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.

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.

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)

Organization, Collaborators