Presentation on theme: "Paul M. Vespa (Medical PI) Neil Martin (Surgical PI)"— Presentation transcript:
1Intraoperative CT guided Endoscopic Surgery for Intracerebral Hemorrhage (ICES) Paul M. Vespa (Medical PI)Neil Martin (Surgical PI)UCLA Department of Neurosurgery
2Outline Introductions of centers and investigators Overview of MISTIE and how ICES fits inDescribe Specific Aims of ICESReview preliminary dataDiscuss the surgical techniqueDescribe key steps in the studyDescribe processes for data aquistion, data submission, data analysis, safety analysis, investigator feedbackOutline the timelines for the study
3General plan for ICES-MISTIE partnership Modify MISTIE to a three arm, Phase 2 StudyStereotactic Thrombolysis, Endoscopic, and Medical ArmsMISTIE abandons 3 mg q 8 hr tier (20 subjects)ICES randomizes 3:1 those 20 subjectsICES studies safety, surgical technique development, training, center validationOutcome comparison using MISTIE and ICES controlsContinue tissue gene substudyPlanning for Phase 3 comparison trial
5The ICES centers UCLA: Neil Martin, Paul Vespa MGH: Bob Carter, Chris OgilvyPittsburgh: Amin Kassam, Johnathan EnghUVA: Neal KassellFairfax/Georgetown: Jim EcklundColumbia: Sander Connolley, Stefan MayerUCSF: Geoffrey Manley, Shirley StiverJefferson: Robert RosenwasserCase Western: Warren Selman
6Central Aim of ICESThe central aim of this study is to demonstrate that Intraoperative stereotactic CT-guided Endoscopic Surgery (ICES) is a feasible, safe, and technically effective treatment for patients with acute intracerebral hemorrhage.
7Aim 1Specific Aim 1: To determine that intraoperative stereotactic CT-guided endoscopic surgery results in an immediate reduction in hemorrhage volume by ≥ 66% in 80% of surgically treated patients and to determine strategic methods that ensure successful evacuation.Hypothesis 1: Surgical Technique1a. It will be feasible to use an image guidance method of planning the surgical trajectory that bisects the long axis of the hematoma and ends at the deepest portion of the hematoma, while avoiding eloquent cortex. A formal scoring system will be used to determine a trajectory score based on trajectory and depth.1b. The extent of hematoma volume reduction will be a function of the surgical trajectory score.1c. To determine the minimal suction pressure necessary to obtain maximal hematoma removal.Sub Aim 1: To determine if recurrent bleeding occurs within the immediate post-operative period.Hypothesis for Sub Aim 1: Recurrent bleeding will occur after 1 hour and before 24 hours after surgery.
8Aim 2Specific Aim 2: To determine that intraoperative stereotactic CT-guided endoscopic surgery has a similar safety and hematoma reduction profile as compared with the MISTIE technique.Hypothesis 2: Outcome Assessment and Comparisons of ICES to MISTIE2a. The percentage of hematoma reduction will be greater for the ICES procedure as compared with MISTIE at 1 hour after surgery.2b. The percentage of hematoma reduction will be greater for the ICES procedure as compared with MISTIE at 24 hours after surgery.2b. The percentage of rebleeding or other immediate surgical complication will be similar between ICES and MISTIE.2c. The mortality rate will be similar between ICES and MISTIE surgical arms.2d. The mortality rate in the surgical arms, ICES and MISTIE, will be lower than that of the medical control arm.2e. The rates of cerebritis and meningitis will be similar between the ICES and MISTIE surgical arms.
9Sub Aim 2Sub-Aim 2: To determine that intraoperative stereotactic CT-guided endoscopic surgery and MISTIE results in a reduction FLAIR positive edema surrounding the hematoma as compared with medical arm patients.Hypothesis for Sub-aim 2:2f. The presence of a perihematomal FLAIR positive edema will be less than that seen in medical arm patients.2g. There will be no new FLAIR positive tracts along the endoscopy or MISTIE trajectory.
10Aim 3Specific Aim 3: To develop a endoscopic registry that enables development of innovations in the endoscopic technique and compare the safety of these innovations with the standard endoscopic technique.Hypothesis for Aim 3: Modifications to the endoscopic technique will enable complete evacuation of the hematoma, including intraventricular blood.
11Preliminary Data for ICES at UCLA Single center data Phase 1: 10 randomized pts6 surgical and 4 medical controlsProductivity: 4 manuscriptsMiller et al: Image Guided Endoscopic Evacuation of Intracerebral Hemorrhage. Surgical Neurology 2008 May;69(5):441-6.Burgess et al: Development and validation of a simple conversion model for comparison of intracerebral hemorrhage volumes measured on CT and gradient echo MRI (in press)Carmichael et al: Genomic profiles of damage and protection in human intracerebral hemorrhage (submitted)
14Comparison Endoscopic Arm 80 ± 13 % reduction in ICH volume 20% Mortality1 patient with post-op rebleedMedical Arm72 ± 132 % growth in ICH volume50% mortality
15Genomic profiles of damage and protection in human intracerebral hemorrhage Carmichael et al, JCBFM 20081. Surgical tissue has high quality RNA for gene expression analysis.2. The gene expression differences between peri- hematomal tissue and control tissue are highly significant3. Bioinformatics analysis: Induction of molecular networks of inflammatory chemokine andcytokine signaling and counter-inflammatory networks: annexin and TGFb4. Hemorrhage induces a coordinated down regulation of NMDA receptor and downstream intracellular neuronal signaling pathwaysThis correlates with microdialysis data showing elevated extracellular glutamate in the brain surrounding the ICH (Miller et al 2007)Addresses mechanism of surgical success resulting from less excitotoxic edema
16Steps in the ICES protocol Initial Evaluation of patient with intracerebral hemorrhage in the emergency departmentInitial CT or MRI of the brainStereotactic CT scan performed ( 6 hour stabilization scan)Additional diagnostic testing based on clinical suspicion: Cerebral Angiogram or CTAInitial treatment with standard of neurocritical care for ICH (Broderick et al, 2007). Decision about placement of external ventricular drain will based on standard of care guidelines (ie intraventricular blood, hydrocephalus, suspected elevated intracranial pressure).Patient and family discussion, consent, and randomization into the study protocol.Preoperative planning using the Stereotactic CT scan that is registered into the image guidance systemICES Operation within 48 hours of bleed onsetNeurointensive care delivered as per standard of careOngoing study activities (imaging, neurologic scoring, etc) in the ICUStructured follow up exam and imagingImages and other data sent electronically to the Surgical Center for quality control and data analysis
18Surgical Technique Initial Screen and MRI Prepare for OR Stereotactic placement of burr holeStereotactic trajectory for endoscopeGraded Suction of hematoma at 2/3 and 1/3 depthHemostasisLeave catheter in cavityPost evacuation imaging
23Surgical Key Steps – 1 General anesthesia Formal time out Preliminary endoscopic trajectoryAvoid eloquent cortexPosition the patientApply stereotactic Guide and register the patientSimulation of trajectory using offsetTake Picture 1 (screenshot)
24Surgical Key Steps - 2 Scalp Incision and burr hole Examine cortical surfaceRegistration of endoscope sheathSimulation of endoscope sheath trajectoryUse OffsetTake Picture 2Insert endoscope sheath to desired depth – position 12/3 of hematoma depthTake picture 3 (no offset)Begin graded suction of hematoma50 mm Hg starting, 50 mm Hg increments
25Surgical Key Steps - 3Record volume of blood aspirated at each suction gradePull back endoscope sheath to position 21/3 depth of hematomaRepeat graded suction processStart at 50 mm Hg, 50 mm Hg incrementsRecord volume of blood aspirated at each suction grade at position 2
26Surgical Key Steps - 4 Use endoscope to visualize hematoma bed Perform hemostasisReview the volume of blood evacuatedVisually inspect cortical surfaceRemove the endoscope sheath and endoscopeInsert 3mm Ventricular catheter into hematoma bed to position 1 depthClose the surgical wound in standard fashionPlace catheter to drainage at +5 cm heightPerform post-evacuation scan