Distributive shock - pyridoxalated haemoglobin polyoxyethylene

Shock is a collapse or near collapse that results from inadequate delivery of oxygen to the cells. If it is caused by poor distribution of blood flow it is termed distributive shock. It involves peripheral vasodilation, tissue ischaemia and hypotension, and can lead to multiple organ failure and even death.

There are a number of potential causes, including bacterial infection, drug overdose, an-aphylaxis or the abnormal opening of blood vessels because of neurologic dysfunction. An overproduction of nitric oxide is implicated in a number of conditions, including distributive shock, so using a nitric oxide scavenger drug could be of great benefit.

One of these, pyridoxalated haemoglobin polyoxyethylene, or PHP, is being developed by German company Curacyte as a potential treatment for distributive shock.¹ Its efficacy and safety have been investigated in a randomised multicentre Phase IIc trial in 62 patients with systemic inflammatory response syndromes, who were dependent on catecholamines after fluid resuscitation.² The patients were given a conventional catecholamines therapy plus placebo, or catecholamines along with PHP. The new drug had the effect of raising systemic blood pressure, and had a number of other positive effects, such as reduced need for ventilation and shorter stays in hospital. It was well tolerated, and gave no increase in morbidity.

Trials are continuing, and PHP is also in early stage trials as a potential additional drug for patients with metastatic melanoma and renal cell carcinoma, along with interleukin-2 treatment, where nitric oxide related hypertension is often a dose limiting factor and shock a common side-effect.