Perioperative cardiovascular monitoring of high-risk patients: a consensus of 12

Jean-Louis Vincent, Paolo Pelosi, Rupert Pearse, Didier Payen, Azriel Perel, Andreas Hoeft, Stefano Romagnoli, V Marco Ranieri, Carole Ichai, Patrice Forget, Giorgio Della Rocca, Andrew Rhodes, Jean-Louis Vincent, Paolo Pelosi, Rupert Pearse, Didier Payen, Azriel Perel, Andreas Hoeft, Stefano Romagnoli, V Marco Ranieri, Carole Ichai, Patrice Forget, Giorgio Della Rocca, Andrew Rhodes

Abstract

A significant number of surgical patients are at risk of intra- or post-operative complications or both, which are associated with increased lengths of stay, costs, and mortality. Reducing these risks is important for the individual patient but also for health-care planners and managers. Insufficient tissue perfusion and cellular oxygenation due to hypovolemia, heart dysfunction or both is one of the leading causes of perioperative complications. Adequate perioperative management guided by effective and timely hemodynamic monitoring can help reduce the risk of complications and thus potentially improve outcomes. In this review, we describe the various available hemodynamic monitoring systems and how they can best be used to guide cardiovascular and fluid management in the perioperative period in high-risk surgical patients.

Figures

Figure 1
Figure 1
The compromise between accuracy and invasiveness of monitoring systems. CO, cardiac output; PA, pulmonary artery.
Figure 2
Figure 2
Possible choice of monitoring system in relation to a patient’s degree of perioperative risk. CO, cardiac output; PAC, pulmonary artery catheter; PPV, pulse pressure variation; ScvO2, central venous oxygen saturation.
Figure 3
Figure 3
Both hypo- and hypervolemia are associated with more complications. CVA, cerebrovascular accident; MOF, multiple organ failure.

References

    1. Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008;372:139–44.
    1. Jhanji S, Thomas B, Ely A, Watson D, Hinds CJ, Pearse RM. Mortality and utilisation of critical care resources amongst high-risk surgical patients in a large NHS trust. Anaesthesia. 2008;63:695–700.
    1. Pearse RM, Harrison DA, James P, Watson D, Hinds C, Rhodes A, et al. Identification and characterisation of the high-risk surgical population in the UK. Crit Care. 2006;10:R81.
    1. Lobo SM, de Oliveira NE. Clinical review: What are the best hemodynamic targets for noncardiac surgical patients? Crit Care. 2013;17:210.
    1. Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005;242:326–41.
    1. Hamilton MA, Cecconi M, Rhodes A. A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients. Anesth Analg. 2011;112:1392–402.
    1. Gurgel ST. do Nascimento P Jr. Maintaining tissue perfusion in high-risk surgical patients: a systematic review of randomized clinical trials. Anesth Analg. 2011;112:1384–91.
    1. Cecconi M, Corredor C, Arulkumaran N, Abuella G, Ball J, Grounds RM, et al. Clinical review: Goal-directed therapy-what is the evidence in surgical patients? The effect on different risk groups. Crit Care. 2013;17:209.
    1. Jhanji S, Lee C, Watson D, Hinds C, Pearse RM. Microvascular flow and tissue oxygenation after major abdominal surgery: association with post-operative complications. Intensive Care Med. 2009;35:671–7.
    1. Marjanovic G, Villain C, Juettner E, zur Hausen A, Hoeppner J, Hopt UT, et al. Impact of different crystalloid volume regimes on intestinal anastomotic stability. Ann Surg. 2009;249:181–5.
    1. Kulemann B, Timme S, Seifert G, Holzner PA, Glatz T, Sick O, et al. Intraoperative crystalloid overload leads to substantial inflammatory infiltration of intestinal anastomoses - a histomorphological analysis. Surgery. 2013;154:596–603.
    1. Nessim C, Sideris L, Turcotte S, Vafiadis P, Lapostole AC, Simard S, et al. The effect of fluid overload in the presence of an epidural on the strength of colonic anastomoses. J Surg Res. 2013;183:567–73.
    1. Pizov R, Eden A, Bystritski D, Kalina E, Tamir A, Gelman S. Hypotension during gradual blood loss: waveform variables response and absence of tachycardia. Br J Anaesth. 2012;109:911–8.
    1. Vincent JL, Rhodes A, Perel A, Martin GS, Della Rocca G, Vallet B, et al. Clinical review: update on hemodynamic monitoring - a consensus of 16. Crit Care. 2011;15:229.
    1. Legrand M, Dupuis C, Simon C, Gayat E, Mateo J, Lukaszewicz AC, et al. Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Crit Care. 2013;17:R278.
    1. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008;134:172–8.
    1. Vincent JL, Weil MH. Fluid challenge revisited. Crit Care Med. 2006;34:1333–7.
    1. Thiele RH, Bartels K, Gan TJ. Cardiac output monitoring: a contemporary assessment and review. Crit Care Med. 2015;43:177–85.
    1. Cannesson M, Pestel G, Ricks C, Hoeft A, Perel A. Hemodynamic monitoring and management in patients undergoing high risk surgery: a survey among North American and European anesthesiologists. Crit Care. 2011;15:R197.
    1. Repesse X, Bodson L, Vieillard-Baron A. Doppler echocardiography in shocked patients. Curr Opin Crit Care. 2013;19:221–7.
    1. Maltais S, Costello WT, Billings FT, Bick JS, Byrne JG, Ahmad RM, et al. Episodic monoplane transesophageal echocardiography impacts postoperative management of the cardiac surgery patient. J Cardiothorac Vasc Anesth. 2013;27:665–9.
    1. Rhodes A, Cusack RJ, Newman PJ, Grounds RM, Bennett ED. A randomised, controlled trial of the pulmonary artery catheter in critically ill patients. Intensive Care Med. 2002;28:256–64.
    1. Harvey S, Harrison DA, Singer M, Ashcroft J, Jones CM, Elbourne D, et al. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet. 2005;366:472–7.
    1. Harvey S, Young D, Brampton W, Cooper AB, Doig G, Sibbald W, et al. Pulmonary artery catheters for adult patients in intensive care. Cochrane Database Syst Rev. 2006;3:CD003408.
    1. Shah MR, Hasselblad V, Stevenson LW, Binanay C, O’Connor CM, Sopko G, et al. Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials. JAMA. 2005;294:1664–70.
    1. Vincent JL, Pinsky MR, Sprung CL, Levy M, Marini JJ, Payen D, et al. The pulmonary artery catheter: in medio virtus. Crit Care Med. 2008;36:3093–6.
    1. Vincent JL. The pulmonary artery catheter. J Clin Monit Comput. 2012;26:341–5.
    1. Gardner RM. Direct blood pressure measurement - dynamic response requirements. Anesthesiology. 1981;54:227–36.
    1. Hamzaoui O, Monnet X, Richard C, Osman D, Chemla D, Teboul JL. Effects of changes in vascular tone on the agreement between pulse contour and transpulmonary thermodilution cardiac output measurements within an up to 6-hour calibration-free period. Crit Care Med. 2008;36:434–40.
    1. Oren-Grinberg A. The PiCCO Monitor. Int Anesthesiol Clin. 2010;48:57–85.
    1. Bendjelid K, Marx G, Kiefer N, Simon TP, Geisen M, Hoeft A, et al. Performance of a new pulse contour method for continuous cardiac output monitoring: validation in critically ill patients. Br J Anaesth. 2013;111:573–9.
    1. Cecconi M, Fawcett J, Grounds RM, Rhodes A. A prospective study to evaluate the accuracy of pulse power analysis to monitor cardiac output in critically ill patients. BMC Anesthesiol. 2008;8:3.
    1. Cecconi M, Dawson D, Grounds RM, Rhodes A. Lithium dilution cardiac output measurement in the critically ill patient: determination of precision of the technique. Intensive Care Med. 2009;35:498–504.
    1. Senn A, Button D, Zollinger A, Hofer CK. Assessment of cardiac output changes using a modified FloTrac/Vigileo algorithm in cardiac surgery patients. Crit Care. 2009;13:R32.
    1. Cecconi M, Fasano N, Langiano N, Divella M, Costa MG, Rhodes A, et al. Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional anaesthesia. Crit Care. 2011;15:R132.
    1. Romano SM, Pistolesi M. Assessment of cardiac output from systemic arterial pressure in humans. Crit Care Med. 2002;30:1834–41.
    1. Scolletta S, Bodson L, Donadello K, Taccone FS, Devigili A, Vincent JL, et al. Assessment of left ventricular function by pulse wave analysis in critically ill patients. Intensive Care Med. 2013;39:1025–33.
    1. Romagnoli S, Romano SM, Bevilacqua S, Ciappi F, Lazzeri C, Peris A, et al. Cardiac output by arterial pulse contour: reliability under hemodynamic derangements. Interact Cardiovasc Thorac Surg. 2009;8:642–6.
    1. Penaz J. Criteria for set point estimation in the volume clamp method of blood pressure measurement. Physiol Res. 1992;41:5–10.
    1. Westerhof N, Lankhaar JW, Westerhof BE. The arterial Windkessel. Med Biol Eng Comput. 2009;47:131–41.
    1. Stover JF, Stocker R, Lenherr R, Neff TA, Cottini SR, Zoller B, et al. Noninvasive cardiac output and blood pressure monitoring cannot replace an invasive monitoring system in critically ill patients. BMC Anesthesiol. 2009;9:6.
    1. Bogert LW, Wesseling KH, Schraa O, Van Lieshout EJ, de Mol BA, van Goudoever J, et al. Pulse contour cardiac output derived from non-invasive arterial pressure in cardiovascular disease. Anaesthesia. 2010;65:1119–25.
    1. Broch O, Renner J, Gruenewald M, Meybohm P, Schottler J, Caliebe A, et al. A comparison of the Nexfin(R) and transcardiopulmonary thermodilution to estimate cardiac output during coronary artery surgery. Anaesthesia. 2012;67:377–83.
    1. Bubenek-Turconi SI, Craciun M, Miclea I, Perel A. Noninvasive continuous cardiac output by the Nexfin before and after preload-modifying maneuvers: a comparison with intermittent thermodilution cardiac output. Anesth Analg. 2013;117:366–72.
    1. Thom O, Taylor DM, Wolfe RE, Cade J, Myles P, Krum H, et al. Comparison of a supra-sternal cardiac output monitor (USCOM) with the pulmonary artery catheter. Br J Anaesth. 2009;103:800–4.
    1. Gueret G, Kiss G, Rossignol B, Bezon E, Wargnier JP, Miossec A, et al. Cardiac output measurements in off-pump coronary surgery: comparison between NICO and the Swan-Ganz catheter. Eur J Anaesthesiol. 2006;23:848–54.
    1. Tachibana K, Imanaka H, Takeuchi M, Takauchi Y, Miyano H, Nishimura M. Noninvasive cardiac output measurement using partial carbon dioxide rebreathing is less accurate at settings of reduced minute ventilation and when spontaneous breathing is present. Anesthesiology. 2003;98:830–7.
    1. Hofer CK, Buhlmann S, Klaghofer R, Genoni M, Zollinger A. Pulsed dye densitometry with two different sensor types for cardiac output measurement after cardiac surgery: a comparison with the thermodilution technique. Acta Anaesthesiol Scand. 2004;48:653–7.
    1. Ball TR, Culp BC, Patel V, Gloyna DF, Ciceri DP, Culp WC., Jr Comparison of the endotracheal cardiac output monitor to thermodilution in cardiac surgery patients. J Cardiothorac Vasc Anesth. 2010;24:762–6.
    1. Gujjar AR, Muralidhar K, Banakal S, Gupta R, Sathyaprabha TN, Jairaj PS. Non-invasive cardiac output by transthoracic electrical bioimpedence in post-cardiac surgery patients: comparison with thermodilution method. J Clin Monit Comput. 2008;22:175–80.
    1. Squara P, Denjean D, Estagnasie P, Brusset A, Dib JC, Dubois C. Noninvasive cardiac output monitoring (NICOM): a clinical validation. Intensive Care Med. 2007;33:1191–4.
    1. Raval NY, Squara P, Cleman M, Yalamanchili K, Winklmaier M, Burkhoff D. Multicenter evaluation of noninvasive cardiac output measurement by bioreactance technique. J Clin Monit Comput. 2008;22:113–9.
    1. Garisto C, Favia I, Ricci Z, Romagnoli S, Haiberger R, Polito A, et al. Pressure recording analytical method and bioreactance for stroke volume index monitoring during pediatric cardiac surgery. Paediatr Anaesth. 2015;25:143–9.
    1. Critchley LA, Critchley JA. A meta-analysis of studies using bias and precision statistics to compare cardiac output measurement techniques. J Clin Monit Comput. 1999;15:85–91.
    1. Cecconi M, Rhodes A, Poloniecki J, Della Rocca G, Grounds RM. Bench-to-bedside review: the importance of the precision of the reference technique in method comparison studies - with specific reference to the measurement of cardiac output. Crit Care. 2009;13:201.
    1. Squara P, Cecconi M, Rhodes A, Singer M, Chiche JD. Tracking changes in cardiac output: methodological considerations for the validation of monitoring devices. Intensive Care Med. 2009;35:1801–8.
    1. Critchley LA, Lee A, Ho AM. A critical review of the ability of continuous cardiac output monitors to measure trends in cardiac output. Anesth Analg. 2010;111:1180–92.
    1. Perel A, Habicher M, Sander M. Bench-to-bedside review: Functional hemodynamics during surgery - should it be used for all high-risk cases? Crit Care. 2013;17:203.
    1. Desebbe O, Cannesson M. Using ventilation-induced plethysmographic variations to optimize patient fluid status. Curr Opin Anaesthesiol. 2008;21:772–8.
    1. Sandroni C, Cavallaro F, Marano C, Falcone C, De Santis P, Antonelli M. Accuracy of plethysmographic indices as predictors of fluid responsiveness in mechanically ventilated adults: a systematic review and meta-analysis. Intensive Care Med. 2012;38:1429–37.
    1. Forget P, Lois F, de Kock M. Goal-directed fluid management based on the pulse oximeter-derived pleth variability index reduces lactate levels and improves fluid management. Anesth Analg. 2010;111:910–4.
    1. Forget P, Lois F, Kartheuser A, Leonard D, Remue C, de Kock M. The concept of titration can be transposed to fluid management but does is change the volumes? Randomised trial on pleth variability index during fast-track colonic surgery. Curr Clin Pharmacol. 2013;8:110–4.
    1. Mahjoub Y, Lejeune V, Muller L, Perbet S, Zieleskiewicz L, Bart F, et al. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth. 2014;112:681–5.
    1. Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med. 2009;37:2642–7.
    1. Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369:428–37.
    1. Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Esposito DC, Pasqualucci Mde O, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308:1651–9.
    1. Cannesson M, Le Manach Y, Hofer CK, Goarin JP, Lehot JJ, Vallet B, et al. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a ‘gray zone’ approach. Anesthesiology. 2011;115:231–41.
    1. Monnet X, Teboul JL. Passive leg raising. Intensive Care Med. 2008;34:659–63.
    1. Michard F. Long live dynamic parameters! Crit Care. 2014;18:413.
    1. Chawla LS, Zia H, Gutierrez G, Katz NM, Seneff MG, Shah M. Lack of equivalence between central and mixed venous oxygen saturation. Chest. 2004;126:1891–6.
    1. Dueck MH, Klimek M, Appenrodt S, Weigand C, Boerner U. Trends but not individual values of central venous oxygen saturation agree with mixed venous oxygen saturation during varying hemodynamic conditions. Anesthesiology. 2005;103:249–57.
    1. Reinhart K, Rudolph T, Bredle DL, Hannemann L, Cain SM. Comparison of central-venous to mixed-venous oxygen saturation during changes in oxygen supply/demand. Chest. 1989;95:1216–21.
    1. Lorentzen AG, Lindskov C, Sloth E, Jakobsen CJ. Central venous oxygen saturation cannot replace mixed venous saturation in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2008;22:853–7.
    1. Glamann DB, Lange RA, Hillis LD. Incidence and significance of a ‘step-down’ in oxygen saturation from superior vena cava to pulmonary artery. Am J Cardiol. 1991;68:695–7.
    1. Barratt-Boyes BG, Wood EH. The oxygen saturation of blood in the venae cavae, right-heart chambers, and pulmonary vessels of healthy subjects. J Lab Clin Med. 1957;50:93–106.
    1. Dahn MS, Lange MP, Jacobs LA. Central mixed and splanchnic venous oxygen saturation monitoring. Intensive Care Med. 1988;14:373–8.
    1. Lee J, Wright F, Barber R, Stanley L. Central venous oxygen saturation in shock: a study in man. Anesthesiology. 1972;36:472–8.
    1. Ho KM, Harding R, Chamberlain J, Bulsara M. A comparison of central and mixed venous oxygen saturation in circulatory failure. J Cardiothorac Vasc Anesth. 2010;24:434–9.
    1. Turnaoglu S, Tugrul M, Camci E, Cakar N, Akinci O, Ergin P. Clinical applicability of the substitution of mixed venous oxygen saturation with central venous oxygen saturation. J Cardiothorac Vasc Anesth. 2001;15:574–9.
    1. Reinhart K, Kersting T, Fohring U, Schafer M. Can central-venous replace mixed-venous oxygen saturation measurements during anesthesia? Adv Exp Med Biol. 1986;200:67–72.
    1. Collaborative Study Group on Perioperative ScvO2 Monitoring Multicentre study on peri- and postoperative central venous oxygen saturation in high-risk surgical patients. Crit Care. 2006;10:R158.
    1. Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg. 2000;90:1052–9.
    1. Donati A, Loggi S, Preiser JC, Orsetti G, Munch C, Gabbanelli V, et al. Goal-directed intraoperative therapy reduces morbidity and length of hospital stay in high-risk surgical patients. Chest. 2007;132:1817–24.
    1. Van der Linden P, Schmartz D, Gilbart E, Engelman E, Vincent JL. Effects of propofol, etomidate, and pentobarbital on critical oxygen delivery. Crit Care Med. 2000;28:2492–9.
    1. Perz S, Uhlig T, Kohl M, Bredle DL, Reinhart K, Bauer M, et al. Low and ‘supranormal’ central venous oxygen saturation and markers of tissue hypoxia in cardiac surgery patients: a prospective observational study. Intensive Care Med. 2011;37:52–9.
    1. Fuller BM, Dellinger RP. Lactate as a hemodynamic marker in the critically ill. Curr Opin Crit Care. 2012;18:267–72.
    1. Meregalli A, Oliveira RP, Friedman G. Occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients. Crit Care. 2004;8:R60–5.
    1. Bakker J, Coffernils M, Leon M, Gris P, Vincent JL. Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest. 1991;99:956–62.
    1. Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182:752–61.
    1. Jansen TC, van Bommel J, Woodward R, Mulder PG, Bakker J. Association between blood lactate levels, Sequential Organ Failure Assessment subscores, and 28-day mortality during early and late intensive care unit stay: a retrospective observational study. Crit Care Med. 2009;37:2369–74.
    1. McKendry M, McGloin H, Saberi D, Caudwell L, Brady AR, Singer M. Randomised controlled trial assessing the impact of a nurse delivered, flow monitored protocol for optimisation of circulatory status after cardiac surgery. BMJ. 2004;329:258.
    1. Pearse R, Dawson D, Fawcett J, Rhodes A, Grounds RM, Bennett ED. Early goal-directed therapy after major surgery reduces complications and duration of hospital stay. A randomised, controlled trial [ISRCTN38797445] Crit Care. 2005;9:R687–93.
    1. Bundgaard-Nielsen M, Holte K, Secher NH, Kehlet H. Monitoring of peri-operative fluid administration by individualized goal-directed therapy. Acta Anaesthesiol Scand. 2007;51:331–40.
    1. Wilson J, Woods I, Fawcett J, Whall R, Dibb W, Morris C, et al. Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery. BMJ. 1999;318:1099–103.
    1. Lobo SM, Salgado PF, Castillo VG, Borim AA, Polachini CA, Palchetti JC, et al. Effects of maximizing oxygen delivery on morbidity and mortality in high-risk surgical patients. Crit Care Med. 2000;28:3396–404.
    1. Lopes MR, Oliveira MA, Pereira VO, Lemos IP, Auler JO, Jr, Michard F. Goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery: a pilot randomized controlled trial. Crit Care. 2007;11:R100.
    1. Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, et al. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA. 2014;311:2181–90.
    1. Morris C. Oesophageal Doppler monitoring, doubt and equipoise: evidence based medicine means change. Anaesthesia. 2013;68:684–8.
    1. Scheeren TW, Wiesenack C, Gerlach H, Marx G. Goal-directed intraoperative fluid therapy guided by stroke volume and its variation in high-risk surgical patients: a prospective randomized multicentre study. J Clin Monit Comput. 2013;27:225–33.
    1. Goepfert MS, Richter HP, Zu EC, Gruetzmacher J, Rafflenbeul E, Roeher K, et al. Individually optimized hemodynamic therapy reduces complications and length of stay in the intensive care unit: a prospective, randomized controlled trial. Anesthesiology. 2013;119:824–36.
    1. Fellahi JL, Parienti JJ, Hanouz JL, Plaud B, Riou B, Ouattara A. Perioperative use of dobutamine in cardiac surgery and adverse cardiac outcome: propensity-adjusted analyses. Anesthesiology. 2008;108:979–87.
    1. Pearse RM, Belsey JD, Cole JN, Bennett ED. Effect of dopexamine infusion on mortality following major surgery: individual patient data meta-regression analysis of published clinical trials. Crit Care Med. 2008;36:1323–9.
    1. Takala J, Meier-Hellmann A, Eddleston J, Hulstaert P, Sramek V. Effect of dopexamine on outcome after major abdominal surgery: a prospective, randomized, controlled multicenter study. European Multicenter Study Group on Dopexamine in Major Abdominal Surgery. Crit Care Med. 2000;28:3417–23.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit