What pharmacologic intervention has the strongest evidence for preventing post-traumatic stress disorder (PTSD) in a patient undergoing coronary artery bypass graft (CABG) and heart valve repair?

Hydrocortisone Has the Strongest Evidence for PTSD Prevention in Cardiac Surgery Patients

Based on the highest quality systematic review evidence, hydrocortisone is the pharmacologic intervention with the strongest evidence for preventing PTSD in patients undergoing cardiac surgery, with moderate quality evidence showing it reduces PTSD onset by 83% (RR 0.17). 1

Evidence Quality and Strength

The 2014 Cochrane systematic review analyzing nine randomized controlled trials provides the most rigorous assessment of pharmacologic PTSD prevention strategies. 1 This analysis included 345 participants exposed to various traumas, including cardiac surgery, and evaluated multiple agents over 12 weeks or less.

Hydrocortisone: The Clear Winner

• Hydrocortisone demonstrated moderate quality evidence for efficacy in four trials with 165 participants, showing an 83% reduction in PTSD onset (RR 0.17; 95% CI 0.05 to 0.56; P = 0.004). 1
• The number needed to treat is remarkably low at 7-13 patients, meaning between 7 and 13 patients need treatment to prevent one case of PTSD. 1
• Three of four hydrocortisone trials showed superiority over placebo in reducing PTSD symptoms at a median of 4.5 months post-event. 1
• Drop-outs due to treatment-emergent side effects were low. 1

Why Other Options Fall Short

Propranolol (Option D) showed only low quality evidence with no statistical benefit:

• Three trials with 118 participants found no significant PTSD prevention (RR 0.62; 95% CI 0.24 to 1.59; P = 0.32). 1
• While propranolol reduces emotional memory consolidation when given immediately after trauma 2, the clinical trial evidence does not support its efficacy for PTSD prevention in this population. 1

Escitalopram (Option A) has no evidence for PTSD prevention:

• A single trial showed no superiority over placebo for preventing PTSD onset. 1
• While escitalopram is recommended for treating depression after cardiac surgery 3, this is distinct from PTSD prevention.

Clonazepam (Option C) and benzodiazepines should be avoided:

• No evidence supports benzodiazepines for PTSD prevention. 1
• Guidelines explicitly recommend avoiding benzodiazepines in postoperative patients as they precipitate delirium and worsen cognitive dysfunction. 3

Ketamine (Option B) was not evaluated in the systematic review and lacks evidence for PTSD prevention in cardiac surgery patients. 1

Clinical Context for Cardiac Surgery

Depression and anxiety are highly prevalent in CABG patients, with approximately 32-55% experiencing clinically significant symptoms preoperatively and 26-34% postoperatively. 4, 5 However, the question specifically addresses PTSD prevention, not depression or anxiety management.

Important distinction: While cognitive behavioral therapy is first-line for treating postoperative depression 6, 3, and beta-blockers are recommended for anxiety in cardiac patients 7, these interventions target different outcomes than PTSD prevention.

Critical Limitations

• Seven of nine included trials had high risk of bias, with issues including differential drop-outs, unclear allocation concealment, and early termination based on treatment response. 1
• The evidence base consists of small studies with multiple methodological limitations. 1
• Further research is necessary to confirm these findings and identify optimal dosing and timing. 1

The Answer is E. Hydrocortisone - it is the only agent with moderate quality evidence demonstrating significant PTSD prevention in trauma-exposed patients, including those undergoing cardiac surgery.