Cardiac Autonomic Dysfunction and Perioperative Outcomes

Neurosurgical Patients Clinical Trial

— CADPONS  

Official title:

Cardiac Autonomic Dysfunction and Perioperative Outcomes After Neurosurgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05230641
• Other study ID #: NIMHANS/33 IEC(BS&NS DIV)/2021
• Status: Completed
• Start date: March 1, 2022
• Est. completion date: March 31, 2023

Study information

• Verified date: July 2023
• Source: National Institute of Mental Health and Neuro Sciences, India
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The autonomic nervous system (ANS) is cardinal for maintaining systemic homeostasis and is pivotal for the baseline regulation and modulation of vital cardiovascular, hemodynamic, respiratory, gastrointestinal, and body temperature regulating functions. Pathological perturbations of the ANS leading to cardiac dysautonomia (CAD) affect one in 1000 population. Autonomic dysfunction can occur from a variety of pathological conditions such as ischemic heart disease, systemic hypertension, diabetes mellitus, neurological illnesses, neurotrauma, and cervical spine diseases. When patients with dysautonomia present for surgical procedures, they may manifest severe hemodynamic responses that may be less responsive to pharmacological interventions. Pre-existing autonomic dysfunction accentuates perioperative hemodynamic fluctuations during stressful events like direct laryngoscopy, endotracheal intubation, and extubation, and can result in major adverse cardiac events (MACE). The complications arising from CAD can prolong the duration of hospital stay and contribute to morbidity and mortality. Preoperative diagnosis of CAD helps in anticipation of and preparation for potentially severe adverse events in the perioperative period. Most neurosurgical patients are not candidates for detailed ANS examination in the supine and standing positions due to their underlying neurological condition. Real-time assessment of heart rate variability (HRV) using the ANSiscope equipment provides information on the sympathovagal balance during the immediate preoperative period and aids in the simple rapid bedside assessment of CAD. This study aims to examine the incidence of CAD through HRV assessment in neurosurgical patients, identify the potential risk factors for CAD in this population, and evaluate the impact of CAD on perioperative outcomes.

Description:

Demographic and baseline clinical data including comorbid conditions and medication history will be collected. Baseline hemodynamic parameters - heart rate (HR) and systolic, diastolic, and mean blood pressure (SBP, DBP, MAP), rate pressure product (RPP) calculated as the product of HR and SBP and ANSindex (which informs the degree of dysautonomia and is derived noninvasively from a recording of 572 R wave to R wave intervals on an electrocardiogram) will be recorded in the immediate preoperative period.

Assessment of risk factors for preoperative CAD The investigators will explore potential risk factors for CAD in neurosurgical patients. The investigators postulate some known factors such as anxiety which will be diagnosed using the Visual analog scale for anxiety (VAS-A), age, gender, neurosurgical pathology, site-specific surgery (high cervical pathology, structural brain lesions, brainstem lesion, etc.), pre-existing diabetes mellitus and hypertension, and medications used for their treatment, higher American Society of Anesthesiology (ASA) grade, etc. to be associated with CAD in neurosurgical patients.

The investigators will explore the association between CAD and perioperative outcomes. Major Adverse Cardiac Events during Intra and postoperative period, in-hospital mortality, and duration of postoperative ICU and hospital stay.

Anesthesia will be administered as per the existing practice. Hemodynamic parameters HR, SBP, DBP, MAP at following time points - before and 1 and 2 min after induction of general anesthesia, before and at 1, 3, and 5 mins after tracheal intubation, and before and at 1, 3, and 5 mins after skull pin application, where applicable. Adverse hemodynamic events - persistent hypotension, arrhythmias, myocardial ischemia, cardiac failure, cardiac arrest) during the early (after anesthetic induction and before surgical incision), late (surgical incision to surgical closure) intraoperative period, recovery period (end of anesthesia to discharge from the operating room), post-anesthesia care unit (PACU) period (from arrival to discharge from PACU) and early postoperative period (up to 72 hours after surgery), neurological status (Glasgow Coma Scale) at hospital discharge, and duration of ICU and hospital stay will be recorded. The core temperature will be monitored during the intraoperative period to detect hypothermia (<35o C) or hyperthermia (>37.5 o C).

Sample size and statistical analysis Previous studies in the non-neurosurgical populations have determined the prevalence of CAD to vary from 25 to 73%. Considering an average prevalence of 50% in the neurosurgical population and a possible 5% margin of error, a sample size of 383 would be necessary for achieving a 95% confidence level. Hence the investigators plan to recruit 400 patients over a period of 1 year to account for potential dropouts from the study.

Data will be analyzed using Statistical Package for the Social Sciences (SPSS) or R software. Continuous variables will be compared by t-test, qualitative data by chi2 test, or Fisher exact test. Logistic regression will be used to identify the risk factors for cardiac autonomic dysfunction. A p < 0.05 will be considered statistically significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• aged between 18 and 80 years

• belonging to ASA grade 1-4

• scheduled for craniotomies or spinal surgeries under anesthesia

Exclusion Criteria:

• scheduled for redo procedures

• patients with preoperative arrhythmias and cardiac failure

• patients on preoperative inotropic support

• pregnant neurosurgical patients

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Neurosurgical Patients
• Primary Dysautonomias

Intervention

Other:
• No intervention
This is a prospective observational study

Locations

Country	Name	City	State
India	NIMHANS hospital	Bangalore	Karnataka

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Mental Health and Neuro Sciences, India	DyAnsys, Inc., Vision Group on Science and Technology

Country where clinical trial is conducted

India, 

References & Publications (13)

Abhishekh HA, Nisarga P, Kisan R, Meghana A, Chandran S, Trichur Raju, Sathyaprabha TN. Influence of age and gender on autonomic regulation of heart. J Clin Monit Comput. 2013 Jun;27(3):259-64. doi: 10.1007/s10877-012-9424-3. Epub 2013 Jan 8. — View Citation

Chakraborty T, Kramer CL, Wijdicks EFM, Rabinstein AA. Dysautonomia in Guillain-Barre Syndrome: Prevalence, Clinical Spectrum, and Outcomes. Neurocrit Care. 2020 Feb;32(1):113-120. doi: 10.1007/s12028-019-00781-w. — View Citation

Cheshire WP, Freeman R, Gibbons CH, Cortelli P, Wenning GK, Hilz MJ, Spies JM, Lipp A, Sandroni P, Wada N, Mano T, Kim HA, Kimpinski K, Iodice V, Idiaquez J, Thaisetthawatkul P, Coon EA, Low PA, Singer W. Corrigendum to "Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology" [Clin. Neurophysiol. 132(2) (2021) 666-682]. Clin Neurophysiol. 2021 May;132(5):1194. doi: 10.1016/j.clinph.2021.02.006. Epub 2021 Mar 6. No abstract available. — View Citation

Farbood A, Sahmeddini MA, Bayat S, Karami N. The effect of preoperative depression and anxiety on heart rate variability in women with breast cancer. Breast Cancer. 2020 Sep;27(5):912-918. doi: 10.1007/s12282-020-01087-y. Epub 2020 Apr 7. — View Citation

Hogan AM, Luck C, Woods S, Ortu A, Petkov S. The Effect of Orthostatic Hypotension Detected Pre-Operatively on Post-Operative Outcome. J Am Geriatr Soc. 2021 Mar;69(3):767-772. doi: 10.1111/jgs.16966. Epub 2020 Dec 11. — View Citation

Ideguchi M, Kajiwara K, Yoshikawa K, Sadahiro H, Nomura S, Fujii M, Suzuki M. Characteristics of intraoperative abnormal hemodynamics during resection of an intra-fourth ventricular tumor located on the dorsal medulla oblongata. Neurol Med Chir (Tokyo). 2013;53(10):655-62. doi: 10.2176/nmc.oa2012-0401. Epub 2013 Sep 27. — View Citation

Katsanos AH, Korantzopoulos P, Tsivgoulis G, Kyritsis AP, Kosmidou M, Giannopoulos S. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions. Int J Cardiol. 2013 Jul 31;167(2):328-34. doi: 10.1016/j.ijcard.2012.06.107. Epub 2012 Jul 16. — View Citation

Keyl C, Lemberger P, Palitzsch KD, Hochmuth K, Liebold A, Hobbhahn J. Cardiovascular autonomic dysfunction and hemodynamic response to anesthetic induction in patients with coronary artery disease and diabetes mellitus. Anesth Analg. 1999 May;88(5):985-91. doi: 10.1097/00000539-199905000-00004. — View Citation

Knuttgen D, Weidemann D, Doehn M. Diabetic autonomic neuropathy: abnormal cardiovascular reactions under general anesthesia. Klin Wochenschr. 1990 Dec 4;68(23):1168-72. doi: 10.1007/BF01815272. — View Citation

McGrane S, Atria NP, Barwise JA. Perioperative implications of the patient with autonomic dysfunction. Curr Opin Anaesthesiol. 2014 Jun;27(3):365-70. doi: 10.1097/ACO.0000000000000072. — View Citation

Mustafa HI, Fessel JP, Barwise J, Shannon JR, Raj SR, Diedrich A, Biaggioni I, Robertson D. Dysautonomia: perioperative implications. Anesthesiology. 2012 Jan;116(1):205-15. doi: 10.1097/ALN.0b013e31823db712. — View Citation

Padley JR, Ben-Menachem E. Low pre-operative heart rate variability and complexity are associated with hypotension after anesthesia induction in major abdominal surgery. J Clin Monit Comput. 2018 Apr;32(2):245-252. doi: 10.1007/s10877-017-0012-4. Epub 2017 Mar 14. — View Citation

Polderman JAW, Sperna Weiland NH, Klaver MH, Biginski J, Horninge M, Hollmann MW, DeVries JH, Immink RV, Preckel B, Hermanides J. The prevalence of cardiovascular autonomic neuropathy and its influence on post induction hemodynamic variables in patients with and without diabetes; A prospective cohort study. PLoS One. 2018 Nov 26;13(11):e0207384. doi: 10.1371/journal.pone.0207384. eCollection 2018. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of cardiac autonomic dysfunction in neurosurgical patients	To study the prevalence of cardiac autonomic dysfunction in neurosurgical patients	Before anesthesia administration for surgery
Secondary	Risk factors of cardiac autonomic dysfunction in neurosurgical patients	To identify risk factors of cardiac autonomic dysfunction in neurosurgical patients	Baseline
Secondary	Impact of cardiac autonomic dysfunction on hemodynamic stress response	To assess the impact of cardiac autonomic dysfunction on hemodynamic stress response to laryngoscopy and intubation, anesthetic induction, and tracheal extubation	During anesthesia procedure for surgery
Secondary	Impact of cardiac autonomic dysfunction on hemodynamic instability	To assess the impact of cardiac autonomic dysfunction on incidence, duration and severity of intraoperative hypotension and hypertension and requirement of pharmacological intervention	During surgery
Secondary	Impact of cardiac autonomic dysfunction on Major Adverse Cardiac Events	To assess the impact of cardiac autonomic dysfunction on Major Adverse Cardiac Events namely, new onset myocardial ischemia, congestive cardiac failure, cardiac arrhythmias, cardiac arrest requiring resuscitation	During and after surgery till discharge from the hospital, an average of 1 week
Secondary	Impact of cardiac autonomic dysfunction on temperature instability	To assess the impact of cardiac autonomic dysfunction on incidence of hypothermia and hyperthermia	During surgery
Secondary	Impact of cardiac autonomic dysfunction on duration of hospital stay	To assess the impact of cardiac autonomic dysfunction on duration of ICU and hospital stay	After surgery till the time of discharge from the hospital, an average of 1 week
Secondary	Impact of cardiac autonomic dysfunction on in-hospital mortality	To assess the impact of cardiac autonomic dysfunction on in-hospital mortality	After surgery till the time of discharge from the hospital, an average of 1 week