Skip to main content
Erschienen in: Intensive Care Medicine 12/2011

01.12.2011 | Original

New insights into weaning from mechanical ventilation: left ventricular diastolic dysfunction is a key player

verfasst von: John Papanikolaou, Demosthenes Makris, Theodosios Saranteas, Dimitrios Karakitsos, Elias Zintzaras, Andreas Karabinis, Georgia Kostopanagiotou, Epaminondas Zakynthinos

Erschienen in: Intensive Care Medicine | Ausgabe 12/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To investigate the diagnostic performance of Doppler echocardiography (DE) in predicting the outcome of weaning from mechanical ventilation in patients without overt cardiac disease.

Methods

Fifty critical care noncardiac patients who fulfilled predetermined criteria for weaning underwent DE before and at the end of spontaneous breathing trial (pre-SBT/end-SBT, respectively). “Conventional” mitral inflow analysis and “advanced” DE parameters [tissue Doppler imaging (TDI)-derived mitral/tricuspid annular velocities and color M-mode Doppler velocity of propagation (V p)] were used to assess left ventricular (LV) diastolic function/filling pressures. Weaning was considered successful if patients had been extubated after successful SBT and sustained spontaneous breathing for more than 48 h.

Results

Twenty-eight patients (56%) failed weaning: 23 patients failed SBT and 5 required reintubation within 48 h. Weaning failure was associated with the degree of LV diastolic dysfunction at pre-SBT (P = 0.01). Patients who failed weaning presented evidence of increased LV filling pressures at pre-SBT, by demonstrating increased E/E m and E/V p ratios compared with patients with successful outcome (P ≤ 0.004); pre-SBT values of lateral E/E m greater than 7.8 and E/V p greater than 1.51 predicted weaning failure with an area under the curve, sensitivity (%), and specificity (%) of 0.86, 79, and 100, and 0.74, 75, and 73, respectively. Lateral E/E m was the only factor independently associated with weaning failure before SBT; OR (95% CI) 5.62 (1.17–26.96), P = 0.03.

Conclusions

Our findings suggest that LV diastolic dysfunction is significantly associated with weaning outcome in critically ill patients with preserved LV systolic function. An E/E m ratio greater than 7.8 may identify patients at high risk of weaning failure.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A, Welte T (2007) Weaning from mechanical ventilation. Eur Respir J 29:1033–1056PubMedCrossRef Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A, Welte T (2007) Weaning from mechanical ventilation. Eur Respir J 29:1033–1056PubMedCrossRef
2.
Zurück zum Zitat Vallverdú I, Calaf N, Subirana M, Net A, Benito S, Mancebo J (1998) Clinical characteristics, respiratory functional parameters, and outcome of a two-hour T-piece trial in patients weaning from mechanical ventilation. Am J Respir Crit Care Med 158:1855–1862PubMed Vallverdú I, Calaf N, Subirana M, Net A, Benito S, Mancebo J (1998) Clinical characteristics, respiratory functional parameters, and outcome of a two-hour T-piece trial in patients weaning from mechanical ventilation. Am J Respir Crit Care Med 158:1855–1862PubMed
3.
Zurück zum Zitat Yang KL, Tobin MJ (1991) A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 324:1445–1450PubMedCrossRef Yang KL, Tobin MJ (1991) A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 324:1445–1450PubMedCrossRef
4.
Zurück zum Zitat Lamia B, Monnet X, Teboul JL (2005) Weaning-induced cardiac dysfunction. In: Yearbook of intensive care and emergency medicine. 1st edn. Springer, Heidelberg, pp 239–245 Lamia B, Monnet X, Teboul JL (2005) Weaning-induced cardiac dysfunction. In: Yearbook of intensive care and emergency medicine. 1st edn. Springer, Heidelberg, pp 239–245
5.
Zurück zum Zitat Kennedy SK, Weintraub RM, Skillman JJ (1977) Cardiorespiratory and sympathoadrenal responses during weaning from controlled ventilation. Surgery 82:233–240PubMed Kennedy SK, Weintraub RM, Skillman JJ (1977) Cardiorespiratory and sympathoadrenal responses during weaning from controlled ventilation. Surgery 82:233–240PubMed
6.
Zurück zum Zitat Gobel FL, Norstrom LA, Nelson RR, Jorgensen CR, Wang Y (1978) The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 57:549–556PubMed Gobel FL, Norstrom LA, Nelson RR, Jorgensen CR, Wang Y (1978) The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 57:549–556PubMed
7.
Zurück zum Zitat McGregor M (1979) Current concepts: pulsus paradoxus. N Engl J Med 301:480-482 McGregor M (1979) Current concepts: pulsus paradoxus. N Engl J Med 301:480-482
8.
Zurück zum Zitat Buda AJ, Pinsky MR, Ingels NB Jr, Daughters GT 2nd, Stinson EB, Alderman EL (1979) Effect of intrathoracic pressure on left ventricular performance. N Engl J Med 301:453–459PubMedCrossRef Buda AJ, Pinsky MR, Ingels NB Jr, Daughters GT 2nd, Stinson EB, Alderman EL (1979) Effect of intrathoracic pressure on left ventricular performance. N Engl J Med 301:453–459PubMedCrossRef
9.
Zurück zum Zitat Hurford WE, Favorito F (1995) Association of myocardial ischemia with failure to wean from mechanical ventilation. Crit Care Med 23:1475–1480PubMedCrossRef Hurford WE, Favorito F (1995) Association of myocardial ischemia with failure to wean from mechanical ventilation. Crit Care Med 23:1475–1480PubMedCrossRef
10.
Zurück zum Zitat Frazier SK, Brom H, Widener J, Pender L, Stone KS, Moser DK (2006) Prevalence of myocardial ischemia during mechanical ventilation and weaning and its effects on weaning success. Heart Lung 35:363–373PubMedCrossRef Frazier SK, Brom H, Widener J, Pender L, Stone KS, Moser DK (2006) Prevalence of myocardial ischemia during mechanical ventilation and weaning and its effects on weaning success. Heart Lung 35:363–373PubMedCrossRef
11.
Zurück zum Zitat Boussuges A, Pinet C, Molenat F, Burnet H, Ambrosi P, Badier M, Sainty JM, Orehek J (2000) Left atrial and ventricular filling in chronic obstructive pulmonary disease. An echocardiographic and Doppler study. Am J Respir Crit Care Med 162:670–675PubMed Boussuges A, Pinet C, Molenat F, Burnet H, Ambrosi P, Badier M, Sainty JM, Orehek J (2000) Left atrial and ventricular filling in chronic obstructive pulmonary disease. An echocardiographic and Doppler study. Am J Respir Crit Care Med 162:670–675PubMed
12.
Zurück zum Zitat Lamia B, Maizel J, Ochagavia A, Chemla D, Osman D, Richard C, Teboul JL (2009) Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation. Crit Care Med 37:1696–1701PubMedCrossRef Lamia B, Maizel J, Ochagavia A, Chemla D, Osman D, Richard C, Teboul JL (2009) Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation. Crit Care Med 37:1696–1701PubMedCrossRef
13.
Zurück zum Zitat Caille V, Amiel JB, Charron C, Belliard G, Vieillard-Baron A, Vignon P (2010) Echocardiography: a help in the weaning process. Crit Care 14:R120PubMedCrossRef Caille V, Amiel JB, Charron C, Belliard G, Vieillard-Baron A, Vignon P (2010) Echocardiography: a help in the weaning process. Crit Care 14:R120PubMedCrossRef
14.
Zurück zum Zitat Bernard F, Denault A, Babin D, Goyer C, Couture P, Couturier A, Buithieu J (2001) Diastolic dysfunction is predictive of difficult weaning from cardiopulmonary bypass. Anesth Analg 92:291–298PubMedCrossRef Bernard F, Denault A, Babin D, Goyer C, Couture P, Couturier A, Buithieu J (2001) Diastolic dysfunction is predictive of difficult weaning from cardiopulmonary bypass. Anesth Analg 92:291–298PubMedCrossRef
15.
Zurück zum Zitat Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I et al (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367PubMed Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I et al (1989) Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2:358–367PubMed
16.
Zurück zum Zitat El-Khatib MF, Jamaleddine GW, Khoury AR, Obeid MY (2002) Effect of continuous positive airway pressure on the rapid shallow breathing index in patients following cardiac surgery. Chest 121:475–479PubMedCrossRef El-Khatib MF, Jamaleddine GW, Khoury AR, Obeid MY (2002) Effect of continuous positive airway pressure on the rapid shallow breathing index in patients following cardiac surgery. Chest 121:475–479PubMedCrossRef
17.
Zurück zum Zitat Mekontso-Dessap A, de Prost N, Girou E, Braconnier F, Lemaire F, Brun-Buisson C, Brochard L (2006) B-type natriuretic peptide and weaning from mechanical ventilation. Intensive Care Med 32:1529–1536PubMedCrossRef Mekontso-Dessap A, de Prost N, Girou E, Braconnier F, Lemaire F, Brun-Buisson C, Brochard L (2006) B-type natriuretic peptide and weaning from mechanical ventilation. Intensive Care Med 32:1529–1536PubMedCrossRef
18.
Zurück zum Zitat Grasso S, Leone A, De Michele M, Anaclerio R, Cafarelli A, Ancona, Stripoli T, Bruno F, Pugliese P, Dambrosio M, Dalfino L, Di Serio F, Fiore T (2007) Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease. Crit Care Med 35:96–105PubMedCrossRef Grasso S, Leone A, De Michele M, Anaclerio R, Cafarelli A, Ancona, Stripoli T, Bruno F, Pugliese P, Dambrosio M, Dalfino L, Di Serio F, Fiore T (2007) Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease. Crit Care Med 35:96–105PubMedCrossRef
19.
Zurück zum Zitat Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 10:165–193PubMedCrossRef Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 10:165–193PubMedCrossRef
20.
Zurück zum Zitat Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36PubMed Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36PubMed
21.
Zurück zum Zitat DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845PubMedCrossRef DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845PubMedCrossRef
22.
Zurück zum Zitat Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J (2007) Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176:532–555PubMedCrossRef Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J (2007) Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176:532–555PubMedCrossRef
23.
Zurück zum Zitat Sturgess DJ, Marwick TH, Joyce CJ, Jones M, Venkatesh B (2007) Tissue Doppler in critical illness: a retrospective cohort study. Crit Care 11:R97PubMedCrossRef Sturgess DJ, Marwick TH, Joyce CJ, Jones M, Venkatesh B (2007) Tissue Doppler in critical illness: a retrospective cohort study. Crit Care 11:R97PubMedCrossRef
24.
Zurück zum Zitat Jafri SM, Lavine S, Field BE, Bahorozian MT, Carlson RW (1990) Left ventricular diastolic function in sepsis. Crit Care Med 18:709–714PubMedCrossRef Jafri SM, Lavine S, Field BE, Bahorozian MT, Carlson RW (1990) Left ventricular diastolic function in sepsis. Crit Care Med 18:709–714PubMedCrossRef
25.
Zurück zum Zitat Wu CK, Lee JK, Chiang FT, Yang CH, Huang SW, Hwang JJ, Lin JL, Tseng CD, Chen JJ, Tsai CT (2011) Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase. Crit Care Med 39:984–992PubMedCrossRef Wu CK, Lee JK, Chiang FT, Yang CH, Huang SW, Hwang JJ, Lin JL, Tseng CD, Chen JJ, Tsai CT (2011) Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase. Crit Care Med 39:984–992PubMedCrossRef
26.
Zurück zum Zitat Miyamoto M, McClure DE, Schertel ER, Andrews PJ, Jones GA, Pratt JW, Ross P, Myerowitz PD (1998) Effects of hypoproteinemia-induced myocardial edema on left ventricular function. Am J Physiol 274:H937–H944PubMed Miyamoto M, McClure DE, Schertel ER, Andrews PJ, Jones GA, Pratt JW, Ross P, Myerowitz PD (1998) Effects of hypoproteinemia-induced myocardial edema on left ventricular function. Am J Physiol 274:H937–H944PubMed
27.
Zurück zum Zitat Chattopadhyay S, Alamgir MF, Nikitin NP, Rigby AS, Clark AL, Cleland JG (2010) Lack of diastolic reserve in patients with heart failure and normal ejection fraction. Circ Heart Fail 3:35–43PubMedCrossRef Chattopadhyay S, Alamgir MF, Nikitin NP, Rigby AS, Clark AL, Cleland JG (2010) Lack of diastolic reserve in patients with heart failure and normal ejection fraction. Circ Heart Fail 3:35–43PubMedCrossRef
28.
Zurück zum Zitat Lemaire F, Teboul JL, Cinotti L, Giotto G, Abrouk F, Steg G, Macquin-Mavier I, Zapol WM (1988) Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology 69:171–179PubMedCrossRef Lemaire F, Teboul JL, Cinotti L, Giotto G, Abrouk F, Steg G, Macquin-Mavier I, Zapol WM (1988) Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology 69:171–179PubMedCrossRef
29.
Zurück zum Zitat Routsi C, Stanopoulos I, Zakynthinos E, Politis P, Papas V, Zervakis D, Zakynthinos S (2010) Nitroglycerin can facilitate weaning of difficult-to-wean chronic obstructive pulmonary disease patients: a prospective interventional non-randomized study. Crit Care 14:R204PubMedCrossRef Routsi C, Stanopoulos I, Zakynthinos E, Politis P, Papas V, Zervakis D, Zakynthinos S (2010) Nitroglycerin can facilitate weaning of difficult-to-wean chronic obstructive pulmonary disease patients: a prospective interventional non-randomized study. Crit Care 14:R204PubMedCrossRef
30.
Zurück zum Zitat European Study Group on Diastolic Heart Failure (1998) How to diagnose diastolic heart failure. Eur Heart J 19:990–1003 European Study Group on Diastolic Heart Failure (1998) How to diagnose diastolic heart failure. Eur Heart J 19:990–1003
31.
Zurück zum Zitat Yuda S, Inaba Y, Fujii S, Kokubu N, Yoshioka T, Sakurai S, Nishizato K, Fujii N, Hashimoto A, Uno K, Nakata T, Tsuchihashi K, Miura T, Ura N, Natori H, Shimamoto K (2006) Assessment of left ventricular ejection fraction using long-axis systolic function is independent of image quality: a study of tissue Doppler imaging and m-mode echocardiography. Echocardiography 23:846–852PubMedCrossRef Yuda S, Inaba Y, Fujii S, Kokubu N, Yoshioka T, Sakurai S, Nishizato K, Fujii N, Hashimoto A, Uno K, Nakata T, Tsuchihashi K, Miura T, Ura N, Natori H, Shimamoto K (2006) Assessment of left ventricular ejection fraction using long-axis systolic function is independent of image quality: a study of tissue Doppler imaging and m-mode echocardiography. Echocardiography 23:846–852PubMedCrossRef
32.
Zurück zum Zitat Vinereanu D, Nicolaides E, Tweddel AC, Fraser AG (2005) “Pure” diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure. Eur J Heart Fail 7:820–828PubMedCrossRef Vinereanu D, Nicolaides E, Tweddel AC, Fraser AG (2005) “Pure” diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure. Eur J Heart Fail 7:820–828PubMedCrossRef
33.
Zurück zum Zitat García-Fernández MA, Azevedo J, Moreno M, Bermejo J, Pérez-Castellano N, Puerta P, Desco M, Antoranz C, Serrano JA, García E, Delcán JL (1999) Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging. Eur Heart J 20:496–505PubMedCrossRef García-Fernández MA, Azevedo J, Moreno M, Bermejo J, Pérez-Castellano N, Puerta P, Desco M, Antoranz C, Serrano JA, García E, Delcán JL (1999) Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging. Eur Heart J 20:496–505PubMedCrossRef
34.
Zurück zum Zitat Vignon P, AitHssain A, François B, Preux PM, Pichon N, Clavel M, Frat JP, Gastinne H (2008) Echocardiographic assessment of pulmonary artery occlusion pressure in ventilated patients: a transoesophageal study. Crit Care 12:R18PubMedCrossRef Vignon P, AitHssain A, François B, Preux PM, Pichon N, Clavel M, Frat JP, Gastinne H (2008) Echocardiographic assessment of pulmonary artery occlusion pressure in ventilated patients: a transoesophageal study. Crit Care 12:R18PubMedCrossRef
35.
Zurück zum Zitat Rivas-Gotz C, Manolios M, Thohan V, Nagueh SF (2003) Impact of left ventricular ejection fraction on estimation of left ventricular filling pressures using tissue Doppler and flow propagation velocity. Am J Cardiol 91:780–784PubMedCrossRef Rivas-Gotz C, Manolios M, Thohan V, Nagueh SF (2003) Impact of left ventricular ejection fraction on estimation of left ventricular filling pressures using tissue Doppler and flow propagation velocity. Am J Cardiol 91:780–784PubMedCrossRef
36.
Zurück zum Zitat Combes A, Arnoult F, Trouillet JL (2004) Tissue Doppler imaging estimation of pulmonary artery occlusion pressure in ICU patients. Intensive Care Med 30:75–81PubMedCrossRef Combes A, Arnoult F, Trouillet JL (2004) Tissue Doppler imaging estimation of pulmonary artery occlusion pressure in ICU patients. Intensive Care Med 30:75–81PubMedCrossRef
37.
Zurück zum Zitat Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, Hoffmann W, Poller W, Schultheiss HP, Pauschinger M, Tschöpe C (2007) Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 116:637–647PubMedCrossRef Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, Hoffmann W, Poller W, Schultheiss HP, Pauschinger M, Tschöpe C (2007) Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 116:637–647PubMedCrossRef
38.
Zurück zum Zitat González-Vilchez F, Ayuela J, Ares M, Mata NS, González AG, Durán RM (2002) Comparison of Doppler echocardiography, color M-mode Doppler, and Doppler tissue imaging for the estimation of pulmonary capillary wedge pressure. J Am Soc Echocardiogr 15:1245–1250PubMedCrossRef González-Vilchez F, Ayuela J, Ares M, Mata NS, González AG, Durán RM (2002) Comparison of Doppler echocardiography, color M-mode Doppler, and Doppler tissue imaging for the estimation of pulmonary capillary wedge pressure. J Am Soc Echocardiogr 15:1245–1250PubMedCrossRef
39.
Zurück zum Zitat Licker M, Cikirikcioglu M, Inan C, Cartier V, Kalangos A, Theologou T, Cassina T, Diaper J (2010) Preoperative diastolic function predicts the onset of left ventricular dysfunction following aortic valve replacement in high-risk patients with aortic stenosis. Crit Care 14:R101PubMedCrossRef Licker M, Cikirikcioglu M, Inan C, Cartier V, Kalangos A, Theologou T, Cassina T, Diaper J (2010) Preoperative diastolic function predicts the onset of left ventricular dysfunction following aortic valve replacement in high-risk patients with aortic stenosis. Crit Care 14:R101PubMedCrossRef
Metadaten
Titel
New insights into weaning from mechanical ventilation: left ventricular diastolic dysfunction is a key player
verfasst von
John Papanikolaou
Demosthenes Makris
Theodosios Saranteas
Dimitrios Karakitsos
Elias Zintzaras
Andreas Karabinis
Georgia Kostopanagiotou
Epaminondas Zakynthinos
Publikationsdatum
01.12.2011
Verlag
Springer-Verlag
Erschienen in
Intensive Care Medicine / Ausgabe 12/2011
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-011-2368-0

Weitere Artikel der Ausgabe 12/2011

Intensive Care Medicine 12/2011 Zur Ausgabe

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.