Double-blind placebo-controlled study of the hyperventilation provocation test and the validity of the hyperventilation syndrome

Background Hyperventilation syndrome (HVS) describes a set of somatic and psychological symptoms thought to result from episodic or chronic hyperventilation. Recognition of symptoms during the hyperventilation provocation test (HVPT) is the most widely used criterion for diagnosis of HVS. We have investigated the validity of the HVPT and of the concept of HVS. Methods In a randomised, double-blind, crossover design, the ability of 115 patients with suspected HVS to recognise symptoms during the HVPT was compared with the ability to recognise symptoms during a placebo test (isocapnic overbreathing, with carbon dioxide levels maintained by manual titration). 30 patients who had positive results on the HVPT underwent ambulatory transcutaneous monitoring of pCO2 to ascertain whether they hyperventilated during spontaneous symptom attacks. Findings Of the 115 patients who underwent the HVPT and the placebo test, 85 (74%) reported symptom recognition during the HVPT (positive diagnosis HVS). Of that subset, 56 were also positive on the placebo test (false-positive), and 29 were negative on the placebo test (true-positive). False-positive and true-positive patients did not differ in symptom profile or in physiological variables. During ambulatory monitoring (15 true-positive, 15 false-positive) 22 attacks were registered. Transcutaneous end-tidal pCO2 decreased during only seven. The decreases were slight and apparently followed the onset of the attack, which suggests that hyperventilation is a consequence rather than a cause of the attack. There were no apparent differences between false-positive and true-positive patients. Interpretation The HVPT is invalid as a diagnostic test for HVS. Hyperventilation seems a negligible factor in the experience of spontaneous symptoms. The term HVS should be avoided.