A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management

Abstract

Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD.Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure –Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively.Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ≥ 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype.Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

Effect of flurbiprofen axetil on postoperative delirium for elderly patients

“…It was indicated that patients undergoing MIS suffered a less incidence of POD and lower inflammatory markers compared with those with open surgeries, consistent with a lower degree of stress response (Tan et al, ). However, recent work suggested that intraoperative CO 2 control may be an independent marker of POD risk (El‐Gabalawy et al, ; Mutch & El‐Gabalawy, ). Previous studies revealed that mild hypercapnia and substantial vasodilation in the brain induced during MIS resulted in alterations in cerebrovascular reactivity to a CO 2 stress in patients that may be used to identify patients at cognitive risk (Wang et al, ).…”

Brain BOLD MRI O2and CO2stress testing: Implications for perioperative neurocognitive disorder following surgery

“…This signal has previously been identified as a biomarker for POND in these patients after surgery. 23 As such, examination of the potential consequences of alterations in CVR to respiratory gases during anaesthesia and surgery appears warranted.…”

“…Alternative considerations include neuroinflammatory effects consequent with surgical stress 181920 , and premorbid risk factors (e.g., cognitive dysfunction, psychiatric illness, increasing age) which may influence the incidence of POND. 32122 More recent work suggests that a multi-factorial approach, described as a stress-diathesis model 23 , may provide further insights. In this model, the conduct of anaesthesia, which includes the management of respiratory gases during mechanical ventilation, may contribute to the stress of the perioperative period in vulnerable individuals (the diathesis) and is associated with development of POND.…”

“…In this model, the conduct of anaesthesia, which includes the management of respiratory gases during mechanical ventilation, may contribute to the stress of the perioperative period in vulnerable individuals (the diathesis) and is associated with development of POND. 23 Although respiratory end-tidal gas control is a fundamental principle of anaesthetic management, the range of end-tidal (ET) O2 and CO2 typically seen during the conduct of anaesthesia can significantly deviate from the awake baseline state, but has not been considered as a potential contributor to POND in previous investigations. Periods of both hypocapnia during mechanical ventilation and hypercapnia during the reestablishment of spontaneous ventilation are common.…”

The hydra of anesthetic neurotoxicity: Myth or reality?

“…Recent findings from the adult literature regarding postoperative delirium (POD) and cognitive dysfunction in the elderly, also considered to reflect potential anesthetic neurotoxicity, may help in this regard. El‐Gabalawy et al have proposed a stress‐diathesis model to investigate the phenomenon. In preliminary work, an underlying propensity or diathesis, determined by preoperative neurocognitive testing and/or MRI imaging, coupled with a stress—anesthesia and surgery—is more predictive of postoperative delirium than anesthetic duration per se.…”