A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management
Renée El-Gabalawy, Ronak Patel, Kayla Kilborn, Caitlin Blaney, Christopher Hoban, Lawrence Ryner, Duane Funk, Regina Legaspi, Joseph A Fisher, James Duffin, David J Mikulis, W Alan C Mutch, Renée El-Gabalawy, Ronak Patel, Kayla Kilborn, Caitlin Blaney, Christopher Hoban, Lawrence Ryner, Duane Funk, Regina Legaspi, Joseph A Fisher, James Duffin, David J Mikulis, W Alan C Mutch
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.
Keywords: neuroimaging; neuropathophysiology; neuropsychological; peri-operative care; post-operative delirium; stress-diathesis.
Figures
References
- American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th Edn. Washington, DC.
- Avidan M. S., Maybrier H. R., Abdallah A. B., Jacobsohn E., Vlisides P. E., Pryor K. O., et al. . (2017). Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet 6736, 1–9. 10.1016/S0140-6736(17)31467-8
- Baranov D., Bickler P. E., Crosby G. J., Culley D. J., Eckenhoff M. F., Eckenhoff R. G., et al. . (2009). Consensus statement: first international workshop on anesthetics and Alzheimer's disease. Anesth. Analg. 108, 1627–1630. 10.1213/ane.0b013e318199dc72
- Beals J. K., Carter L. B., Jevtovic Todorovic V. (2003). Neurotoxicity of nitrous oxide and ketamine is more severe in aged than in young rat brain. Ann. N.Y. Acad. Sci. 993:115; discussion 123–124. 10.1111/j.1749-6632.2003.tb07518.x
- Dasgupta M., Dumbrell A. C. (2006). Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J. Am. Geriatr. Soc. 54, 1578–1589. 10.1111/j.1532-5415.2006.00893.x
- Dasgupta M., Hillier L. M. (2010). Factors associated with prolonged delirium: a systematic review. Int. Psychogeriatr. 22, 373–394. 10.1017/S1041610209991517
- Desmond J. E., Glover G. H. (2002). Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical power analyses. J. Neurosci. Methods 118, 115–128. 10.1016/S0165-0270(02)00121-8
- Enzinger C., Fazekas F., Ropele S., Schmidt R. (2007). Progression of cerebral white matter lesions - clinical and radiological considerations. J. Neurol. Sci. 257, 5–10. 10.1016/j.jns.2007.01.018
- Fierstra J., Sobczyk O., Battisti-Charbonney A., Mandell D. M., Poublanc J., Crawley A. P., et al. . (2013). Measuring cerebrovascular reactivity: what stimulus to use? J. Physiol. 591, 5809–5821. 10.1113/jphysiol.2013.259150
- Fierstra J., Spieth S., Tran L., Conklin J., Tymianski M., ter Brugge K. G., et al. . (2011). Severely impaired cerebrovascular reserve in patients with cerebral proliferative angiopathy. J. Neurosurg. Pediatr. 8, 310–315. 10.3171/2011.6.PEDS1170
- Fong T. G., Bogardus S. T., Daftary A., Auerbach E., Blumenfeld H., Modur S., et al. . (2006). Cerebral perfusion changes in older delirious patients using 99mTc HMPAO SPECT. J. Gerontol. A. Biol. Sci. Med. Sci. 61, 1294–1299. 10.1093/gerona/61.12.1294
- Fong T. G., Davis D., Growdon M. E., Albuquerque A., Inouye S. K. (2015). The interface between delirium and dementia in elderly adults. Lancet. Neurol. 14, 823–832. 10.1016/S1474-4422(15)00101-5
- Fong T. G., Jones R. N., Shi P., Marcantonio E. R., Yap L., Rudolph J. L., et al. (2009). Delirium accelerates cognitive decline in Alzheimer's disease. Neurology 72, 1570–1575. 10.1212/WNL.0b013e3181a4129a
- Gao Y.-Z., Zhang J. J., Liu H., Wu G. Y., Xiong L., Shu M. (2013). Regional cerebral blood flow and cerebrovascular reactivity in Alzheimer's disease and vascular dementia assessed by arterial spinlabeling magnetic resonance imaging. Curr. Neurovasc. Res. 10, 49–53. 10.2174/156720213804806016
- Han J. S., Abou-Hamden A., Mandell D. M., Poublanc J., Crawley A. P., Fisher J. A., et al. . (2011). Impact of extracranial-intracranial bypass on cerebrovascular reactivity and clinical outcome in patients with symptomatic moyamoya vasculopathy. Stroke 42, 3047–3054. 10.1161/STROKEAHA.111.615955
- Henry J. D., Crawford J. R., Phillips L. H. (2004). Verbal fluency performance in dementia of the Alzheimer's type: a meta-analysis. Neuropsychologia 42, 1212–1222. 10.1016/j.neuropsychologia.2004.02.001
- Hshieh T. T., Dai W., Cavallari M., Guttmann C. R., Meier D. S., Schmitt E. M., et al. (2016). Cerebral blood flow MRI in the nondemented elderly is not predictive of post-operative delirium but is correlated with cognitive performance. J. Cereb. Blood Flow Metab. 37, 1386–1397. 10.1177/0271678X16656014
- Inouye S. K., Kosar C. M., Tommet D., Schmitt E. M., Puelle M. R., Saczynski J. S., et al. . (2014a). The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts. Ann. Intern. Med. 160, 526–533. 10.7326/M13-1927
- Inouye S. K., Westendorp R. G. J., Saczynski J. S. (2014b). Delirium in elderly people. Lancet 383, 911–922. 10.1016/S0140-6736(13)60688-1
- Insel T., Cuthbert B., Garvey M., Heinssen R., Pine D. S., Quinn K., et al. . (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748–751. 10.1176/appi.ajp.2010.09091379
- Ishida K., Berger M., Nadler J., Warner D. S. (2014). Anesthetic neuroprotection: antecedents and an appraisal of preclinical and clinical data quality. Curr. Pharm. Des. 20, 5751–5765. 10.2174/1381612820666140204111701
- Jevtovic-Todorovic V. (2016). General anesthetics and neurotoxicity: how much do we know? Anesthesiol. Clin. 34, 439–451. 10.1016/j.anclin.2016.04.001
- Jones R. N., Marcantonio E. R., Saczynski J. S., Tommet D., Gross A. L., Travison T. G., et al. (2016). Preoperative cognitive performance dominates risk for delirium among older adults. J. Geriatr. Psychiatry Neurol. 29, 320–327. 10.1177/0891988716666380
- Kerchner G. A., Racine C. A., Hale S., Wilheim R., Laluz V., Miller B. L., et al. . (2012). Cognitive processing speed in older adults: relationship with white matter integrity. PLoS ONE 7:425. 10.1371/journal.pone.0050425
- Kroenke K., Spitzer R. L., Williams J. B. (2001). The PHQ-9: validity of a brief depression severity measure. J. Gen. Intern. Med. 16, 606–613. 10.1046/j.1525-1497.2001.016009606.x
- Lei S. Y., Hache M., Loepke A. W. (2014). Clinical research into anesthetic neurotoxicity: does anesthesia cause neurological abnormalities in humans? J. Neurosurg. Anesthesiol. 26, 349–357. 10.1097/ANA.0000000000000117
- Leslie D. L., Marcantonio E. R., Zhang Y., Leo-Summers L., Inouye S. K. (2008). One-year health care costs associated with delirium in the elderly population. Arch. Intern. Med. 168, 27–32. 10.1001/archinternmed.2007.4
- Mandell D. M., Han J. S., Poublanc J., Crawley A. P., Stainsby J. A., Fisher J. A., et al. . (2008). Mapping cerebrovascular reactivity using blood oxygen level-dependent MRI in patients with arterial steno-occlusive disease: comparison with arterial spin labeling MRI. Stroke 39, 2021–2028. 10.1161/STROKEAHA.107.506709
- Martins S., Fernandes L. (2012). Delirium in elderly people: a review. Front. Neurol. 3:101. 10.3389/fneur.2012.00101
- Mason S. E., Noel-Storr A., Ritchie C. W. (2010). The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J. Alzheimers Dis. 22(Suppl. 3), 67–79. 10.3233/JAD-2010-101086
- Mutch W. A. C., Ellis M. J., Graham M. R., Wourms V., Raban R., Fisher J. A., et al. . (2014). Brain MRI CO2 stress testing: a pilot study in patients with concussion. PLoS ONE 9:181. 10.1371/journal.pone.0102181
- Mutch W. A. C., Ellis M. J., Ryner L. N., Ruth Graham M., Dufault B., Gregson B., et al. . (2015). Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome. J. Neurosurg. 125, 648–660. 10.3171/2015.6.JNS15972
- Mutch W. A. C., Graham M. R., Halliday W. C., Thiessen D. B., Girling L. G. (1993a). Use of neuroanesthesia adjuncts (hyperventilation and mannitol administration) improves neurological outcome after thoracic aortic cross-clamping in dogs. Stroke 24, 1204–1210. 10.1161/01.STR.24.8.1204
- Mutch W. A. C., Graham M. R., Halliday W. C., Teskey J. M., Thomson I. R. (1993b). Paraplegia following thoracic aortic cross-clamping in dogs: no difference in neurological outcome with a barbiturate versus isoflurane. Stroke 24, 1554–1560. 10.1161/01.STR.24.10.1554
- Olney J. W., Young C., Wozniak D. F., Jevtovic-Todorovic V., Ikonomidou C. (2004). Do pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol. Sci. 25, 135–139. 10.1016/j.tips.2004.01.002
- O'Sullivan R., Inouye S. K., Meagher D. (2014). Delirium and depression: inter-relationship and clinical overlap in elderly people. Lancet. Psychiatry 1, 303–311. 10.1016/S2215-0366(14)70281-0
- Pantoni L. (2008). Leukoaraiosis: from an ancient term to an actual marker of poor prognosis. Stroke 39, 1401–1403. 10.1161/STROKEAHA.107.505602
- Salata K., Katznelson R., Scott Beattie W., Carroll J., Lindsay T. F., Djaiani G. (2012). Endovascular versus open approach to aortic aneurysm repair surgery: rates of postoperative delirium. Can. J. Anesth. 59, 556–561. 10.1007/s12630-012-9695-7
- Sam K., Crawley A. P., Poublanc J., Conklin J., Sobczyk O., Mandell D. M., et al. . (2016a). Vascular dysfunction in Leukoaraiosis. Am. J. Neuroradiol. 37, 2258–2264. 10.3174/ajnr.A4888
- Sam K., Peltenburg B., Conklin J., Sobczyk O., Poublanc J., Crawley A. P., et al. . (2016b). Cerebrovascular reactivity and white matter integrity. Neurology 87, 2333–2339. 10.1212/WNL.0000000000003373
- Slessarev M., Han J., Mardimae A., Prisman E., Preiss D., Volgyesi G., et al. . (2007). Prospective targeting and control of end-tidal CO2 and O2 concentrations. J. Physiol. 581, 1207–1219. 10.1113/jphysiol.2007.129395
- Sobczyk O., Battisti-Charbonney A., Fierstra J., Mandell D. M., Poublanc J., Crawley A. P., et al. (2014). A conceptual model for CO2-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI. Neuroimage 92, 56–68. 10.1016/j.neuroimage.2014.01.051
- Soiza R. L., Sharma V., Ferguson K., Shenkin S. D., Seymour D. G., Maclullich A. M. J. (2008). Neuroimaging studies of delirium: a systematic review. J. Psychosom. Res. 65, 239–248. 10.1016/j.jpsychores.2008.05.021
- Spitzer R. L., Kroenke K., Williams J. B. W., Löwe B. (2006). A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch. Intern. Med. 166, 1092–1097. 10.1001/archinte.166.10.1092
- Sprooten E., Rasgon A., Goodman M., Carlin A., Leibu E., Lee W. H., et al. . (2017). Addressing reverse inference in psychiatric neuroimaging: meta-analyses of task-related brain activation in common mental disorders. Hum. Brain Mapp. 38, 1846–1864. 10.1002/hbm.23486
- Strøm C., Rasmussen L. S., Sieber F. E. (2014). Should general anaesthesia be avoided in the elderly? Anaesthesia (69 Suppl.) 1, 35–44. 10.1111/anae.12493
- van den Boogaard M., Schoonhoven L., van der Hoeven J. G., van Achterberg T., Pickkers P. (2012). Incidence and short-term consequences of delirium in critically ill patients: a prospective observational cohort study. Int. J. Nurs. Stud. 49, 775–783. 10.1016/j.ijnurstu.2011.11.016
- Vasunilashorn S. M., Guess J., Ngo L., Fick D., Jones R. N., Schmitt E. M., et al. . (2016). Derivation and validation of a severity scoring method for the 3-minute diagnostic interview for confusion assessment method–defined delirium. J. Am. Geriatr. Soc. 64, 1684–1689. 10.1111/jgs.14234
- Xu B., Qiao Q., Chen M., Rastogi R., Luo D., Bi Q. (2015). Relationship between neurological complications, cerebrovascular and cerebral perfusion following off-pump coronary artery bypass grafting. Neurol. Res. 37, 421–426. 10.1179/1743132815Y.0000000030
- Yokota H., Ogawa S., Kurokawa A., Yamamoto Y. (2003). Regional cerebral blood flow in delirium patients. Psychiatry Clin. Neurosci. 57, 337–339. 10.1046/j.1440-1819.2003.01126.x
- Young J., Inouye S. K. (2007). Delirium in older people. BMJ 334, 842–846. 10.1136/
Source: PubMed