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

Phase 4TerminatedNCT01555554

University of California, San Francisco59 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Post-traumatic Stress Disorder

Interventions

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.

PlaceboOTHER

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.

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

ICU Length of Stay

Measured using patient medical records

Time frame: Truncated at 30 days after admission to ICU

Hospital Length of Stay

Measured using patient medical records

Time frame: Truncated at 30 days after admission to ICU

Postoperative Delirium

Measured using Confusion Assessment Method (CAM-CAM-ICU)

Time frame: 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

Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week

Secondary Outcomes

Perioperative Complications

Measured using patient medical records

Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week

Pain Intensity

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.

Time frame: 12 months

Pain Unpleasantness

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.

Time frame: 12 months

Perioperative Opioids Use

Measured using patient medical records.

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

Required Mechanical Ventilation

Measured using patient medical records

Time frame: Participants will be followed for the duration of hospital stay, an expected average of 1 week

Change in Posttraumatic Diagnostic Scale (PDS) PTSD Symptoms Severity Score

The Posttraumatic Diagnostic Scale (PDS) Scale includes a PTSD Symptoms Severity Score ranging from 0 to 51, with higher scores indicating more severe depression.

Time frame: Baseline and 12 months

Change in Mental Component Summary (MCS) Scores From the Short Form-36 Questionnaire (SF-36)

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.

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

Change in Physical Component Summary (PCS) Scores From the Short Form-36 Questionnaire (SF-36)

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.

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

Change in Pittsburgh Sleep Quality Index (PSQI) Score

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

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

Change in Beck Depression Inventory (BDI) Score

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).

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

Postoperative Neurocognitive Dysfunction Score

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.

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

30-day, 3-month, and 1-year Mortality

Measured using patient medical records

Time frame: Participants will be followed from preoperative baseline to 1 year postoperative

Postoperative Complications

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.

Time frame: Participants will be followed to 1 year postoperative

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes