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

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

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).

Study Overview

• Status: Completed
• Conditions: Brain Injuries; Subarachnoid Hemorrhage
• Intervention / Treatment: Procedure: Cerebral perfusion pressure-targeted therapy; Procedure: Modified Lund concept

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Department of Neurosurgery, Clinical Centre University of Sarajevo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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]);
Active Comparator: Intracranial pressure-targeted therapy	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Sarajevo
• Investigators: Principal Investigator: Kemal Dizdarevic, MD, MSc, PhD, Department of Neurosurgery, Clinical Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: September 20, 2010
• First Submitted That Met QC Criteria: September 20, 2010
• First Posted (Estimate): September 21, 2010

Study Record Updates

• Last Update Posted (Estimate): September 21, 2010
• Last Update Submitted That Met QC Criteria: September 20, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: subarachnoid hemorrhage; intracranial pressure; traumatic brain injury; microdialysis; secondary brain ischemia; modified Lund concept; cerebral perfusion pressure
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Brain Ischemia; Ischemia; Brain Injuries; Hemorrhage; Subarachnoid Hemorrhage
• Other Study ID Numbers: 030531674