CO2 provocation of panic: symptomatic and manometric evaluation in patients with noncardiac chest pain

Occult panic disorder (PD) may underlie 10-43% of chest pain syndromes in patients with normal coronary arteries. A variety of agents, such as intravenous lactate, oral caffeine, and inhaled CO2, has been identified that may provoke panic attacks in susceptible patients. The aims of this study were (1) to better define the relationship between noncardiac chest pain syndromes and panic disorder; and (2) to assess the diagnostic utility of PD provocative testing with inhaled CO2 in eliciting chest pain and/or esophageal manometric disturbances.

Fourteen patients with chest pain syndromes and negative coronary angiograms or stress thallium tests were evaluated for PD and underwent (1) standard esophageal manometry followed by continuous manometric recording; (2) inhalation by face mask of room air or 35% CO2, single blinded, in random order; (3) a previously validated Acute Panic Inventory questionnaire administered before and immediately after each inhalation; and (4) Tensilon 10 mg i.v. administration.

Of 14 patients, 8 met DSM-IIIR criteria for panic disorder. Mean Acute Panic Inventory scores (reflecting panic symptoms) increased significantly after CO2 inhalation relative to room air in all patients. Of 14 patients, 8 (4 PD, 4 non-PD) experienced chest pain after CO2 inhalation, whereas no patient had chest pain after room air inhalation. Of 14 patients, 5 had pain with Tensilon (4 of 5 whom responded to CO2). No specific manometric abnormalities occurred during any chest pain episode.

CO2 inhalation is as effective as Tensilon in provoking chest pain in patients with noncardiac chest pain. The high prevalence of PD in such patients suggests that CO2 inhalation, a known panicogen, may be useful in evaluating such patients. The mechanism of CO2 induced chest pain remains unknown, but does not appear to be attributable to demonstrable esophageal motility abnormalities.