A Study Comparing Modified Lund Concept and Cerebral Perfusion Pressure-targeted Therapy in Secondary Brain Ischaemia.

Summary

Secondary brain ischaemia (SBI) usually develops after aneurysmal subarachnoid haemorrhage (SAH) and severe traumatic brain injury (TBI). The current management strategies are based on intracranial pressure-targeted therapy (ICP-targeted) with cerebral microdialysis monitoring (modified Lund concept) or cerebral perfusion pressure-targeted therapy (CPP-targeted). We present a randomised controlled study to compare the two management strategies.

The hypotheses of the study were:

* SBI developed after aneurysmal SAH and severe TBI share the same crucial characteristics and any treatment applied will essentially treat the same underlying pathophysiology.
* ICP-targeted therapy with cerebral microdialysis monitoring according to the modified Lund concept is superior to CPP-targeted therapy in managing comatose patients with SBI after aneurysmal SAH and severe TBI.

Sixty comatose operated patients with SBI following aneurysmal SAH and severe TBI were randomized into ICP-targeted therapy with cerebral microdialysis monitoring and CPP-targeted therapy groups. Mortality rates in both groups were calculated and biochemical signs of cerebral ischaemia were analysed using cerebral microdialysis. Outcome for cerebral microdialysis was measured as poor outcome (Glasgow Outcome Scale score 1, 2 and 3) or good outcome (Glasgow Outcome Scale score 4 and 5).

Conditions

• Brain Injuries
• Subarachnoid Hemorrhage

Interventions

PROCEDURE

Modified Lund concept

After surgical evacuation of intracranial mass lesion and clipping of aneurysm the objectives were achieved: * Reduction of cerebral energy metabolism with fentanyl (2-5 µg/kg/h) and thiopenthal (0.5-3 mg/kg/h); * Maintenance of colloid osmotic pressure with administration of red cell and albumin/plasma transfusions to maintain Hb/s 125-140 g/L and Alb/s ≈40 g/L; * Reduction of capillary hydrostatic pressure with α2-agonist clonidine (0.4-0.8 µg/kg, 1 x 4-6 iv.) and maintaining normovolaemia; * Reduction of mean arterial pressure and neuroprotection with Nimodipine infusion 5 ml per hour for 21 days and Urapidil 200 mg /200 ml, 7-10 ml/h. * Control of ICP, which can be in majority of patients, kept at values below 15 mmHg.

PROCEDURE

Cerebral perfusion pressure-targeted therapy

* ICP monitoring using an external ventricular drain and CSF drainage as a first measure if ICP was increased (over 15-20 mmHg); * Maintenance of CPP over 70-80 mmHg (Triple 'H' therapy = 3L/24 hours including 1L of colloids - 5% albumin; drugs = dopamine, dobutamine); * No hyperventilation if ICP was under 20-25 mmHg and hyperventilation as a third measure if ICP was increased; * Osmotherapy (20% manitol, bolus 150-350 ml or 10% manitol, 50 ml/h for 10 hours and standard electrolytes \[Na, Cl and K\]);

Sponsors & Collaborators

• University of Sarajevo

  lead OTHER

Principal Investigators

• Kemal Dizdarevic, MD, MSc, PhD · Department of Neurosurgery, Clinical Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

16 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-01-31

Primary Completion

2008-06-30

Completion

2008-07-31

Countries

• Bosnia and Herzegovina

Study Locations