Feasibility of Breathwork Intervention With Older Adults After Knee Surgery

Official title

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

Overview

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.

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.

Interventions

• 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 se
• 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.

Primary outcome measures

• Study Feasibility via Recruitment [Time frame: Through study completion, an average of 4.5 months]
• Study Feasibility via Retention [Time frame: Through study completion, an average of 4.5 months]
• Study Feasibility via Receipt of Saliva Samples [Time frame: Through study completion, an average of 4.5 months]
• Study Feasibility via Postoperative Morbidity Survey Completion [Time frame: Through study completion, an average of 4.5 months]
• Box Breathing Intervention Feasibility via Box Breathing Completion Survey [Time frame: Through study completion, an average of 4.5 months]
• Box Breathing Intervention Feasibility via Feasibility of Intervention Measure (FIM) [Time frame: Measured one time on the evening of Postoperative Day 3]
• Box Breathing Intervention Acceptability via Acceptability of Intervention Measure (AIM) [Time frame: Measured one time on the evening of Postoperative Day 3]
• Box Breathing Intervention Appropriateness via Intervention Appropriateness Measure (IAM) [Time frame: Measured one time on the evening of Postoperative Day 3]
• TriPeaks Video Attention Control Task Feasibility via Attention Control Task Completion Survey [Time frame: Through study completion, an average of 4.5 months]
• TriPeaks Video Attention Control Task Feasibility via Feasibility of Intervention Measure (FIM) [Time frame: Measured one time on the evening of Postoperative Day 3]

Secondary outcome measures (5)

• Postoperative Pain as Assessed by the Numeric Rating Scale (NRS), 11-point [Time frame: Measured one time on the evening of Postoperative Day 3]
• Postoperative Anxiety as Assessed by the State Anxiety Inventory (SAI) [Time frame: 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) [Time frame: Measured one time on the evening of Postoperative Day 3]
• Quality of Recovery as Assessed by the Quality of Recovery, Short Form (QoR-15) [Time frame: 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 [Time frame: Measured upon waking, 30 minutes after waking, and at bedtime on both Postoperative Day 2 and Day 3]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

United States · 1 center

• The University of Arizona — Tucson

Publications

• Szulczewski MT. Training of paced breathing at 0.1 Hz improves CO2 homeostasis and relaxation during a paced breathing task. PLoS One. 2019 Jun 20;14(6):e0218550. doi: 10.1371/journal.pone.0218550. eCollection 2019. PMID 31220170
• Sturgeon JA, Yeung EW, Zautra AJ. Respiratory sinus arrhythmia: a marker of resilience to pain induction. Int J Behav Med. 2014 Dec;21(6):961-5. doi: 10.1007/s12529-014-9386-6. PMID 24421149
• Bentley TGK, D'Andrea-Penna G, Rakic M, Arce N, LaFaille M, Berman R, Cooley K, Sprimont P. Breathing Practices for Stress and Anxiety Reduction: Conceptual Framework of Implementation Guidelines Based on a Systematic Review of the Published Literature. Brain Sci. 2023 Nov 21;13(12):1612. doi: 10.3390/brainsci13121612. PMID 38137060
• Gerritsen RJS, Band GPH. Breath of Life: The Respiratory Vagal Stimulation Model of Contemplative Activity. Front Hum Neurosci. 2018 Oct 9;12:397. doi: 10.3389/fnhum.2018.00397. eCollection 2018. PMID 30356789
• Russo MA, Santarelli DM, O'Rourke D. The physiological effects of slow breathing in the healthy human. Breathe (Sheff). 2017 Dec;13(4):298-309. doi: 10.1183/20734735.009817. PMID 29209423
• Chin MS, Kales SN. Understanding mind-body disciplines: A pilot study of paced breathing and dynamic muscle contraction on autonomic nervous system reactivity. Stress Health. 2019 Oct;35(4):542-548. doi: 10.1002/smi.2887. Epub 2019 Sep 5. PMID 31347763
• Chaitanya S, Datta A, Bhandari B, Sharma VK. Effect of Resonance Breathing on Heart Rate Variability and Cognitive Functions in Young Adults: A Randomised Controlled Study. Cureus. 2022 Feb 13;14(2):e22187. doi: 10.7759/cureus.22187. eCollection 2022 Feb. PMID 35308668
• Balban MY, Neri E, Kogon MM, Weed L, Nouriani B, Jo B, Holl G, Zeitzer JM, Spiegel D, Huberman AD. Brief structured respiration practices enhance mood and reduce physiological arousal. Cell Rep Med. 2023 Jan 17;4(1):100895. doi: 10.1016/j.xcrm.2022.100895. Epub 2023 Jan 10. PMID 36630953

Identifiers

NCT: NCT07464860 · STUDY00007185

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗