Proenkephalin A 119-159 as a marker of illness

The aim of my PhD project is to explore the role of the new biomarker proenkephalin A 119-159 (penKid) as a marker of illness.

We have analysed penKid in 1978 critically ill patients and published a first manuscript in ICM experimental. We found that plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality.

I am engaged in three active projects. One of the projects is a retrospective observational study with primary aim to assess if a combination of three biomarkers, biologically active adrenomedullin (bio-ADM), penKid, and circulating dipeptidyl peptidase 3 (cDPP3), measured at admission to the intensive care unit (ICU), is useful for prognostication, in critically ill sepsis patients. These biomarkers are associated with mortality and organ dysfunction in the ICU individually, but the combined effect of all three has not been explored.

The second project is also retrospective observational study, analysing penKid in trauma patients. Our aim is to explore if penKid is predictive for neurologic functional level in traumatic brain injury patients.

The third ongoing project is a case-control study, investigating the role of penKid in chronic pain. PenKid is a surrogate marker for the instable enkephalins, a part of the endogenous pain relief system. We measure penKid in plasma and cerebrospinal fluid in patients suffering from chronic inguinal pain after inguinal hernia repair surgery and healthy controls. In addition to penKid, we measure proinflammatory mediators, perform qualitative sensory testing and sleep registration.

We plan to do a prospective study. We will analyse penKid in plasma and cerebrospinal fluid in traumatic brain injury patients and healthy controls. Our hypothesis is that penKid is a marker of brain injury.

Reliable and early risk assessment for death and morbidity in critical illness is crucial. The critically ill patients shall be identified early and receive intensive treatment. Patients who are too sick and frail to gain from intensive care shall be identified early, and strenuous intensive care at end of life, shall be avoided.

Risk for mortality in critical illness is currently assessed on admission to the critical care unit using a scoring system. Several variables are weighed together - age, comorbidity, incidence and degree of physiological disturbance over a 2-hour interval in connection with arrival in intensive care (1 hour before and after arrival).

Proenkephalin A 119-159 (penKid) is a protein that can be measured and evaluated in a fast and simple way, using a bedside blood test. We have found that penKid is prognostic for mortality in critically ill patients. We measured penKid in 1978 critically ill patients. Consistent with earlier studies, we found that elevated penKid may be an early marker of kidney failure. In addition, we found a relationship between elevated blood penKid levels and neurologic dysfunction. We will explore if penKid may be a marker of brain injury.

PenKid is produced together with enkephalins, signalling molecules that has potent pain killing effects. The biologic effects of penKid are not known, but the blood level of penKid mirror the level of enkephalins. One of my projects focus on the relationship between penKid and pain. Exploring the biological effects of penKid could possibly open up for new ways of treatment for critically ill patients.