Therapeutic Hypothermia: 2011 Research Update Richard R. Riker MD, FCCM Chest Medicine Associates South Portland, Maine
Agenda NMBA, Sedation, and Shivering Seizures Prognostication Early = Staging Late = Care decisions
Sedation and Analgesia HACA: midazolam 0.125 mkh (10), Fentanyl 2 ukh (160) (adjusted), pancuronium q2 h NEJM 2002; 346: 549 Bernard: small doses midazolam + vecuronium NEJM 2002; 346: 557 Oddo: midazolam 0.1 mkh (8), Fentanyl 1.5 ukh (120), vecuronium Crit Care Med 2006; 34: 1865 Busch: fentanyl, midazolam, cistracurium Acta Anaesth Scand 2006; 50: 1277
Chamorro. Anesth Analg 2010; 110:1328 35
Sedation and Analgesia Most centers use continuous or intermittent NMB 18-36% awareness of NMB in ICU studies Kaplan. Critical Care 2000; 4:S110 Wagner. Pharmacotherapy 1998 18:358 MMC protocol for BIS monitoring during NMB Usual target for BIS NMBA = 40-60 Hypothermia lowers BIS values 1.1 units per ºC Mathew. J Clin Anaesth 2001; 13:301 MMC target BIS during TH and NMB = <50 Use the BIS value AFTER NMB if intermittent
Sedation and Analgesia Is deeper sedation an important part of TH? Seizure prevention or treatment Reduce O2 metabolism Does deeper sedation just confound prognosis?
Sedation-Agitation Scale 7 Dangerous agitation 6 Very agitated 5 Agitated 4 Calm and cooperative 3 Sedated 2 Very sedated 1 Unarousable Riker. Crit Care Med 1999; 27:1325
Sedation-Agitation Scale 3 Sedated Awakens to loud verbal stimuli or gentle shaking but drifts off again, follows simple commands 2 Very sedated Arouses to physical stimuli but does not communicate or follow commands, may move spontaneously 1 Unarousable Minimal or no response to noxious stimuli, does not communicate or follow commands Riker. Crit Care Med 1999; 27:1325
Use of BIS Monitoring TH Adequate sedation during NMBA Recognition of awake patient Recognition of shivering Recognition of seizures Very Early Prognostication
100 90 80 70 60 50 40 30 20 10 0 #22 BIS or EMG 16:17 16:41 17:05 17:29 17:53 18:17 18:41 19:05 19:29 19:53 20:17 20:41 21:05 21:29 21:53 22:17 22:41 23:06 23:30 23:54 S BIS 84-27 EMG 48-27 Temp 33.2 AVGBIS AVGEMG S BIS 71-42 EMG 43-26 Temp 33.0
Shivering Progresses cephalad to caudad, more intense as extremities and large muscle groups involved Shivering Severity Index Validated by EMG and metabolic cart 1. prodrome - masseter humming fasciculations 2. facial / neck shivering visible teeth chatter 3. chest / trunk visible and palpable shivering 4. extremities total body shaking - rigors Holtzclaw. AACN Clin Issues 2004; 15:267
Shivering- BSAS Holtzclaw Shivering Severity Index 1. prodrome - masseter humming fasciculations 2. facial / neck shivering visible teeth chatter 3. chest / trunk visible and palpable shivering 4. extremities total body shaking - rigors Badjatia. Stroke 2008; 39:3247
100 90 80 70 60 50 40 30 20 10 0 TH 008 Sept 2005 12:57 13:52 14:47 15:42 16:37 17:32 18:27 19:22 20:17 21:12 22:07 23:02 23:57 0:53 1:48 2:43 3:38 4:33 5:28 8:45 9:40 S BIS 92-4 EMG 56-28 Temp 36.6 AVGBIS AVGEMG BIS 76-8 EMG 38-28 Temp 32.5 S S BIS 89-12 EMG 45-28 Temp 32.2 GB GB
#15 0 10 20 30 40 50 60 70 80 90 100 14:24:00 14:41:00 14:58:00 15:15:00 15:32:00 15:49:00 16:06:00 16:23:00 16:40:00 16:57:00 17:14:00 17:31:00 17:48:00 18:05:00 18:22:00 18:39:00 18:56:00 19:13:00 19:30:00 19:47:00 20:04:00 20:21:00 20:38:00 20:55:00 21:12:00 21:29:00 21:46:00 22:03:00 22:20:00 22:37:00 22:54:00 23:11:00 23:28:00 23:45:00 time BIS 20 30 40 50 60 70 80 EMG AVGBIS AVGSR SQI/10 AVGEMG
Recognizing Shivering Hourly documentation BSAS BSAS when NMBA dosed Low water temp on Arctic Sun = thermogenesis High EMG signal on BIS monitor Confounders Myoclonus Seizures Posturing
EMG on BIS as Shiver Detector May. Resuscitation 2011 (in press)
EMG on BIS as Shiver Detector May. Resuscitation 2011 (in press)
EMG on BIS as Shiver Detector May. Resuscitation 2011 (in press)
Agenda NMBA, Sedation, and Shivering Seizures Prognostication Early = Staging Late = Care decisions
Seizures Hard to differentiate from shivering, myoclonus High incidence of non-convulsive status SOFT marker of poor outcome Don t know how best to treat Don t know if can treat, or if changes outcome ceeg routinely apply during daytime Watch closely during rewarming Fosphenytoin - levetiracetam Case reports of delayed awakening with status
Seizures 19 children TH after CA with ceeg monitor during hypothermia (24 h), rewarming (12 24 h), and additional 24 hours of normothermia Electrographic seizures in 47% (9/19), and 32% (6/19) developed status epilepticus Seizures were nonconvulsive in 67% (6/9) and electrographically generalized in 78% (7/9) Seizures commenced in late hypothermic or rewarming periods (8/9) Electrographic seizures and status epilepticus are common, often not detectable clinically Abend. Neurology 2009;72:1931
Seizures 10 (53%) with no Sz 9 (47%) Sz/SE Abend. Neurology 2009;72:1931
Seizures 70 ICU / EMU pts at high risk of seizures were recorded simultaneously for >24 h with a 4-channel bedside monitoring system (Datex-Ohmeda) with a subhairline montage and a standard EEG machine (XLTEK) using the 10-20 system standard electrode placement Recordings were interpreted independently 4-channel recordings had a sensitivity of 68% and 98% specificity for seizure detection sensitivity of 39% and specificity of 92% for detection of spikes and PLEDs The 4-channel EEG = limited, practical usefulness for seizure detection when ceeg monitoring not available Young GB. Neurocritical Care 2009;11:416-9
Agenda NMBA, Sedation, and Shivering Seizures Prognostication Early = Staging Late = Care decisions
Cerebral Performance Category 1. Good Cerebral Performance Conscious: Alert, able to work and lead a normal life. May have minor psychological or neurological deficits (mild dysphasia, nonincapacitating hemiparesis, or minor cranial nerve abnormalities) 2. Moderate Cerebral Disability Conscious. Sufficient cerebral function for part-time work in sheltered environment or independent activities of daily life (dressing, traveling by public transportation, and preparing food). May have hemiplegia, seizures, ataxia, dsysarthria, dysphasia, or permanent memory or mental changes 3. Severe Cerebral Disability Conscious. Dependent on others for daily support because of impaired brain function (in an institution or at home with exceptional family effort). At least limited cognition. Includes a wide range of cerebral abnormalities from ambulatory with severe memory disturbance or dementia precluding independent existence to paralytic and able to communicate only with eyes, as in the locked-in syndrome 4. Coma, Vegetative State Not conscious. Unaware of surroundings, no cognition. No verbal or psychological interactions with environment 5. Death - Certified brain dead or dead by traditional criteria. Booth. JAMA 2004; 291:870
Accuracy for Coma Prognosis PRE-TH Booth. JAMA 2004; 291:870
Wijdicks. Neurology 2006; 67:203
Caution With Wijdicks AAN Criteria Myoclonus status D1 (FPR 0-8%) Morris J Neurol Neurosurg Psych 1998; 64:267-8 3 cases with myoclonic seizures early made good recovery Absent or extensor motor response after D3 (FPR 0-6%) 1 st proposed Levy 1985 JAMA Predicting Outcome from H-I Coma Thenayan Neurology 2008; 71:1535-7 2 of 14 GCS M1 or 2 regained awareness 14% (0-33% 95% CI)
Neurology Consultation and TH Late consult for outcome prediction No definitive prognostication until 72 hours AFTER REWARMING CA 24h TH 12h RW 24h 48h 72 h 1 2 3 Outcome Prediction ceeg
Very Early Outcome Predictor P P
Very Early Outcome Predictor Would allow more aggressive therapy for the 50% with a poor outcome despite 24 hours at 33 C Would allow cardiologists to stratify invasive Rx No good early predictors exist Time to ROSC Age Initial Rhythm VT/VF vs other EEG as an early predictor in animal models
BIS1 vs Good Outcome (CPC 1-2) TH 123 100 BIS 86-44 EMG 51-26 SR 0-1 Temp 34.6 BIS EMG SR 90 80 70 60 50 40 30 20 10 0 21:41 10:07 11:44 13:21 14:58 16:35 18:12 19:49 21:26 23:03 0:40 2:17 3:54 5:31 7:08 8:45 10:22 11:59 13:36 15:13 16:50 18:27 20:04 Time BIS, EMG, SR
BIS1 vs Poor Outcome (CPC 3-5) TH 129 100 90 80 70 60 50 40 30 20 10 0 21:27 23:06 0:45 2:24 4:03 5:42 7:22 9:01 10:40 12:19 13:58 15:37 17:16 18:55 20:38 22:17 23:56 1:35 3:14 4:53 6:32 8:11 9:50 BIS 88-9 EMG 43-27 SR 0-95 Temp 36.5 BIS EMG SR BIS, EMG, SR Time
BIS1 Predicts Outcome Seder. Intensive Care Med 2010; 36(2):281-8
BIS1 Predicts Outcome Seder. Intensive Care Med 2010; 36(2):281-8
% Good Outcome* by BIS1 Decile * Based on best CPC during hospitalization 34-38 39-41 44-63 BIS range for decile (median) 28-32 % Good outcome by decile 18-26 7-13 14-17 0-1 2-4 5-6 Seder. Intensive Care Med 2010; 36(2):281-8