Pilot study of a protocol to administer inhaled nitric oxide to treat severe acute submassive pulmonary embolism

Inhaled nitric oxide has been reported to benefit patients with acute pulmonary embolism (PE). To date, all published literature has derived from case reports or case series conducted without a structured protocol. Here we report the results of a phase I trial with a predefined clinical protocol to treat patients with CT-demonstrated, submassive PE and moderate to severe dyspnoea.

Patients were recruited from the emergency department of an academic teaching hospital. Informed consent and the entire treatment protocol was administered by a study physician. Nitric oxide was administered using a commercial device (Inovent) and a custom-made non-rebreathing face mask. The NO concentration was increased at 1 ppm/min (parts per million) until a maximum of 25 ppm and continued for 120 min and then weaned at 1 ppm/min. Dyspnoea was assessed with the Borg score, oxygenation by pulse oximetry, and haemodynamic status by shock index (HR/SBP).

Eight patients were enrolled. All patients tolerated the entire protocol without adverse events, and all had decreased numerical Borg score by >50%. The changes from baseline to 155 min were as follows: Borg score 7.5±2.5 to 2.3±1.9 (p=0.06, Signed rank test), SaO2% 93±5 to 97±3 and shock index 1.0±0.11 to 0.86±0.09. No patient experienced worsening during weaning.

Inhaled NO reduced dyspnoea without adverse events in eight patients with severe submassive PE. This protocol can serve as the basis for a phase II trial or for a compassionate use protocol.