give lorazepam Page 1 UC SF First known description of status epilepticus (Sakikku cuneiform, ca. 700 B.C) NEUROCRITICAL CARE PROGRAM

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1 Update on Neurocritical Care J. Claude Hemphill III, MD, MAS Special Thanks to: Jan Claassen, MD, PhD Division of Critical Care Neurology Columbia University Disclosures Research Support: NIH/NINDS Stock options: Ornim Kenneth Rainin Chair in Neurocritical Care Associate Professor of Clinical Neurology and Neurological Surgery University of California, San Francisco Director, Neurocritical Care San Francisco General Hospital UC SF NEUROCRITICAL CARE PROGRAM First known description of status epilepticus (Sakikku cuneiform, ca. 700 B.C) give lorazepam Slide courtesy of Tom Bleck, MD Neurocritical Care Highlights Neuromonitoring in NICU Advanced Neuromonitoring for Secondary Brain Injury Nonconvulsive seizures in the neurocritical care unit Treating Global Cerebral Ischemia (GCI) Monitoring of neurologic function in patients at high risk for Primary brain injury from procedure or condition Secondary brain injury after a prior neurologic insult The primary focus of Neurocritical Care for CNS problems is the prevention, identification, and treatment of secondary brain injury. Page 1

2 Categories of Neuromonitors Intracranial Monitors - location Clinical Clinical Neurologic examination Physiologic Pressure - ICP, BP Flow - CBF, TCD Electrical - EEG, EP Metabolic Metabolic Oxygen Metabolites - glucose, lactate, EAAs Hemphill JC and Smith WS. Harrison s Principles of Internal Medicine (17 th ed), 2008 Oxygen Equations Tissue PO 2 Monitoring C O2 = 1.34 x Hgb x O 2 sat x PO 2 O 2 delivery = Ca O2 x CBF AVDO 2 CMRO 2 O 2 ER = Ca O2 - Cv Cv O2 = AVDO 2 x CBF Normal Values CBF 54 ml/100gm/min AVDO ml/dl CMRO ml/100gm/min O 2 ER 35% SjVO 2 62% = O 2 consumption = AVDO 2 = SaO 2 - SvO 2 O 2 delivery CaO 2 SaO 2 Direct measurement of tissue oxygen tension P bt O 2 (P ti O 2 ) Local measurement Part of ICP-bolt system Experimental use in Europe since 1992 Approved for use in Europe, Canada, and US (6 yrs) Tissue PO 2 as direct measure of oxygen metabolism? Page 2

3 UCSF P bt O 2 Monitoring Cerebral Microdialysis Blood capillary Cell Extracellular fluid Microdialysis catheter Glucose Lactate Pyruvate Glycerol Glutamate Urea Cerebral Blood Flow Effects of Hyperventilation on P bt O 2 Thermal Diffusion Flowmetry - TDF 60 - Less than 1 mm diameter flexible probe mm Hg P bt O 2 L/P L/P=lactate/pyruvate ratio Minutes Secondary Ischemia identified by advanced neuromonitoring Page 3

4 FDA Approved Advanced Neuromonitoring Devices Licox Brain Tissue Monitor PO 2, Temp (now in single probe) Integra Neurosciences Thermal-diffusion Perfusion Monitor Quantitative cerebral blood flow Hemedex Microdialysis Lactate, pyruvate, glutamate, other substances CMA Current Approach at SFGH All patients with ICP monitor get P bt O 2, S j VO 2, CBF (if available) Selective use of ceeg Start with standardized orders CPP > 60, ICP < 20, P bt O 2 > 15, S j VO 2 > 60% Test autoregulation (usually daily) and adjust CPP goal accordingly Metabolic monitors as early warning signs Guides to optimal front-end parameters (e.g. BP, ICP, CPP, ETCO 2 Not currently using oxygen directed therapy if other parameters are acceptable Continuous EEG: Surface and Depth Jan Claassen, MD, PhD Assistant Professor of Neurology Division of Critical Care Neurology Columbia University College of Physicians & Surgeons New York, NY Continuous EEG monitoring The technique: prolonged (hrs, days or wks) of continuously recorded digital EEG in critically ill patients Potential applications Ictal activity Ischemia or hypoxia Prognostication Endpoint for treatment Multimodality brain monitoring Controversial EEG patterns Artifacts Page 4

5 Epidemiology Convulsive SE: cases per persons Shorvon 2000 NCSZ or NCSE: unknown. No population based studies! Neuro ICU prevalence: NCSz 18% to 34% NCSE 10% Jordan JCN 1993; Pandian ArchNeurol 2004; Claassen Neurol 2004 ER: 37% of 198 patients undergoing urgent EEG for altered MS Privitera EpilRes 1994 NCSZ Predictors 1. Coma: 56% of comatose pts vs. 12% 2. Young age: 36% of pts <18 yo vs. 17% of pts > Epilepsy in the past medical history: 41% vs. 16%, or remote risk factors for szs 4. Convulsive seizures prior to monitoring: 43% of pts with vs. 12% 5. Periodic discharges (PLEDs or GPEDs) or Suppression-burst 6. Oculomotor abnl s: nystag, hippus or eye deviation 7. Cardiac or respiratory arrest 8. Sepsis Varelas Neurol 2003; Husain JNNP 2003, Claassen Neurol 2004; Oddo CCM 2009 CEEG findings in 570 patients N NCS Epilepsy-related seizures 51 31% CNS infection 35 26% Brain tumor 43 23% Post neurosurgery 13 23% Toxic-metabolic encephalopathy 38 21% Subarachnoid hemorrhage % Traumatic brain injury 51 18% Hypoxic-ischemic encephalopathy 25 16% Unexplained decrease in LOC % Intracerebral hemorrhage 45 13% Ischemic stroke 56 9% Claassen Neurol 2004 CEEG to guide titration of medications Is a routine EEG enough? N=105 Routine EEG (>= 30 mins) cdveeg (mean 2.9 d) Clin events EEG szs 21% 11% 40% 27% P Pandian ArchNeurol 2004 Time to record the first seizure Claassen Neurol 2004 Continuous IV AEDs esp. refractory status epilepticus PTB gtt for ICP management (goal suppression-burst) Potential: titrate HHT in vasospasm treatment I do not believe that one can treat refractory status epilepticus without continuous EEG monitoring any more than one would treat complex cardiac arrhythmias without electrocardiographic monitoring. Bleck ArchNeurol 2002 Page 5

6 Surface EEG and ICE as part of invasive multimodality brain monitoring? Licox-monitor: PBtO2, ICP/CPP (brain temp) EVD: ICP/CPP SJVO2 Hemedex: brain perfusion Microdialysis: lac, pyr, gluc, glut, glyc, Scalp electrodes: 21 disc or needle electrodes ICE: eight-contact Spencer intracortical Electrode (AD-Tech, Racine, WI) EVD with 12 EEG recording electrodes Surface EEG and Microdialysis: 31 yo man with encephalitis and refractory status epilepticus on PTB gtt Kurtz CurrOpCCM 2009 ICE vs. surface EEG: improved signal-to-noise ratio 20 yo woman with TBI shivering on hypothermia ICE vs. surface EEG: unmasks seizures not seen on the scalp 74 yo woman with SAH (HH grade III) Waziri AnnNeurol 2009 Waziri AnnNeurol 2009 Page 6

7 Conclusions Majority of ICU seizures clinically not detected Crucial after GCSE or RSE NCSE/NCSz are frequent with or without acute brain injury, significance needs to be determined Great promise for ischemia Many questions unanswered: ictal interictal continuum, treatment of NCSZ, role in multimodality Future: real-time seizure detection may become feasible (neurotelemetry) Treatment one day may be directed to multimodality parameters in comatose ICU patients Cardiac Arrest 62 yo man collapsed suddenly at the San Francisco Giants baseball game Bystander CPR done for 10 minutes Automated external debrillator (AED) used 911 emergency medical service called Paramedics arrived Initial rhythm v fib Shocked into sinus rhythm Total time to ROSC (return of spontaneous circulation) 14 minutes Arrived at hospital 35 minutes after start of cardiac arrest Heart rate 85 sinus rhythm; Blood pressure 134/68 Not awake Treating post-arrest global cerebral ischemia Old way Wait 3 days and prognosticate Levy criteria JAMA, 1985 New way Mild hypothermia (neuroprotection) Page 7

8 Hypothermia clinical trials European study NEJM 2002; 346: V fib arrest; still comatose after resuscitation 24 hours of external cooling (special mattress) 33 0 C 6 month outcome (NNT=number needed to treat=6)» Hypothermia 55%» Normothermia 39% (RR 1.4 { }) 1.81}) Australian study NEJM 2002; 346: V fib arrest; still comatose after resuscitation 12 hours of surface cooling; often started prehospital Outcome at hospital discharge (NNT=4)» Hypothermia 49%» Normothermia 26% (P=0.046) 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Unconscious adult patients with return of spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32 C to 34 C (89.6 F to 93.2 F) for 12 to 24 hours when the initial rhythm was ventricular fibrillation (Class IIa). Lost in Translation? Abella, B. et al. Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey. Resuscitation 64 (2005) Similar therapy may be beneficial for patients with non-vf arrest out of hospital or for in-hospital arrest (Class IIb). Who s responsible? Neurologist? Cardiologist? Intensivist? Emergency Physician? Circulation November 28, 2005 Breakdown of multidisciplinary system, with patient caught in the middle. Neurocritical care and everyone is responsible. Page 8

9 Cooling after Cardiac Arrest Evidence-based Neurocritical Care? Hypothermia as neuroprotective Perfusion has been restored to brain Many methods Surface blankets Endovascular Cold saline You need a protocol Intensive-care medicine has become the art of managing extreme complexity. Atul Gawande So what makes a difference in neurocritical care patient outcomes? Traditional focus Did the drug improve outcome in a large clinical trial? Did patients who have the procedure have better outcome? Emerging focus Expertise matters Face validity you want the best surgeon Pronovost, JAMA,, 2002 systematic review of 26 studies Presence of intensivist ass. w/ better outcomes Only 1 neuroicu studied Dramatic Variability Across Hospitals Neurocritical Care Improves Outcome SAH Bardach NS, Zhao S, Gress DR, Lawton MT, Johnston SC. Association between subarachnoid hemorrhage outcomes and number of cases treated at California hospitals. Stroke. 2002;33: Cardiac Arrest Carr BG, Kahn JM, Merchant RM et al. Inter-hospital variability in post-cardiac arrest mortality. Resuscitation 2009;80: ICH Hemphill JC, 3rd, Newman J, Zhao S, Johnston SC. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke. 2004;35(5): Head Trauma Trooskin SZ, Copes WS, Bain LW, Peitzman AB, Cooney RN, Jubelirer RA. Variability in trauma center outcomes for patients with moderate intracranial injury. J Trauma. 2004;57(5): Diringer MN, Edwards DF. Admission to a neurologic/neurosurgical intensive care unit is associated with reduced mortality rate after intracerebral hemorrhage. Crit Care Med. Mar 2001;29(3): Suarez JI, Zaidat OO, Suri MF, et al. Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team. Crit Care Med. Nov 2004;32(11): Varelas P, Eastwood D, Yun H, et al. Impact of a neurointensivist on outcomes in patients with head trauma treated in a neurosciences intensive care unit. J Neurosurg. 2006;104: Varelas PN, Schultz L, Conti M, Spanaki M, Genarrelli T, Hacein-Bey L. The impact of a neuro-intensivist on patients with stroke admitted to a neurosciences intensive care unit. Neurocrit Care. 2008;9(3): Josephson SA, Douglas VC, Lawton MT, English JD, Smith WS, Ko NU. Improvement in intensive care unit outcomes in patients with subarachnoid hemorrhage after initiation of neurointensivist co-management. J Neurosurg Page 9

10 Update on Neurocritical Care Concepts of neuromonitoring for secondary brain injury Relevant to TBI and stroke (ischemic/ich/sah) New approaches to monitoring oxygen delivery and metabolism Incidence and importance of non-convulsive seizures in the neurocritical care unit Detection through ceeg (continuous EEG) Intracortical electrodes as part of advanced neuromonitoring paradigm Neuroprotection works Global cerebral ischemia cool that brain Part of regular care today Expertise Matters UCSF Stroke and Neurocritical Care Neurocritical Care Wade Smith, MD,PhD Nerissa Ko, MD Vineeta Singh, MD J. Claude Hemphill III, MD,MAS Vascular Neurology Clay Johnston, MD,PhD Mai Nguyen-Huynh, MD Anthony Kim, MD Sharon Poisson, MD Neurohospitalist Program Andy Josephson, MD Vanja Douglas, MD Cerebrovascular Neurosurgery Michael Lawton, MD Neurointerventional Radiology Chris Dowd, MD Van Halbach, MD Randy Higashida, MD Steven Hetts, MD Joey English, MD,PhD SFGH Neurosurgery Geoffrey Manley, MD,PhD Shirley Stiver, MD,PhD NIH K23NS041240, NIH U10NS058931, UC Discovery Program Page 10