АкушерствоАнатомияАнестезиологияВакцинопрофилактикаВалеологияВетеринарияГигиенаЗаболеванияИммунологияКардиологияНеврологияНефрологияОнкологияОториноларингологияОфтальмологияПаразитологияПедиатрияПервая помощьПсихиатрияПульмонологияРеанимацияРевматологияСтоматологияТерапияТоксикологияТравматологияУрологияФармакологияФармацевтикаФизиотерапияФтизиатрияХирургияЭндокринологияЭпидемиология

Внедрение, проблемы ресурса и ревизия

Прочитайте:
  1. V1: ПРОБЛЕМЫ ЭВТАНАЗИИ В РФ
  2. V1: СОВРЕМЕННЫЕ ПРОБЛЕМЫ ДОНОРСТВА
  3. V1: СОВРЕМЕННЫЕ ПРОБЛЕМЫ ДОНОРСТВА
  4. Актуальность проблемы
  5. Бюрократия и проблемы формирования конституционной экономики
  6. Бюрократия и проблемы формирования конституционной экономики
  7. ВАШИ ПСИХОЛОГИЧЕСКИЕ ПРОБЛЕМЫ ВОЗНИКАЮТ ПОТОМУ, ЧТО ВЫ С РОЖДЕНИЯ ЖИВЕТЕ В ВООБРАЖАЕМОМ ВАМИ СХЕМАТИЧНОМ ИДЕАЛЬНОМ МИРЕ.
  8. ВИЛОЧКОВАЯ ЖЕЛЕЗА (ПРОБЛЕМЫ)
  9. Возможные как следствие проблемы

 

8.1 Местное выполнение

Есть сообщения, что внедрение умеренной гипотермии после остановки сердца отстает в большей части развитого мира – несколько обзоров последних двух лет сообщают,

что только приблизительно 25% ОИТ когда-либо использовали эту терапию [3]. [215-218]

Однако, об успешном внедрение гипотермии сейчас сообщают много центров [2 +]. [15 38 39 59 114 219]

Алгоритм помощи после остановки сердца включает [4]: [12]

1. Ранняя коронарная реперфузия и нормализация гемодинамики

2. Контроль вентиляции

3. Контроль за глюкозой крови

4. Температурный контроль

5. Лечение судорожных приступов.

 

Местное внедрение алгоритма лечения после остановки сердца требует сотрудничества

врачей и медсестер нескольких специальностей, в частности, специалистов, работающих в области интенсивной терапии и реанимации, экстренной медицинской помощи и кардиологии. Адаптация местных протоколов оказания помощи должна быть проведена совместно представителями всех этих дисциплин.

 

8.2 Привлечение ресурса

Многие из вмешательств, применяемых в постреанимационный период, не требуют

дорогого оборудования. У более дорогих систем охлаждения есть небольшие преимущества, но они, в любом случае, не являются существенными. Достижение адекватного среднего артериального давления и контроль глюкозы крови - также относительно недорогие вмешательства. В некоторые системах здравоохранения отсутствие интервенционных систем кардиологии мешает осуществлению своевременного ЧКВ в первые 24 часа, но в большинстве случаев возможно достигнуть ранней реперфузии посредством тромболитической терапии. Использование гипотермии не должно значительно увеличивать продолжительность пребывания в ОИТ. Данные, подтверждающие это, ожидаются.

 

8.3 Ключевые пункты для ревизии

Оказание помощи после остановки сердца должно быть предметом регулярной ревизии. Результат лечения пациентов, поступивших в ОИТ после остановки сердца, должен быть предметом регулярной и непрерывной ревизии.

 

8.4 Рекомендации для исследования

Следующие ключевые вопросы исследований, касающиеся послереанимационного периода, должны быть адаптированы из данных, собранных рабочими группами AHA/ILCOR [4]. [10 220].

 

8.4.1 Эпидемиология

Изучение и контроль тенденций прогноза после остановки сердца в Великобритании.

 

8.4.2 Патофизиология

1. Механизмы и время течения комы после остановки сердца

2. Механизмы и продолжительность нейродегенерации после остановки сердца

3. Механизмы и продолжительность миокардиальной дисфункции после остановки сердца

4. Механизмы и продолжительность доставки кислорода и его утилизации после остановки сердца

5. Роль внутрисосудистой коагуляции в дисфункции и недостаточности органов после остановки сердца

6. Механизм, продолжительность и значение надпочечниковой недостаточности после остановки сердца.

 

8.4.3 Терапия

1. Оптимальное применение терапевтической гипотермии у пациента после остановки сердца.

a. Какая польза для пациентов?

b. Оптимальная целевая температура, начало, продолжительность, и уровень нагревания

c. Самая эффективная техника охлаждения – внешняя или внутренняя

d. Показания для использования миорелаксантов

 

2. Показания для раннего чрезкожного коронарного вмешательства

3. Оптимальная терапия миокардиальной дисфункции после остановки сердца:

a. медикаментозная

b. механическая

4. Клиническая польза контролируемой реоксигенации

5. Клиническая польза достижения ранней оптимизации гемодинамики

6. Оптимальные цели (параметры и целевые диапазоны) для ранней оптимизации гемодинамики:

a. Среднее артериальное давление

b. Центральное венозное давление

c. Насыщение кислородом центральной венозной крови и смешанной венозной крови

d. Концентрация гемоглобина и переливание крови

e. Концентрация лактата

f. Диурез

g. Доставка кислорода

h. Другое.

7. Клиническая польза контроля за глюкозой и оптимального целевого диапазона глюкозы.

8. Роль высоко-объемного гемодиализа

9. Роль ранней глюкокортикоидной терапии

10. Роль профилактического назначения антиконвульсантов

11. Роль определенного периода седации и вентиляции

12. Роль нейропротективных препаратов.

 

8.4.4 Прогноз

1. Оптимальная схема принятия решения для определения нецелесообразности дальнейшего продолжения лечения

2. Воздействие терапевтической гипотермии на достоверность предсказания

нецелесообразности.

 

8.4.5 Педиатрия

1. Доказательства возможности применения для детей знаний, упомянутых выше

2. Роль экстракорпоральной мембранной оксигенации в терапии остановки сердца у детей и в ведении детей после остановки.

 

8.4.5 Барьеры

1. Наиболее эффективный подход для осуществления терапевтической гипотермии и

оптимизация помощи пациентам после остановки сердца

2. Ценность региональной помощи после остановки сердца специализированными центрами.

 

Ссылки

1. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world:

Global Burden of Disease Study. Lancet 1997; 349: 1269-76.

2. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the

United States, 1989 to 1998. Circulation 2001; 104: 2158-63.

3. Pell JP, Sirel JM, Marsden AK, et al. Presentation, management, and

outcome of out of hospital cardiopulmonary arrest: comparison by underlying

aetiology. Heart 2003; 89: 839-42.

4. Cobb LA, Fahrenbruch CE, Olsufka M, Copass MK. Changing incidence of

out-of-hospital ventricular fibrillation, 1980-2000. JAMA 2002; 288: 3008-13.

5. Atwood C, Eisenberg MS, Herlitz J, Rea TD. Incidence of EMS-treated out-ofhospital

cardiac arrest in Europe. Resuscitation 2005; 67: 75-80.

6. Hodgetts TJ, Kenward G, Vlackonikolis I, et al. Incidence, location and

reasons for avoidable in-hospital cardiac arrest in a district general hospital.

Resuscitation 2002; 54: 115-23.

7. Gwinnutt CL, Columb M, Harris R. Outcome after cardiac arrest in adults in

UK hospitals: effect of the 1997 guidelines. Resuscitation 2000; 47: 125-35.

8. Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation of

adults in the hospital: a report of 14720 cardiac arrests from the National

Registry of Cardiopulmonary Resuscitation. Resuscitation 2003; 58: 297-308.

9. Adrie C, Adib-Conquy M, Laurent I, et al. Successful cardiopulmonary

resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation

2002; 106: 562-8.

10. Neumar R, Nolan JP. AHA/ILCOR Post-Cardiac Arrest Statement of Science.

Circulation 2008; In Press.

11. Soar J, Nolan JP. Mild hypothermia for post cardiac arrest syndrome. BMJ

2007; 335: 459-60.

12. Nolan JP, Soar J. Post resuscitation care – time for a care bundle?

Resuscitation 2008; 76.

13. Nolan JP, Laver SR, Welch CA, et al. Outcome following admission to UK

intensive care units after cardiac arrest: a secondary analysis of the ICNARC

Case Mix Programme Database. Anaesthesia 2007; 62: 1207-16.

14. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an

intensive care unit following cardiac arrest. Intensive Care Med 2004; 30:

2126-8.

15. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised

treatment protocol for post resuscitation care after out-of-hospital cardiac

arrest. Resuscitation 2007.

16. Langhelle A, Tyvold SS, Lexow K, et al. In-hospital factors associated with

improved outcome after out-of-hospital cardiac arrest. A comparison between

four regions in Norway. Resuscitation 2003; 56: 247-63.

17. Langhelle A, Nolan J, Herlitz J, et al. Recommended guidelines for reviewing,

reporting, and conducting research on post-resuscitation care: the Utstein

style. Resuscitation 2005; 66: 271-83.

18. Herlitz J, Engdahl J, Svensson L, et al. Major differences in 1-month survival

between hospitals in Sweden among initial survivors of out-of-hospital cardiac

arrest. Resuscitation 2006; 70: 404-9.

19. International Liaison Committee on Resuscitation. 2005 International

Consensus on Cardiopulmonary Resuscitation and Emergency

Cardiovascular Care Science with Treatment Recommendations.

Resuscitation 2005; 67: 157-341.

20. Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation of cerebral blood

flow in patients resuscitated from cardiac arrest. Stroke 2001; 32: 128-32.

21. Buunk G, van der Hoeven JG, Meinders AE. Cerebrovascular reactivity in

comatose patients resuscitated from a cardiac arrest. Stroke 1997; 28: 1569-

73.

22. Buunk G, van der Hoeven JG, Meinders AE. A comparison of near-infrared

spectroscopy and jugular bulb oximetry in comatose patients resuscitated

from a cardiac arrest. Anaesthesia 1998; 53: 13-9.

23. Roine RO, Launes J, Nikkinen P, Lindroth L, Kaste M. Regional cerebral

blood flow after human cardiac arrest. A hexamethylpropyleneamine oxime

single photon emission computed tomographic study. Arch Neurol 1991; 48:

625-9.

24. Beckstead JE, Tweed WA, Lee J, MacKeen WL. Cerebral blood flow and

metabolism in man following cardiac arrest. Stroke 1978; 9: 569-73.

25. Buunk G, van der Hoeven JG, Frolich M, Meinders AE. Cerebral

vasoconstriction in comatose patients resuscitated from a cardiac arrest?

Intensive Care Med 1996; 22: 1191-6.

26. Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged

hyperventilation in patients with severe head injury: a randomized clinical trial.

J Neurosurg 1991; 75: 731-9.

27. Vereczki V, Martin E, Rosenthal RE, et al. Normoxic resuscitation after

cardiac arrest protects against hippocampal oxidative stress, metabolic

dysfunction, and neuronal death. J Cereb Blood Flow Metab 2006; 26: 821-

35.

28. Richards EM, Fiskum G, Rosenthal RE, Hopkins I, McKenna MC. Hyperoxic

reperfusion after global ischemia decreases hippocampal energy metabolism.

Stroke 2007; 38: 1578-84.

29. Balan IS, Fiskum G, Hazelton J, Cotto-Cumba C, Rosenthal RE. Oximetryguided

reoxygenation improves neurological outcome after experimental

cardiac arrest. Stroke 2006; 37: 3008-13.

30. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac

arrhythmias. N Engl J Med 2001; 345: 1473-82.

31. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation 1998; 98: 2334-51.

32. Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography

in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336: 1629-

33.

33. Bendz B, Eritsland J, Nakstad AR, et al. Long-term prognosis after out-ofhospital

cardiac arrest and primary percutaneous coronary intervention.

Resuscitation 2004; 63: 49-53.

34. Keelan PC, Bunch TJ, White RD, Packer DL, Holmes DR, Jr. Early direct

coronary angioplasty in survivors of out-of-hospital cardiac arrest. Am J

Cardiol 2003; 91: 1461-3, A6.

35. Quintero-Moran B, Moreno R, Villarreal S, et al. Percutaneous coronary

intervention for cardiac arrest secondary to ST-elevation acute myocardial

infarction. Influence of immediate paramedical/medical assistance on clinical

outcome. J Invasive Cardiol 2006; 18: 269-72.

36. Garot P, Lefevre T, Eltchaninoff H, et al. Six-month outcome of emergency

percutaneous coronary intervention in resuscitated patients after cardiac

arrest complicating ST-elevation myocardial infarction. Circulation 2007; 115:

1354-62.

37. Gorjup V, Radsel P, Kocjancic ST, Erzen D, Noc M. Acute ST-elevation

myocardial infarction after successful cardiopulmonary resuscitation.

Resuscitation 2007; 72: 379-85.

38. Hovdenes J, Laake JH, Aaberge L, Haugaa H, Bugge JF. Therapeutic

hypothermia after out-of-hospital cardiac arrest: experiences with patients

treated with percutaneous coronary intervention and cardiogenic shock. Acta

Anaesthesiol Scand 2007; 51: 137-42.

39. Knafelj R, Radsel P, Ploj T, Noc M. Primary percutaneous coronary

intervention and mild induced hypothermia in comatose survivors of

ventricular fibrillation with ST-elevation acute myocardial infarction.

Resuscitation 2007; 74: 227-34.

40. Bottiger BW, Bode C, Kern S, et al. Efficacy and safety of thrombolytic

therapy after initially unsuccessful cardiopulmonary resuscitation: a

prospective clinical trial. Lancet 2001; 357: 1583-5.

41. van Campen LC, van Leeuwen GR, Verheugt FW. Safety and efficacy of

thrombolysis for acute myocardial infarction in patients with prolonged out-ofhospital

cardiopulmonary resuscitation. Am J Cardiol 1994; 73: 953-5.

42. Abu-Laban RB, Christenson JM, Innes GD, et al. Tissue plasminogen

activator in cardiac arrest with pulseless electrical activity. N Engl J Med

2002; 346: 1522-8.

43. 2005 International Consensus on Cardiopulmonary Resuscitation and

Emergency Cardiovascular Care Science with Treatment Recommendations.

Part 5: Acute coronary syndromes. Resuscitation 2005; 67: 249-69.

44. Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary

angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J

Med 2003; 349: 733-42.

45. Berger PB, Ellis SG, Holmes DR, Jr., et al. Relationship between delay in

performing direct coronary angioplasty and early clinical outcome in patients

with acute myocardial infarction: results from the global use of strategies to

open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial.

Circulation 1999; 100: 14-20.

46. A clinical trial comparing primary coronary angioplasty with tissue

plasminogen activator for acute myocardial infarction. The Global Use of

Strategies to Open Occluded Coronary Arteries in Acute Coronary

Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. N Engl J Med

1997; 336: 1621-8.

47. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute

myocardial infarction complicated by cardiogenic shock. SHOCK

Investigators. Should We Emergently Revascularize Occluded Coronaries for

Cardiogenic Shock. N Engl J Med 1999; 341: 625-34.

48. Widimsky P, Budesinsky T, Vorac D, et al. Long distance transport for primary

angioplasty vs immediate thrombolysis in acute myocardial infarction. Final

results of the randomized national multicentre trial--PRAGUE-2. Eur Heart J

2003; 24: 94-104.

49. Zijlstra F, Patel A, Jones M, et al. Clinical characteristics and outcome of

patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation

treated by primary coronary angioplasty or thrombolytic therapy for acute

myocardial infarction. Eur Heart J 2002; 23: 550-7.

50. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary

angioplasty versus immediate thrombolysis in acute myocardial infarction: a

meta-analysis. Circulation 2003; 108: 1809-14.

51. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous

thrombolytic therapy for acute myocardial infarction: a quantitative review of

23 randomised trials. Lancet 2003; 361: 13-20.

52. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary

angioplasty and intravenous thrombolytic therapy for acute myocardial

infarction: a quantitative review [published correction appears in JAMA.

1998;279:1876]. JAMA 1997; 278: 2093-8.

53. Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated

percutaneous coronary interventions for ST-elevation myocardial infarction:

quantitative review of randomised trials. Lancet 2006; 367: 579-88.

54. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in

survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 2002; 40: 2110-6.

55. Ruiz-Bailen M, Aguayo de Hoyos E, Ruiz-Navarro S, et al. Reversible

myocardial dysfunction after cardiopulmonary resuscitation. Resuscitation

2005; 66: 175-81.

56. Kern KB, Hilwig RW, Rhee KH, Berg RA. Myocardial dysfunction after

resuscitation from cardiac arrest: an example of global myocardial stunning. J

Am Coll Cardiol 1996; 28: 232-40.

57. Adrie C, Adib-Conquy M, Laurent I, et al. Successful cardiopulmonary

resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation

2002; 106: 562-8.

58. Mullner M, Sterz F, Binder M, et al. Arterial blood pressure after human

cardiac arrest and neurological recovery. Stroke 1996; 27: 59-62.

59. Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L. From evidence to clinical

practice: effective implementation of therapeutic hypothermia to improve

patient outcome after cardiac arrest. Crit Care Med 2006; 34: 1865-73.

60. Myerburg RJ, Briese FW, Conde C, et al. Long-term antiarrhythmic therapy in

survivors of prehospital cardiac arrest. Initial 18 months' experience. JAMA

1977; 238: 2621-4.

61. Somberg JC, Laux B, Wynn J, Keefe D, Miura DS. Lorcainide therapy in a

cardiac arrest population. Am Heart J 1986; 111: 648-53.

62. Moosvi AR, Goldstein S, VanderBrug Medendorp S, et al. Effect of empiric

antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims

with coronary artery disease. Am J Cardiol 1990; 65: 1192-7.

63. Haverkamp W, Martinez-Rubio A, Hief C, et al. Efficacy and safety of d,lsotalol

in patients with ventricular tachycardia and in survivors of cardiac

arrest. J Am Coll Cardiol 1997; 30: 487-95.

64. Hallstrom AP, Cobb LA, Yu BH, Weaver WD, Fahrenbruch CE. An

antiarrhythmic drug experience in 941 patients resuscitated from an initial

cardiac arrest between 1970 and 1985. Am J Cardiol 1991; 68: 1025-31.

65. Peter T, Hamer A, Weiss D, Mandel WJ. Prognosis after sudden cardiac

death without associated myocardial infarction: one year follow-up of empiric

therapy with amiodarone. Am Heart J 1984; 107: 209-13.

66. Randomized antiarrhythmic drug therapy in survivors of cardiac arrest (the

CASCADE Study). The CASCADE Investigators. Am J Cardiol 1993; 72: 280-

7.

67. Wever EFD, Hauer RNW, Van Capelle FJL, et al. Randomized study of

implantable defibrillator as first-choice therapy versus conventional strategy in

postinfarct sudden death survivors. Circulation 1995; 91: 2195-203.

68. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in

patients resuscitated from near-fatal ventricular arrhythmias. The

Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. N Engl

J Med 1997; 337: 1576-83.

69. Connolly SJ, Gent M, Roberts RS, et al. Canadian implantable defibrillator

study (CIDS): A randomized trial of the implantable cardioverter defibrillator

against amiodarone. Circulation 2000; 101: 1297-302.

70. Connolly SJ, Hallstrom AP, Cappato R, et al. Metal-analysis of the

implantable cardioverter defibrillator secondary prevention trials. Eur Heart J

2000; 21: 2071-8.

71. Hennersdorf MG, Niebch V, Vester EG, et al. Long-term follow-up of sudden

cardiac arrest survivors and electrophysiologically guided antiarrhythmic

therapy. Cardiology 2003; 99: 190-7.

72. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers,

amiodarone plus beta-blockers, or sotalol for prevention of shocks from

implantable cardioverter defibrillators: the OPTIC Study: a randomized trial.

Jama 2006; 295: 165-71.

73. Martin GB, Nowak RM, Cisek JE, Carden DL, Tomlanovich MC.

Hyperkalemia during human cardiopulmonary resuscitation: incidence and

ramifications. J Emerg Med 1989; 7: 109-13.

74. Hekimian G, Baugnon T, Thuong M, et al. Cortisol levels and adrenal reserve

after successful cardiac arrest resuscitation. Shock 2004; 22: 116-9.

75. Schultz CH, Rivers EP, Feldkamp CS, et al. A characterization of

hypothalamic-pituitary-adrenal axis function during and after human cardiac

arrest. Crit Care Med 1993; 21: 1339-47.

76. Pene F, Hyvernat H, Mallet V, et al. Prognostic value of relative adrenal

insufficiency after out-of-hospital cardiac arrest. Intensive Care Med 2005; 31:

627-33.

77. Kim JJ, Lim YS, Shin JH, et al. Relative adrenal insufficiency after cardiac

arrest: impact on postresuscitation disease outcome. Am J Emerg Med 2006;

24: 684-8.

78. Miller JB, Donnino MW, Rogan M, Goyal N. Relative adrenal insufficiency in

post-cardiac arrest shock is under-recognized. Resuscitation 2007.

79. Tsai MS, Huang CH, Chang WT, et al. The effect of hydrocortisone on the

outcome of out-of-hospital cardiac arrest patients: a pilot study. Am J Emerg

Med 2007; 25: 318-25.

80. Adrie C, Monchi M, Laurent I, et al. Coagulopathy after successful

cardiopulmonary resuscitation following cardiac arrest: implication of the

protein C anticoagulant pathway. J Am Coll Cardiol 2005; 46: 21-8.

81. Laurent I, Adrie C, Vinsonneau C, et al. High-volume hemofiltration after outof-

hospital cardiac arrest: a randomized study. J Am Coll Cardiol 2005; 46:

432-7.

82. Neumar RW. Molecular mechanisms of ischemic neuronal injury. Ann Emerg

Med 2000; 36: 483-506.

83. Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999; 79: 1431-

568.

84. Bano D, Nicotera P. Ca2+ signals and neuronal death in brain ischemia.

Stroke 2007; 38: 674-6.

85. Ames A, 3rd, Wright RL, Kowada M, Thurston JM, Majno G. Cerebral

ischemia. II. The no-reflow phenomenon. Am J Pathol 1968; 52: 437-53.

86. Wolfson SK, Jr., Safar P, Reich H, et al. Dynamic heterogeneity of cerebral

hypoperfusion after prolonged cardiac arrest in dogs measured by the stable

xenon/CT technique: a preliminary study. Resuscitation 1992; 23: 1-20.

87. Nishizawa H, Kudoh I. Cerebral autoregulation is impaired in patients

resuscitated after cardiac arrest. Acta Anaesthesiol Scand 1996; 40: 1149-53.

88. Angelos MG, Ward KR, Hobson J, Beckley PD. Organ blood flow following

cardiac arrest in a swine low-flow cardiopulmonary bypass model.

Resuscitation 1994; 27: 245-54.

89. Buunk G, van der Hoeven JG, Meinders AE. Cerebral blood flow after cardiac

arrest. Neth J Med 2000; 57: 106-12.

90. Sakabe T, Tateishi A, Miyauchi Y, et al. Intracranial pressure following

cardiopulmonary resuscitation. Intensive Care Med 1987; 13: 256-9.

91. Morimoto Y, Kemmotsu O, Kitami K, Matsubara I, Tedo I. Acute brain swelling

after out-of-hospital cardiac arrest: pathogenesis and outcome. Crit Care Med

1993; 21: 104-10.

92. Torbey MT, 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: 2163-7.

93. Iida K, Satoh H, Arita K, et al. Delayed hyperemia causing intracranial

hypertension after cardiopulmonary resuscitation. Crit Care Med 1997; 25:

971-6.

94. Rello J, Diaz E, Roque M, Valles J. Risk factors for developing pneumonia

within 48 hours of intubation. Am J Respir Crit Care Med 1999; 159: 1742-6.

95. Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug

disposition, metabolism, and response: A focus of hypothermia-mediated

alterations on the cytochrome P450 enzyme system. Crit Care Med 2007; 35:

2196-204.

96. Zandbergen EG, Hijdra A, Koelman JH, et al. Prediction of poor outcome

within the first 3 days of postanoxic coma. Neurology 2006; 66: 62-8.

97. Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardiopulmonary

resuscitation: relation to seizures and myoclonus. Neurology 1988; 38: 401-5.

98. Levy DE, Caronna JJ, Singer BH, et al. Predicting outcome from hypoxicischemic

coma. JAMA 1985; 253: 1420-6.

99. Snyder BD, Hauser WA, Loewenson RB, et al. Neurologic prognosis after

cardiopulmonary arrest, III: seizure activity. Neurology 1980; 30: 1292-7.

100. Ingvar M. Cerebral blood flow and metabolic rate during seizures.

Relationship to epileptic brain damage. Ann N Y Acad Sci 1986; 462: 194-

206.

101. Caviness JN, Brown P. Myoclonus: current concepts and recent advances.

Lancet Neurol 2004; 3: 598-607.

102. Wijdicks EF. Propofol in myoclonus status epilepticus in comatose patients

following cardiac resuscitation. J Neurol Neurosurg Psychiatry 2002; 73: 94-5.

103. Rundgren M, Rosen I, Friberg H. Amplitude-integrated EEG (aEEG) predicts

outcome after cardiac arrest and induced hypothermia. Intensive Care Med

2006; 32: 836-42.

104. Takino M, Okada Y. Hyperthermia following cardiopulmonary resuscitation.

Intensive Care Med 1991; 17: 419-20.

105. Takasu A, Saitoh D, Kaneko N, Sakamoto T, Okada Y. Hyperthermia: is it an

ominous sign after cardiac arrest? Resuscitation 2001; 49: 273-7.

106. Hickey RW, Kochanek PM, Ferimer H, et al. Induced hyperthermia

exacerbates neurologic neuronal histologic damage after asphyxial cardiac

arrest in rats. Crit Care Med 2003; 31: 531-5.

107. Zeiner A, Holzer M, Sterz F, et al. Hyperthermia after cardiac arrest is

associated with an unfavorable neurologic outcome. Arch Intern Med 2001;

161: 2007-12.

108. Coimbra C, Boris-Moller F, Drake M, Wieloch T. Diminished neuronal damage

in the rat brain by late treatment with the antipyretic drug dipyrone or cooling

following cerebral ischemia. Acta Neuropathol (Berl) 1996; 92: 447-53.

109. Coimbra C, Drake M, Boris-Moller F, Wieloch T. Long-lasting neuroprotective

effect of postischemic hypothermia and treatment with an antiinflammatory/

antipyretic drug: evidence for chronic encephalopathic

processes following ischemia. Stroke 1996; 27: 1578-85.

110. Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia

to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;

346: 549-56.

111. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of

out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;

346: 557-63.

112. Holzer M, Bernard SA, Hachimi-Idrissi S, et al. Hypothermia for

neuroprotection after cardiac arrest: systematic review and individual patient

data meta-analysis. Crit Care Med 2005; 33: 414-8.

113. Bernard SA, Jones BM, Horne MK. Clinical trial of induced hypothermia in

comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 1997;

30: 146-53.

114. Busch M, Soreide E, Lossius HM, Lexow K, Dickstein K. Rapid

implementation of therapeutic hypothermia in comatose out-of-hospital

cardiac arrest survivors. Acta Anaesthesiol Scand 2006; 50: 1277-83.

115. Arrich J. Clinical application of mild therapeutic hypothermia after cardiac

arrest. Crit Care Med 2007; 35: 1041-7.

116. Holzer M, Mullner M, Sterz F, et al. Efficacy and safety of endovascular

cooling after cardiac arrest: cohort study and Bayesian approach. Stroke

2006; 37: 1792-7.

117. 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: 275-81.

118. Kim F, Olsufka M, Longstreth WT, Jr., et al. Pilot randomized clinical trial of

prehospital induction of mild hypothermia in out-of-hospital cardiac arrest

patients with a rapid infusion of 4 degrees C normal saline. Circulation 2007;

115: 3064-70.

119. Bernard S, Buist M, Monteiro O, Smith K. Induced hypothermia using large

volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital

cardiac arrest: a preliminary report. Resuscitation 2003; 56: 9-13.

120. Virkkunen I, Yli-Hankala A, Silfvast T. Induction of therapeutic hypothermia

after cardiac arrest in prehospital patients using ice-cold Ringer's solution: a

pilot study. Resuscitation 2004; 62: 299-302.

121. Al-Senani FM, Graffagnino C, Grotta JC, et al. A prospective, multicenter pilot

study to evaluate the feasibility and safety of using the CoolGard System and

Icy catheter following cardiac arrest. Resuscitation 2004; 62: 143-50.

122. Kliegel A, Losert H, Sterz F, et al. Cold simple intravenous infusions

preceding special endovascular cooling for faster induction of mild

hypothermia after cardiac arrest--a feasibility study. Resuscitation 2005; 64:

347-51.

123. Haugk M, Sterz F, Grassberger M, et al. Feasibility and efficacy of a new noninvasive

surface cooling device in post-resuscitation intensive care medicine.

Resuscitation 2007.

124. Kim F, Olsufka M, Carlbom D, et al. Pilot study of rapid infusion of 2 L of 4

degrees C normal saline for induction of mild hypothermia in hospitalized,

comatose survivors of out-of-hospital cardiac arrest. Circulation 2005; 112:

715-9.

125. Polderman KH, Rijnsburger ER, Peerdeman SM, Girbes AR. Induction of

hypothermia in patients with various types of neurologic injury with use of

large volumes of ice-cold intravenous fluid. Crit Care Med 2005; 33: 2744-51.

126. Kliegel A, Janata A, Wandaller C, et al. Cold infusions alone are effective for

induction of therapeutic hypothermia but do not keep patients cool after

cardiac arrest. Resuscitation 2007; 73: 46-53.

127. Diringer MN, Reaven NL, Funk SE, Uman GC. Elevated body temperature

independently contributes to increased length of stay in neurologic intensive

care unit patients. Crit Care Med 2004; 32: 1489-95.

128. Keller E, Imhof HG, Gasser S, Terzic A, Yonekawa Y. Endovascular cooling

with heat exchange catheters: a new method to induce and maintain

hypothermia. Intensive Care Med 2003; 29: 939-43.

129. Schmutzhard E, Engelhardt K, Beer R, et al. Safety and efficacy of a novel

intravascular cooling device to control body temperature in neurologic

intensive care patients: a prospective pilot study. Crit Care Med 2002; 30:

2481-8.

130. Guluma KZ, Hemmen TM, Olsen SE, Rapp KS, Lyden PD. A trial of

therapeutic hypothermia via endovascular approach in awake patients with

acute ischemic stroke: methodology. Acad Emerg Med 2006; 13: 820-7.

131. Agnew DM, Koehler RC, Guerguerian AM, et al. Hypothermia for 24 hours

after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is

sustained 10 days after rewarming. Pediatr Res 2003; 54: 253-62.

132. Hicks SD, DeFranco DB, Callaway CW. Hypothermia during reperfusion after

asphyxial cardiac arrest improves functional recovery and selectively alters

stress-induced protein expression. J Cereb Blood Flow Metab 2000; 20: 520-

30.

133. Sterz F, Safar P, Tisherman S, et al. Mild hypothermic cardiopulmonary

resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit

Care Med 1991; 19: 379-89.

134. Xiao F, Safar P, Radovsky A. Mild protective and resuscitative hypothermia

for asphyxial cardiac arrest in rats. Am J Emerg Med 1998; 16: 17-25.

135. Katz LM, Young AS, Frank JE, Wang Y, Park K. Regulated hypothermia

reduces brain oxidative stress after hypoxic-ischemia. Brain Res 2004; 1017:

85-91.

136. Abella BS, Zhao D, Alvarado J, et al. Intra-arrest cooling improves outcomes

in a murine cardiac arrest model. Circulation 2004; 109: 2786-91.

137. Lawrence EJ, Dentcheva E, Curtis KM, et al. Neuroprotection with delayed

initiation of prolonged hypothermia after in vitro transient global brain

ischemia. Resuscitation 2005; 64: 383-8.

138. Kuboyama K, Safar P, Radovsky A, et al. Delay in cooling negates the

beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest

in dogs: a prospective, randomized study. Crit Care Med 1993; 21: 1348-58.

139. Wolff B, Machill K, Schumacher D, Schulzki I, Werner D. Early achievement

of mild therapeutic hypothermia and the neurologic outcome after cardiac

arrest. Int J Cardiol 2008.

140. Hovland A, Nielsen EW, Kluver J, Salvesen R. EEG should be performed

during induced hypothermia. Resuscitation 2006; 68: 143-6.

141. Polderman KH, Peerdeman SM, Girbes AR. Hypophosphatemia and

hypomagnesemia induced by cooling in patients with severe head injury. J

Neurosurg 2001; 94: 697-705.

142. Polderman KH. Application of therapeutic hypothermia in the intensive care

unit. Opportunities and pitfalls of a promising treatment modality--Part 2:

Practical aspects and side effects. Intensive Care Med 2004; 30: 757-69.

143. Calle PA, Buylaert WA, Vanhaute OA. Glycemia in the post-resuscitation

period. The Cerebral Resuscitation Study Group. Resuscitation 1989; 17

Suppl: S181-8; discussion S99-206.

144. Longstreth WT, Jr., Diehr P, Inui TS. Prediction of awakening after out-ofhospital

cardiac arrest. N Engl J Med 1983; 308: 1378-82.

145. Longstreth WT, Jr., Inui TS. High blood glucose level on hospital admission

and poor neurological recovery after cardiac arrest. Ann Neurol 1984; 15: 59-

63.

146. Longstreth WT, Jr., Copass MK, Dennis LK, et al. Intravenous glucose after

out-of-hospital cardiopulmonary arrest: a community-based randomized trial.

Neurology 1993; 43: 2534-41.

147. Mackenzie CF. A review of 100 cases of cardiac arrest and the relation of

potassium, glucose, and haemoglobin levels to survival. West Indian Med J

1975; 24: 39-45.

148. Mullner M, Sterz F, Binder M, et al. Blood glucose concentration after

cardiopulmonary resuscitation influences functional neurological recovery in

human cardiac arrest survivors. J Cereb Blood Flow Metab 1997; 17: 430-6.

149. Skrifvars MB, Pettila V, Rosenberg PH, Castren M. A multiple logistic

regression analysis of in-hospital factors related to survival at six months in

patients resuscitated from out-of-hospital ventricular fibrillation. Resuscitation

2003; 59: 319-28.

150. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress

hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a

systematic overview. Stroke 2001; 32: 2426-32.

151. Baird TA, Parsons MW, Phanh T, et al. Persistent poststroke hyperglycemia

is independently associated with infarct expansion and worse clinical

outcome. Stroke 2003; 34: 2208-14.

152. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in

the critically ill patients. N Engl J Med 2001; 345: 1359-67.

153. Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ.

Insulin therapy protects the central and peripheral nervous system of

intensive care patients. Neurology 2005; 64: 1348-53.

154. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in

the medical ICU. N Engl J Med 2006; 354: 449-61.

155. Katz LM, Wang Y, Ebmeyer U, Radovsky A, Safar P. Glucose plus insulin

infusion improves cerebral outcome after asphyxial cardiac arrest.

Neuroreport 1998; 9: 3363-7.

156. Oksanen T, Skrifvars MB, Varpula T, et al. Strict versus moderate glucose

control after resuscitation from ventricular fibrillation. Intensive Care Med

2007.

157. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in

critically ill patients. JAMA 2003; 290: 2041-7.

158. Losert H, Sterz F, Roine RO, et al. Strict normoglycaemic blood glucose

levels in the therapeutic management of patients within 12h after cardiac

arrest might not be necessary. Resuscitation 2007.

159. Marik PE, Varon J. Intensive insulin therapy in the ICU: is it now time to jump

off the bandwagon? Resuscitation 2007; 74: 191-3.

160. Watkinson P, Barber VS, Young JD. Strict glucose control in the critically ill.

BMJ 2006; 332: 865-6.

161. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. 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:

203-10.

162. Skogvoll E, Isern E, Sangolt GK, Gisvold SE. In-hospital cardiopulmonary

resuscitation. 5 years' incidence and survival according to the Utstein

template. Acta Anaesthesiol Scand 1999; 43: 177-84.

163. Di Bari M, Chiarlone M, Fumagalli S, et al. Cardiopulmonary resuscitation of

older, inhospital patients: immediate efficacy and long-term outcome. Crit

Care Med 2000; 28: 2320-5.

164. Schwenzer KJ, Smith WT, Durbin CG, Jr. Selective application of

cardiopulmonary resuscitation improves survival rates. Anesth Analg 1993;

76: 478-84.

165. Ballew KA, Philbrick JT, Caven DE, Schorling JB. Predictors of survival

following in-hospital cardiopulmonary resuscitation. A moving target. Arch

Intern Med 1994; 154: 2426-32.

166. Tunstall-Pedoe H, Bailey L, Chamberlain DA, et al. Survey of 3765

cardiopulmonary resuscitations in British hospitals (the BRESUS Study):

methods and overall results. BMJ 1992; 304: 1347-51.

167. Cooper S, Janghorbani M, Cooper G. A decade of in-hospital resuscitation:

outcomes and prediction of survival? Resuscitation 2006; 68: 231-7.

168. de Vos R, Koster RW, De Haan RJ, et al. In-hospital cardiopulmonary

resuscitation: prearrest morbidity and outcome. Arch Intern Med 1999; 159:

845-50.

169. Cooper S, Cade J. Predicting survival, in-hospital cardiac arrests:

resuscitation survival variables and training effectiveness. Resuscitation

1997; 35: 17-22.

170. Rogove HJ, Safar P, Sutton-Tyrrell K, Abramson NS. Old age does not

negate good cerebral outcome after cardiopulmonary resuscitation: analyses

from the brain resuscitation clinical trials. The Brain Resuscitation Clinical

Trial I and II Study Groups. Crit Care Med 1995; 23: 18-25.

171. Adrie C, Cariou A, Mourvillier B, et al. Predicting survival with good

neurological recovery at hospital admission after successful resuscitation of

out-of-hospital cardiac arrest: the OHCA score. Eur Heart J 2006; 27: 2840-5.

172. Mullner M, Sterz F, Domanovits H, et al. The association between blood

lactate concentration on admission, duration of cardiac arrest, and functional

neurological recovery in patients resuscitated from ventricular fibrillation.

Intensive Care Med 1997; 23: 1138-43.

173. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead,

vegetative, or severely neurologically impaired? Assessing outcome for

comatose survivors of cardiac arrest. JAMA 2004; 291: 870-9.

174. Edgren E, Hedstrand U, Kelsey S, Sutton-Tyrrell K, Safar P. Assessment of

neurological prognosis in comatose survivors of cardiac arrest. BRCT I Study

Group. Lancet 1994; 343: 1055-9.

175. Madl C, Grimm G, Kramer L, et al. Early prediction of individual outcome after

cardiopulmonary resuscitation. Lancet 1993; 341: 855-8.

176. Chen R, Bolton CF, Young B. Prediction of outcome in patients with anoxic

coma: a clinical and electrophysiologic study. Crit Care Med 1996; 24: 672-8.

177. Johkura K, Komiyama A, Kuroiwa Y. Vertical conjugate eye deviation in

postresuscitation coma. Ann Neurol 2004; 56: 878-81.

178. Bassetti C, Bomio F, Mathis J, Hess CW. Early prognosis in coma after

cardiac arrest: a prospective clinical, electrophysiological, and biochemical

study of 60 patients. J Neurol Neurosurg Psychiatry 1996; 61: 610-5.

179. Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of myoclonus status

in comatose survivors of cardiac arrest. Ann Neurol 1994; 35: 239-43.

180. Cheliout-Heraut F, Durand MC, Clair B, Gajdos P, Raphael JC. [Importance

of evoked potentials in the evolutive prognosis of coma during cerebral anoxia

in adults]. Neurophysiol Clin 1992; 22: 269-80.

181. Pfeifer R, Borner A, Krack A, et al. 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: 49-55.

182. Zandbergen EG, de Haan RJ, Stoutenbeek CP, Koelman JH, Hijdra A.

Systematic review of early prediction of poor outcome in anoxic-ischaemic

coma. Lancet 1998; 352: 1808-12.

183. Arnoldus EP, Lammers GJ. Postanoxic coma: good recovery despite

myoclonus status. Ann Neurol 1995; 38: 697-8.

184. Harper SJ, Wilkes RG. Posthypoxic myoclonus (the Lance-Adams syndrome)

in the intensive care unit. Anaesthesia 1991; 46: 199-201.

185. Morris HR, Howard RS, Brown P. Early myoclonic status and outcome after

cardiorespiratory arrest. J Neurol Neurosurg Psychiatry 1998; 64: 267-8.

186. Edgren E, Hedstrand U, Nordin M, Rydin E, Ronquist G. Prediction of

outcome after cardiac arrest. Crit Care Med 1987; 15: 820-5.

187. Hockaday JM, Potts F, Epstein E, Bonazzi A, Schwab RS.

Electroencephalographic Changes in Acute Cerebral Anoxia from Cardiac or

Respiratory Arrest. Electroencephalogr Clin Neurophysiol 1965; 18: 575-86.

188. Lemmi H, Hubbert CH, Faris AA. The electroencephalogram after

resuscitation of cardiocirculatory arrest. J Neurol Neurosurg Psychiatry 1973;

36: 997-1002.

189. Young GB, Doig G, Ragazzoni A. Anoxic-ischemic encephalopathy: clinical

and electrophysiological associations with outcome. Neurocrit Care 2005; 2:

159-64.

190. Berek K, Lechleitner P, Luef G, et al. Early determination of neurological

outcome after prehospital cardiopulmonary resuscitation. Stroke 1995; 26:

543-9.

191. 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: 721-6.

192. Gendo A, Kramer L, Hafner M, et al. Time-dependency of sensory evoked

potentials in comatose cardiac arrest survivors. Intensive Care Med 2001; 27:

1305-11.

193. Logi F, Fischer C, Murri L, Mauguiere F. The prognostic value of evoked

responses from primary somatosensory and auditory cortex in comatose

patients. Clin Neurophysiol 2003; 114: 1615-27.

194. Tiainen M, Kovala TT, Takkunen OS, Roine RO. Somatosensory and

brainstem auditory evoked potentials in cardiac arrest patients treated with

hypothermia. Crit Care Med 2005; 33: 1736-40.

195. Tiainen M, Roine RO, Pettila V, Takkunen O. Serum neuron-specific enolase

and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke

2003; 34: 2881-6.

196. 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: 1133-8.

197. 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: 2363-6.

198. Dauberschmidt R, Zinsmeyer J, Mrochen H, Meyer M. Changes of neuronspecific

enolase concentration in plasma after cardiac arrest and

resuscitation. Mol Chem Neuropathol 1991; 14: 237-45.

199. Rosen H, Rosengren L, Herlitz J, Blomstrand C. Increased serum levels of

the S-100 protein are associated with hypoxic brain damage after cardiac

arrest. Stroke 1998; 29: 473-7.

200. Bottiger BW, Mobes S, Glatzer R, et al. Astroglial protein S-100 is an early

and sensitive marker of hypoxic brain damage and outcome after cardiac

arrest in humans. Circulation 2001; 103: 2694-8.

201. Longstreth WT, Jr., Clayson KJ, Sumi SM. Cerebrospinal fluid and serum

creatine kinase BB activity after out-of-hospital cardiac arrest. Neurology

1981; 31: 455-8.

202. Clemmensen P, Strandgaard S, Rasmussen S, Grande P. Cerebrospinal fluid

creatine kinase isoenzyme BB levels do not predict the clinical outcome in

patients unconscious following cardiac resuscitation. Clin Cardiol 1987; 10:

235-6.

203. Roine RO, Somer H, Kaste M, Viinikka L, Karonen SL. Neurological outcome

after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme

analysis. Arch Neurol 1989; 46: 753-6.

204. Tirschwell DL, Longstreth WT, Jr., Rauch-Matthews ME, et al. Cerebrospinal

fluid creatine kinase BB isoenzyme activity and neurologic prognosis after

cardiac arrest. Neurology 1997; 48: 352-7.

205. Rothstein TL, Thomas EM, Sumi SM. Predicting outcome in hypoxic-ischemic

coma. A prospective clinical and electrophysiologic study. Electroencephalogr

Clin Neurophysiol 1991; 79: 101-7.

 


Дата добавления: 2015-09-27 | Просмотры: 571 | Нарушение авторских прав







При использовании материала ссылка на сайт medlec.org обязательна! (0.141 сек.)