Naloxone and TRH in the treatment of shock and trauma: what future roles?

Endogenous opioid peptides are released in response to stressful situations, such as circulatory shock, both as hormones and as central and peripheral neurotransmitters. Naloxone, an opiate antagonist, improves cardiovascular function in a variety of animal models of shock caused by endotoxemia, hemorrhage, anaphylaxis, or spinal trauma. Administration of thyrotropin-releasing hormone (TRH) in supraphysiologic doses also has pressor effects in these shock models. Given acutely after injury, TRH improves recovery in models of spinal trauma; however, the experimental effects of TRH do not involve action at the opiate receptor. Clinical evaluation of the use of naloxone in patients with shock has been largely limited to treatment of sepsis. The paucity of prospective, randomized trials makes these clinical data difficult to evaluate, but in septic patients the use of naloxone does not seem to improve survival. The use of naloxone in shock of other etiologies has not been clinically investigated, and may hold greater promise. Acute-phase treatment of spinal trauma victims with TRH is currently undergoing clinical trials.