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

NCT ID: NCT01206283

Last Updated: 2010-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2008-07-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Cerebral perfusion pressure-targeted

15 comatose operated patients after aneurysmal subarachnoid haemorrhage and severe traumatic brain injury respectively were managed postoperatively using cerebral perfusion pressure-targeted therapy according to the American Associations of Neurological Surgeons. Results were categorised into different Glasgow Outcome Scores.

Group Type: ACTIVE_COMPARATOR

Cerebral perfusion pressure-targeted therapy

Intervention Type: PROCEDURE

• 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]);

Intracranial pressure-targeted therapy

Group Type: ACTIVE_COMPARATOR

Modified Lund concept

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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]);

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• patients with subarachnoid haemorrhage who had anterior circulation aneurysm rupture only
• multiple anterior aneurysm rupture
• severe traumatic brain injury with isolated head injury and intradural focal lesions only

Exclusion Criteria

• Glasgow Outcome Score of 3 with or without brainstem reflexes
• Significant co-morbidities
• posterior circulation aneurysm
• multisystem injuries
• diffuse axonal injuries

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sarajevo

OTHER

Sponsor Role: lead

Responsible Party

Clinical Center University of Sarajevo, Bosnia and Herzegovina

Principal Investigators

Kemal Dizdarevic, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurosurgery, Clinical Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Locations

Department of Neurosurgery, Clinical Centre University of Sarajevo

Sarajevo, , Bosnia and Herzegovina

Countries

Bosnia and Herzegovina

Other Identifiers

030531674

Identifier Type: -

Identifier Source: org_study_id