Download PDF
Semin Neurol 2011; 31(2): 216-225
DOI: 10.1055/s-0031-1277991
© Thieme Medical Publishers

Post-Cardiac Arrest Encephalopathy

Wei Xiong1 , Robert E. Hoesch2 , Romergryko G. Geocadin1
  • 1Department of Neurology, Department of Neurosurgery, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Neurosciences Critical Care; Department of Neurology, University of Utah School of Medicine, Clinical Neurosciences Center, Salt Lake City, Utah
Further Information

Publication History

Publication Date:
17 May 2011 (online)

    Permissions and Reprints

ABSTRACT

Brain injury continues to be a leading cause of mortality and morbidity in patients resuscitated after cardiac arrest. During periods of hypoxia and ischemia, numerous mechanisms contribute to the initial and secondary injury of the brain. Though many drugs and therapies have been evaluated for neuroprotection, only therapeutic hypothermia has been proven to be effective. Accurate prognostication after cardiac arrest is essential, and can be achieved with careful neurologic examination and several ancillary tests utilizing neurophysiology, neuroimaging, and biochemistry. Practice guidelines are now available for prognostication and postresuscitation care, with emphasis on improving survival and quality of life. Also reviewed are a wide spectrum of postarrest neurologic complications and their targeted treatments.

KEYWORDS

Cardiac arrest - anoxic - hypoxic - ischemic - hypoxic-ischemic - encephalopathy

REFERENCES

  • 1 Geocadin R G, Koenig M A, Jia X, Stevens R D, Peberdy M A. Management of brain injury after resuscitation from cardiac arrest.  Neurol Clin. 2008;  26 (2) 487-506, ix ix
    CrossrefPubMedGoogle Scholar
  • 2 Zheng Z J, Croft J B, Giles W H, Mensah G A. Sudden cardiac death in the United States, 1989 to 1998.  Circulation. 2001;  104 (18) 2158-2163
    CrossrefPubMedGoogle Scholar
  • 3 Geocadin R G, Buitrago M M, Torbey M T, Chandra-Strobos N, Williams M A, Kaplan P W. Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest.  Neurology. 2006;  67 (1) 105-108
    CrossrefPubMedGoogle Scholar
  • 4 Neumar R W, Nolan J P, Adrie C et al.. Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, Interamerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and The Stroke Council.  Circulation. 2008;  118 (23) 2452-2483
    CrossrefPubMedGoogle Scholar
  • 5 Hypothermia after Cardiac Arrest Study Group . Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.  N Engl J Med. 2002;  346 (8) 549-556
    CrossrefPubMedGoogle Scholar
  • 6 Bernard S A, Gray T W, Buist M D et al.. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.  N Engl J Med. 2002;  346 (8) 557-563
    CrossrefPubMedGoogle Scholar
  • 7 Schiff N D, Giacino J T, Kalmar K et al.. Behavioural improvements with thalamic stimulation after severe traumatic brain injury.  Nature. 2007;  448 (7153) 600-603
    CrossrefPubMedGoogle Scholar
  • 8 Peberdy M A, Callaway C W, Neumar R W et al.. Part 9: Post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.  Circulation. 2010;  122 (18, Suppl 3) S768-S786
    CrossrefPubMedGoogle Scholar
  • 9 Wagner IV S R, Lanier W L. Metabolism of glucose, glycogen, and high-energy phosphates during complete cerebral ischemia. A comparison of normoglycemic, chronically hyperglycemic diabetic, and acutely hyperglycemic nondiabetic rats.  Anesthesiology. 1994;  81 (6) 1516-1526
    CrossrefPubMedGoogle Scholar
  • 10 Hammer M D, Krieger D W. Hypothermia for acute ischemic stroke: not just another neuroprotectant.  Neurologist. 2003;  9 (6) 280-289
    CrossrefPubMedGoogle Scholar
  • 11 Obrenovitch T P, Garofalo O, Harris R J et al.. Brain tissue concentrations of ATP, phosphocreatine, lactate, and tissue pH in relation to reduced cerebral blood flow following experimental acute middle cerebral artery occlusion.  J Cereb Blood Flow Metab. 1988;  8 (6) 866-874
    CrossrefPubMedGoogle Scholar
  • 12 Lee J M, Grabb M C, Zipfel G J, Choi D W. Brain tissue responses to ischemia.  J Clin Invest. 2000;  106 (6) 723-731
    CrossrefPubMedGoogle Scholar
  • 13 Bright R, Mochly-Rosen D. The role of protein kinase C in cerebral ischemic and reperfusion injury.  Stroke. 2005;  36 (12) 2781-2790
    CrossrefPubMedGoogle Scholar
  • 14 Jean W C, Spellman S R, Nussbaum E S, Low W C. Reperfusion injury after focal cerebral ischemia: the role of inflammation and the therapeutic horizon.  Neurosurgery. 1998;  43 (6) 1382-1396 discussion 1396-1397
    PubMedGoogle Scholar
  • 15 Hossmann K A. Ischemia-mediated neuronal injury.  Resuscitation. 1993;  26 (3) 225-235
    CrossrefPubMedGoogle Scholar
  • 16 Ames III A, Wright R L, Kowada M, Thurston J M, Majno G. Cerebral ischemia. II. The no-reflow phenomenon.  Am J Pathol. 1968;  52 (2) 437-453
    PubMedGoogle Scholar
  • 17 Blomqvist P, Wieloch T. Ischemic brain damage in rats following cardiac arrest using a long-term recovery model.  J Cereb Blood Flow Metab. 1985;  5 (3) 420-431
    CrossrefPubMedGoogle Scholar
  • 18 Smith M L, Auer R N, Siesjö B K. The density and distribution of ischemic brain injury in the rat following 2-10 min of forebrain ischemia.  Acta Neuropathol. 1984;  64 (4) 319-332
    CrossrefPubMedGoogle Scholar
  • 19 Takemoto O, Tomimoto H, Yanagihara T. Induction of c-fos and c-jun gene products and heat shock protein after brief and prolonged cerebral ischemia in gerbils.  Stroke. 1995;  26 (9) 1639-1648
    CrossrefPubMedGoogle Scholar
  • 20 Plum M DF, Posner MDJB. Diagnosis of Stupor and Coma. Philadelphia: F.A. Davis Company; 1976
    Google Scholar
  • 21 Berek K, Jeschow M, Aichner F. The prognostication of cerebral hypoxia after out-of-hospital cardiac arrest in adults.  Eur Neurol. 1997;  37 (3) 135-145
    CrossrefPubMedGoogle Scholar
  • 22 Jennett B, Adams J H, Murray L S, Graham D I. Neuropathology in vegetative and severely disabled patients after head injury.  Neurology. 2001;  56 (4) 486-490
    CrossrefPubMedGoogle Scholar
  • 23 Quality Standards Subcommittee of the American Academy of Neurology .Assessment and management of patients in the persistent vegetative state: AAN Practice Guidelines. St. Paul, MN: American Academy of Neurology; 1995
    Google Scholar
  • 24 Giacino J T, Ashwal S, Childs N et al.. The minimally conscious state: definition and diagnostic criteria.  Neurology. 2002;  58 (3) 349-353
    CrossrefPubMedGoogle Scholar
  • 25 Snyder B D, Hauser W A, Loewenson R B, Leppik I E, Ramirez-Lassepas M, Gumnit R J. Neurologic prognosis after cardiopulmonary arrest: III. Seizure activity.  Neurology. 1980;  30 (12) 1292-1297
    CrossrefPubMedGoogle Scholar
  • 26 Lu-Emerson C, Khot S. Neurological sequelae of hypoxic-ischemic brain injury.  NeuroRehabilitation. 2010;  26 (1) 35-45
    PubMedGoogle Scholar
  • 27 Wijdicks E F, Hijdra A, Young G B, Bassetti C L, Wiebe S. Quality Standards Subcommittee of the American Academy of Neurology . Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 2006;  67 (2) 203-210
    CrossrefPubMedGoogle Scholar
  • 28 Young G B, Gilbert J J, Zochodne D W. The significance of myoclonic status epilepticus in postanoxic coma.  Neurology. 1990;  40 (12) 1843-1848
    CrossrefPubMedGoogle Scholar
  • 29 Wijdicks E F, Parisi J E, Sharbrough F W. Prognostic value of myoclonus status in comatose survivors of cardiac arrest.  Ann Neurol. 1994;  35 (2) 239-243
    CrossrefPubMedGoogle Scholar
  • 30 Lance J W, Adams R D. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy.  Brain. 1963;  86 111-136
    CrossrefPubMedGoogle Scholar
  • 31 Khot S, Tirschwell D L. Long-term neurological complications after hypoxic-ischemic encephalopathy.  Semin Neurol. 2006;  26 (4) 422-431
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Diamond A L, Callison R C, Shokri J, Cruz-Flores S, Kinsella L J. Paroxysmal sympathetic storm.  Neurocrit Care. 2005;  2 (3) 288-291
    CrossrefPubMedGoogle Scholar
  • 33 Hawker K, Lang A E. Hypoxic-ischemic damage of the basal ganglia. Case reports and a review of the literature.  Mov Disord. 1990;  5 (3) 219-224
    CrossrefPubMedGoogle Scholar
  • 34 Bhatt M H, Obeso J A, Marsden C D. Time course of postanoxic akinetic-rigid and dystonic syndromes.  Neurology. 1993;  43 (2) 314-317
    CrossrefPubMedGoogle Scholar
  • 35 Peskine A, Rosso C, Picq C, Caron E, Pradat-Diehl P. Neurological sequelae after cerebral anoxia.  Brain Inj. 2010;  24 (5) 755-761
    CrossrefPubMedGoogle Scholar
  • 36 Cronberg T, Lilja G, Rundgren M, Friberg H, Widner H. Long-term neurological outcome after cardiac arrest and therapeutic hypothermia.  Resuscitation. 2009;  80 (10) 1119-1123
    CrossrefPubMedGoogle Scholar
  • 37 Roine R O, Kajaste S, Kaste M. Neuropsychological sequelae of cardiac arrest.  JAMA. 1993;  269 (2) 237-242
    CrossrefPubMedGoogle Scholar
  • 38 Sasson C, Rogers M A, Dahl J, Kellermann A L. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis.  Circ Cardiovasc Qual Outcomes. 2010;  3 (1) 63-81
    CrossrefPubMedGoogle Scholar
  • 39 Nichol G, Thomas E, Callaway C W Resuscitation Outcomes Consortium Investigators et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome.  JAMA. 2008;  300 (12) 1423-1431
    CrossrefPubMedGoogle Scholar
  • 40 Saklayen M, Liss H, Markert R. In-hospital cardiopulmonary resuscitation. Survival in 1 hospital and literature review.  Medicine (Baltimore). 1995;  74 (4) 163-175
    CrossrefPubMedGoogle Scholar
  • 41 Young G B. Clinical practice. Neurologic prognosis after cardiac arrest.  N Engl J Med. 2009;  361 (6) 605-611
    CrossrefPubMedGoogle Scholar
  • 42 Levy D E, Caronna J J, Singer B H, Lapinski R H, Frydman H, Plum F. Predicting outcome from hypoxic-ischemic coma.  JAMA. 1985;  253 (10) 1420-1426
    CrossrefPubMedGoogle Scholar
  • 43 Zandbergen E G, Hijdra A, Koelman J H PROPAC Study Group et al. Prediction of poor outcome within the first 3 days of postanoxic coma.  Neurology. 2006;  66 (1) 62-68
    CrossrefPubMedGoogle Scholar
  • 44 Al Thenayan E, Savard M, Sharpe M, Norton L, Young B. Predictors of poor neurologic outcome after induced mild hypothermia following cardiac arrest.  Neurology. 2008;  71 (19) 1535-1537
    CrossrefPubMedGoogle Scholar
  • 45 Robinson L R, Micklesen P J, Tirschwell D L, Lew H L. Predictive value of somatosensory evoked potentials for awakening from coma.  Crit Care Med. 2003;  31 (3) 960-967
    CrossrefPubMedGoogle Scholar
  • 46 Lee Y C, Phan T G, Jolley D J, Castley H C, Ingram D A, Reutens D C. Accuracy of clinical signs, SEP, and EEG in predicting outcome of hypoxic coma: a meta-analysis.  Neurology. 2010;  74 (7) 572-580
    CrossrefPubMedGoogle Scholar
  • 47 Madl C, Kramer L, Domanovits H et al.. Improved outcome prediction in unconscious cardiac arrest survivors with sensory evoked potentials compared with clinical assessment.  Crit Care Med. 2000;  28 (3) 721-726
    CrossrefPubMedGoogle Scholar
  • 48 Zandbergen E G, Koelman J H, de Haan R J, Hijdra A. PROPAC-Study Group . SSEPs and prognosis in postanoxic coma: only short or also long latency responses?.  Neurology. 2006;  67 (4) 583-586
    CrossrefPubMedGoogle Scholar
  • 49 Tiainen M, Kovala T T, Takkunen O S, Roine R O. Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients treated with hypothermia.  Crit Care Med. 2005;  33 (8) 1736-1740
    CrossrefPubMedGoogle Scholar
  • 50 Guérit J M, de Tourtchaninoff M, Soveges L, Mahieu P. The prognostic value of three-modality evoked potentials (TMEPs) in anoxic and traumatic comas.  Neurophysiol Clin. 1993;  23 (2-3) 209-226
    CrossrefPubMedGoogle Scholar
  • 51 Chen R, Bolton C F, Young B. Prediction of outcome in patients with anoxic coma: a clinical and electrophysiologic study.  Crit Care Med. 1996;  24 (4) 672-678
    CrossrefPubMedGoogle Scholar
  • 52 Young G B, Kreeft J H, McLachlan R S, Demelo J. EEG and clinical associations with mortality in comatose patients in a general intensive care unit.  J Clin Neurophysiol. 1999;  16 (4) 354-360
    CrossrefPubMedGoogle Scholar
  • 53 Rossetti A O, Oddo M, Logroscino G, Kaplan P W. Prognostication after cardiac arrest and hypothermia: a prospective study.  Ann Neurol. 2010;  67 (3) 301-307
    PubMedGoogle Scholar
  • 54 Young G B. The EEG in coma.  J Clin Neurophysiol. 2000;  17 (5) 473-485
    CrossrefPubMedGoogle Scholar
  • 55 Geraghty M C, Torbey M T. Neuroimaging and serologic markers of neurologic injury after cardiac arrest.  Neurol Clin. 2006;  24 (1) 107-121, vii vii
    CrossrefPubMedGoogle Scholar
  • 56 Torbey M T, Selim M, Knorr J, Bigelow C, Recht L. Quantitative analysis of the loss of distinction between gray and white matter in comatose patients after cardiac arrest.  Stroke. 2000;  31 (9) 2163-2167
    CrossrefPubMedGoogle Scholar
  • 57 Wijman C A, Mlynash M, Caulfield A F et al.. Prognostic value of brain diffusion-weighted imaging after cardiac arrest.  Ann Neurol. 2009;  65 (4) 394-402
    CrossrefPubMedGoogle Scholar
  • 58 Berek K, Lechleitner P, Luef G et al.. Early determination of neurological outcome after prehospital cardiopulmonary resuscitation.  Stroke. 1995;  26 (4) 543-549
    CrossrefPubMedGoogle Scholar
  • 59 DeVolder A G, Goffinet A M, Bol A, Michel C, de Barsy T, Laterre C. Brain glucose metabolism in postanoxic syndrome. Positron emission tomographic study.  Arch Neurol. 1990;  47 (2) 197-204
    CrossrefPubMedGoogle Scholar
  • 60 Schaafsma A, de Jong B M, Bams J L, Haaxma-Reiche H, Pruim J, Zijlstra J G. Cerebral perfusion and metabolism in resuscitated patients with severe post-hypoxic encephalopathy.  J Neurol Sci. 2003;  210 (1-2) 23-30
    CrossrefPubMedGoogle Scholar
  • 61 Pfeifer R, Börner A, Krack A, Sigusch H H, Surber R, Figulla H R. Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale.  Resuscitation. 2005;  65 (1) 49-55
    CrossrefPubMedGoogle Scholar
  • 62 Fogel W, Krieger D, Veith M et al.. Serum neuron-specific enolase as early predictor of outcome after cardiac arrest.  Crit Care Med. 1997;  25 (7) 1133-1138
    CrossrefPubMedGoogle Scholar
  • 63 Martens P, Raabe A, Johnsson P. Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia.  Stroke. 1998;  29 (11) 2363-2366
    CrossrefPubMedGoogle Scholar
  • 64 Wong K C. Physiology and pharmacology of hypothermia.  West J Med. 1983;  138 (2) 227-232
    PubMedGoogle Scholar
  • 65 Erecinska M, Thoresen M, Silver I A. Effects of hypothermia on energy metabolism in mammalian central nervous system.  J Cereb Blood Flow Metab. 2003;  23 (5) 513-530
    CrossrefPubMedGoogle Scholar
  • 66 Sick T J, Xu G, Pérez-Pinzón M A. Mild hypothermia improves recovery of cortical extracellular potassium ion activity and excitability after middle cerebral artery occlusion in the rat.  Stroke. 1999;  30 (11) 2416-2421 discussion 2422
    CrossrefPubMedGoogle Scholar
  • 67 Busto R, Globus M Y, Dietrich W D, Martinez E, Valdés I, Ginsberg M D. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain.  Stroke. 1989;  20 (7) 904-910
    CrossrefPubMedGoogle Scholar
  • 68 Harada K, Maekawa T, Tsuruta R et al.. Hypothermia inhibits translocation of CaM kinase II and PKC-alpha, beta, gamma isoforms and fodrin proteolysis in rat brain synaptosome during ischemia-reperfusion.  J Neurosci Res. 2002;  67 (5) 664-669
    CrossrefPubMedGoogle Scholar
  • 69 Globus M Y, Alonso O, Dietrich W D, Busto R, Ginsberg M D. Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia.  J Neurochem. 1995;  65 (4) 1704-1711
    PubMedGoogle Scholar
  • 70 Zheng Z, Yenari M A. Post-ischemic inflammation: molecular mechanisms and therapeutic implications.  Neurol Res. 2004;  26 (8) 884-892
    CrossrefPubMedGoogle Scholar
  • 71 Fukuda H, Tomimatsu T, Watanabe N et al.. Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia-ischemia.  Brain Res. 2001;  910 (1-2) 187-191
    CrossrefPubMedGoogle Scholar
  • 72 Niwa M, Hara A, Iwai T et al.. Relationship between magnitude of hypothermia during ischemia and preventive effect against post-ischemic DNA fragmentation in the gerbil hippocampus.  Brain Res. 1998;  794 (2) 338-342
    CrossrefPubMedGoogle Scholar
  • 73 Hachimi-Idrissi S, Corne L, Ebinger G, Michotte Y, Huyghens L. Mild hypothermia induced by a helmet device: a clinical feasibility study.  Resuscitation. 2001;  51 (3) 275-281
    CrossrefPubMedGoogle Scholar
  • 74 Holzer M, Bernard S A, Hachimi-Idrissi S, Roine R O, Sterz F, Müllner M. Collaborative Group on Induced Hypothermia for Neuroprotection After Cardiac Arrest . Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis.  Crit Care Med. 2005;  33 (2) 414-418
    CrossrefPubMedGoogle Scholar
  • 75 Abella B S, Rhee J W, Huang K N, Vanden Hoek T L, Becker L B. Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey.  Resuscitation. 2005;  64 (2) 181-186
    CrossrefPubMedGoogle Scholar
  • 76 Merchant R M, Soar J, Skrifvars M B et al.. Therapeutic hypothermia utilization among physicians after resuscitation from cardiac arrest.  Crit Care Med. 2006;  34 (7) 1935-1940
    CrossrefPubMedGoogle Scholar
  • 77 Laver S R, Padkin A, Atalla A, Nolan J P. Therapeutic hypothermia after cardiac arrest: a survey of practice in intensive care units in the United Kingdom.  Anaesthesia. 2006;  61 (9) 873-877
    CrossrefPubMedGoogle Scholar
  • 78 Wolfrum S, Radke P W, Pischon T, Willich S N, Schunkert H, Kurowski V. Mild therapeutic hypothermia after cardiac arrest - a nationwide survey on the implementation of the ILCOR guidelines in German intensive care units.  Resuscitation. 2007;  72 (2) 207-213
    CrossrefPubMedGoogle Scholar
  • 79 Caviness J N, Brown P. Myoclonus: current concepts and recent advances.  Lancet Neurol. 2004;  3 (10) 598-607
    CrossrefPubMedGoogle Scholar
  • 80 Frucht S, Fahn S. The clinical spectrum of posthypoxic myoclonus.  Mov Disord. 2000;  15 (Suppl 1) 2-7
    CrossrefPubMedGoogle Scholar
  • 81 Datta S, Hart G K, Opdam H, Gutteridge G, Archer J. Post-hypoxic myoclonic status: the prognosis is not always hopeless.  Crit Care Resusc. 2009;  11 (1) 39-41
    PubMedGoogle Scholar
  • 82 Thömke F, Weilemann S L. Poor prognosis despite successful treatment of postanoxic generalized myoclonus.  Neurology. 2010;  74 (17) 1392-1394
    CrossrefPubMedGoogle Scholar
  • 83 Krauss G L, Bergin A, Kramer R E, Cho Y W, Reich S G. Suppression of post-hypoxic and post-encephalitic myoclonus with levetiracetam.  Neurology. 2001;  56 (3) 411-412
    CrossrefPubMedGoogle Scholar
  • 84 Baguley I J. Autonomic complications following central nervous system injury.  Semin Neurol. 2008;  28 (5) 716-725
    Article in Thieme ConnectPubMedGoogle Scholar
  • 85 Morris H R, Howard R S, Brown P. Early myoclonic status and outcome after cardiorespiratory arrest.  J Neurol Neurosurg Psychiatry. 1998;  64 (2) 267-268
    CrossrefPubMedGoogle Scholar
  • 86 Arnoldus E P, Lammers G J. Postanoxic coma: good recovery despite myoclonus status.  Ann Neurol. 1995;  38 (4) 697-698
    PubMedGoogle Scholar
  • 87 Harper S J, Wilkes R G. Posthypoxic myoclonus (the Lance-Adams syndrome) in the intensive care unit.  Anaesthesia. 1991;  46 (3) 199-201
    CrossrefPubMedGoogle Scholar
  • 88 Fugate J E, Wijdicks E F, Mandrekar J et al.. Predictors of neurologic outcome in hypothermia after cardiac arrest.  Ann Neurol. 2010;  68 (6) 907-914
    CrossrefPubMedGoogle Scholar

Romergryko G GeocadinM.D. 

Director, Neurosciences Critical Care Division; Department of Neurology, Department of Anesthesiology and Critical Care Medicine

Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287

Email: rgeocad1@jhmi.edu

      >