Neuro Protective Anesthesia During Cerebral Aneurysm Repair Jon JordanCRNA, MSNA Staff CRNA Providence Anesthesia
Objectives • Identify mechanisms of brain injury during intracranial aneurysm surgery. • Compare and contrast current therapeutic modalities used to reduce brain injury • Select an anesthetic plan utilizing medications and or therapies designed to reduce brain injury during cerebral aneurysm repair.
Neuronal injury and death • Early ischemic neuronal death is primarily caused by excitotoxicity. • Mitochondrial function lost • Delayed death is caused by apoptosis Cottrell, J. & Young, W. Neuroanesthesia (5th ed.).
Brain Ischemia • Global ischemia, cessation of blood flow for greater than 8 minutes. • Focal ischemia, contains three regions. 1st region receives no blood flow. 2nd Penumbra, receives collateral flow and is partially ischemic. 3rd Area surrounding penumbra that receives normal blood
Ischemia Induced Changes Vascular changes Neuronal changes • Red cell sludging • Hypoperfusion • Vasospasm • ATP reduction • Na+ influx, K+ efflux • Intracellular acidosis • High cellular Ca++ concentration • Ca++ activated proteases • Caspase activation • Free radical production • Excitatory amino acid release
Goals of Neuro protective Anesthesia • Maintain cerebral perfusion. • Utilize an anesthetic plan that prevents cerebral ischemia, limits excitotoxicity process • Reduce the risk of pre and intra operative rupture. • Facilitate surgical exposure ( relax the brain). • Minimize reperfusion injury. • Plan for prompt awakening to facilitate neurological exam (good grade SAH only)
Cerebral Blood flow • 20%-25% of cardiac output goes to the brain • Circle of Willis is primary collateral blow flow pathway. • Complete circle with well developed collaterals present in only 18%-20% of population. • Deliberate hypertension , 30%-40% above baseline is indicated in acute arterial occlusion or vasospasm. • Szabo and Colleagues concluded increases in BP upon induction of up to 37% above baseline did not cause AVM rupture, (MAP 118 + 7mmHg)
SAH Grading Assessments Grades Criteria • Hunt and Hess, a modification of Botterells original grading system. • Grading of SAH • Most commonly used system. • Evaluates LOC comparatively to degree of SAH and operative risk 0 Unruptured aneurysm • Asymptomatic or slight HA or slight nuchal rigidty • Moderate to severe HA, nuchal rigidity. No neuro deficit other than cranial nerve palsy. • Drowsiness, conusion, or mild focal deficits. • Stupor, mild or severe hemiparesis, possible early decerebrate rigidity, vegetative disturbance. • Deep coma, decerebrate rigidity, moribund appearance Pong,R. Lam, A. Cottrell and Young’s Neuroanesthesia 2010
57 yo Female A 57 yo female presents to the ED with a c/o of recent onset of headache along with visual changes. An angio CT performed demonstrates no embolic or hemorrhagic stroke ; yet displays a 5mm cerebral aneurysm in the anterior circulation, Hunt Hess grade o. The question now becomes do we prepare to coil or clip, and what are the differences?
Coiling or Clipping • Clipping • Coiling
Coiling means a trip to INR • Can we safely administer general anesthesia outside of the operating room. • Need for invasive monitoring remains the same. • Now were going to introduce medications that can definitely effect neuro protection. a. Systemic heparinization / reverasal. b. Contrast media (anaphylactoid reaction) c. Need for neuro muscular blockade d. Need for rapid reversal and emergence for detailed exam .
Communication with the Surgeon Unruptured Aneurysm Ruptured Aneurysm with SAH • Baseline Neuro exam • Where is the aneurysm located? • How large is it? • Difficulty of surgical exposure? • Will temporary clips be used, if so how long is anticipated clip time? • Baseline Neuro exam. • Onset time of injury? • Clinical grading of SAH. • Size and location of aneurysm? • Stability of the patient for surgery? • Assessment of other confounding co-morbidities
Maintaining Autoregulation • Aneurysm with SAH presents an impairment in autoregulation and a rightward shift in the lower limit of autoregulation. • Grade of SAH correlates directly with degree of autoregulatory impairment. • Degree of autoregulation impairment closely correlates with incidence of vasospasm. • May result in delayed ischemic injury and deficits.
Autoregulation • MAP of 50-60/150-160 mmHg • Negated by hypercapnia, arterial hypoxemia and the use of volatile anesthetic gases. • Also attenuated in the area surrounding an acute cerebral infarction as vessels are typically maximally vasodilated
Timing of Surgery • International Cooperative study on the timing of aneurysm surgery (1990) • Same day as SAH found 50% of brains to be tight. • Only 20% found to be tight after 10 days. • North American results showed outcomes were best when surgery performed within 3 days, differing for overall results which showed no difference between early or late surgery.
Reperfusion Injury • Occurs when perfusion is restored to previously ischemic tissue areas. • Reduced perfusion to area due to neutrophil adhesion on vascular endothelium. • Free oxygen radicals are formed which react with polyunsaturated fatty acid disrupting cell membranes • Formation of free radicals is associated with both apoptosis and necrotic cell death. • May be mitigated by NMDA antagonists as well as NOS inhibitors.
Perioperative Monitoring • Standard anesthetic monitoring including twitch monitor. • Intra arterial pressure monitoring. Level transducer to base of skull. • Two large bore 14ga – 16ga IV catheters • Consider triple lumen or Cordis placement. • Uses of jugular bulb oxygen saturation remains investigative. • Trans cranial doppler use currently remains impractical.
Patient Positioning • Anterior circulation aneurysms, patient supine for a frontal temporal incision. • Basilar tip aneurysms, lateral position for a subtemporal incision. • Vertebral or Basilar aneurysm, seated or park bench position for suboccipital incision.
Patient Positioning • Ensure alignment of the neck to promote adequate venous drainage. • Once positioned palpate the neck to ensure no venous obstruction. • Venous outflow obstruction will cause the brain to remain tight
Induction • Induction is a critical time period. • 7% incidence of rupture during induction of anesthesia. • Potential unstable hemodynamics. • Blunting sympathetic responses to laryngoscopy or other painful stimulation is essential. • Goal is to maintain current hemodynamics if they are stable.
Pharmacology of Cerebral Protection Induction / Maintenance Adjunctive neuro protectants • Thiopental • Propofol • Fentanyl, Sufentanil, remifentanyl • Etomidate • Ativan vs. Midazolam • Rocuronium,vecuronium, vsatracurium, cisatracurium • Magnesium sulfate • Methylene Blue • Anti epileptic drugs • Mannitol • Steroids • Free radical scavengers • Antioxidants
Benzodiazepines • Decrease CMRO2, CBF and minimal change in ICP. • Preserved autoregulation. • Potent anticonvulsants. • May cause respiratory depression leading to hypercapnia and elevated ICP • Diazepam; t 1/2 21 – 37 hrs. To long for quick wakeup. • Lorazepam; t ½ 10 – 20 hrs. Again to long for quick wakeup and exam • Midazolam; t ½ 1 – 4 hrs. May have similar protective effects against hypoxia or cerebral ischemia similar to barbiturates.
Thiopental • One of few drugs shown to be protective against ischemic damage in humans • Cerebral vasoconstrictor, reduces CMRO2 and CBF. • Reduced CMRO2 ( 55% - 60%) is primary mechanism of protection. • Blocks Na+, K+ and Ca++ fluxes, free radical scavenger, decreases ICP • May cause inverse steal. • National shortage.
Propofol • Cerebrovascular profile much like barbiturates • Decreases CMRO2, CBF and ICP. Autoregulation remains intact. • Chemically similar to phenol based free radical scavengers • Potent antioxidant properties • Prevents lipid peroxidation • Protective against oxidative stress, hypo energy metabolism and free radical mediated injury
Etomidate • Cerebral vasoconstrictor, reduces CBF, ICP and CMRO2 35% -45%. • Autoregulation is preserved. • May activate seizure foci. • Can cause cerebral desaturation with induction doses. • Burst suppression with High doses.
Lidocaine • Dose related reduction in CMRO2 and CBF • Low dose possess anticonvulsant activities. • Dose with induction augments the sedative effects of propofol. • May further reduce incidence of ischema related damage when given at clinical doses (1.5mg/kg) following burst suppressive doses of barbiturates or propofol. (reduces CMRO2 by 15% -20%) • High doses result in seizure activity
Narcotics • Fentanyl. Decreases ICP and cerebral blood volume with no effect on perfusion pressure. No histamine release • Sufentanil. May cause vasodilitation which will increase cerebral blood volume and ICP. Not the best choice • Remifentanil. Ultra short acting, much like fentanyl in its ability to decrease ICP and CBV with no effect on CPP. May be best when quick wake up is needed for neuro exam
Dexmedetomidine • Produces decrease in sympathetic activity by inhibiting norepinephrine release. • Excess catecholamine levels correlate with increased ischemic neuronal damage. • Decreases CBF with little or no change in CMRO2. • Can be used in conjunction with volatile agents or as part of TIVA.
NeurmuscularBlockaide Vecuronium, Little to no change in CBF, ICP or CMRO2. No histamine release. Rocuronium. Much like vecuronium. Rapid onset at higher doses make it more preferable to succinylcholine for rapid sequence induction. Atracurium. No significant effect on CBF, CMRO2 or ICP. High doses may cayse histamine release. Cisatracurium. Near similar or weaker effects than atracurium with less histamine release
Hyperventilation • CBF has near linear relationship with arterial PaCO2 when between 20-80 mmHg. • CBF is altered 2-3% for every 1 mmHg change in PaCO2 or 1-2ml/100g/min. • CBV will change approximately 1% for every 1 mmHg change in PaCO2 • Reducing PaCO2 causing cerebral vasoconstriction, reducing brain volume.
Hyperventilation • Excessive hyperventilation may lead to excessive vasoconstriction causing further brain ischemia. • Vasoconstriction resulting in reduced brain tension may cause an unruptured aneurysm to rupture. • Hyperventilation should be limited to a paCO2 of 25 – 35 while the dura is open. • A slow return to normal CO2
Mannitol • Osmotic diuretic, dose of 0.25 – 1 gram/kg. • Should be administered once the bone flap is removed over 15 minutes. • Biphasic effect as initial increase in plasma osmolality will cause cerebral vasodilitation. • May cause transient shift in serum electrolytes as intravascular volume increase. (increase in serum K+, decrease in Na+). • Free radical scavenger.
Choice of Volatile Agents • Isoflurane (0.5% - 1%). Minimal increase in CBF. Dose dependent loss of autoregulation. • Desflurane (4% - 6%). Much like Isoflurane. Low blood gas solubility, high concentration may cause undesirable sympathetic stimulation. Sevoflurane Unique property over other volatile agents in that autoregulation remains preserved at all concentrations.
IV Fluid and Blood Viscosity Crystalloids • 0.9 normal saline • Lactated Ringers Colloids • 5% Albumin. SAFE trial revealed increased mortality in patients resuscitated with albumin. • Component of triple H therapy. • Reduced blood viscosity reduces cerebral vascular resistance. • Initial goals of 33% Hct due to concern for reduced oxygen carrying capacity. • Due to increased morbidity mortality associated with transfusion an Hct of 27 – 30% could be tolerated.
Magnesium Sulfate • Essential element in over 300 enzyme systems • Long known vasodilatory properties make peri-operative use in neuro surgery questionable. • Post operative use indicated for treatment of reperfusion injury associated with vasoconstriction. • Meta-analysis by Wong et al in2011 on use of Magnesium sulfate in patients with Subarachnoid hemorrhage and delayed cerebral infarction (DCI). • Six studies, 875 patients, Result was no beneficial effect of magnesium sulfate infusion on DCI Wong et al. Critical Care 2011
Methylene Blue • Autoxidizable phenothiazine with potent antioxidant properties. • Easily crosses the blood brain barrier. • Animal models have demonstrated the neuroprotective effects of MB not only as an antioxidant but also by triggering functional network changes in brain metabolism. • A potential valuable tool for reducing oxidative stress and energy hypometabolism (Rojas, J. Simola, N. Kermath, B. et al. Journal of Neuroscience. 2009
Hypothermia • Mild hypothermia, temp 33c to 35 • Reduces CMRO2by 7% for each degree of change • Nasopharyngeal temperature may best correlate to actual brain temperature. • Deep hypothermia (13c – 21c) in conjunction with circulatory arrest may be indicated for clipping of basilar or giant aneurysms
IHAST • Mild Intraoperative Hypothermia during Surgery for Intracranial Aneurysm Trial(IHAST) 2005. • 30 participating centers with 2856 surgeries for SAH. • 1001 patients with good grade (WFNS) score of I II or III and SAH no more than 14 days prior to surgery. • Intraoperative (hypothermia target temp of 33c) or normothermia (target temp of 36.5c). • Pt’s evaluated at POD 90 using Glasgow Outcome scale, Rankin Scale, Barthel Index and NIH Stroke scale.
IHAST Results • No significant difference in ICU Length of stay, hospitalization, death rates 6% or discharge destination. • Hypothermia 66% compared to Normothermia 63% had a Glasgow Outcome score of 1. odds ratio 1.14; 95%CI P=0.32. • Hypothermia showed no improvement in outcomes in patients undergoing craniotomy for good grade SAH. • Increased incidence of Bacteremia in hypothermia group • Results further validated in Cochran Reviews meta analysis published in 2012.
Prior to Clip Placement • Check BP, ETCO2 and twitch monitor. • The dura is open, hyperventilation and ETCO2 should be optimal. • Normotension should be the absolute lower limit unless otherwise indicated (acute rupture). • Patient coughing or movement could catastrophic. Re paralyze prior to manipulation. • Plan for disaster i.e. acute rupture. Need to lower MAP ASAP. Be prepared to reduce cardiac output, nitrate based vasodilators are not the best choice.
Cerebral Vasospasm • Structural and pathological changes within the vessel intima. • Swelling and necrosis of smooth muscle. • Hypothesized that vasoactive substances found in the blood in the cisterns induce changes. • Currently thought to be oxyhemoglobin, deoxyhemoglobin in conjunction with endothelium derived relaxing factor or nitric oxide.
Cerebral Vasospasm • Accounts for 13.5% of major morbidity and mortality. • Incidence and severity correlate to amount of blood found in basal cisterns • 40-60% occurrence rate by cerebral angiography. • Clinically significant vasospasms occur in only 20-30% of patients. • Angiographically detectable vasospasm is usually not detected until at least 72 hours after SAH, peaks at 7 days and usually not seen after two weeks • 50% of patients who develop significant vasospasm will die or develop serious neurological deficits.
Putting it all together • No definitive solution. • Know what you have to work with before you start. • Work to preserve autoregulation. • Antioxidant therapy • Tight control of BP. • Avoid histamine releasing drugs or therapies • Prepare for the worst case scenario
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