High Spinal Anesthesia and the Incidence of Delirium After Cardiac Surgery

High Spinal Anesthesia and the Incidence of Delirium After Cardiac Surgery: a Randomized-controlled Feasibility Trial

This is a feasibility study to determine if enough patients undergoing elective or urgent cardiac surgery, can be enrolled in a study where patients are randomized to receive high spinal anesthesia as an adjunct to general anesthesia for their cardiac surgery. The primary clinical outcome will be the incidence of post-operative delirium.

Study Overview

• Status: Active, not recruiting
• Conditions: Post-Operative Confusion
• Intervention / Treatment: Drug: Intrathecal bupivacaine and morphine

Detailed Description

Intervention

Patients will be randomized to either general anesthesia (GA) or HSA + GA.

1. Spinal group: will receive high spinal anesthesia with hyperbaric bupivacaine (0.3 to 0.6 mgs/kg) + preservative free morphine (3 mcg/kg).
2. Standard intraoperative monitors will include ECG, pulse oximetry, end-tidal CO2 and anesthetic gas measurement, quantitative EEG monitoring (BIS monitor), arterial line, central venous pressure line and any other monitor as clinically indicated.
3. Conduct of the general anesthetic will not be protocolized. It will be a pragmatic study. The attending anesthesiologist will attempt to have a BIS score of 20- 40 during the operation.
4. Intraoperative physiological data (mean blood pressure, end-tidal anesthetic gas concentrations, BIS score) will be recorded and downloaded to a laptop computer using the Trend Face Solo acquisition system for subsequent analysis.
5. The routine postoperative care map for the postoperative cardiac intensive care unit (ICCS) will be followed.
6. All patients will be assessed by the study investigator for presence/absence of delirium on postoperative days 1,2 & 3, as well as routine nursing assessment by the delirium assessment tool CAM-ICU, routinely done by nursing staff. Chart reviews will be conducted to confirm any additional incidence of delirium.
7. All patients will be contacted at one and three months after surgery and asked to complete a ten-minute survey (Postop QoR-15 questionnaire) assessing their quality of recovery.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (>18 years old) patients
• Undergoing elective or urgent cardiac surgical procedures with cardiopulmonary bypass

Exclusion Criteria:

• Contraindications to spinal anesthesia such as active anticoagulation, clopidogrel within 7 days of surgery, ticagrelor within 3 days of surgery and all other contraindications to lumbar puncture
• Pre-existing psychiatric diagnoses such as schizophrenia or manic-depressive disorder
• Complex aortic surgery (> hemi-arch repair, descending thoracic surgery)
• Difficult airway requiring an awake intubation
• BMI > 50

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High spinal anesthesia; Spinal group: will receive high spinal anesthesia with hyperbaric bupivacaine (0.3 to 0.6 mgs/kg) + preservative free morphine (3 mcg/kg).; Standard intraoperative monitors will include ECG, pulse oximetry, end-tidal CO2 and anesthetic gas measurement, quantitative EEG monitoring (BIS monitor), arterial line, central venous pressure line and any other monitor as clinically indicated.; Conduct of the general anesthetic will not be protocolized. It will be a pragmatic study. The attending anesthesiologist will attempt to have a BIS score of 20- 40 during the operation.	Drug: Intrathecal bupivacaine and morphine; Spinal group: will receive high spinal anesthesia with hyperbaric bupivacaine (0.3 to 0.6 mgs/kg) + preservative free morphine (3 mcg/kg).; Other Names: Drug: bupivacaine 0.75% in dextrose (0.3 to 0.6 mls/kg); Drug: preservative free morphine 3 mcg/kg
No Intervention: Control group; Standard intraoperative monitors will include ECG, pulse oximetry, end-tidal CO2 and anesthetic gas measurement, quantitative EEG monitoring (BIS monitor), arterial line, central venous pressure line and any other monitor as clinically indicated.; Conduct of the general anesthetic will not be protocolized. It will be a pragmatic study. The attending anesthesiologist will attempt to have a BIS score of 20- 40 during the operation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	Mean number of patients recruited per week) (n)	One year
Protocol adherence measure - establishment of spinal anesthetic	In order to assess protocol adherence (%), in patients randomized to spinal anesthesia, an 80% success rate in establishing a spinal anesthetic will be considered as protocol adherence.	Day of surgery
Protocol adherence measure - completion of delirium assessments	In order to assess protocol adherence (%), completion of 90% of scheduled delirium assessments will be considered protocol adherence.	Day of surgery until five days post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early incidence of post-operative delirium	Duration of delirium (days) as assessed by the number of positive Confusion Assessment Method (CAM) as assessed by study investigator	Day of surgery until five days post-operatively
Verification of early incidence of post-operative delirium	Duration of delirium (days) as assessed by the number of positive CAM Scores as assessed by nursing/physicians (by chart review).	Day of surgery until five days post-operatively
Late incidence of post-operative delirium	Duration of delirium (days) as assessed by the number of positive CAM scores as assessed by study investigator from post-operative day 6 to post-operative day 14 or discharge from hospital	Post-operative day 6 until post-operative day 14 or discharge from hospital whichever occurs first.
Verification of late incidence of post-operative delirium	Duration of delirium (days) as assessed by the number of positive CAM scores as assessed by nursing/physicians (by chart review) from post-operative day 6 to discharge from hospital	Post-operative day 6 until post-operative day 14 or discharge from hospital, whichever occurs first.
Use of haloperidol post-operatively	Incidence (%) and total dose of haloperidol, in milligrams, for treatment of agitation as ordered by attending medical staff from day of surgery to discharge from hospital	Day of surgery until post-operative day 14 or discharge from hospital, whichever occurs first.
Use of quetiapine post-operatively	Incidence (%) and total dose of quetiapine, in milligrams, for treatment of agitation as ordered by attending medical staff from day of surgery to discharge from hospital.	Day of surgery until post-operative day 14 or discharge from hospital, whichever occurs first.
Use of risperidone post-operatively	Incidence (%) and total dose of risperidone, in milligrams, for treatment of agitation as ordered by attending medical staff from day of surgery to discharge from hospital.	Day of surgery until post-operative day 14 or discharge from hospital, whichever occurs first.
Use of dexmedetomidine post-operatively	Incidence (%) of use of dexmedetomidine infusions, for treatment of agitation as ordered by attending medical staff from day of surgery to discharge from the intensive care unit.	Day of surgery until post-operative day 5 or discharge from the intensive care unit whichever comes first..

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of intraoperative extubation	Incidence of extubation in the operating room (%)	Day of surgery
Duration of ICU intubation	Duration of ICU intubation in hours for those patients brought intubated to the ICU	Day of surgery until post-operative day 14 or discharge from hospital, whichever occurs first.
Post-operative pain scores at rest	VAS pain scores (visual analog score) (0 is no pain, 10 is the worst pain possible) at rest for 3 days post-operatively.	Post-operative day 1 until post-operative day 3
Post-operative pain scores with deep breathing	VAS pain scores (0 is no pain, 10 is the worst pain possible) with deep breathing for 3 days post-operatively.	Post-operative day 1 until post-operative day 3
Post-operative hydromorphone administered	Total hydromorphone use including intravenous and oral administration will be recorded for the first 48 hours postoperatively. Hydromorphone totals will be converted to morphine equivalents using MD Calcs algorithm (https://www.mdcalc.com/morphine-milligram-equivalents-mme-calculator).	Day of surgery until post-operative day 3
Post-operative fentanyl administered	Total fentanyl use including intravenous and oral administration will be recorded for the first 48 hours postoperatively. Fentanyl totals will be converted to morphine equivalents using MD Calcs algorithm (https://www.mdcalc.com/morphine-milligram-equivalents-mme-calculator).	Day of surgery until post-operative day 3
Post-operative codeine administered	Total codeine use including intravenous and oral administration will be recorded for the first 48 hours postoperatively. Codeine totals will be converted to morphine equivalents using MD Calcs algorithm (https://www.mdcalc.com/morphine-milligram-equivalents-mme-calculator).	Day of surgery until post-operative day 3
Post-operative morphine administered	Total morphine use, in milligrams, including intravenous and oral administration will be recorded for the first 48 hours postoperatively.	Day of surgery until post-operative day 3
Intraoperative hypotension	Length of time (mins) mean arterial blood pressure is less than 55 mmHg	Day of surgery
Intraoperative end-tidal gas concentration	Mean intraoperative end-tidal gas concentration (%)	Day of surgery
Intraoperative depth of anesthesia	Mean intraoperative bispectral index (BIS). The BIS scale range is from 0 to 100, with 0 representing no measurable electrical brain activity and 100 the electrical activity of an awake, conscious individual. Currently BIS scores are attempted to be kept between 20 and 40 during surgery to ensure adequate depth of anesthesia.	Day of surgery
Intraoperative sufentanil administered	Total dose of intraoperative sufentanil in micrograms. Sufentanil dosage will be converted to morphine equivalents using the MD Calcs algorithm (https://www.mdcalc.com/morphine-milligram-equivalents-mme-calculator)	Day of surgery
Intraoperative hydromorphone administered	Total dose of intraoperative hydromorphone in milligrams. Hydromorphone doses will be converted to morphine equivalents using the MD Calcs algorithm (https://www.mdcalc.com/morphine-milligram-equivalents-mme-calculator)	Day of surgery
Intraoperative midazolam administered	Total dose of intraoperative midazolam in milligrams.	Day of surgery
Intraoperative ketamine administered	Total dose of intraoperative ketamine in milligrams	Day of surgery
Intraoperative glucose level	Highest intraoperative glucose level in millimoles per litre.	Day of surgery
Intraoperative insulin administered	Total intraoperative insulin administered in units of insulin.	Day of surgery
Total RBC utilization	Total RBC administered (units) both intraoperatively, and postoperatively until post-operative day 3..	Day of surgery until post-operative day 3
Total platelet utilization	Total units of platelets administered (adult doses of platelets ) both intraoperatively, and postoperatively until post-operative day 3	Day of surgery until post-operative day 3
Return to OR for bleeding	Incidence of a return to the operating room for bleeding (%)	Day of surgery until post-operative day 3
Vasopressor (norepinephrine or phenylephrine or vasopressin) use at 12 hours	Incidence of use of either norepinephrine, phenylephrine or vasopressin at 12 hours postoperatively (%)	First 12 hours postoperatively
Vasopressor (norepinephrine, phenylephrine or vasopressin) use at 24 hours	Incidence of use of norepinephrine, phenylephrine or vasopressin administered at 24 hours postoperatively (%)	12 to 24 hours postoperatively
Vasopressor (norepinephrine, phenylephrine or vasopressin) use at >24 hours	Incidence of norepinephrine, phenylephrine or vasopressin use longer than 24 hours postoperatively (%)	Post-operative day 2 to post-operative day 7
Incidence of re-intubation	Incidence of re-intubation postoperatively (%) from day of surgery to discharge from hospital	Day of surgery until 14 days post-operatively or discharge from hospital, whichever occurs first.
ICU re-admission	Incidence of re-admission to ICU for any reason from post-operative day 2 to post-operative day 14 or discharge from hospital (%)	Post-operative day 2 until post-operative day 14 or discharge from hospital, whichever occurs first.
Hospital length of stay	Postoperative hospital length of stay in days	Time (days) in hospital from post-operative 1 to 30 (or through discharge from hospital)
ICU length of stay	Postoperative ICU length of stay in days	Time (days) in ICU from post-operative day 1 to 5 (or through discharge from hospital)
Major medical complications	Incidence of major medical complications (%) defined as one or more of: a. Atrial fibrillation b. Pneumonia c. Acute kidney injury (defined as a doubling of pre-operative creatinine) d. Need for dialysis e. Wound infection f. Stroke g. Other	Day of surgery until post-operative day 14 or discharge from hospital, whichever occurs first.
Post-operative quality of recovery - one month	Postoperative quality of life score (Postop QoR-15) will be used to assess quality of recovery at one month postoperatively. The Post QoR-15 scale ranges from 0 to 150, with 0 representing the poorest quality of recovery and 150 the best quality of recovery.	30 days post surgery
Post-operative quality of recovery - three months	Postoperative quality of life score (Postop QoR-15) will be used to assess quality of recovery at three month postoperatively. The Post QoR-15 scale ranges from 0 to 150, with 0 representing the poorest quality of recovery and 150 the best quality of recovery.	90 days post surgery
Post-operative creatinine level	Highest post-operative creatinine (umol/l) level recorded during hospital stay.	Day of surgery until 14 days post-operatively or hospital discharge, whichever occurs first.

Collaborators and Investigators

• Sponsor: University of Manitoba
• Investigators: Study Director: Doug Maguire, MD, University of Manitoba

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Spinal anesthesia; Cardiac surgery; Delirium
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Confusion; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Morphine
• Other Study ID Numbers: HS23755 B2020:026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No