Perioperative Propranolol in Patients With Post Traumatic Stress Disorder (PTSD)

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Prophylactic, Perioperative Propranolol on Peri- and Postoperative Complications in Patients With Post Traumatic Stress Disorder

Conditions
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Post-traumatic Stress Disorder

Intervention / Treatment
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* Drug: Propranolol Hydrochloride
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Anticipated postoperative hospital admission (defined as at least one overnight hospital stay) Exclusion Criteria: Veterans will be excluded if: They are on beta blocker therapy at the time of the preoperative baseline assessment They report sensitivity or allergies to propranolol, or a history of PTSD exacerbation with prior propranolol therapy 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 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 Pregnancy Current use of medication that may involve potentially dangerous interaction with propranolol 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). Open-heart surgery and intracranial surgery

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol Hydrochloride<br> | Drug: Propranolol Hydrochloride<br>* 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.<br>* Other names: Bedranol SR Sandoz;|
| Placebo Comparator: Placebo Group<br> | Other: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU length of stay | Measured using patient medical records | Truncated at 30 days after admission to ICU | 
| Hospital length of stay | Measured using patient medical records | Truncated at 30 days after admission to ICU | 
| Postoperative delirium | Measured using Confusion Assessment Method (CAM-CAM-ICU) | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Postoperative renal dysfunction | Measured using Serum Creatinine laboratory values | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative complications | Measured using patient medical records | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Pain intensity | Measured using the Numerical Rating Scale | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Pain unpleasantness | Measured using the Numerical Rating Scale | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Analgesics use | Measured using patient medical records | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Length of intubation and mechanical ventilation | Measured using patient medical records | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Post Traumatic Stress Disorder symptomatology | Measured using the Posttraumatic Diagnostic Scale (PDS) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Quality of Life | Measured using Short Form-36 Questionnaire (SF-36) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Functional status | Measured using Short Form-36 Questionnaire (SF-36) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Sleep Quality | Measured using the Pittsburgh Sleep Quality Index (PSQI) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Depression symptoms | Measured using the Beck Depression Inventory (BDI) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Postoperative Neurocognitive Dysfunction Score | Measured using the Mini Mental State Examination (MMSE) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| 30-day, 3-month, and 1-year mortality | Measured using patient medical records | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Postoperative complications | Measured using patient medical records | Participants will be followed to 1 year postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-traumatic stress disorder, Propranolol, surgery, anesthesia