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

Study Overview
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Brief Summary
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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).

Official Title
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Modified Lund Concept Versus Cerebral Perfusion Pressure-targeted Therapy: A Randomized Controlled Study in Patients With Secondary Brain Ischaemia.

Conditions
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Brain Injuries, Subarachnoid Hemorrhage

Intervention / Treatment
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* Procedure: Modified Lund concept
* Procedure: Cerebral perfusion pressure-targeted therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cerebral perfusion pressure-targeted<br>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. | Procedure: Cerebral perfusion pressure-targeted therapy<br>* 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]);<br>|
| Active Comparator: Intracranial pressure-targeted therapy<br> | Procedure: Modified Lund concept<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate | Measurement of outcome was done using the Glasgow Outcome Scale (GOS) after each specific intervention in all the patients. GOS 1 - dead, 2- vegetative, 3- severe disabled, 4- moderate disabled, 5- independent. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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traumatic brain injury, subarachnoid hemorrhage, secondary brain ischemia, microdialysis, modified Lund concept, cerebral perfusion pressure, intracranial pressure