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

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

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 Overview

• Status: Terminated
• Conditions: Post-traumatic Stress Disorder
• Intervention / Treatment: Drug: Propranolol Hydrochloride; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	Other: Placebo; 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.
Experimental: Propranolol Hydrochloride	Drug: Propranolol 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.; Other Names: Inderal; Inderal LA; Avlocardyl; Deralin; Dociton; Inderalici; InnoPran XL; Sumial; Anaprilinum; Avlocardyl Retard; Bedranol SR Sandoz

What is the study measuring?

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
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
Perioperative complications	Measured using patient medical records	Participants will be followed for the duration of hospital stay, an expected average of 1 week
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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: United States Department of Defense; Northern California Institute of Research and Education
• Investigators: Principal Investigator: Marek Brzezinski, M.D., Ph.D., University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: March 5, 2012
• First Submitted That Met QC Criteria: March 13, 2012
• First Posted (Estimate): March 15, 2012

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: anesthesia; surgery; Propranolol; Post-traumatic stress disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: W81XWH-10-2-0078