Objectives:To determine the effect of breathing helium-oxygen (HELIOX) mixtures on pulmonary gas exchange during severe asthma.Design:A retrospective case-match control design was used to compare the changes in alveolar to arterial gradient [(A-a)gradient] in the first 2 hrs of mechanical ventilation (MV) for status asthmaticus (SA) in patients who received HELIOX with those who did not. Patients were matched for diagnosis of asthma, ventilatory failure, ventilator mode and settings, and equivalent pharmacologic therapy.Setting:The adult and pediatric intensive care units of a tertiary-care hospital.Subjects:Adult and pediatric patients undergoing MV for SA.Interventions:Use of HELIOX or standard nitrogen-oxygen mixtures during MV.Measurements and Main Results:A total of 11 patients receiving HELIOX in the first 2 hrs of MV for SA were compared with 11 case-matched controls who did not. At baseline, the HELIOX and control groups had similar (A-a)gradients (216 ± 92 torr and 226 ± 82 torr, respectively). The (A-a)gradient decreased significantly to 85 ± 44 torr after initiation of ventilation with HELIOX (p< .0003), whereas it did not change significantly in the control group in a similar time frame and during identical treatment without HELIOX. The reduction in (A-a)gradient in the HELIOX group facilitated a reduction in FIO2from 0.8 ± 0.2 initially to 0.4 ± 0.1 at the time of the second blood gas determination, thus permitting greater concentrations of helium to be administered.Conclusions:MV with HELIOX improves (A-a)gradient in patients with SA. Although this improvement adds little to routine therapy with supplemental oxygen, it does permit reduction in concentration of inspired oxygen to levels that maximize helium concentration and thus permit full benefits of HELIOX on lung mechanics to be realized in even the most severely ill asthmatics.