Aortic StenosisNCT00348920
The Effects of High Spinal Anesthesia on Heart Function, Stress Response and Pain Control in Aortic Valve Surgery
A study testing High Spinal and General Anesthesia in people with Aortic Stenosis, run by University of Manitoba at 1 site in Canada.
Trial summary
This study is looking at the effects of high spinal anesthesia (also known as total spinal anesthesia) combined with general anesthesia versus general anesthesia alone on the following: Stress response: Patients undergoing aortic valve replacement surgery have a large incision and a complex operation where they must… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis
- What is being tested?
- High Spinal and General Anesthesia
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2007to Jul 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Undergoing surgery for aortic valve replacement due to aortic stenosis with or without CABG.
Who cannot join
- INR > 1.4, PTT > 40 seconds
- platelet count < 80, 000 per microlitre
- local infection or deformity at the site of administration of the spinal anesthetic
- raised intracranial pressure or evolving neurological deficit at the time of surgery
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of High Spinal Anesthesia on Hemodynamics, Stress Response, Renal Function and Post-operative Pain Control in Patients Undergoing Aortic Valve Replacement for Aortic Stenosis
This study is looking at the effects of high spinal anesthesia (also known as total spinal anesthesia) combined with general anesthesia versus general anesthesia alone on the following:
Stress response: Patients undergoing aortic valve replacement surgery have a large incision and a complex operation where they must be placed on the heart-lung machine. The body reacts to the heart-lung machine, increasing the stress response.
Read more
High spinal anesthesia using local anesthetics when combined with general anesthesia has been shown to block some of the stress response to surgery and the response to the heart-lung machine. This study will examine if blood levels of stress hormones and also inflammatory mediators can be lowered with the use of high spinal anesthesia.
Heart function: High spinal anesthesia in combination with general anesthesia may help the heart work better when there is a narrowed valve (aortic stenosis). The heart may also have improved ability to pump blood with this anesthetic technique.
Lung function and post-operative pain control: After surgery, patients often have pain which prevents them from taking deep breaths and coughing. This can lead to pneumonia. This study will also examine if the post-operative pain relief provided by spinal morphine (given together with the spinal anesthetic) can provide any better pain control following surgery. By doing this, we want to see if patients can take bigger breaths after their surgery when spinal morphine is used, and try to prevent the complications that occur if patients are not able to breath deeply after surgery.
Read the detailed description
It is hypothesized that high spinal anesthesia combined with general anesthesia decreases the intraoperative stress and inflammatory response and improve post-operative pain control and respiratory function in this patient population. It is also hypothesized that the technique will provide stable intraoperative hemodynamics during aortic valve replacement surgery.
Stress response: Levels of hormones such as epinephrine, norepinephrine and cortisol are elevated during cardiac surgery and on the initiation of cardiopulmonary bypass. This stress response has previously been shown to be blunted with the use of high spinal anesthesia when combined with general anesthesia in coronary artery bypass surgery patients (Lee, Grocott, et al).
Inflammatory response: In addition to the stress response there is also an accentuated inflammatory response. With contact of the patient's blood to the artificial bypass circuit, there is activation of various plasma protease pathways that generate multiple proinflammatory mediators. Complement levels and cytokine levels also rise. Clinical organ dysfunction involving the cardiovascular, pulmonary, renal and neurological systems can ultimately result. The effects of high spinal anesthesia on the inflammatory response that occurs with bypass have not been studied.
Hemodynamics: It has previously been shown that high-spinal anesthesia for coronary artery bypass surgery provides stable intra-operative hemodynamics (Kowalewski, MacAdams, et al; Lee, Grocott, et al.). Although the use of spinal anesthesia in patients with aortic stenosis has been considered to be relatively contra-indicated, total spinal anesthesia may actually improve cardiac function by decreasing systemic afterload and increasing myocardial contractility.
Post-operative analgesia and pulmonary function: The spinal administration of opioids, such as morphine, has been shown to improve post-operative pain management in patients having both cardiac and non-cardiac surgery (Jacobsohn, Lee, et al). Total spinal anesthesia with bupivacaine and spinal morphine combined with general anesthesia may also improve post-operative pain management and facilitate improved post-operative lung function.
- Conditions
- Aortic Stenosis
- Being tested
- High Spinal and General Anesthesia
- Keywords
- Aortic Valve, Aortic Stenosis, High Spinal Anesthesia, Total Spinal Anesthesia, Stress Response, Inflammatory Mediators, Renal Function, Hemodynamic Stability
- Medical subject headings
- Aortic Valve Stenosis, Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Spinal and General AnesthesiaProcedure or surgery
Also called Bupivacaine, Epimorph
Spinal bupivacaine 0.75% in dextrose, 6 mls (45mg) and preservative free morphine 3 mcg/kg (to a maximum of 300 mcg).
| Study group | Role | What they receive |
|---|---|---|
| 1- General Anesthesia | No intervention | General Anesthesia includes administration of a routine cardiac anesthetic as per institutional norms. |
| 2- High Spinal and General Anesthesia | Experimental | High Spinal and General Anesthesia includes a high dose intrathecal anesthetic administered prior to the induction of a standardized cardiac general anesthetic. Receives: Procedure: High Spinal and General Anesthesia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stress response as measured by levels of circulating epinephrine, norepinephrine, and cortisol.
Measured: Multiple time points
Inflammatory response as measured by levels of circulating inflammatory mediators (e.g. interleukin-6, interleukin-8, interleukin-10, C-reactive protein, TNF-alpha).
Measured: Multiple time points
Blood glucose control (amount of insulin required to keep blood glucose 5-8 mmol/L). Renal function as measured by serum creatinine.
Measured: Multiple time points
Secondary outcomes (4)
Vasopressor requirements to keep mean blood pressure between 60-80 mm Hg.
Measured: Multiple time points
Left ventricular wall motion score index as measured by TTE and TEE.
Measured: Multiple time points
Hemodynamics including cardiac output and cardiac index, heart rate, systemic arterial and pulmonary arterial blood pressures, central venous pressure, and systemic and pulmonary vascular resistance.
Measured: Multiple time points
Time to extubation.
Measured: Time of extubation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2006 (estimated)
- Study startFeb 2007
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- St. Boniface Hospital, Health Sciences Centre Foundation, Manitoba
- Responsible party
- Principal investigator, Trevor William R. Lee, University of Manitoba
- Investigators
- Trevor WR Lee, MD, Principal investigator, Department of Anesthesia and Perioperative Medicine, St. Boniface General Hospital, University of ManitobaStephen E Kowalski, MD, Principal investigator, Department of Anesthesia, Health Sciences Centre, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00348920
- Sponsor's protocol ID
- AOTSA1
- Status last verified
- Jul 2013
- First submitted
- 5 Jul 2006
- Last updated
- 24 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lee TW, Grocott HP, Schwinn D, Jacobsohn E; Winnipeg High-Spinal Anesthesia Group. High spinal anesthesia for cardiac surgery: effects on beta-adrenergic receptor function, stress response, and hemodynamics. Anesthesiology. 2003 Feb;98(2):499-510. doi: 10.1097/00000542-200302000-00032.
PubMed 12552211Kowalewski R, MacAdams C, Froelich J, Neil S, Maitland A. Anesthesia supplemented with subarachnoid bupivacaine and morphine for coronary artery bypass surgery in a child with Kawasaki disease. J Cardiothorac Vasc Anesth. 1996 Feb;10(2):243-6. doi: 10.1016/s1053-0770(96)80246-1. No abstract available.
PubMed 8850406Jacobsohn E, Lee TW, Amadeo RJ, Syslak PH, Debrouwere RG, Bell D, Klock PA, Tymkew H, Avidan M; University of Manitoba Health Sciences Centre Cardiac Anesthesia Group. Low-dose intrathecal morphine does not delay early extubation after cardiac surgery. Can J Anaesth. 2005 Oct;52(8):848-57. doi: 10.1007/BF03021781.
PubMed 16189338Lee TW, Kowalski S, Falk K, Maguire D, Freed DH, HayGlass KT. High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study. PLoS One. 2016 Mar 1;11(3):e0149942. doi: 10.1371/journal.pone.0149942. eCollection 2016.
PubMed 26930568
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of High Spinal Anesthesia on Hemodynamics, Stress Response, Renal Function and Post-operative Pain Control in Patients Undergoing Aortic Valve Replacement for Aortic Stenosis
- ClinicalTrials.gov ID
- NCT00348920
- Acronym / sponsor ID
- AOTSA1
- Conditions
- Aortic Stenosis
- Keywords
- Aortic Valve, Aortic Stenosis, High Spinal Anesthesia, Total Spinal Anesthesia, Stress Response, Inflammatory Mediators, Renal Function, Hemodynamic Stability
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- St. Boniface Hospital, Health Sciences Centre Foundation, Manitoba
- Study start
- Feb 2007
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 6 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is looking at the effects of high spinal anesthesia (also known as total spinal anesthesia) combined with general anesthesia versus general anesthesia alone on the following:
Stress response: Patients undergoing aortic valve replacement surgery have a large incision and a complex operation where they must be placed on the heart-lung machine. The body reacts to the heart-lung machine, increasing the stress response.
High spinal anesthesia using local anesthetics when combined with general anesthesia has been shown to block some of the stress response to surgery and the response to the heart-lung machine. This study will examine if blood levels of stress hormones and also inflammatory mediators can be lowered with the use of high spinal anesthesia.
Heart function: High spinal anesthesia in combination with general anesthesia may help the heart work better when there is a narrowed valve (aortic stenosis). The heart may also have improved ability to pump blood with this anesthetic technique.
Lung function and post-operative pain control: After surgery, patients often have pain which prevents them from taking deep breaths and coughing. This can lead to pneumonia. This study will also examine if the post-operative pain relief provided by spinal morphine (given together with the spinal anesthetic) can provide any better pain control following surgery. By doing this, we want to see if patients can take bigger breaths after their surgery when spinal morphine is used, and try to prevent the complications that occur if patients are not able to breath deeply after surgery.
Detailed description
It is hypothesized that high spinal anesthesia combined with general anesthesia decreases the intraoperative stress and inflammatory response and improve post-operative pain control and respiratory function in this patient population. It is also hypothesized that the technique will provide stable intraoperative hemodynamics during aortic valve replacement surgery.
Stress response: Levels of hormones such as epinephrine, norepinephrine and cortisol are elevated during cardiac surgery and on the initiation of cardiopulmonary bypass. This stress response has previously been shown to be blunted with the use of high spinal anesthesia when combined with general anesthesia in coronary artery bypass surgery patients (Lee, Grocott, et al).
Inflammatory response: In addition to the stress response there is also an accentuated inflammatory response. With contact of the patient's blood to the artificial bypass circuit, there is activation of various plasma protease pathways that generate multiple proinflammatory mediators. Complement levels and cytokine levels also rise. Clinical organ dysfunction involving the cardiovascular, pulmonary, renal and neurological systems can ultimately result. The effects of high spinal anesthesia on the inflammatory response that occurs with bypass have not been studied.
Hemodynamics: It has previously been shown that high-spinal anesthesia for coronary artery bypass surgery provides stable intra-operative hemodynamics (Kowalewski, MacAdams, et al; Lee, Grocott, et al.). Although the use of spinal anesthesia in patients with aortic stenosis has been considered to be relatively contra-indicated, total spinal anesthesia may actually improve cardiac function by decreasing systemic afterload and increasing myocardial contractility.
Post-operative analgesia and pulmonary function: The spinal administration of opioids, such as morphine, has been shown to improve post-operative pain management in patients having both cardiac and non-cardiac surgery (Jacobsohn, Lee, et al). Total spinal anesthesia with bupivacaine and spinal morphine combined with general anesthesia may also improve post-operative pain management and facilitate improved post-operative lung function.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1- General Anesthesia | No intervention | –General Anesthesia includes administration of a routine cardiac anesthetic as per institutional norms. |
| 2- High Spinal and General Anesthesia | Experimental | Procedure: High Spinal and General AnesthesiaHigh Spinal and General Anesthesia includes a high dose intrathecal anesthetic administered prior to the induction of a standardized cardiac general anesthetic. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Undergoing surgery for aortic valve replacement due to aortic stenosis with or without CABG.
Key exclusion criteria (4 listed)
- INR > 1.4, PTT > 40 seconds
- platelet count < 80, 000 per microlitre
- local infection or deformity at the site of administration of the spinal anesthetic
- raised intracranial pressure or evolving neurological deficit at the time of surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High Spinal and General AnesthesiaAlso: Bupivacaine, EpimorphSpinal bupivacaine 0.75% in dextrose, 6 mls (45mg) and preservative free morphine 3 mcg/kg (to a maximum of 300 mcg). | Procedure or surgery | 2- High Spinal and General Anesthesia |
Primary outcome
Stress response as measured by levels of circulating epinephrine, norepinephrine, and cortisol.
Time frame: Multiple time points
Inflammatory response as measured by levels of circulating inflammatory mediators (e.g. interleukin-6, interleukin-8, interleukin-10, C-reactive protein, TNF-alpha).
Time frame: Multiple time points
Blood glucose control (amount of insulin required to keep blood glucose 5-8 mmol/L). Renal function as measured by serum creatinine.
Time frame: Multiple time points
4 secondary outcomes
Vasopressor requirements to keep mean blood pressure between 60-80 mm Hg.
Time frame: Multiple time points
Left ventricular wall motion score index as measured by TTE and TEE.
Time frame: Multiple time points
Hemodynamics including cardiac output and cardiac index, heart rate, systemic arterial and pulmonary arterial blood pressures, central venous pressure, and systemic and pulmonary vascular resistance.
Time frame: Multiple time points
Time to extubation.
Time frame: Time of extubation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2013.
- Background: PubMed 12552211Lee TW, Grocott HP, Schwinn D, Jacobsohn E; Winnipeg High-Spinal Anesthesia Group. High spinal anesthesia for cardiac surgery: effects on beta-adrenergic receptor function, stress response, and hemodynamics. Anesthesiology. 2003 Feb;98(2):499-510. doi: 10.1097/00000542-200302000-00032.
- Background: PubMed 8850406Kowalewski R, MacAdams C, Froelich J, Neil S, Maitland A. Anesthesia supplemented with subarachnoid bupivacaine and morphine for coronary artery bypass surgery in a child with Kawasaki disease. J Cardiothorac Vasc Anesth. 1996 Feb;10(2):243-6. doi: 10.1016/s1053-0770(96)80246-1. No abstract available.
- Background: PubMed 16189338Jacobsohn E, Lee TW, Amadeo RJ, Syslak PH, Debrouwere RG, Bell D, Klock PA, Tymkew H, Avidan M; University of Manitoba Health Sciences Centre Cardiac Anesthesia Group. Low-dose intrathecal morphine does not delay early extubation after cardiac surgery. Can J Anaesth. 2005 Oct;52(8):848-57. doi: 10.1007/BF03021781.
- Derived from this study: PubMed 26930568Lee TW, Kowalski S, Falk K, Maguire D, Freed DH, HayGlass KT. High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study. PLoS One. 2016 Mar 1;11(3):e0149942. doi: 10.1371/journal.pone.0149942. eCollection 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Trevor WR Lee, MD principal investigator
Department of Anesthesia and Perioperative Medicine, St. Boniface General Hospital, University of Manitoba
Stephen E Kowalski, MD principal investigator
Department of Anesthesia, Health Sciences Centre, University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High Spinal and General Anesthesia in people with Aortic Stenosis, run by University of Manitoba at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stress response as measured by levels of circulating epinephrine, norepinephrine, and cortisol. (time frame: Multiple time points). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00348920, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2013.