Post-traumatic Stress Disorder
Conditions
Keywords
Post-traumatic stress disorder, Propranolol, surgery, anesthesia
Brief summary
Understanding what treatments may facilitate perioperative care of Veterans with posttraumatic stress disorder (PTSD) is of great importance to the U.S. health care system. Patients with PTSD are characterized by elevated central nervous system catecholamine concentrations and exaggerated and prolonged adrenergic responses to stress stimuli. At present, there are no data on the effects of perioperative beta blocker therapy in patients with PTSD, despite the rising significance of PTSD in Veteran populations. This prospective, double-blind study proposes to randomize 150 Veterans with PTSD scheduled for orthopedic, thoracic or vascular surgery at the San Francisco VA Medical Center to either a 14-day course of propranolol or placebo. This study will then follow these Veterans for a one-year period to evaluate the effects of the intervention on Veterans' surgical outcomes. The investigators hypothesize that patients with PTSD randomized to the propranolol group will demonstrate a reduced incidence of perioperative and postoperative morbidity and mortality.
Interventions
DRUGPropranolol Hydrochloride
Propranolol will be taken for a total of 14 days. On the morning of the surgery, prior to entry into the operating room, patients will receive the first dose of the study drug (the PDR recommended starting dose of Propranolol XL- Extended Release). Patients will take one 60 mg pill on the morning of surgery. On post operative day #1, patients will take one pill of receive propranolol XL 80 mg (once daily by mouth). On post operative days #2-#9, patients will take one pill of propranolol XL 120 mg (once daily by mouth). On post operative days #10-11, patients will take one pill of propranolol XL 80 mg (once daily by mouth). On post operative days #12-13, patients will take one pill of propranolol XL 60 mg (once daily by mouth). This will complete the course of propranolol.
OTHERPlacebo
The placebo pill will be taken for a total of 14 days. On the morning of the surgery, prior to entry into the operating room, patients will receive the first placebo pill to be taken once daily by mouth. On post operative days #1-13, patients will take one placebo pill (once daily by mouth). This will complete the course of the placebo.
Sponsors
University of California, San Francisco
United States Department of Defense
Northern California Institute of Research and Education
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects scheduled for any surgical procedure under general anesthesia or combined general-regional anesthesia, with the exception of open-heart or intracranial surgery. Regional anesthesia includes: 1) Epidural anesthesia, 2) Sub-arachnoid block (spinal), or 3)any regional nerve block 2. Anticipated postoperative hospital admission (defined as at least one overnight hospital stay)
Exclusion criteria
Veterans will be excluded if: 1. They are on beta blocker therapy at the time of the preoperative baseline assessment 2. They report sensitivity or allergies to propranolol, or a history of PTSD exacerbation with prior propranolol therapy 3. Veterans who fulfill the AHA/ACC level I recommendation criteria for perioperative beta blocker therapy (e.g., metoprolol, atenolol) and should not be randomized to placebo group 4. Medical exclusions criteria: high grade heart block without pacemaker (all patients with 2nd and 3rd degree heart block), marked resting bradycardia (heart rate ≤ 55 beats per minute), blood pressure \< 100 mmHg, uncompensated congested heart failure, severe hyperactive airway disease, and Raynaud's disease 5. Pregnancy 6. Current use of medication that may involve potentially dangerous interaction with propranolol 7. Circumstances that, in the opinion of the principal investigator, would preclude participation in a study of this type (e.g. medical concerns or difficulty in long-term followup). 8. Open-heart surgery and intracranial surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ICU Length of Stay | Truncated at 30 days after admission to ICU | Measured using patient medical records |
| Hospital Length of Stay | Truncated at 30 days after admission to ICU | Measured using patient medical records |
| Postoperative Delirium | Participants will be followed for the duration of hospital stay, an expected average of 1 week | Measured using Confusion Assessment Method (CAM-CAM-ICU) |
| Postoperative Renal Dysfunction | Participants will be followed for the duration of hospital stay, an expected average of 1 week | Measured using Serum Creatinine laboratory values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perioperative Complications | Participants will be followed for the duration of hospital stay, an expected average of 1 week | Measured using patient medical records |
| Pain Intensity | 12 months | Pain intensity was measured using a Numerical Rating Scale (NRS). The range of the NRS is 0 and 10, where zero represents no pain at all and 10 represents the worst pain ever possible. |
| Pain Unpleasantness | 12 months | Measured using the Numerical Rating Scale (NRS). The range of the NRS is 0 and 10, where zero represents no pain at all and 10 represents the worst pain ever possible. |
| Perioperative Opioids Use | Participants will be followed from preoperative baseline to 1 year postoperative | Measured using patient medical records. |
| Required Mechanical Ventilation | Participants will be followed for the duration of hospital stay, an expected average of 1 week | Measured using patient medical records |
| Change in Posttraumatic Diagnostic Scale (PDS) PTSD Symptoms Severity Score | Baseline and 12 months | The Posttraumatic Diagnostic Scale (PDS) Scale includes a PTSD Symptoms Severity Score ranging from 0 to 51, with higher scores indicating more severe depression. |
| Change in Mental Component Summary (MCS) Scores From the Short Form-36 Questionnaire (SF-36) | Participants will be followed from preoperative baseline to 1 year postoperative | The Mental Component Summary (MCS) score is derived from the Short Form-36 Questionnaire (SF-36), a validated measure of health-related quality of life. Scores range from 0 to 100, with higher scores indicating better mental health and lower scores indicating worse mental health. |
| Change in Physical Component Summary (PCS) Scores From the Short Form-36 Questionnaire (SF-36) | Participants will be followed from preoperative baseline to 1 year postoperative | The Physical Component Summary (PCS) score is derived from the Short Form-36 Questionnaire (SF-36), a validated measure of health-related quality of life. Scores range from 0 to 100, with higher scores indicating better physical health and lower scores indicating worse physical health. |
| Change in Pittsburgh Sleep Quality Index (PSQI) Score | Participants will be followed from preoperative baseline to 1 year postoperative | The Pittsburgh Sleep Quality Index (PSQI) is a validated self-reported questionnaire assessing sleep quality. Total scores range from 0 to 21, with higher scores indicating worse sleep quality and lower scores indicating better sleep quality |
| Change in Beck Depression Inventory (BDI) Score | Participants will be followed from preoperative baseline to 1 year postoperative | The Beck Depression Inventory (BDI) is a validated self-report measure of depressive symptoms. Total scores range from 0 to 63, with higher scores indicating more severe depressive symptoms (worse outcome) and lower scores indicating fewer or minimal symptoms (better outcome). |
| Postoperative Neurocognitive Dysfunction Score | Participants will be followed from preoperative baseline to 1 year postoperative | The Mini-Mental State Examination (MMSE) is a widely used screening tool for cognitive function. Total scores range from 0 to 30, with higher scores indicating better cognitive function and lower scores indicating greater cognitive impairment. |
| 30-day, 3-month, and 1-year Mortality | Participants will be followed from preoperative baseline to 1 year postoperative | Measured using patient medical records |
| Postoperative Complications | Participants will be followed to 1 year postoperative | Measured using patient medical records - Composite outcome measure that included, delirium, stroke, myocardial infarction, acute kidney injury, new atrial fibrilation, infection, or congestive heart failure between the surgery and 1-yr. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarek Brzezinski, M.D., Ph.D.
University of California, San Francisco
Participant flow
Pre-assignment details
A total of 14,504 patients were screened for eligibility with 126 providing written consent and undergoing PDS assessment and 83 subjects potentially meeting inclusion criteria. Of those 83, 24 subjects were not found to not meet inclusion criteria due to postponement in surgery, change in condition, or due to the stress associated with talking about the trauma. Ultimately, only 59 participants met all inclusion criteria and were enrolled out of the originally planned 110 subjects anticipated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.75 years STANDARD_DEVIATION 8.75 |
| Race/Ethnicity, Customized Non-white or hispanic | 19 Participants |
| Race/Ethnicity, Customized White | 40 Participants |
| Region of Enrollment United States | 59 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 0 / 29 | 0 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
None listed