due to the biological aging process. Older adults comprise nearly half of surgical patients worldwide, and this number is expected to increase in the next 10-20 years as the aging population continues to grow. TKA is the most common procedure undergone by older adults, and the rate of TKA procedures is also expected to rise. Despite perioperative guidelines and protocols to prevent postoperative complications, the prevalence of postoperative complications following TKA is approximately 12%. Given these statistics, millions of older adults undergoing TKA may be at risk for postoperative complications and their associated morbidities in the coming decades. Therefore, additional interventions are needed to combat postoperative complications in this population.

The body's natural response to surgery, also known as the surgical stress response (SSR), contributes to postoperative complications through complex mechanisms involving the autonomic nervous system (ANS). Increased sympathetic nervous system (SNS) activity, or the body's fight-or-flight response, causes dysregulation in feedback systems that regulate the stress response, potentially leading to poorer outcomes. Interventions, such as breathwork, that induce the parasympathetic nervous system (PNS), or the body's rest-and-digest response, have been shown to balance the ANS, regulate stress biology, and improve outcomes. This study will examine the feasibility of adding a breathwork intervention (Box Breathing), compared to an attention control, to standard perioperative care for older adults undergoing TKA. This study will also examine the proof of concept that Box Breathing, compared to an attention control, may help regulate the SSR by assessing an objective measure of stress-related biology, diurnal cortisol rhythm, and gathering self-report information on pain, anxiety, depression, and quality of recovery following TKA.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Pain; Stress Psychological; Stress Physiology; Cortisol; Breathing Exercises; Relaxation; Postoperative Anxiety; Postoperative Depression; Relaxation Therapy; Stress Physiological; Hypothalamic Pituitary Adrenal; Breathing Techniques; Surgical Stress Response; Quality of Recovery (QoR-15)
• Intervention / Treatment: Behavioral: A 5-minute Asynchronous Breathwork Intervention; Behavioral: A 5-minute Asynchronous Card Game Video

Detailed Description

Postoperative complications, defined as any event deviating from normal recovery,1 negatively affect patients' physiological and psychological well-being and impose major financial burdens on healthcare systems.2-4 Of the estimated 312 million surgeries performed annually, 7-20% result in one or more complications.5-7 Surgery accounts for nearly 40% of hospital expenditures, with postoperative complications responsible for over half of these costs.2,8 Complications range from mild (e.g., nausea, constipation) to severe (e.g., infection, sepsis), contributing to postoperative morbidities such as pain, anxiety, and depression, and even mortality if undertreated.4,6,9 Their intensity is influenced by procedure type, patient risk factors, and perioperative management.10-14 Older adults (≥65 years) are especially vulnerable, as aging alters neuroendocrine and immune functions critical for recovery.9,15,16 They comprise 32-53% of surgical patients worldwide,15,17 a number projected to rise by at least 10% by 2030.7,18 Total knee arthroplasty (TKA) represents approximately 55% of procedures in this group and is expected to increase by 14% by 2040.19,20 Despite advances in surgical practice, about 12% of older adults experience complications after TKA.21,22 With the aging population expanding, millions may face increased risk for postoperative complications and associated morbidities.

A primary mechanism contributing to these complications is the surgical stress response (SSR), an innate neuroendocrine, metabolic, and immune reaction designed to maintain homeostasis after tissue injury.3,6,9 When surgery occurs, the paraventricular nucleus (PVN) of the hypothalamus detects physiological stress signals and triggers activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis.6,9 The HPA axis regulates circulating cortisol and diurnal rhythm,23,24 but excessive SNS activation during surgery disrupts this system, causing prolonged cortisol elevation and flattened diurnal slopes.9,25 Flatter cortisol slopes have been linked to greater postoperative pain, anxiety, and depression.23,24,26 Therefore, dysregulation of the HPA axis may amplify postoperative morbidities, especially in older adults.9,23,27 Although the SSR is necessary for healing,9,28,29 autonomic imbalance caused by persistent SNS activity and reduced parasympathetic nervous system (PNS) output can last for weeks after surgery.9,28,30 Evidence suggests that strengthening PNS output may rebalance the ANS, attenuate the stress response, and improve recovery outcomes.29,31-33 Given the growing number of older adults undergoing TKA, there is a clear need for safe behavioral interventions that activate the PNS to mitigate SSR dysregulation and related complications.

The PNS, or "rest and digest" system, restores balance after SNS activation.34-36 This system is primarily mediated by the vagus nerve, which regulates involuntary processes such as heart rate, respiration, and digestion.34,37,38 Vagal signaling between the brain, lungs, and heart generates respiratory sinus arrhythmia (RSA), a rhythmic heart rate fluctuation with breathing that serves as a biomarker of vagal tone and PNS activity.40,41 Higher vagal tone reflects greater parasympathetic capacity and correlates with improved psychological and physiological well-being.33,41 The vagus nerve also modulates the HPA axis by regulating corticotropin-releasing hormone (CRH) in the PVN, which influences downstream ACTH and cortisol release.9,34,42 Research shows an inverse relationship between vagal tone and HPA activity,34,42,43 suggesting that decreased vagal tone, as seen in dysregulation by the SSR, correlates with poorer psychological outcomes such as pain, anxiety, and depression.44,45 Enhancing vagal tone through interventions that promote RSA may therefore facilitate autonomic balance, HPA regulation, and improved postoperative recovery.

Breathwork is a promising nonpharmacological approach to achieve this effect. Defined as the intentional regulation of breath rate and rhythm to influence physiological states,32,46 breathwork can strengthen PNS output and counteract the SNS overactivation during the SSR.31,33 Practices such as resonance breathing, where respiration is slowed to four to seven breaths per minute, naturally elicit RSA and increase vagal tone.47-49 Resonance breathing has been linked to HPA regulation (50) and reductions in pain, anxiety, and depression.46,51,52 However, few studies have examined its impact on postoperative outcomes in older adults following TKA.

This study investigates Box Breathing as a feasible addition to Perioperative care as usual (CAU) for older adults undergoing TKA. Box Breathing is a controlled breathwork technique where each section of the practice (inhalations, exhalations, and breath retentions) is equal in duration.46,53 The practice can be tailored to achieve resonance breathing rates that stimulate RSA, elevate vagal tone, and activate the PNS.47-49 Box Breathing is accessible, low-cost, and easily taught, requiring minimal time commitments and no equipment, which supports its feasibility among older surgical patients.

Preliminary studies suggest that Box Breathing improves physiological and psychological outcomes by enhancing PNS activity and reducing SNS arousal.46,53,54 Controlled breath retentions may further decrease stress and anxiety by improving carbon dioxide tolerance.51,55 The current study proposes that Box Breathing may attenuate SSR-induced HPA dysregulation and flattening of diurnal cortisol slopes, thereby improving pain, anxiety, depression, and quality of recovery in older adults undergoing TKA.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Devon E Cobos Garcia, PhD Candidate, MS, BSN; Phone Number: 904-477-7960; Email: decg0131@arizona.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Adults aged 65 years or older of any sex, gender and ethnic background who meet the following criteria will be eligible to enroll in the present study:

Inclusion Criteria:

• scheduled for elective TKA within the next week to two months (can be second knee, but cannot be a revision of the original knee)
• self-reported good health, including denial of debilitating illness that may affect participation in or be potentially exacerbated by deep, controlled breathing (i.e., chronic obstructive pulmonary disorder [COPD], symptomatic or advanced heart failure, complete heart block, glaucoma, epilepsy)
• denial of conditions that alter cortisol release or that require corticosteroid therapy (i.e., Cushing's syndrome, Addison's disease, pituitary tumors, adrenal gland tumors, asthma)
• denial of severe psychiatric or cognitive conditions that warrant the need for a durable power of attorney (DPOA)
• able to understand written and verbal English.

Exclusion Criteria:

• currently taking oral, injectable, intranasal, topical, or inhaled corticosteroid medications (i.e., prednisone, hydrocortisone, dexamethasone, methylprednisolone, methylprednisolone acetate, triamcinolone, betamethasone, mometasone, fluticasone, budesonide, clobetasol)
• do not have the technology requirements to complete data collection (i.e., participant does not have a smartphone, tablet, laptop, or desktop computer; lack of reliable internet)

The following exclusion criteria may affect participants' ability to remain in the study following enrollment:

• Development of complications during surgery that require prolonged hospitalization into Postoperative Day (POD) 2 (e.g., postoperative intubation and ventilation requirements, intractable pain, intractable nausea/vomiting, signs of infection or sepsis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group - Box Breathing Intervention; Participants in this group will complete a 5-minute virtual Box Breathing session three times a day for two consecutive days following surgery on Postoperative Day 2 and 3. The Box Breathing intervention will be delivered asynchronously via a YouTube video created by the PI and accessed by participants via REDCap. Participants will also collect saliva samples three times per day (upon waking, 30 minutes after waking, and at bedtime) on Postoperative Day 2 and 3 to measure diurnal cortisol rhythm. Participants will fill out a 1-item survey about the Box Breathing session and a 1-item survey about saliva sample collection after each session and collection timepoint. Participants will also complete seven additional surveys regarding pain, anxiety, depression, and quality of recovery on the evening of Postoperative Day 3 after the final Box Breathing session.	Behavioral: A 5-minute Asynchronous Breathwork Intervention; Participants will be guided through the Box Breathing intervention with a pre-recorded YouTube video created by the PI. The video will be embedded into REDCap and delivered online asynchronously to provide flexibility and will be the same for all six sessions. The video will consist of a simple box pattern displayed on the screen with movement around the box that coincides with the PI's voiceover recording of the Box Breathing sequence. . Each session will be five minutes in length, with each section (e.g., inhalation, exhalation, breath retention) of the exercise lasting approximately four seconds. The sequence of each Box Breathing session is performed by breathing through the nose as follows: inhale for 4 seconds, hold the inhalation (lungs "full") for 4 seconds, exhale for 4 seconds, hold the exhalation (lungs "empty") for 4 seconds, and then return to inhaling for 4 seconds. Participants will be encouraged to exhale through the mouth if exhaling through the nose is not accessible.
Active Comparator: Attention Control Group - TriPeaks Video; Participants in this group will complete a 5-minute virtual TriPeaks Video session three times a day for two consecutive days following surgery on Postoperative Day 2 and 3. The TriPeaks Video will be delivered asynchronously via a YouTube video created by the PI and accessed by participants via REDCap. Participants will also collect saliva samples three times per day (upon waking, 30 minutes after waking, and at bedtime) on Postoperative Day 2 and 3 to measure diurnal cortisol rhythm. Participants will fill out a 1-item survey about the TriPeaks Video session and a 1-item survey about saliva sample collection after each session and collection timepoint. Participants will also complete seven additional surveys regarding pain, anxiety, depression, and quality of recovery on the evening of Postoperative Day 3 after the final TriPeaks Video session.	Behavioral: A 5-minute Asynchronous Card Game Video; Participants will watch the TriPeaks video, a pre-recorded YouTube video created by the PI. The video will be embedded into REDCap and delivered online asynchronously to provide flexibility and will be the same for all six sessions. The video will consist of a screen recording of the PI playing the card game TriPeaks. Each session will be five minutes in length to match the Box Breathing intervention dosage and delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Feasibility via Recruitment	Enroll a nationwide sample of N=32 older adults (≥65 years of age) scheduled for elective Total Knee Arthroplasty that meet eligibility criteria within the rolling three- to six-month recruitment campaign period	Through study completion, an average of 4.5 months
Study Feasibility via Retention	Overall study attrition is ≤25%, with no more than 10% differential attrition between the experimental and control groups, calculated by dividing the number of participants who drop out by total participants enrolled in the study.	Through study completion, an average of 4.5 months
Study Feasibility via Receipt of Saliva Samples	Study team receipt of 80% of salivary cortisol samples collected.	Through study completion, an average of 4.5 months
Study Feasibility via Postoperative Morbidity Survey Completion	Collection of 80% of postoperative morbidity surveys (Numeric Rating Scale, 11-point; State Anxiety Inventory; Patient-Reported Outcomes Measurement Information System Depression - Short Form 4a; and Quality of Recovery, Short Form)	Through study completion, an average of 4.5 months
Box Breathing Intervention Feasibility via Box Breathing Completion Survey	80% of the 1-item Box Breathing Completion surveys completed with "Yes", with "Yes" answers indicating the participant completed the Box Breathing session for that day (Postoperative Day 2 and 3) and time (Morning, Afternoon, Evening), and "No" indicating the participant did not complete the Box Breathing session for that day (Postoperative Day 2 and 3) and time (Morning, Afternoon, Evening).	Through study completion, an average of 4.5 months
Box Breathing Intervention Feasibility via Feasibility of Intervention Measure (FIM)	Score ≥15 on the FIM for Box Breathing Intervention per participant. The FIM is a 4-item, Likert-type survey used to measure implementation success. The score range is 4 to 20. The higher the score, the greater the feasibility of implementation.	Measured one time on the evening of Postoperative Day 3
Box Breathing Intervention Acceptability via Acceptability of Intervention Measure (AIM)	Score ≥15 on the AIM for Box Breathing Intervention per participant. The AIM is a 4-item, Likert-type survey used to measure implementation success. The score range is 4 to 20. The higher the score, the greater the acceptability of implementation.	Measured one time on the evening of Postoperative Day 3
Box Breathing Intervention Appropriateness via Intervention Appropriateness Measure (IAM)	Score ≥15 on the AIM for Box Breathing Intervention per participant. The IAM is a 4-item, Likert-type survey used to measure implementation success. The score range is 4 to 20. The higher the score, the greater the appropriateness of implementation.	Measured one time on the evening of Postoperative Day 3
TriPeaks Video Attention Control Task Feasibility via Attention Control Task Completion Survey	80% of the 1-item Attention Control Task Completion surveys completed with "Yes", with "Yes" answers indicating the participant completed the Attention Control Task (TriPeaks Video) session for that day (Postoperative Day 2 and 3) and time (Morning, Afternoon, Evening), and "No" indicating the participant did not complete the Attention Control Task (TriPeaks Video) session for that day (Postoperative Day 2 and 3) and time (Morning, Afternoon, Evening).	Through study completion, an average of 4.5 months
TriPeaks Video Attention Control Task Feasibility via Feasibility of Intervention Measure (FIM)	Score ≥15 on the FIM for Attention Control Task (TriPeaks Video) per participant. The FIM is a 4-item, Likert-type survey used to measure implementation success. The score range is 4 to 20. The higher the score, the greater the feasibility of implementation.	Measured one time on the evening of Postoperative Day 3
TriPeaks Video Attention Control Task Acceptability via Acceptability of Intervention Measure (AIM)	Score ≥15 on the AIM for Attention Control Task (TriPeaks Video) per participant. The AIM is a 4-item, Likert-type survey used to measure implementation success. The score range is 4 to 20. The higher the score, the greater the acceptability of implementation.	Measured one time on the evening of Postoperative Day 3
TriPeaks Video Attention Control Task Appropriateness via Intervention Appropriateness Measure (IAM)	Score ≥15 on the IAM for Attention Control Task (TriPeaks Video) per participant. The IAM is a 4-item, Likert-type survey used to measure implementation success. The score range is 4 to 20. The higher the score, the greater the appropriateness of implementation.	Measured one time on the evening of Postoperative Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain as Assessed by the Numeric Rating Scale (NRS), 11-point	A 1-item, unidimensional 11-point scale (ranging from 0 to 10) used to measure pain intensity at the moment of completing the scale. The higher the score, the more pain the person is experiencing (the higher the score, the worse the outcome).	Measured one time on the evening of Postoperative Day 3
Postoperative Anxiety as Assessed by the State Anxiety Inventory (SAI)	A 20-item, Likert-type survey used to measure state anxiety (how anxious a person feels in that moment). Reversed scoring is used for 10 of the items that do not exhibit anxiety. The score range is 20 to 80. The higher the score, the greater the state anxiety (the higher the score, the worse the outcome).	Measured one time on the evening of Postoperative Day 3
Postoperative Depression as Assessed by the Patient-Reported Outcomes Measurement Information System Depression - Short Form 4a (PROMIS-Depression-4a)	A 4-item, Likert-type survey used to measure the severity of depression. The score range is 4 to 20, where higher scores indicate increased depression (the higher the score, the worse the outcome). For this study, survey has been modified from the recall timeline of "last 7 days" to the recall timeline of "last 2 days" to capture symptoms postoperatively.	Measured one time on the evening of Postoperative Day 3
Quality of Recovery as Assessed by the Quality of Recovery, Short Form (QoR-15)	A 15-item (short-form version of the QoR-40) Likert-type survey used to measure quality of postoperative recovery. Reversed scoring is used for items 11-15. The score range is 0 to 150, with higher scores indicating higher quality of recovery (the higher the score, the better the outcome).	Measured one time on the evening of Postoperative Day 3
Diurnal Cortisol Rhythm Variables (AUC and slope) as Assessed by Amount of Cortisol in Saliva Samples		Measured upon waking, 30 minutes after waking, and at bedtime on both Postoperative Day 2 and Day 3

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Principal Investigator: Devon E Cobos Garcia, PhD Candidate, University of Arizona; Study Chair: Ruth E Taylor-Piliae, PhD, University of Arizona; Study Chair: Thaddeus W W Pace, PhD, University of Arizona

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Estimated): April 6, 2026
• Primary Completion (Estimated): August 6, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 11, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Postoperative Pain; Total Knee Arthroplasty; Quality of Recovery; Postoperative Complications; Breathing Exercises; Hypothalamic-Pituitary-Adrenal Axis; Breathwork; Surgical Stress Response; Breathing Techniques; Postoperative Depression; Postoperative Anxiety; Diurnal Cortisol Rhythm
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathologic Processes; Behavioral Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Pain, Postoperative; Stress, Psychological; Postoperative Complications
• Other Study ID Numbers: STUDY00007185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No