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

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.