ICCM 2007

Intravenous MicrodialysisIntravenous Microdialysis::

A tool for diagnosis and drug developmentA tool for diagnosis and drug development

Mark O’Connell PhD MIBiol CBiol

Director, Probe Scientific Limited

20 September 2007

Any view or opinions expressed are solely those of the author and do not represent the view of the Board unless specifically stated.

MicroEye® sitting beside and within an 18G venous access device

Intravenous microdialysisIntravenous microdialysis- solutions- solutions

Leicester 22 June 2007

Current practices for monitoring?Current practices for monitoring?

Leicester 22 June 2007

Van Den Berghe et al (2001)

Reported that during a 12 month study on 1,550 ICU patients receiving intensive insulin therapy reduced mortality by 42%.overall in-hospital mortality by 34%

bloodstream infections by 46%acute renal failure requiring dialysis or haemofiltration by 41%the median number of red-cell transfusion by 50%critical illness polyneuropathy by 44%

The total hospitalisation cost - intensive treatment group was €6,067,237 (€7,931 per patient) - conventional treatment group was €8,275,394 (€10,569 per patient).

The excess cost of intensive care unit hospitalisation in the conventional versus the intensive treatment group was €2,638 per patient.

Crit Care Med 2006 Vol. 34, No. 3

N Engl J Med. 2001 Nov 8;345(19):1359-67.

Time / min

Dru

g c

once

ntra

tion

Blood sample

Blood Drug Concentration v TimeConventional blood withdrawal

Time / min

Dru

g c

once

ntra

tion

Microdialysis

Blood sample

Blood Drug Concentration v Time using intravenous microdialysis

Basildon and Thurrock University Hospitals NHSFoundation Trust

Blood sample age monitoring device – Paul Cervi & Tony Everitt

• Pre-analytical delay of more than 4 hrs affect the accuracy of certain critical analytes and can adversely influence clinical outcome.

• Clinicians increasingly depend on reliable blood analysis but 30% of samples are more than 4hrs old.

• red cells• white cells• plasma

– platelets– clotting factors– serum

• proteins• lipids• sugars• salts• water

Blood Composition Remove by

centrifugation

clotting

Precipitation / UF

Metabolite Biosensor

CoverCoverMembraneMembrane

G.O.D. orG.O.D. orB.S.A LayerB.S.A Layer(Pt/Carbon)(Pt/Carbon)

DialectricDialectric(Glass)(Glass)

CeramicCeramicSubstrateSubstrate(96% AI203)(96% AI203)

PlatinumPlatinumConductorConductor

Leicester 22 June 2007

• Tissue biopsy

• Discontinuous

• Composition dynamics

– Clotting

– Degradation

• Uncomfortable

• Infectious (disposal)

• Storage is a problem

• Delays

Problems with blood withdrawal?Problems with blood withdrawal?

Leicester 22 June 2007

Clinical Intravenous Clinical Intravenous MicroMicrodialysisdialysis

Chemical monitoring of intensive care patients using intravenous microdialysisH. Stjernstrom, T. Karlsson, U. Ungerstedt, L. HilleredIntensive Care Medicine; 1993; Vol.19:423-428

Clinical drug monitoring by microdialysis: application to levodopa therapy in Parkinson’s diseaseMark T. O’Connell, Francois Tison, Niall P. Quinn and Philip N. PatsalosBritish Journal of Pharmacology 1996; Vol.42:765-769

Antiepileptic Drug Pharmacokinetics in Patents with Epilepsy Using a New Microdialysis Probe: Preliminary ObservationsPN Patsalos, MT O’Connell, HC Doheny, JWAS Sander and SD ShorvonActa Neurochirurgica. Supplement; 1996; Vol. 67:59-62

MicroEyeMicroEye® ® - the future- the future