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Perioperative Brain Health

Lindberg AP, Flexman AM. Perioperative stroke after non-cardiac, non- neurological surgery. BJA Education, 2020;21(2), 59-65.

Bottom line: Symptomatic stroke occurs at a rate of 0.1-0.9% after non-cardiac surgery.  Elective surgery should be delayed for 9 months after a previous stroke in most patients, while emergency surgery should not be delayed.  Patients should be screened for risk factors of peri-operative stroke, which include older age and history of prior stroke. Covert, or asymptomatic, stroke within 1 week of surgery was found at a rate of 7% in patients over the age of 65 undergoing non-cardiac surgery, and may be associated with increased delirium and cognitive decline at one year. 

Major points:

1. Symptomatic stroke occurs at a rate of 0.1-0.9% in non-cardiac, non-neurologic surgery. It is an independent risk factor of 30 day morbidity and mortality.  After peri-operative overt stroke, in-hospital mortality increases by approximately 20%.

2. Elective surgery at 3 months post stroke was associated with a 68 fold increase in a recurrent postoperative stroke. A delay in surgery by 9 months post stroke was associated with the lowest risk of post-operative stroke.

3. Covert stroke occurred at a rate of 7% in a prospective cohort of patients >65 years of age who underwent elective, non-cardiac surgery and received a perfusion weight brain MRI within a week of surgery.  Those with covert stroke were more likely to experience post-operative delirium and cognitive decline. 

4. While intraoperative hypotension may be a risk factor for perioperative stroke, most strokes occur post-operatively. It is unclear what the optimal intraoperative arterial blood pressure target is. 

5. Regional anesthesia is not supported by literature to decrease risk of perioperative stroke over general anesthesia.


Sprung J, Roberts RO, Weingarten TN, et al. Postoperative delirium in elderly patients is associated with subsequent cognitive impairment. Br J Anaesth. 2017;119(2):316-323. doi:10.1093/bja/aex130

Bottom line: This retrospective study on 2,014 patients >65 years old at the Mayo Clinic in Rochester reported two findings: (a) elderly patients who had MCI or dementia pre-operatively, were more likely to develop post-operative delirium (POD) (8.7% vs 2.6%); (b) elderly patients who were cognitively normal pre-operatively and then went on to develop POD were more likely to be subsequently diagnosed with MCI/dementia within 1 year follow-up compared to those who did not have an episode of POD (33.3% vs 9%). 

Major points:

1. Out of 2,014 patients, only 74 (3.7%) developed POD - a much lower rate than what has been cited in literature. Potential explanations include: half the procedures were outpatient/same-day, low rate of hospitalization post-op (only 36% stayed for longer than 1 day post-op), delirium was only screened for 72h post-op, high-risk patients (those with pre-op delirium) were excluded.

2. The incidence of POD increased significantly with increased chronological age and fewer years of education. It was more common in men and more common after orthopaedic, cardiovascular and thoracic surgeries. 

3. The finding that in cognitively normal patients, POD is associated with an increased risk of subsequent diagnosis of MCI/dementia within 1-year post-op has two possible explanations:

(a) POD delirium is simply a marker for accelerated cognitive decline or low cognitive reserve. Once, the surgical stress resolves, the patient returns to their accelerated trajectory. The stress of surgery simply gives us an early insight into which patients have a low cognitive reserve and are more likely to develop MCI/dementia even if the surgery had not taken place.

(b) The surgical stimulus is the insult that changes the trajectory of cognitive decline in the cognitively normal patient leading to an earlier diagnosis of MCI/dementia compared to if the surgery had not taken place.

4. Distinguishing which of the two scenarios above is accurate is clinically relevant, since if (a) were true, it might be less relevant to intervene to decrease POD since it does not improve long term cognitive outcomes. Instead, these patients should receive long-term neuro-cognitive follow-up. Conversely, if (b) were true, the clinician would want to use all available tools to screen for high-risk patients and then intervene to reduce the risk of POD in order to improve long term cognitive outcomes. 

Watt J, Tricco AC, Talbot-Hamon C, et al. Identifying Older Adults at Risk of Delirium Following Elective Surgery: A Systematic Review and Meta-Analysis. J Gen Intern Med. 2018;33(4):500-509. doi:10.1007/s11606-017-4204-x

Bottom line: This 2018 meta-analyses of 37 studies involving 8557 patients showed that the most important prognosticators for post-operative delirium were: (a) history of delirium, (b) frailty and (c) cognitive impairment.

Major points:

1. The incidence of post-operative delirium was 18.7%. It was most common in cardiac surgery (23.6%) and least common in vascular surgery (12.7%). 

2. Other than the three strongest factors predictors of post-operative delirium the following also had an association: psychotropic medication use, smoking status, older age (especially > 80), higher ASA and impairment in ADLs/IADLs. Having an available caregiver post-operatively was found to be the only protective factor. Alcohol use was not associated with post-op delirium. 

3. Four of the risk factors identified are modifiable in the pre-operative period: smoking status, frailty, availability of caregiver support and psychotropic medication use. This highlights target areas for "pre-habilitation" in the high-risk-for-delirium pre-operative patient. 

4. In all studies in which it was studied, post-operative delirium was shown to have a significant association with post-operative mortality, increased complications, increased LOS and discharge to institution/care facility (as opposed to home). Given that there exist effective interventions for preventing post-operative delirium, routine pre-operative screening should be performed to identify high-risk patients so that subsequent preventative measures can be implemented.

    Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, Ma D, Wang DX. Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. Br J Surg. 2020 Jan;107(2):e123-e132. doi: 10.1002/bjs.11354. PMID: 31903588

    Bottom Line: Delirium is a common complication after major surgery in older patients and is associated with worse outcomes. This single-centre, double-blind, randomized controlled trial found that intraoperative dexmedetomidine reduced the incidence of delirium within 5 days of surgery in a population of patients aged 60 years or older having elective, major, non-cardiac surgery. 


    Major Points:


    1. Perioperative delirium is multifactorial and may be related to deep anesthesia, the surgical stress response, pain, and opioid use. Dexmedetomidine may reduce anesthetic and opioid requirements and blunt the surgical stress response.

    2. Previous studies examining the effect of dexmedetomidine on postoperative delirium in adults were limited by small sample size or not using depth of anesthesia monitoring.

    3. Dexmedetomidine, administered as a 0.6mcg/kg loading dose followed by a 0.5mcg/kg/h infusion, reduced postoperative delirium (5.5 vs. 10.3%, RR 0.53, CI 0.30-0.94).

    4. The rate of non-delirium complications was also lower in the dexmedetomidine group (19.4 vs. 26.1%, RR 0.74, CI 0.55-0.99). Postoperative pain scores, morphine consumption, ICU admission, and 30-day mortality did not differ between groups.

    5. The rates of acute agitation, tachycardia, and PONV were lower in the dexmedetomidine group. Other than bradycardia, rates of adverse events (hypo- and hypertension, delayed extubation, oversedation) did not differ between groups. 

    van Norden J, Spies CD, Borchers F, Mertens M, Kurth J, Heidgen J, Pohrt A, Mueller A. The effect of peri-operative dexmedetomidine on the incidence of postoperative delirium in cardiac and non-cardiac surgical patients: a randomised, double-blind placebo-controlled trial. Anaesthesia. 2021 Oct;76(10):1342-1351. doi: 10.1111/anae.15469. Epub 2021 May 7. PMID: 33960404.

    Bottom line: Significant reduction in post operative delirium incidence when administered perioperative dexmedetomidine in open major abdominal surgery and CABG with CPB (18% dexmedetomidine vs 44% placebo). No difference in severity or duration of delirium.​ At follow up to POD # 90 no patients in dexmedetomidine group and 5 patients (26% p=0.029) in the placebo group died. No significant difference in ICU or hospital length of stay, severity of illness scores, MMSE scores, POCD, QOL assessment or sleep.


    Major points:

    1. Incidental significant reduction in POD # 1 reported anxiety as assessed by postoperative faces Anxiety scale score > 1.

    2. No difference in bradycardic episodes between groups, with less HR variability in the dexmedetomidine group.

    3. Small Sample size. Strict inclusion and exclusion criteria (of 484 only 63 were randomized). e.g. MMSE < 24, audiovisual impairment, previous CVA with any deficits. Arguably excluded the patient population that we are worried about post-operative delirium in

    4. Robust study methodology. Blinded to investigators, clinicians and patient. Demographic variables of both control and study group were similar (median MMSE 29 both groups). Although only assessed patients 2 times per day, mitigated this potential design flaw with a structured chart review for missed episodes

    5. pEEG with Sedline was employed and PSI was > 25 for all patients with avoidance of burst suppression. This additional monitoring might be confounding results and reduced the overall rate of delirium in both groups.

    Chen CC, Li HC, Liang JT, Lai IR, Purnomo JDT, Yang YT, Lin BR, Huang J, Yang CY, Tien YW, Chen CN, Lin MT, Huang GH, Inouye SK. Effect of a Modified Hospital Elder Life Program on Delirium and Length of Hospital Stay in Patients Undergoing Abdominal Surgery: A Cluster Randomized Clinical Trial. JAMA Surg. 2017 Sep 1;152(9):827-834. doi: 10.1001/jamasurg.2017.1083. PMID: 28538964; PMCID: PMC5710459.

    Bottom Line:

    This cluster randomized control trial evaluated the effects of a modified Hospital Elder Life Program (mHELP) on the incidence of delirium and hospital length of stay for patients >65 years of age undergoing elective abdominal surgery, primarily for tumor resection. Conclusively, older patients undergoing major abdominal surgery for resection of malignant tumor had markedly reduced rates of incident delirium and shorter LOS when they received mHELP.


    Major points:

    1. The intervention was performed consistently for 30 minutes per day by a trained nurse clinician, and consisted of 3 components: orienting communication, oral and nutritional assistance, and early mobilization. Patients were randomly assigned to the interventional group or to standard hospital care.


    2. Delirium was assessed using the Confusion Assessment Model. Delirium developed in the mHELP group in 13 cases (6.6%), whereas the control group had 27 cases (15.1%). These differences were statistically significant with a relative risk of 0.44 for delirium (95%CI, 0.23-0.83; P = .008), demonstrating a risk reduction of 56%.


    3. The mHELP group had a 2-day reduction in length of stay (LOS).

    Vlisides PE, Mentz G, Leis AM, Colquhoun D, McBride J, Naik BI, Dunn LK, Aziz MF, Vagnerova K, Christensen C, Pace NL. Carbon Dioxide, Blood Pressure, and Perioperative Stroke: A Retrospective Case–Control Study. Anesthesiology. 2022 Oct 1;137(4):434-45.

    Bottom Line:

    Perioperative stroke has an incidence of up to 3% in high-risk noncardiac surgical patients and is associated with increased mortality, disability and prolonged hospitalization. This multicenter, retrospective case-control study using case data from the Multicenter Perioperative Outcomes Group showed that intraoperative hypotension and both hypo- and hypercarbia were independently associated with postoperative ischemic stroke in non-cardiac, non-intracranial and non-major vascular surgeries.


    Major points:

    1. Mean arterial pressures less than 55 mmHg was strongly associated with stroke risk. There was an approximately 10-17% increased relative risk of stroke per 10 units (mmHg-min).

    2. End-tidal carbon dioxide of 30 or less was associated with approximately 7% increased relative risk of stroke per 10 units (mmHg-min) while end-tidal carbon dioxide of 45 mmHg or greater conferred a 10% increased relative risk of stroke per 10 units (mmHg-min).

    3. Majority of strokes occurred within the first 3 postoperative days with the majority affecting the middle cerebral artery territory. Less than 30% of patients who suffered a stroke were discharged home.

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