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

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.