Současný koncept mozkové oximetrie v kardiochirurgii dospělých


Autoři: Javier G. Castillo 1;  Amanda J. Rhee 2;  George Silvay 2
Působiště autorů: Department of Cardiothoracic Surgery, The Mount Sinai Medical Center, New York, NY 1;  Department of Anesthesiology, The Mount Sinai Medical Center, New York, NY 2
Vyšlo v časopise: Anest. intenziv. Med., 23, 2012, č. 5, s. 242-252
Kategorie: Anesteziologie - Přehledový článek

Souhrn

Přes významné pokroky v chirurgické léčbě a operační technice se závažné pooperační komplikace vyskytují u 2–5 % kardiochirurgických pacientů. Cerebrální oxymetrie nabízí možnost okamžitého monitorování v situacích, které mohou vést k poškození mozkové tkáně. Přes nové pokroky vinfra-neared spektrometrii a získané informace z klinických studií, neprobíhá zavádění do klinické praxe tak rychle, jak se očekávalo. Důvodem jsou a) rozdíly mezi výzkumem modelových sitacích a použitím v biologických tkáních; b) chyby při obsluze; c) pohybové artefakty a multidistanční měření a d) rozdíly mezi jednotlivými přístroji. Přehledový článek popisuje použití mozkové oxymetrie u dospělých kardiochirurgických pacientů, ukazuje na přednosti a nedostatky metody, shrnuje hlavní vlastnosti nejpoužívanějších přístrojů a poskytuje aktuální přehled literárních údajů.

Klíčová slova:
neurologický výsledek – pooperační komplikace – mozková oxymetrie – kardiochirurgie


Zdroje

1. Filsoufi, F., Rahmanian, P. B., Castillo, J. G., Bronster, D., Adams, D. H. Incidence, topography, predictors and long- -term survival after stroke in patients undergoing coronary artery bypass grafting. Ann. Thorac. Surg., 2008, 85, p. 862–870.

2. Newman, M. F., Kirchner, J. L., Phillips-Bute, B., Gaver, V., Grocott, H., Jones, R. H., Mark, D. B., Reves, J. G., Blumenthal, J. A. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N. Engl. J. Med., 2001, 344, p. 395–402.

3. Steinbrook, R. Public report cards – cardiac surgery and beyond. N. Engl. J. Med., 2006, 355, p. 1847–1849.

4. de Vries, J. W., Visser, G. H., Bakker, P. F. Neuromonitoring in defibrillation threshold testing. A comparison between eeg, near-infrared spectroscopy and jugular bulb oximetry. J. Clin. Monit., 1997, 13, p. 303–307.

5. Schwarz, G., Litscher, G. Transcranial cerebral oximetry, transcranial doppler sonography, and heart rate variability: Useful neuromonitoring tools in anaesthesia and intensive care? Eur. J. Anaesthesiol., 2002, 19, p. 543–549.

6. Murkin, J. M., Arango, M. Near-infrared spectroscopy as an index of brain and tissue oxygenation. Br. J. Anaesth., 2009, 103 Suppl 1:i3–13.

7. McCormick, P. W., Stewart, M., Goetting, M. G., Dujovny, M., Lewis, G., Ausman, J. I. Noninvasive cerebral optical spectroscopy for monitoring cerebral oxygen delivery and hemodynamics. Crit. Care Med., 1991, 19, p. 89–97.

8. Benaron, D. A., Parachikov, I. H., Cheong, W. F., Friedland, S., Rubinsky, B. E., Otten, D. M., Liu, F. W., Levinson, C. J., Murphy, A. L., Price, J. W., Talmi, Y., Weersing, J. P., Duckworth, J. L., Horchner, U. B., Kermit, E. L. Design of a visible-light spectroscopy clinical tissue oximeter. J. Biomed. Opt., 2005, 10, 44–45.

9. Germon, T. J., Evans, P. D., Barnett, N. J., Wall, P., Manara, A. R., Nelson, R. J. Cerebral near infrared spectroscopy: Emitter-detector separation must be increased. Br. J. Anaesth., 1999, 82, p. 831–837.

10. Banaji, M., Mallet, A., Elwell, C. E., Nicholls, P., Cooper, C. E. A model of brain circulation and metabolism: Nirs signal changes during physiological challenges. PLoS Comput. Biol., 2008, 4:e1000212.

11. Trivedi, N. S., Ghouri, A. F., Lai, E., Shah, N. K., Barker, S. J. Pulse oximeter performance during desaturation and resaturation: A comparison of seven models. J. Clin. Anesth., 1997, 9, p. 184–188.

12. Pattinson, K. T., Imray, C. H., Wright, A. D. What does cerebral oximetry measure? Br. J. Anaesth., 2005, 94, 863, author reply p. 863–864.

13. Gratton, E., Toronov, V., Wolf, U., Wolf, M., Webb, A. Measurement of brain activity by near-infrared light. J. Biomed. Opt., 2005, 10, 11008.

14. Wolf, M., Wolf, U., Toronov, V., Michalos, A., Paunescu, L. A., Choi, J. H., Gratton, E. Different time evolution of oxyhemoglobin and deoxyhemoglobin concentration changes in the visual and motor cortices during functional stimulation: A near-infrared spectroscopy study. Neuroimage, 2002, 16, p. 704–712.

15. Nelson, L. A., McCann, J. C., Loepke, A. W., Wu, J., Ben Dor, B., Kurth, C. D. Development and validation of a multiwavelength spatial domain near-infrared oximeter to detect cerebral hypoxia-ischemia. J. Biomed. Opt., 2006, 11, 064022.

16. Tisdall, M. M., Tachtsidis, I., Leung, T. S., Elwell, C. E., Smith, M. Near-infrared spectroscopic quantification of changes in the concentration of oxidized cytochrome c oxidase in the healthy human brain during hypoxemia. J. Biomed. Opt., 2007, 12:024002.

17. Al-Rawi, P. G., Smielewski, P., Kirkpatrick, P. J. Evaluation of a near-infrared spectrometer (niro 300) for the detection of intracranial oxygenation changes in the adult head. Stroke, 2001, 32, p. 2492–2500.

18. Wahr, J. A., Tremper, K. K., Samra, S., Delpy, D. T. Near- -infrared spectroscopy: Theory and applications. J. Cardiothorac. Vasc. Anesth., 1996, 10, p. 406–418.

19. Yoshitani, K., Kawaguchi, M., Miura, N., Okuno, T., Kanoda, T., Ohnishi, Y., Kuro, M. Effects of hemoglobin concentration, skull thickness, and the area of the cerebrospinal fluid layer on near-infrared spectroscopy measurements. Anesthesiology, 2007, 106, p. 458–462.

20. Maniewski, R., Liebert, A., Kacprzak, M. Time resolved optical spectroscopy system for cerebral oxygenation imaging. Conf. Proc. IEEE Eng. Med. Biol. Soc., 2005, 1, p. 201–204.

21. Moller, J. T., Pedersen, T., Rasmussen, L. S., Jensen, P. F., Pedersen, B. D., Ravlo, O., Rasmussen, N. H., Espersen, K., Johannessen, N. W., Cooper, J. B. et al. Randomized evaluation of pulse oximetry in 20,802 patients: I. Design, demography, pulse oximetry failure rate, and overall complication rate. Anesthesiology, 1993;78:436-444

22. Hoffman, G. M. Neurologic monitoring on cardiopulmonary bypass: What are we obligated to do? Ann. Thorac. Surg., 2006, 81, S2373–2380.

23. Macmillan, C. S., Andrews, P. J. Cerebrovenous oxygen saturation monitoring: Practical considerations and clinical relevance. Intensive Care Med., 2000, 26, p. 1028–1036.

24. Pedersen, T. Does perioperative pulse oximetry improve outcome? Seeking the best available evidence to answer the clinical question. Best Pract. Res. Clin. Anaesthesiol., 2005, 19, p. 111-123–

25. Shaaban Ali, M., Harmer, M., Latto, I. Jugular bulb oximetry during cardiac surgery. Anaesthesia, 2001, 56, p. 24–37.

26. Yoshitani, K., Kawaguchi, M., Iwata, M., Sasaoka, N., Inoue, S., Kurumatani, N., Furuya, H. Comparison of changes in jugular venous bulb oxygen saturation and cerebral oxygen saturation during variations of haemoglobin concentration under propofol and sevoflurane anaesthesia. Br. J. Anaesth., 2005, 94, p. 341–346.

27. Orihashi, K., Sueda, T., Okada, K., Imai, K. Malposition of selective cerebral perfusion catheter is not a rare event. Eur. J. Cardiothorac. Surg., 2005, 27, p. 644–648.

28. Janelle, G. M., Mnookin, S., Gravenstein, N., Martin, T. D., Urdaneta, F. Unilateral cerebral oxygen desaturation during emergent repair of a debakey type 1 aortic dissection: Potential aversion of a major catastrophe. Anesthesiology, 2002, 96, p. 1263–1265.

29. Han, S. H., Kim, C. S., Lim, C., Kim, W. H. Obstruction of the superior vena cava cannula detected by desaturation of the cerebral oximeter. J. Cardiothorac. Vasc. Anesth., 2005, 19, p. 420–421.

30. Sakamoto, T., Duebener, L. F., Laussen, P. C., Jonas, R. A. Cerebral ischemia caused by obstructed superior vena cava cannula is detected by near-infrared spectroscopy. J. Cardiothorac. Vasc. Anesth., 2004, 18, p. 293–303.

31. Germon, T. J., Kane, N. M., Manara, A. R., Nelson, R. J. Near-infrared spectroscopy in adults: Effects of extracranial ischaemia and intracranial hypoxia on estimation of cerebral oxygenation. Br. J. Anaesth., 1994, 73, p. 503–506.

32. Papadimos, T. J., Marco, A. P. Cerebral oximetry and an unanticipated circulatory arrest. Anaesthesia, 2004, 59, p. 309–310.

33. Prabhune, A., Sehic, A., Spence, P. A., Church, T., Edmonds, H. L., Jr. Cerebral oximetry provides early warning of oxygen delivery failure during cardiopulmonary bypass. J. Cardiothorac. Vasc. Anesth., 2002, 16, p. 204–206.

34. Yeh, T., Jr., Austin, E. H., Sehic, A., Edmonds, H. L., Jr. Rapid recognition and treatment of cerebral air embolism: The role of neuromonitoring. J. Thorac. Cardiovasc. Surg., 2003, 126, p. 589–591.

35. Fischer, G. W., Stone, M. E. Cerebral air embolism recognized by cerebral oximetry. Semin. Cardiothorac. Vasc. Anesth., 2009, 13, p. 56–59.

36. Moritz, S., Rochon, J., Volkel, S., Hilker, M., Hobbhahn, J., Graf, B. M., Arlt, M. Determinants of cerebral oximetry in patients undergoing off-pump coronary artery bypass grafting: An observational study. Eur. J. Anaesthesiol., 2010, 27, p. 542–549.

37. Talpahewa, S. P., Lovell, A. T., Angelini, G. D., Ascione, R. Effect of cardiopulmonary bypass on cortical cerebral oxygenation during coronary artery bypass grafting. Eur. J. Cardiothorac. Surg., 2004, 26, p. 676–681.

38. Alie, R. F., Hymes, W., Kooperman, S. Intra-aortic balloon counterpulsation in an off-pump procedure shows improved cerebral perfusion by near-infrared spectroscopy. Journal of cardiothoracic and vascular anesthesia, 2010, 24, p. 300–302.

39. Heringlake, M., Garbers, C., Kabler, J. H., Anderson, I., Heinze, H., Schon, J., Berger, K. U., Dibbelt, L., Sievers, H. H., Hanke, T. Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery. Anesthesiology, 2011, 114, p. 58–69.

40. MacLeod, D. Simultaneous comparison of fore-sight and invos cerebral oximeters to jugular bulb and arterial co-oximetry measurements in healthy volunteers. 31st Annual Meeeting of the Society of Cardiovascular Anesthesiologists, 2009.

41. Tobias, J. D. Cerebral oximetry monitoring with near infrared spectroscopy detects alterations in oxygenation before pulse oximetry. J. Intensive Care Med., 2008, 23, p. 384–388.

42. Hock, C., Muller-Spahn, F., Schuh-Hofer, S., Hofmann, M., Dirnagl, U., Villringer, A. Age dependency of changes in cerebral hemoglobin oxygenation during brain activation: A near-infrared spectroscopy study. J. Cereb. Blood Flow Metab., 1995, 15, p. 1103–1108.

43. Kishi, K., Kawaguchi, M., Yoshitani, K., Nagahata, T., Furuya, H. Influence of patient variables and sensor location on regional cerebral oxygen saturation measured by invos 4100 near-infrared spectrophotometers. J. Neurosurg. Anesthesiol., 2003, 15, p. 302–306.

44. Lassnigg, A., Hiesmayr, M., Keznickl, P., Mullner, T., Ehrlich, M., Grubhofer, G. Cerebral oxygenation during cardiopulmonary bypass measured by near-infrared spectroscopy: Effects of hemodilution, temperature, and flow. J. Cardiothorac. Vasc. Anesth., 1999, 13, p. 544–548.

45. Marimon, G. A., Dockery, W. K., Sheridan, M. J., Agarwal, S. Near-infrared spectroscopy cerebral and somatic (renal) oxygen saturation correlation to continuous venous oxygen saturation via intravenous oximetry catheter. J. Crit. Care, 2012, 27, 314, e313–318.

46. Baraka, A., Naufal, M., El-Khatib, M. Correlation between cerebral and mixed venous oxygen saturation during moderate versus tepid hypothermic hemodiluted cardiopulmonary bypass. J. Cardiothorac. Vasc. Anesth., 2006, 20, p. 819–825.

47. O’Dwyer, C., Prough, D. S., Johnston, W. E. Determinants of cerebral perfusion during cardiopulmonary bypass. J. Cardiothorac. Vasc. Anesth., 1996, 10, p. 54–64; quiz 65.

48. Davie, S. N., Grocott, H. P. Impact of extracranial contamination on regional cerebral oxygen saturation: A comparison of three cerebral oximetry technologies. Anesthesiology, 2012, 116, p. 834–840.

49. Vohra, H. A., Modi, A., Ohri, S. K. Does use of intra- -operative cerebral regional oxygen saturation monitoring during cardiac surgery lead to improved clinical outcomes? Interact. Cardiovasc. Thorac. Surg., 2009, 9, p. 318–322.

50. Pringle, J., Roberts, C., Kohl, M., Lekeux, P. Near infrared spectroscopy in large animals: Optical pathlength and influence of hair covering and epidermal pigmentation. Vet. J., 1999, 158, p. 48–52.

51. Thavasothy, M., Broadhead, M., Elwell, C., Peters, M., Smith, M. A comparison of cerebral oxygenation as measured by the niro 300 and the invos 5100 near-infrared spectrophotometers. Anaesthesia, 2002, 57, p. 999–1006.

52. Toraman, F. Comparison of two different devices for measurement of regional cerebral oxygen saturation. 25th Annual Meeting of the European Association of Cardiothoracic Anesthesiologists, 2010.

53. Yoshitani, K., Kawaguchi, M., Tatsumi, K., Kitaguchi, K., Furuya, H. A comparison of the invos 4100 and the niro 300 near-infrared spectrophotometers. Anesth. Analg., 2002, 94, p. 586–590; table of contents.

54. Misra, M., Stark, J., Dujovny, M., Widman, R., Ausman, J. I. Transcranial cerebral oximetry in random normal subjects. Neurol. Res., 1998, 20, p. 137–141.

55. Edmonds, H. L., Jr., Ganzel, B. L., Austin, E. H. Cerebral oximetry for cardiac and vascular surgery. Semin. Cardiothorac. Vasc. Anesth., 2004, 8, p. 147–166.

56. Taillefer, M. C., Denault, A. Y. Cerebral near-infrared spectroscopy in adult heart surgery: Systematic review of its clinical efficacy. Can. J. Anaesth., 2005, 52, p. 79–87.

57. Murkin, J. M., Adams, S. J., Novick, R. J., Quantz, M., Bainbridge, D., Iglesias, I., Cleland, A., Schaefer, B., Irwin, B., Fox, S. Monitoring brain oxygen saturation during coronary bypass surgery: A randomized, prospective study. Anesth. Analg., 2007, 104, p. 51–58.

58. Sakamoto, T., Kurosawa, H., Shin’oka, T., Aoki, M., Isomatsu, Y. The influence of ph strategy on cerebral and collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease: Results of a randomized trial and real-time monitoring. J. Thorac. Cardiovasc. Surg., 2004, 127, p. 12–19.

59. Murkin, J. M. Cerebral oximetry: Monitoring the brain as the index organ. Anesthesiology, 2011, 114, p. 12–13.

60. Slater, J. P., Guarino, T., Stack, J., Vinod, K., Bustami, R. T., Brown, J. M., Rodriguez, A. L., Magovern, C. J., Zaubler, T., Freundlich, K., Parr, G. V. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann. Thorac. Surg., 2009, 87, p. 36–44; discussion p. 44–35.

61. Fischer, G. W., Lin, H. M., Krol, M., Galati, M. F., Di Luozzo, G., Griepp, R. B., Reich, D. L. Noninvasive cerebral oxygenation may predict outcome in patients undergoing aortic arch surgery. The Journal of thoracic and cardiovascular surgery, 2011, 141, p. 815–821.

62. Fischer, G. W., Benni, P. B., Lin, H. M., Satyapriya, A., Afonso, A., Di Luozzo, G., Griepp, R. B., Reich, D. L. Mathematical model for describing cerebral oxygen desaturation in patients undergoing deep hypothermic circulatory arrest. British Journal of Anaesthesia, 2010, 104, p. 59–66.

63. Rifai, L., Winters, J., Friedman, E., Silver, M. A. Initial description of cerebral oximetry measurement in heart failure patients. Congest. Heart Fail., 2012, 18, p. 85–90.

64. Anastasiadis, K., Argiriadou, H., Antonitsis, P., Chalvatzoulis, O., Papakonstantinou, C. Cerebral oximetry-guided antegrade cerebral perfusion in aortic arch surgery. Journal of Cardiothoracic and Vascular Anesthesia, 2011, 25, p. 591–592.

65. Santo, K. C., Barrios, A., Dandekar, U., Riley, P., Guest, P., Bonser, R. S. Near-infrared spectroscopy: An important monitoring tool during hybrid aortic arch replacement. Anesth. Analg., 2008, 107, p. 793–796.

66. Steiner, L. A., Pfister, D., Strebel, S. P., Radolovich, D., Smielewski, P., Czosnyka, M. Near-infrared spectroscopy can monitor dynamic cerebral autoregulation in adults. Neurocrit. Care, 2009, 10, p. 122–128.

67. Davies, L. K., Janelle, G. M. Con: All cardiac surgical patients should not have intraoperative cerebral oxygenation monitoring. J. Cardiothorac. Vasc. Anesth., 2006, 20, p. 450–455.

68. Edmonds, H. L., Jr. All cardiac surgical patients should have intraoperative cerebral oxygenation monitoring. J. Cardiothorac. Vasc. Anesth., 2006, 20, p. 445–449.

69. Hoffman, G. M. Near-infrared spectroscopy should be used for all cardiopulmonary bypass. J. Cardiothorac. Vasc. Anesth., 2006, 20, p. 606–612.

70. Grocott, H. P., Homi, H. M., Puskas, F. Cognitive dysfunction after cardiac surgery: Revisiting etiology. Semin. Cardiothorac. Vasc. Anesth., 2005, 9, p. 123–129.

71. Leggat, C. S., Fischer, G. W. Early detection of an acute cerebral event during cardiopulmonary bypass using a bispectral index monitor. Semin. Cardiothorac. Vasc. Anesth., 2008, 12, p. 80–82.

72. Cohn, S. M., Nathens, A. B., Moore, F. A., Rhee, P., Puyana, J. C., Moore, E. E., Beilman, G. J. Tissue oxygen saturation predicts the development of organ dysfunction during traumatic shock resuscitation. J. Trauma, 2007, 62, p. 44–54; discussion 54–45.

73. Ferrari, M., Mottola, L., Quaresima, V. Principles, techniques, and limitations of near infrared spectroscopy. Can. J. Appl. Physiol., 2004, 29, p. 463–487.

74. Dullenkopf, A., Baulig, W., Weiss, M., Schmid, E. R. Cerebral near-infrared spectroscopy in adult patients after cardiac surgery is not useful for monitoring absolute values but may reflect trends in venous oxygenation under clinical conditions. J. Cardiothorac. Vasc. Anesth., 2007, 21, p. 535–539.

75. Baulig, W. Cerebral oxygen saturation measured by near-infrared-spectroscopy does not reliably detect the cerebral status. 25th Annual Meeting of the European Association of Cardiothoracic Anesthesiologists, 2010.

76. Schwarz, G., Litscher, G., Kleinert, R., Jobstmann, R. Cerebral oximetry in dead subjects. J. Neurosurg. Anesthesiol., 1996, 8, p. 189–193.

77. Maeda, H., Fukita, K., Oritani, S., Ishida, K., Zhu, B. L. Evaluation of post-mortem oxymetry with reference to the causes of death. Forensic. Sci. Int., 1997, 87, p. 201–210.

78. Al-Rawi, P. G., Kirkpatrick, P. J. Tissue oxygen index: Thresholds for cerebral ischemia using near-infrared spectroscopy. Stroke, 2006, 37, p. 2720–2725.

79. Kirkpatrick, P. J., Lam, J., Al-Rawi, P., Smielewski, P., Czosnyka, M. Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. J. Neurosurg., 1998, 89, p. 389–394.

80. Yao, F. S., Tseng, C. C., Ho, C. Y., Levin, S. K., Illner, P. Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery. J. Cardiothorac. Vasc. Anesth., 2004, 18, p. 552–558.

81. Gottesman, R. F., Sherman, P. M., Grega, M. A., Yousem, D. M., Borowicz, L. M., Jr., Selnes, O. A., Baumgartner, W. A., McKhann, G. M. Watershed strokes after cardiac surgery: Diagnosis, etiology, and outcome. Stroke, 2006, 37, p. 2306–2311.

82. Maas, A. I., Citerio, G. Noninvasive monitoring of cerebral oxygenation in traumatic brain injury: A mix of doubts and hope. Intensive Care Med., 2010.

83. Paarmann, H., Heringlake, M., Sier, H., Schoen, J. The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation. Interact. Cardiovasc. Thorac. Surg., 2010.

84. Heringlake, M., Heinze, H., Misfeld, M., Klaus, S., Bechtel, M. Goal-directed hemodynamic optimization in high-risk cardiac surgery patients: A tale from the past or a future obligation? Minerva Anestesiol., 2008, 74, p. 251–258.

85. Hargroves, D. R., Tallis, R. C., Pomeroy, V. M., Bhalla, A. Near-infrared spectroscopy in stroke: From research to clinical practice. Stroke, 2004, 35, 2430; author reply p. 2430–2431.

86. Badner, N. H., Nicolaou, G., Clarke, C. F., Forbes, T. L. Use of spinal near-infrared spectroscopy for monitoring spinal cord perfusion during endovascular thoracic aortic repairs. Journal of cardiothoracic and vascular anesthesia, 2011, 25, p. 316–319.

87. Joshi, B., Brady, K., Lee, J., Easley, B., Panigrahi, R., Smielewski, P., Czosnyka, M., Hogue, C. W., Jr. Impaired autoregulation of cerebral blood flow during rewarming from hypothermic cardiopulmonary bypass and its potential association with stroke. Anesth. Analg., 2010, 110, p. 321–328.

88. Lee, J. K., Kibler, K. K., Benni, P. B., Easley, R. B., Czosnyka, M., Smielewski, P., Koehler, R. C., Shaffner, D. H., Brady, K. M. Cerebrovascular reactivity measured by near-infrared spectroscopy. Stroke, 2009, 40, p. 1820–1826.

Štítky
Anesteziologie a resuscitace Intenzivní medicína

Článek vyšel v časopise

Anesteziologie a intenzivní medicína

Číslo 5

2012 Číslo 5

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Pacient na antikoagulační léčbě v akutní situaci
nový kurz
Autoři: MUDr. Jana Michalcová

Kopřivka a její terapie
Autoři: MUDr. Petra Brodská

Uroinfekce v primární péči
Autoři: MUDr. Marek Štefan

Roztroušená skleróza a plánování těhotenství
Autoři: MUDr. Radek Ampapa

Alergenová imunoterapie v léčbě inhalačních alergií
Autoři:

Všechny kurzy
Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se