Log in | Register

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine

Peter Le Roux| David K. Menon| Giuseppe Citerio| Paul Vespa| Mary Kay Bader| Gretchen M. Brophy| Michael N. Diringer| Nino Stocchetti| Walter Videtta| Rocco Armonda| Neeraj Badjatia| Julian Böesel| Randall Chesnut| Sherry Chou| Jan Claassen| Marek Czosnyka| Michael De Georgia| Anthony Figaji| Jennifer Fugate| Raimund Helbok| David Horowitz| Peter Hutchinson| Monisha Kumar| Molly McNett| Chad Mille
Conference Reports and Expert Panel
Volume 40, Issue 9 / September , 2014

Pages 1189 - 1209

Abstract

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants’ collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Keywords

References

  1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535
    • View reference on PubMed
  2. Jaeschke R, Guyatt GH, Dellinger P et al (2008) Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ 337:a744
    • View reference on PubMed
  3. Rochwerg B, Alhazzani W, Jaeschke R (2014) Clinical meaning of the GRADE rules. Intensive Care Med 40:877–879
    • View reference on PubMed
  4. Andrews JC, Schünemann HJ, Oxman AD, Pottie K, Meerpohl JJ, Coello PA, Rind D, Montori VM, Brito JP, Norris S, Elbarbary M, Post P, Nasser M, Shukla V, Jaeschke R, Brozek J, Djulbegovic B, Guyatt G (2013) GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation’s direction and strength. J Clin Epidemiol 66(7):726–735
    • View reference on PubMed
  5. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, Rind D, Meerpohl J, Dahm P, Schünemann HJ (2011) GRADE guidelines: 1 Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 64(4):383–394
    • View reference on PubMed
  6. Schünemann HJ, Wiercioch W, Etxeandia I, Falavigna M, Santesso N, Mustafa R, Ventresca M, Brignardello-Petersen R, Laisaar KT, Kowalski S, Baldeh T, Zhang Y, Raid U, Neumann I, Norris SL, Thornton J, Harbour R, Treweek S, Guyatt G, Alonso-Coello P, Reinap M, Brozek J, Oxman A, Akl EA (2014) Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise. CMAJ 186(3):E123–E142
    • View reference on PubMed
  7. Wilt TJ, Guyatt G, Kunz R, Macnee W, Puhan MA, Viegi G, Woodhead M, Akl EA, Schünemann HJ, ATS/ERS Ad Hoc Committee on Integrating and Coordinating Efforts in COPD Guideline Development (2012) Deciding what type of evidence and outcomes to include in guidelines: article 5 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report. Proc Am Thorac Soc 9(5):243–250
    • View reference on PubMed
  8. Woolf S, Schünemann HJ, Eccles MP, Grimshaw JM, Shekelle P (2012) Developing clinical practice guidelines: types of evidence and outcomes; values and economics, synthesis, grading, and presentation and deriving recommendations. Implement Sci 4(7):61
  9. Hsu J, Brożek JL, Terracciano L, Kreis J, Compalati E, Stein AT, Fiocchi A, Schünemann HJ (2011) Application of GRADE: making evidence-based recommendations about diagnostic tests in clinical practice guidelines. Implement Sci 10(6):62
  10. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, Alderson P, Glasziou P, Falck-Ytter Y, Schünemann HJ (2011) GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol 64(4):395–400
    • View reference on PubMed
  11. Gill M, Windemuth R, Steele R, Green SM (2005) A comparison of the Glasgow Coma Scale score to simplified alternative scores for the prediction of traumatic brain injury outcomes. Ann Emerg Med 45:37–42
    • View reference on PubMed
  12. Tsau JW, Hemphill JC, Johnston SC, Smith WS, Bonovich DC (2005) Initial Glasgow Coma Scale score predicts outcome following thrombolysis for posterior circulation stroke. Arch Neurol 62:1126–1129
  13. Schefold JC, Storm C, Kruger A, Ploner CJ, Hasper D (2009) The Glasgow Coma Score is a predictor of good outcome in cardiac arrest patients treated with therapeutic hypothermia. Resuscitation 80:658–661
    • View reference on PubMed
  14. Marmarou A, Lu J, Butcher I, McHugh GS, Murray GD, Steyerberg EW, Mushkudiani NA, Choi S, Maas AI (2007) Prognostic value of the Glasgow Coma Scale and pupil reactivity in traumatic brain injury assessed pre-hospital and on enrollment: an IMPACT analysis. J Neurotrauma 24:270–280
    • View reference on PubMed
  15. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL (2005) Validation of a new coma scale: the FOUR score. Ann Neurol 58:585–593
    • View reference on PubMed
  16. Kramer AA, Wijdicks EF, Snavely VL, Dunivan JR, Naranjo LL, Bible S, Rohs T, Dickess SM (2012) A multicenter prospective study of interobserver agreement using the Full Outline of Unresponsiveness score coma scale in the intensive care unit. Crit Care Med 40:2671–2676
    • View reference on PubMed
  17. Gelinas C, Klein K, Naidech AM, Skrobik Y (2013) Pain, sedation, and delirium management in the neurocritically ill: lessons learned from recent research. Semin Respir Crit Care Med 34:236–243
    • View reference on PubMed
  18. Chatelle C, Majerus S, Whyte J, Laureys S, Schnakers C (2012) A sensitive scale to assess nociceptive pain in patients with disorders of consciousness. J Neurol Neurosurg Psychiatry 8(3):1233–1237
  19. Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R, American College of Critical Care Medicine (2013) Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 41:263–306
    • View reference on PubMed
  20. Helbok R, Kurtz P, Schmidt MJ, Stuart MR, Fernandez L, Connolly SE, Lee K, Schmutzhard E, Mayer SA, Claassen J, Badjatia N (2012) Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients. Crit Care 16:R226
    • View reference on PubMed
  21. Mitasova A, Kostalova M, Bednarik J, Michalcakova R, Kasparek T, Balabanova P, Dusek L, Vohanka S, Ely EW (2012) Poststroke delirium incidence and outcomes: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 40(2):484–490
    • View reference on PubMed
  22. Davies KR, Gelb AW, Manninen PH, Boughner DR, Bisnaire D (1991) Cardiac function in aneurysmal subarachnoid haemorrhage: a study of electrocardiographic and echocardiographic abnormalities. Br J Anaesth 67(1):58–63
    • View reference on PubMed
  23. Kopelnik A, Fisher L, Miss JC, Banki N, Tung P, Lawton MT, Ko N, Smith WS, Drew B, Foster E, Zaroff J (2005) Prevalence and implications of diastolic dysfunction after subarachnoid hemorrhage. Neurocrit Care 3(2):132–138
    • View reference on PubMed
  24. Naidech AM, Kreiter KT, Janjua N, Ostapkovich ND, Parra A, Commichau C, Fitzsimmons BF, Connolly ES, Mayer SA (2005) Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation 112(18):2851–2856
    • View reference on PubMed
  25. Naidech AM, Bassin SL, Garg RK, Ault ML, Bendok BR, Batjer HH, Watts CM, Bleck TP (2009) Cardiac troponin I and acute lung injury after subarachnoid hemorrhage. Neurocrit Care 11(2):177–182
    • View reference on PubMed
  26. Mayer SA, Lin J, Homma S, Solomon RA, Lennihan L, Sherman D, Fink ME, Beckford A, Klebanoff LM (1999) Myocardial injury and left ventricular performance after subarachnoid hemorrhage. Stroke 30(4):780–786
    • View reference on PubMed
  27. Tung P, Kopelnik A, Banki N, Ong K, Ko N, Lawton MT, Gress D, Drew B, Foster E, Parmley W, Zaroff J (2004) Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke 35(2):548–551
    • View reference on PubMed
  28. Sugimoto K, Inamasu J, Kato Y, Yamada Y, Ganaha T, Oheda M, Hattori N, Watanabe E, Ozaki Y, Hirose Y (2013) Association between elevated plasma norepinephrine levels and cardiac wall motion abnormality in poor-grade subarachnoid hemorrhage patients. Neurosurg Rev 36(2):259–266
    • View reference on PubMed
  29. Banki NM, Kopelnik A, Dae MW, Miss J, Tung P, Lawton MT, Drew BJ, Foster E, Smith W, Parmley WW, Zaroff JG (2005) Acute neurocardiogenic injury after subarachnoid hemorrhage. Circulation 112(21):3314–3319
    • View reference on PubMed
  30. Mutoh T, Kazumata K, Ajiki M, Ushikoshi S, Terasaka S (2007) Goal-directed fluid management by bedside transpulmonary hemodynamic monitoring after subarachnoid hemorrhage. Stroke 38(12):3218–3224
    • View reference on PubMed
  31. Mendelson AA, Gillis C, Henderson WR, Ronco JJ, Dhingra V, Griesdale DE (2012) Intracranial pressure monitors in traumatic brain injury: a systematic review. Can J Neurol Sci 39(5):571–576
    • View reference on PubMed
  32. Andrews PJ, Sleeman DH, Statham PF, McQuatt A, Corruble V, Jones PA, Howells TP, Macmillan CS (2002) Predicting recovery in patients suffering from traumatic brain injury by using admission variables and physiological data: a comparison between decision tree analysis and logistic regression. J Neurosurg 97(2):326–336
    • View reference on PubMed
  33. Badri S, Chen J, Barber J, Temkin NR, Dikmen SS, Chesnut RM, Deem S, Yanez ND, Treggiari MM (2012) Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Med 38(11):1800–1809
    • View reference on PubMed
  34. Treggiari MM, Schutz N, Yanez ND, Romand JA (2007) Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review. Neurocrit Care. 6(2):104–112
    • View reference on PubMed
  35. Bekar A, Doğan S, Abaş F, Caner B, Korfali G, Kocaeli H, Yilmazlar S, Korfali E (2009) Risk factors and complications of intracranial pressure monitoring with a fiberoptic device. J Clin Neurosci 16(2):236–240
    • View reference on PubMed
  36. Resnick DK, Marion DW, Carlier P (1997) Outcome analysis of patients with severe head injuries and prolonged intracranial hypertension. J Trauma 42(6):1108–1111
    • View reference on PubMed
  37. Kosty JA, Le Roux PD, Levine J, Park S, Kumar MA, Frangos S, Maloney-Wilensky E, Kofke WA (2013) Brief report: a comparison of clinical and research practices in measuring cerebral perfusion pressure: a literature review and practitioner survey. Anesth Analg 117(3):694–698
    • View reference on PubMed
  38. Robertson CS, Valadka AB, Hannay HJ, Contant CF, Gopinath SP, Cormio M, Uzura M, Grossman RG (1999) Prevention of secondary ischemic insults after severe head injury. Crit Care Med 27(10):2086–2095
    • View reference on PubMed
  39. Aries MJ, Czosnyka M, Budohoski KP, Steiner LA, Lavinio A, Kolias AG, Hutchinson PJ, Brady KM, Menon DK, Pickard JD, Smielewski P (2012) Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med 40(8):2456–2463
    • View reference on PubMed
  40. Chesnut RM, Temkin N, Carney N, Dikmen S, Rondina C, Videtta W, Petroni G, Lujan S, Pridgeon J, Barber J, Machamer J, Chaddock K, Celix JM, Cherner M, Hendrix T, Global Neurotrauma Research Group (2012) A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 367(26):2471–2481
    • View reference on PubMed
  41. Arabi YM, Haddad S, Tamim HM, Al-Dawood A, Al-Qahtani S, Ferayan A, Al-Abdulmughni I, Al-Oweis J, Rugaan A (2010) Mortality reduction after implementing a clinical practice guidelines-based management protocol for severe traumatic brain injury. J Crit Care 25(2):190–195
    • View reference on PubMed
  42. Gerber LM, Chiu YL, Carney N, Härtl R, Ghajar J (2013) Marked reduction in mortality in patients with severe traumatic brain injury. J Neurosurg 119(6):1583–1590
    • View reference on PubMed
  43. Alali AS, Fowler RA, Mainprize TG, Scales DC, Kiss A, de Mestral C, Ray JG, Nathens AB (2013) Intracranial pressure monitoring in severe traumatic brain injury: results from the American College of Surgeons Trauma Quality Improvement Program. J Neurotrauma 30(20):1737–1746
    • View reference on PubMed
  44. Steiner LA, Coles JP, Johnston AJ, Chatfield DA, Smielewski P, Fryer TD, Aigbirhio FI, Clark JC, Pickard JD, Menon DK, Czosnyka M (2003) Assessment of cerebrovascular autoregulation in head-injured patients: a validation study. Stroke 34(10):2404
    • View reference on PubMed
  45. Czosnyka M, Smielewski P, Kirkpatrick P, Laing RJ, Menon D, Pickard JD (1997) Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery 41(1):11–17
    • View reference on PubMed
  46. Lavinio A, Timofeev I, Nortje J, Outtrim J, Smielewski P, Gupta A, Hutchinson PJ, Matta BF, Pickard JD, Menon D, Czosnyka M (2007) Cerebrovascular reactivity during hypothermia and rewarming. Br J Anaesth 99(2):237–244
    • View reference on PubMed
  47. Steiner LA, Czosnyka M, Piechnik SK, Smielewski P, Chatfield D, Menon DK, Pickard JD (2002) Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med 30(4):733–738
    • View reference on PubMed
  48. Jubran A, Tobin MJ (1990) Reliability of pulse oximetry in titrating supplemental oxygen therapy in ventilator-dependent patients. Chest 97:1420–1425
    • View reference on PubMed
  49. Sulter G, Elting JW, Stewart R, den Arend A, De Keyser J (2000) Continuous pulse oximetry in acute hemiparetic stroke. J Neurol Sci 179:65–69
    • View reference on PubMed
  50. Anderson CT, Breen PH (2000) Carbon dioxide kinetics and capnography during critical care. Crit Care 4:207–215
    • View reference on PubMed
  51. Pennings FA, Schuurman PR, van den Munckhof P, Bouma GJ (2008) Brain tissue oxygen pressure monitoring in awake patients during functional neurosurgery: the assessment of normal values. J Neurotrauma 25:1173–1177
    • View reference on PubMed
  52. Doppenberg EM, Zauner A, Watson JC, Bullock R (1998) Determination of the ischemic threshold for brain oxygen tension. Acta Neurochir Suppl 71:166–169
    • View reference on PubMed
  53. Ponce LL, Pillai S, Cruz J, Li X, Julia H, Gopinath S, Robertson CS (2012) Position of probe determines prognostic information of brain tissue PO2 in severe traumatic brain injury. Neurosurgery 70(6):1492–1502
    • View reference on PubMed
  54. Pascual JL, Georgoff P, Maloney-Wilensky E, Sims C, Sarani B, Stiefel MF, LeRoux PD, Schwab CW (2011) Reduced brain tissue oxygen in traumatic brain injury: are most commonly used interventions successful? J Trauma 70:535–546
    • View reference on PubMed
  55. Coplin WM, O’Keefe GE, Grady MS, Grant GA, March KS, Winn HR, Lam AM (1997) Thrombotic, infectious, and procedural complications of the jugular bulb catheter in the intensive care unit. Neurosurgery 41:101–107
    • View reference on PubMed
  56. Schoon P, Benito Mori L, Orlandi G, Larralde C, Radrizzani M (2002) Incidence of intracranial hypertension related to jugular bulb oxygen saturation disturbances in severe traumatic brain injury patients. Acta Neurochir Suppl 81:285–287
    • View reference on PubMed
  57. Coles JP, Fryer TD, Smielewski P, Chatfield DA, Steiner LA, Johnston AJ, Downey SP, Williams GB, Aigbirhio F, Hutchinson PJ, Rice K, Carpenter TA, Clark JC, Pickard JD, Menon DK (2004) Incidence and mechanisms of cerebral ischemia in early clinical head injury. J Cereb Blood Flow Metab 24(2):202–211
    • View reference on PubMed
  58. Schneider GH, von Helden A, Lanksch WR, Unterberg A (1995) Continuous monitoring of jugular bulb oxygen saturation in comatose patients—therapeutic implications. Acta Neurochir (Wien) 134:71–75
  59. Zweifel C, Castellani G, Czosnyka M, Helmy A, Manktelow A, Carrera E, Brady KM, Hutchinson PJ, Menon DK, Pickard JD, Smielewski P (2010) Noninvasive monitoring of cerebrovascular reactivity with near infrared spectroscopy in head-injured patients. J Neurotrauma 27:1951–1958
    • View reference on PubMed
  60. Menon DK, Coles JP, Gupta AK, Fryer TD, Smielewski P, Chatfield DA, Aigbirhio F, Skepper JN, Minhas PS, Hutchinson PJ, Carpenter TA, Clark JC, Pickard JD (2004) Diffusion limited oxygen delivery following head injury. Crit Care Med 32:1384–1390
    • View reference on PubMed
  61. Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA (2005) Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab 25:763–774
    • View reference on PubMed
  62. Vajkoczy P, Roth H, Horn P, Lucke T, Thomé C, Hubner U, Martin GT, Zappletal C, Klar E, Schilling L, Schmiedek P (2000) Continuous monitoring of regional cerebral blood flow: experimental and clinical validation of a novel thermal diffusion microprobe. J Neurosurg 93(2):265–274
    • View reference on PubMed
  63. Gesang DZ, Zhang D, Zhao JZ, Wang S, Zhao YL, Wang R, Sun JJ, Meng Z (2009) Laser Doppler flowmeter study on regional cerebral blood flow in early stage after standard superficial temporal artery-middle cerebral artery bypass surgery for Moyamoya disease. Chin Med J (Engl) 122(20):2412–2418
  64. Kincaid MS, Souter MJ, Treggiari MM, Yanez ND, Moore A, Lam AM (2009) Accuracy of transcranial Doppler ultrasonography and single-photon emission computed tomography in the diagnosis of angiographically demonstrated cerebral vasospasm. J Neurosurg 110(1):67–72
    • View reference on PubMed
  65. Lysakowski C, Walder B, Costanza MC, Tramèr MR (2001) Transcranial Doppler versus angiography in patients with vasospasm due to a ruptured cerebral aneurysm: a systematic review. Stroke 32(10):2292–2298
    • View reference on PubMed
  66. Suarez JI, Qureshi AI, Yahia AB, Parekh PD, Tamargo RJ, Williams MA, Ulatowski JA, Hanley DF, Razumovsky AY (2002) Symptomatic vasospasm diagnosis after subarachnoid hemorrhage: evaluation of transcranial Doppler ultrasound and cerebral angiography as related to compromised vascular distribution. Crit Care Med 30(6):1348–1355
    • View reference on PubMed
  67. Turek G, Kochanowicz J, Rutkowski R, Krejza J, Lyson T, Gorbacz K, Zielinska-Turek J, Mariak Z (2012) Accuracy of transcranial colour-coded sonography in the diagnosis of anterior cerebral artery vasospasm. Neurol Neurochir Pol 46(3):233–238
    • View reference on PubMed
  68. Vora YY, Suarez-Almazor M, Steinke DE, Martin ML, Findlay JM (1999) Role of transcranial Doppler monitoring in the diagnosis of cerebral vasospasm after subarachnoid hemorrhage. Neurosurgery 44:1237–1247
    • View reference on PubMed
  69. Naval NS, Thomas CE, Urrutia VC (2005) Relative changes in flow velocities in vasospasm after subarachnoid hemorrhage: a transcranial Doppler study. Neurocrit Care 2(2):133–140
    • View reference on PubMed
  70. Claassen J, Taccone FS, Horn P, Holtkamp M, Stocchetti N, Oddo M (2013) Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM. Intensive Care Med 39(8):1337–1351
    • View reference on PubMed
  71. Varelas PN, Hacein-Bey L, Hether T, Terranova B, Spanaki MV (2004) Emergent electroencephalogram in the intensive care unit: indications and diagnostic yield. Clin EEG Neurosci 35:173–180
    • View reference on PubMed
  72. Rossetti AO, Oddo M, Logroscino G, Kaplan PW (2010) Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol 67:301–307
    • View reference on PubMed
  73. Zandbergen EG, Hijdra A, Koelman JH, van Dijk JG, Ongerboer de Visser BW, Spaans F, Tavy DL, Koelman JH (2006) Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 66:62–68
    • View reference on PubMed
  74. Rossetti AO, Carrera E, Oddo M (2012) Early EEG correlates of neuronal injury after brain anoxia. Neurology 78:796–802
    • View reference on PubMed
  75. Young GB, Jordan KG, Doig GS (1996) An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology 47:83–89
    • View reference on PubMed
  76. Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ (2004) Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 62:1743–1748
    • View reference on PubMed
  77. Bellander BM, Cantais E, Enblad P, Hutchinson P, Nordström CH, Robertson C, Sahuquillo J, Smith M, Stocchetti N, Ungerstedt U, Unterberg A, Olsen NV (2004) Consensus meeting on microdialysis in neurointensive care. Intensive Care Med 30(12):2166–2169
    • View reference on PubMed
  78. Nortje J, Coles JP, Timofeev I, Fryer TD, Aigbirhio FI, Smielewski P, Outtrim JG, Chatfield DA, Pickard JD, Hutchinson PJ, Gupta AK, Menon DK (2008) Effect of hyperoxia on regional oxygenation and metabolism after severe traumatic brain injury: preliminary findings. Crit Care Med 36(1):273–281
    • View reference on PubMed
  79. Larach DB, Kofke WA, Le Roux P (2011) Potential non-hypoxic/ischemic causes of increased cerebral interstitial fluid lactate/pyruvate ratio (LPR): a review of available literature. Neurocrit Care 15(3):609–622
    • View reference on PubMed
  80. Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA (2005) Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab 25(6):763–774
    • View reference on PubMed
  81. Timofeev I, Carpenter KL, Nortje J, Al-Rawi PG, O’Connell MT, Czosnyka M, Smielewski P, Pickard JD, Menon DK, Kirkpatrick PJ, Gupta AK, Hutchinson PJ (2011) Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain 134(Pt 2):484–494
    • View reference on PubMed
  82. Marcoux J, McArthur DA, Miller C, Glenn TC, Villablanca P, Martin NA, Hovda DA, Alger JR, Vespa PM (2008) Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury. Crit Care Med 36(10):2871–2877
    • View reference on PubMed
  83. Skjøth-Rasmussen J, Schulz M, Kristensen SR, Bjerre P (2004) Delayed neurological deficits detected by an ischemic pattern in the extracellular cerebral metabolites in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 100(1):8–15
    • View reference on PubMed
  84. Sarrafzadeh AS, Copin JC, Jimenez Bengualid J, Turck N, Vajkoczy P, Bijlega P, Schaller K, Gasche Y (2012) Matrix metaloproteinase-9 concentration in the cerebral extracellular fluid of patients during the actue phase of aneurismal subarachnoid hemorrhage. Neurol Res 34(5):455–461
    • View reference on PubMed
  85. Nordstrom CH, Reinstrup P, Xu W, Gardenfors A, Ungerstedt U (2003) Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology 98(4):805–807
  86. Hartl R, Gerber LM, Ni Q, Ghajar J (2008) Effect of early nutrition on deaths due to severe traumatic brain injury. J Neurosurg 109:50–56
    • View reference on PubMed
  87. Desachy A, Vuagnat AC, Ghazali AD, Baudin OT, Longuet OH, Calvat SN, Gissot V (2008) Accuracy of bedside glucometry in critically ill patients: influence of clinical characteristics and perfusion index. Mayo Clin Proc 83:400–405
    • View reference on PubMed
  88. Lonjaret L, Claverie V, Berard E, Riu-Poulenc B, Geeraerts T, Genestal M, Fourcade O (2012) Relative accuracy of arterial and capillary glucose meter measurements in critically ill patients. Diabetes Metab 38:230–235
    • View reference on PubMed
  89. Finkielman JD, Oyen LJ, Afessa B (2005) Agreement between bedside blood and plasma glucose measurement in the ICU setting. Chest 127:1749–1751
    • View reference on PubMed
  90. Oddo M, Schmidt JM, Mayer SA, Chiolero RL (2008) Glucose control after severe brain injury. Curr Opin Clin Nutr Metab Care 11:134–139
    • View reference on PubMed
  91. Vespa P, Boonyaputthikul R, McArthur DL, Miller C, Etchepare M, Bergsneider M, Glenn T, Martin N, Hovda D (2006) Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. Crit Care Med 34(3):850–856
    • View reference on PubMed
  92. Ferrie S, Allman-Farinelli M (2013) Commonly used “nutrition” indicators do not predict outcome in the critically ill: a systematic review. Nutr Clin Pract 28:463–484
    • View reference on PubMed
  93. Reignier J, Mercier E, Le Gouge A, Boulain T, Desachy A, Bellec F, Clavel M, Frat JP, Plantefeve G, Quenot JP, Lascarrou JB, Clinical Research in Intensive Care and Sepsis (CRICS) Group (2013) Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA 309:249–256
    • View reference on PubMed
  94. Kramer AH, Zygun DA, Bleck TP, Dumont AS, Kassell NF, Nathan B (2009) Relationship between hemoglobin concentrations and outcomes across subgroups of patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care 10:157–165
    • View reference on PubMed
  95. Smoller BR, Kruskall MS, Horowitz GL (1998) Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes. Am J Clin Pathol 91:701–703
  96. Levine J, Kofke A, Cen L, Faerber J, Elliott JP, Winn HR, Le Roux P (2010) Red blood cell transfusion is associated with infection and extracerebral complications after subarachnoid hemorrhage. Neurosurgery 66:312–318
    • View reference on PubMed
  97. Naidech AM, Bernstein RA, Levasseur K, Bassin SL, Bendok BR, Batjer HH, Bleck TP, Alberts MJ (2009) Platelet activity and outcome after intracerebral hemorrhage. Ann Neurol 65:352–356
    • View reference on PubMed
  98. Goldenberg NA, Jacobson L, Manco-Johnson MJ (2005) Duration of platelet dysfunction after a 7-day course of ibuprofen. Ann Intern Med 142:506–509
    • View reference on PubMed
  99. Naidech AM, Jovanovic B, Liebling S, Garg RK, Bassin SL, Bendok BR, Bernstein RA, Alberts MJ, Batjer HH (2009) Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerebral hemorrhage. Stroke 40:2398–2401
    • View reference on PubMed
  100. Dansirikul C, Lehr T, Liesenfeld KH, Haertter S, Staab A (2012) A combined pharmacometric analysis of dabigatran etexilate in healthy volunteers and patients with atrial fibrillation or undergoing orthopaedic surgery. Thromb Haemost 107:775–785
    • View reference on PubMed
  101. Stangier J, Feuring M (2012) Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis 23:138–143
    • View reference on PubMed
  102. Chee YL, Crawford JC, Watson HG, Greaves M (2008) Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. British Committee for Standards in Haematology. Br J Haematol 140:496–504
    • View reference on PubMed
  103. West KL, Adamson C, Hoffman M (2011) Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature. J Neurosurg 114:9–18
    • View reference on PubMed
  104. Mun JH, Cho KY, Lim BC, Lim JS, Lee RS (2013) Factors related to catheter-induced hemorrhage after brain parenchymal catheterization. Chonnam Med J 49:113–117
    • View reference on PubMed
  105. Krisl JC, Meadows HE, Greenberg CS, Mazur JE (2011) Clinical usefulness of recombinant activated factor VII in patients with liver failure undergoing invasive procedures. Ann Pharmacother 45:1433–1438
    • View reference on PubMed
  106. Lisman T, Bakhtiari K, Pereboom IT, Hendriks HG, Meijers JC, Porte RJ (2010) Normal to increased thrombin generation in patients undergoing liver transplantation despite prolonged conventional coagulation tests. J Hepatol 52:355–361
    • View reference on PubMed
  107. Oddo M, Frangos S, Milby A, Chen I, Maloney-Wilensky E, Murtrie EM, Stiefel M, Kofke WA, Le Roux PD, Levine JM (2009) Induced normothermia attenuates cerebral metabolic distress in patients with aneurysmal subarachnoid hemorrhage and refractory fever. Stroke 40(5):1913–1916
    • View reference on PubMed
  108. Puccio AM, Fischer MR, Jankowitz BT, Yonas H, Darby JM, Okonkwo DO (2009) Induced normothermia attenuates intracranial hypertension and reduces fever burden after severe traumatic brain injury. Neurocrit Care 11(1):82–87
    • View reference on PubMed
  109. Thompson HJ, Pinto-Martin J, Bullock MR (2003) Neurogenic fever after traumatic brain injury: an epidemiological study. J Neurol Neurosurg Psychiatry 74(5):614–619
    • View reference on PubMed
  110. Fernandez A, Schmidt JM, Claassen J, Pavlicova M, Huddleston D, Kreiter KT, Ostapkovich ND, Kowalski RG, Parra A, Connolly ES, Mayer SA (2007) Fever after subarachnoid hemorrhage: risk factors and impact on outcome. Neurology 68(13):1013–1019
    • View reference on PubMed
  111. Singh V, Sharma A, Khandelwal R, Kothari K (2000) Variation of axillary temperature and its correlation with oral temperature. J Assoc Physicians India 48(9):898–900
    • View reference on PubMed
  112. Smith LS (2004) Temperature measurement in critical care adults: a comparison of thermometry and measurement routes. Biol Res Nurs 6(2):117–125
    • View reference on PubMed
  113. Hata JS, Shelsky CR, Hindman BJ, Smith TC, Simmons JS, Todd MM (2008) A prospective, observational clinical trial of fever reduction to reduce systemic oxygen consumption in the setting of acute brain injury. Neurocrit Care 9(1):37–44
    • View reference on PubMed
  114. Oddo M, Frangos S, Maloney-Wilensky E, Andrew Kofke W, Le Roux P, Levine JM (2010) Effect of shivering on brain tissue oxygenation during induced normothermia in patients with severe brain injury. Neurocrit Care 12(1):10–16
    • View reference on PubMed
  115. Choi HA, Ko SB, Presciutti M, Fernandez L, Carpenter AM, Lesch C, Gilmore E, Malhotra R, Mayer SA, Lee K, Claassen J, Schmidt JM, Badjatia N (2011) Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care 14(3):389–394
    • View reference on PubMed
  116. Provencio JJ, Fu X, Siu A, Rasmussen PA, Hazen SL, Ransohoff RM (2010) CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage. Neurocrit Care 12(2):244–251
    • View reference on PubMed
  117. Oconnor E, Venkatesh B, Mashongonyika C, Lipman J, Hall J, Thomas P (2004) Serum procalcitonin and C-reactive protein as markers of sepsis and outcome in patients with neurotrauma and subarachnoid haemorrhage. Anaesth Intensive Care 32(4):465–470
    • View reference on PubMed
  118. Tiainen M, Roine RO, Pettila V, Takkunen O (2003) Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke 34:2881–2886
    • View reference on PubMed
  119. Diaz-Arrastia R, Wang KK, Papa L, Sorani MD, Yue JK, Puccio AM, McMahon PJ, Inoue T, Yuh EL, Lingsma HF, Maas AI, Valadka AB, Okonkwo DO, Manley GT, Track-Tbi Investigators, Casey IS, Cheong M, Cooper SR, Dams-O’Connor K, Gordon WA, Hricik AJ, Menon DK, Mukherjee P, Schnyer DM, Sinha TK, Vassar MJ (2014) Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma 31(1):19–25
    • View reference on PubMed
  120. Czeiter E, Mondello S, Kovacs N, Sandor J, Gabrielli A, Schmid K, Tortella F, Wang KK, Hayes RL, Barzo P, Ezer E, Doczi T, Buki A (2012) Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J Neurotrauma 29:1770–1778
    • View reference on PubMed
  121. Mercier E, Boutin A, Lauzier F, Fergusson DA, Simard J-F, Zarychanski R et al (2013) Predictive value of S-100B protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. BMJ 346:f1757
    • View reference on PubMed
  122. Chou SH-Y, Feske SK, Simmons SL, Konigsberg RG, Orzell SC, Marckmann A, Bourget G, Bauer DJ, De Jager PL, Du R, Arai K, Lo EH, Ning MM (2011) Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outcome following subarachnoid hemorrhage. Transl Stroke Res 2(4):600–607
    • View reference on PubMed
  123. Papa L, Lewis LM, Silvestri S, Falk JL, Giordano P, Brophy GM, Demery JA, Liu MC, Mo J, Akinyi L, Mondello S, Schmid K, Robertson CS, Tortella FC, Hayes RL, Wang KK (2012) Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention. J Trauma Acute Care Surg 72:1335–1344
    • View reference on PubMed
  124. Siman R, Giovannone N, Toraskar N, Frangos S, Stein SC, Levine JM, Kumar MA (2011) Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage. PLoS One 6(12):e28938
    • View reference on PubMed
  125. Kazmierski R, Michalak S, Wencel-Warot A, Nowinski WL (2012) Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients. Neurology 79:1677–1685
    • View reference on PubMed
  126. Knopf L, Staff I, Gomes J, McCullough L (2012) Impact of a neurointensivist on outcomes in critically ill stroke patients. Neurocrit Care 16:63–71
    • View reference on PubMed
  127. Kramer AH, Zygun DA (2013) Declining mortality in neurocritical care patients: a cohort study in Southern Alberta over 11 years. Can J Anesth 60:966–975
    • View reference on PubMed
  128. Damian MS, Ben-Shlomo Y, Howard R, Bellotti T, Harrison D, Griggs K, Rowan K (2013) The effect of secular trends and specialist neurocritical care on mortality for patients with intracerebral hemorrhage, myasthenia gravis and Guillain–Barré syndrome admitted to critical care. Intensive Care Med 39:1405–1412
    • View reference on PubMed
  129. Kramer AH, Zygun DA (2011) Do neurocritical care units save lives? Measuring the impact of specialized ICUs. Neurocrit Care 14:329–333
    • View reference on PubMed
  130. Patel HC, Menon DK, Tebbs S, Hawker R, Hutchinson PJ, Kirkpatrick PJ (2002) Specialist neurocritical care and outcome from head injury. Intensive Care Med 28(5):547–553
    • View reference on PubMed
  131. Elf K, Nilsson P, Enblad P (2002) Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care. Crit Care Med 30(9):2129–2134
    • View reference on PubMed
  132. Naval NS, Chang T, Caserta F, Kowalski RG, Carhuapoma JR, Tamargo RJ (2012) Impact of pattern of admission on outcomes after aneurysmal subarachnoid hemorrhage. J Crit Care 27:532
    • View reference on PubMed
  133. Rincon F, Mayer SA, Rivolta J, Stillman J, Boden-Albala B, Elkind MS, Marshall R, Chong JY (2010) Impact of delayed transfer of critically ill stroke patients from the emergency department to the neuro-ICU. Neurocrit Care 13:75–81
    • View reference on PubMed
  134. English SW, Turgeon AF, Owen E, Doucette S, Pagliarello G, McIntyre L (2013) Protocol management of severe traumatic brain injury in intensive care units: a systematic review. Neurocrit Care 18:131–142
    • View reference on PubMed
  135. Rhodes A, Moreno RP, Azoulay E, Capuzzo M, Chiche JD, Eddleston J, Endacott R, Ferdinande P, Flaatten H, Guidet B, Kuhlen R, León-Gil C, Martin Delgado MC, Metnitz PG, Soares M, Sprung CL, Timsit JF, Valentin A, Task Force on Safety and Quality of European Society of Intensive Care Medicine (ESICM) (2012) Prospectively defined indicators to improve the safety and quality of care for critically ill patients: a report from the Task Force on Safety and Quality of the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 38(4):598–605
    • View reference on PubMed
  136. Lilly CM, Zuckerman IH, Badawi O, Riker RR (2011) Benchmark data from more than 240,000 adults that reflect the current practice of critical care in the United States. Chest 140(5):1232–1242
    • View reference on PubMed
  137. Effken JA, Loeb RG, Kang Y, Lin ZC (2008) Clinical information displays to improve ICU outcomes. Int J Med Inform 77:765–777
    • View reference on PubMed
  138. Koch S, Staggers N, Weir C, Agutter J, Liu D, Westenskow D (2010) Integrated information displays for ICU nurses: field observations, display design, and display evaluation. Proc Hum Fact Ergon Soc Annu Meet 54:932–936
  139. Morris G, Gardner R (1992) Computer Applications. In: Hall J, Schmidt G, Wood L (eds) Principles of critical care. McGraw-Hill, New York, pp 500–514
  140. De Turck F, Decruyenaere J, Thysebaert P, Van Hoecke S, Volckaert B, Danneels C, Colpaert K, De Moor G (2007) Design of a flexible platform for execution of medical decision support agents in the intensive care unit. Comput Biol Med 37:97–112
    • View reference on PubMed
  141. Jacono FF, DeGeorgia MA, Wilson CG, Dick TE, Loparo KA (2010) Data acquisition and complex systems analysis in critical care: developing the intensive care unit of the future. J Healthc Eng 1:337–338
  142. Zhang J (2005) Human-centered computing in health information systems Part 1: analysis and design. J Biomed Inform 38:1–3
    • View reference on PubMed
  143. Mock C, Kobusingye O, Joshipura M, Nguyen S, Arreola-Risa C (2005) Strengthening trauma and critical care globally. Curr Opin Crit Care 11:568–575
    • View reference on PubMed
  144. Sim SK, Lim SL, Lee HK, Liew D, Wong A (2011) Care of severe head injury patients in the Sarawak General Hospital: intensive care unit versus general ward. Med J Malays 66:138–141
  145. De Silva MJ, Roberts I, Perel P, Edwards P, Kenward MG, Fernandes J, Shakur H, Patel V, CRASH Trial Collaborators (2009) Patient outcome after traumatic brain injury in high-, middle- and low-income countries: analysis of data on 8927 patients in 46 countries. Int J Epidemiol 38:452–458
    • View reference on PubMed
  146. Biestro AA, Alberti RA, Soca AE, Cancela M, Puppo CB, Borovich B (1995) Use of indomethacin in brain-injured patients with cerebral perfusion pressure impairment: preliminary report. J Neurosurg 83:627–630
    • View reference on PubMed
  147. Rohlwink UK, Zwane E, Fieggen AG, Argent AC, Le Roux P, Figaji AA (2012) The relationship between intracranial pressure and brain oxygenation in children with severe traumatic brain injury. Neurosurgery 70(5):1220–1230
    • View reference on PubMed
  148. Whitmore RG, Thawani JP, Grady MS, Levine JM, Sanborn MR, Stein SC (2012) Is aggressive treatment of traumatic brain injury cost-effective? J Neurosurg 116:1106–1113
    • View reference on PubMed
  149. Diaz-Arrastia R (2012) Brain tissue oxygen monitoring in traumatic brain injury (TBI) (BOOST 2). http://clinicaltrials.gov/ct2/show/NCT00974259. Accessed 20 May 2014
  150. Hu X, Xu P, Asgari S, Vespa P, Bergsneider M (2010) Forecasting ICP elevation based on prescient changes of intracranial pressure waveform morphology. IEEE Trans Biomed Eng 57(5):1070–1078
    • View reference on PubMed
  151. Lazaridis C, Smielewski P, Steiner LA, Brady KM, Hutchinson P, Pickard JD, Czosnyka M (2013) Optimal cerebral perfusion pressure: are we ready for it? Neurol Res 35(2):138–148
    • View reference on PubMed
  152. Oddo M, Levine J, Frangos S, Maloney-Wilensky E, Carrera E, Daniel R, Magistretti PJ, Le Roux P (2012) Brain lactate metabolism in humans with subarachnoid haemorrhage. Stroke 43(5):1418–1421
    • View reference on PubMed
  153. Güiza F, Depreitere B, Piper I, Van den Berghe G, Meyfroidt G (2013) Novel methods to predict increased intracranial pressure during intensive care and long-term neurologic outcome after traumatic brain injury: development and validation in a multicenter dataset. Crit Care Med 41(2):554–564
    • View reference on PubMed
  154. Narotam PK, Morrison JF, Schmidt MD, Nathoo N (2014) Physiological complexity of acute traumatic brain injury in patients treated with a brain oxygen protocol: utility of symbolic regression (SR) in predictive modeling of a dynamical system. J Neurotrauma 31(7):630–641
    • View reference on PubMed
  155. Kim MN, Durduran T, Frangos S, Edlow BL, Buckley EM, Moss HE, Zhou C, Yu G, Choe R, Maloney-Wilensky E, Wolf RL, Grady MS, Greenberg JH, Levine JM, Yodh AG, Detre JA, Kofke WA (2010) Noninvasive measurement of cerebral blood flow and blood oxygenation using near-infrared and diffuse correlation spectroscopies in critically brain-injured adults. Neurocrit Care 12(2):173–180
    • View reference on PubMed
  156. Cammarata G, Ristagno G, Cammarata A, Mannanici G, Denaro C, Gullo A (2011) Ocular ultrasound to detect intracranial hypertension in trauma patients. J Trauma 71:779–781
    • View reference on PubMed
  157. Chen JW, Gombart ZJ, Rogers S, Gardiner SK, Cecil S, Bullock RM (2011) Pupillary reactivity as an early indicator of increased intracranial pressure: the introduction of the neurological pupil index. Surg Neurol Int 2:82
    • View reference on PubMed
  158. Hartings JA, Bullock MR, Okonkwo DO, Murray LS, Murray GD, Fabricius M, Maas AI, Woitzik J, Sakowitz O, Mathern B, Roozenbeek B, Lingsma H, Dreier JP, Puccio AM, Shutter LA, Pahl C, Strong AJ (2011) Co-Operative Study on Brain Injury Depolarisations. Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study. Lancet Neurol 10(12):1058–1064
    • View reference on PubMed
  159. Ragauskas A, Bartusis L, Piper I, Zakelis R, Matijosaitis V, Petrikonis K, Rastenyte D (2014) Improved diagnostic value of a TCD-based non-invasive ICP measurement method compared with the sonographic ONSD method for detecting elevated intracranial pressure. Neurol Res 36:607–614
    • View reference on PubMed
  160. Vespa PM (2005) Multimodality monitoring and telemonitoring in neurocritical care: from microdialysis to robotic telepresence. Curr Opin Crit Care 11(2):133–138
    • View reference on PubMed
  161. Sivaganesan A, Manly GT, Huang MC (2014) Informatics for neurocritical care: challenges and opportunities. Neurocrit Care 20(1):132–141
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement