Review Article
Five Recurrent Misconceptions Regarding Cardiogenic Shock Management Karim Bendjelid, MD, PhD
Abstract: Medical therapeutic knowledge advances by continual action and reaction between retrospective and prospective evaluation on the one hand and clinical real-life observation and assessment on the other. In this regard, our goal is to articulate and demystify certain myths and misconceptions that impede the optimal management of patients with circulatory failure related to acute cardiac diseases. More specifically, we outline 5 statements that represent misconceptions about cardiogenic shock management that we have frequently faced throughout years of caring for critically ill patients. Moreover, for each statement, we suggest concise, corrective responses. Key Words: cardiogenic shock, shift, paradigms (Cardiology in Review 2014;22: 241–245)
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n clinical medicine, physicians frequently accept paradigms or ideas that have been passed from one generation of doctors to another as being correct, although such ideas have never been subject to scientific examination. Generally, in the absence of evidence-based medicine, these concepts are derived from experience and frequently take on a power of their own. In many situations, the concepts are correct, but this may not always be the case. The present review is written in the context of ongoing efforts to dispel misunderstandings about cardiogenic shock (CS) management in the intensive care unit (ICU). CS is characterized by low cardiac output, with a marked reduction in stroke volume, increased venous pressure, and signs of low organ perfusion. CS mortality remains unacceptably high (40–75%) and has not improved significantly, despite the use of readily available advanced hemodynamic monitoring devices and therapeutic modalities for heart failure.1 Our goal is to articulate and demystify certain myths and misconceptions that impede the optimal management of patients with circulatory failure related to acute cardiac diseases. More specifically, we outline 5 statements that represent misconceptions about CS management that we have frequently faced throughout years of caring for critically ill patients. Moreover, for each statement, we suggest concise, corrective responses.
MISCONCEPTION 1: FAST WEANING FROM SEDATION AND MECHANICAL VENTILATION IS VITAL FOR PATIENTS WITH CS Misconception 1 is the perception that a deeply sedated, mechanically ventilated patient with CS related to acute heart diseases (eg, myocardial infarction, tamponade, and electrical storm)
From the Intensive Care Service, Geneva University Hospitals, the Faculty of Medicine, University of Geneva, and the Geneva Hemodynamic Research Group, Geneva, Switzerland. Disclosure: The author has no conflicts of interest to report. Correspondence: Karim Bendjelid, MD, PhD, Médecin Adjoint Agrégé, Intensive Care Service, Geneva University Hospitals, 4 Rue Gabrielle Perret-Gentil, CH-1211 Geneva 14, Switzerland. E-mail: [email protected]. Copyright © 2014 Lippincott Williams & Wilkins ISSN: 1061-5377/14/2205-0241 DOI: 10.1097/CRD.0000000000000019
should be weaned from sedation and mechanical ventilation (MV) once the cardiac disease triggering CS has been successfully treated. The present misconception is the result of the correct thought that weaning from sedation and MV is vital in the management of many critically ill patients.2 The present strategy is also the result of current guideline recommendations, which advocate early liberation from the ventilator for ICU patients. Indeed, in the past 20 years, concern over the deleterious effects of oversedation has prompted the investigation of ways to safely deliver the appropriate level of sedation to patients without delaying extubation.3,4 Moreover, observational studies and randomized trials have suggested that in contrast to intermittent infusion, a continuous infusion of sedatives increases the risk of developing pneumonia and requiring prolonged MV.5 However, there is also no evidence that justifies early cessation of the use of sedation and MV in patients enduring CS, especially during the first 48 hours following the shock. Indeed, MV with postive end-expiratory pressure (PEEP) has been associated with not only improved hemodynamic measurements but also superior clinical end points. A small study of 18 patients with CS necessitating intra-aortic balloon pump (IABP) placement found that the patients randomized to receive elective MV with 10 cm H2O of PEEP were more likely to be weaned off the IABP and to survive to discharge than patients without MV.6 Thus, an attempt to minimize the duration of sedation and MV to reduce other probable outcomes is at risk of increasing oxygen consumption (VO2) in a patient exhibiting nonoptimal cardiac function (low oxygenated blood flow, ie, DO2) and recent energy debt and organ failure. Because the goal of tissue resuscitation is only to re-equilibrate the DO2/VO2 ratio, attenuating or avoiding hyperadrenergic stress responses via intravenous sedation of patients with CS until the re-establishment of the most important organs’ function is of great interest. VO2 mainly depends on cellular metabolism and could be increased by a rise in this metabolism (eg, agitation, temperature, and muscular activity). Moreover, the energetic cost of spontaneous breathing in patients with CS could be very significant, as Field et al7 estimated the cost of breathing in patients with cardiorespiratory disease to be approximately 24% of the total VO2, with higher values in certain patients.8,9 Therefore, a decrease in VO2 by respiratory support may allow the re-equilibration of the DO2/VO2 ratio until cardiac output and the related DO2 value can improve. This concept is especially important in patients in whom refractory low cardiac output limits DO2. In this regard, several studies demonstrated that a moderate level of PEEP is safe to use in CS and may also provide hemodynamic benefits in left ventricular (LV) failure, which exhibits afterload-sensitive physiology.10 Additionally, patients with coronary artery disease who are receiving MV commonly present electrocardiographic evidence of myocardial ischemia during trials of weaning from ventilation. Thus, intensivists should wonder what effect a sudden withdrawal of sedation might have on the myocardial VO2 balance in CS patients who are at risk of cardiac disease. In this situation, the increased cost of breathing during early weaning from MV can be associated with the apparition of a DO2/VO2 imbalance, resulting in cellular hypoxia. Accordingly, it is our opinion that advice against the withdrawal of deep sedation and MV during the first 48 hours post-CS remains warranted. The present thinking emphasizes minimizing a patient’s
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oxygen needs, providing full respiratory muscle support and gentle transitions, and assuming physiological control.11
MISCONCEPTION 2: THE OPTIMAL BODY TEMPERATURE VALUE IS 37°C IN PATIENTS WITH CS From an analogous perspective regarding sedation and MV in patients with CS, a recent study reported that following out-of-hospital cardiac arrest, therapeutic hypothermia (TH) improves the hemodynamic status,12 despite a significant reduction in the cumulative doses of vasopressors and inotropes, in comparison with matched historical controls without TH. Moreover, recently, TH has been shown to improve cardiac function, suggesting that TH might be considered as a positive inotropic intervention.13 Thus, similar to deep sedation and MV, TH decreases VO2 and allows the re-equilibration of the DO2/VO2 ratio until cardiac output and the related DO2 value can improve (Fig. 1). TH also has other potentially beneficial physiologic effects in patients with CS: as the potential to improve the force development of the human myocardium and hemodynamics, to decrease myocardial damage, and to reduce end-organ injury from prolonged hypoperfusion. This concept is based on robust pathophysiological data from animal models of CS and small case series of human patients with CS, which have demonstrated the positive inotropic effect of low blood temperature on heart failure.14 Moreover, it is well-known that local cooling affects smalland large-vessel pressure and resistance.15 This concept is of great interest when CS patients have been well resuscitated and present ischemia–reperfusion syndrome associated with an inflammatory process and vasoplegia. In this regard, Lim and colleagues16 have already demonstrated that CS nonsurvivors may have low vascular tone, suggesting a distributive component during shock. In the present setting, the use of TH can increase vascular tone and decrease the requirement for vasopressor drugs. Thus, a very important key point when managing patients with CS is to disregard body temperature as a therapeutic target value, a recommendation that promises to be a potential salutary strategy in the near future.
MISCONCEPTION 3: AN INTRA-AORTIC BALLOON PUMP IS USELESS IN PATIENTS WITH CS RELATED TO RIGHT VENTRICULAR FAILURE The third false impression when treating patients with CS is that the impact of an IABP on hemodynamic optimization in the case of right ventricular (RV) failure is not important. Indeed, even if an IABP is the first choice for mechanical circulatory support of the LV, the indications for IABP use in the case of a failing RV are still
FIGURE 1. Evolution of oxygen consumption/O2-delivery relationship at various blood temperatures. Note the drop in the critical O2-delivery point associated with the decrease in temperature. 242 | www.cardiologyinreview.com
controversial.17,18 Indeed, only a few studies have concentrated on the use of an IABP in RV failure.19–21 Several mechanisms have been hypothesized to account for the hemodynamic decompensation of RV failure, including decreased RV cardiac output (series circulatory connection) and altered RV–LV interactions mediated by pericardial constraint and leftward septal shift (ventricular interdependence).22 Because little blood is being pumped to the LV, its filling is compromised, contributing to impaired LV output and systemic pressure, although the left side of the heart itself is normal. Additionally, ischemia has been demonstrated to be an important contributing factor for right heart failure in RV pressure overload.22 Indeed, in the case of high RV hypertension, an increase in central venous pressure and RV end-diastolic volume and pressure augments oxygen demand because of Laplace’s law and reduces coronary driving pressure because of a decrease in the endoepicardial (transmural) free-wall pressure gradient. All these phenomena occur in the presence of systemic hypotension and low coronary pressure. Thus, therapeutic strategies for treating pressure-induced RV failure aim to restore ventricular interactions and reverse RV ischemia. Experimentally, systemic hypertension after aortic constriction or vasopressor use has been reported to increase RV performance by reorganizing ventricular interactions and increasing RV coronary driving pressure.23,24 More notably, the clinical application of these strategies is limited in cases in which vasopressor infusion results in substantial increases in LV afterload, which ultimately causes LV dysfunction. In the present setting, an IABP seems to be a promising addition to systemic vasopressors, as this device unloads the LV and augments both systemic and coronary driving pressure (Fig. 2). Encouraging data reporting the use of an IABP to support a failing RV appear in 2 reports demonstrating beneficial hemodynamic effects on cardiac output and systemic pressure.19–21 These results are logical, as an IABP decreases LV afterload, reduces oxygen consumption, and at the same time increases coronary artery blood flow and oxygen supply to the myocardium by diastolic inflation. The significant improvement in coronary perfusion after IABP use could account for the improvement in both LV and RV function. Indeed, as the RV is contiguous to the LV through the septum, and as RV contractility is assisted by the LV, the latter is considered as the “lion of RV function.”25 Effectively, when the septum is ischemic, not only is the LV function curve impaired but also the RV function curve. The improved myocardial perfusion will then restore RV function both directly and indirectly. Several studies have demonstrated that the LV may contribute to >50% of RV function through ventricular interdependence-related mechanisms.25 In this regard, a previous report demonstrated that low output syndrome predominantly caused by RV allograft failure after heart transplantation may benefit from IABP use.26 Based on the results of a recent, randomized, controlled trial demonstrating that the use of an IABP in patients with CS did not significantly reduce 12-month all-cause mortality,27,28 the European Society of Cardiology has downgraded the recommendation for the use of an IABP in such patients from IC to IIB, while leaving the recommendation for the use of catecholamines at guideline IIA. From a pathophysiological perspective, the present recommendations have to be considered with caution, as IABP use has already proven efficient in low cardiac output syndromes. To date, the present form of hemodynamic support is the only form able to concomitantly decrease RV and LV afterloads and improve coronary and systemic tissue perfusion. In this way, the method reduces the need for inotropic and vasopressor drugs, whose potential benefits must be weighed against possible complications (eg, arrhythmias and high afterload). Therefore, the view that an IABP is useful in patients with CS related to both RV and LV failure is evident for clinicians, who look at the physiology of circulation. © 2014 Lippincott Williams & Wilkins
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Misconceptions of CS Management
FIGURE 2. Electrocardiographic (EKG) and aortic pressure curve of a patient with cardiogenic shock and under an intra-aortic balloon pump (IABP) programmed to assist 1 beat/2. Of note, please see the impact of IABP function on left ventricular performance. Immediately after balloon deflation, the time required for the left ventricle to eject (Δt1) is lower than in absence of IABP function (Δt2) [augmentation of the rate of rise of aortic pressure (Slope ΔP1/Δt1 > Slope ΔP2/Δt2)].
MISCONCEPTION 4: TOTAL ENTERAL NUTRITION IS SAFE IN PATIENTS WITH CS There is an irony in the enthusiasm of physicians, and mainly intensivists and nutritionists, about enteral nutrition (EN) use to improve the outcome of all types of critically ill patients. Even if the present experts’ opinion is correct for most ICU patients, EN could increase the risk of mesenteric ischemia and sepsis in CS patients. Indeed, the use of EN increases mesenteric arterial output, and patients with CS are characterized by a decrease in arterial flow delivery to organs such as the liver, intestine, and kidney.29 In fact, mesenteric blood flow accounts for 15–30% of cardiac output under fasting conditions, and the gut mucosa is a tissue that is particularly sensitive to alterations in its perfusion and oxygen status.30 It is right that patients experiencing heart failure are at a high risk of undernutrition and lean tissue losses. Thus, early optimal nutritional support could be a key point in the management of CS patients to prevent a protein-energy deficit. However, although early EN is usually recommended for most ICU patients, the present way of feeding is not necessarily the most suitable nutritional approach in patients presenting CS. Indeed, parenteral nutrition (PN) administration is associated with a reduction in mesenteric arterial output that could prevent ischemia in the liver and intestine of patients with CS. It is well-known that hypoperfusion in the splanchnic (mesenteric and hepatic) area secondary to CS could affect EN tolerance and intestinal absorption. Severe digestive complications associated with a low mesenteric arterial supply have been reported in ICU patients receiving EN.31 Thus, EN during CS may be associated with an increased risk of mesenteric ischemia, bacterial translocation, and sepsis. Indeed, one of the supposed complications of EN during low-flow states is claimed to be bowel infarction. The mechanism proposed is a decrease in mesenteric blood flow while an increase in splanchnic oxygen demand, triggered by EN, occurs. By examining more than 10,000 consecutive cardiac surgery patients, Chaudhuri et al32 identified one of the predictors of postoperative intestinal ischemia: postoperative atrial fibrillation. Therefore, the early identification of mesenteric ischemia in patients with CS is of great importance, especially because the gastrointestinal tract has been identified as the “motor” of multiple organ failure in ICU patients.33 © 2014 Lippincott Williams & Wilkins
Several studies have investigated human mesenteric circulation during CS. Measuring sublingual microcirculation using orthogonal polarization spectral imaging, De Backer et al34 reported a decreased proportion of functional capillaries in patients with CS compared with healthy controls. In addition, these alterations in the microcirculatory blood flow of the sublingual mucosa (which shares a similar embryologic origin with the digestive mucosa) was correlated with ICU mortality.34 These data suggest that human splanchnic microcirculation may be altered during CS.34 Several other methods of measurement of regional splanchnic blood flow have been evaluated in the ICU setting,35 but validation is problematic because a gold standard does not exist. Recently, measuring fecal pH changes related to altered gut flora have been shown to be a way to monitor intestinal failure and to clarify the significance of microbiota as a marker of splanchnic hypoperfusion.36 This type of elegant functional monitoring could be of interest for critically ill patients experiencing low-flow states, such as CS. Practically, the use of vasoactive drugs is positively correlated with muscle catabolism and negatively correlated with enteral energy intake.37 Thus, vasoactive drugs are also possibly involved in the risk of energy deficit in and undernutrition of CS patients. Additionally, data suggest that continuous EN at a low flow rate of 20 ml/h reduces the risk of severe intestinal complications in CS patients but leads to a negative energy balance that is responsible for infectious or noninfectious complications.38 Effectively, in ICU patients with CS, EN is frequently insufficient to obtain sufficient optimal energy delivery.37 This phenomenon may be related to the fact that catecholamine drugs are independent risk factors for a high gastric aspirate volume and gastrointestinal intolerance.39 In the present setting, associated PN could reduce mesenteric arterial output and its associated risk of mesenteric ischemia. Indeed, either form of nutrition and association is preferable to no nutrition at all. In this regard, recent randomized studies suggest that in patients with insufficient EN, supplementary PN could prevent the worsening of energy deficit and decrease the proportion of infected patients and the duration of MV.40 In conclusion, even if the supposed deleterious effect of EN on ICU patients with CS has never been demonstrated, from a pathophysiological perspective, we can anticipate that a total enteral feeding approach increases mesenteric arterial blood flow and ATP consumption, and may thus induce gut tissue hypoxia in CS patients.41 www.cardiologyinreview.com | 243
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Indeed, certain clinical reports suggest that early EN could be associated with gut ischemia due to alterations in splanchnic blood flow in patients with severe circulatory failure.31,42 The author of the present study agrees that EN cannot be systematically contraindicated in patients with CS, as it cannot be excluded that a slight increase in splanchnic blood flow related to limited EN could be beneficial, reinforcing the intestinal epithelial barrier. However, the evidence seems sufficient to make the statement that supplemental PN may decrease the inadequate hemodynamic response related to total EN in patients with CS. Clearly, the final undercurrent of this discourse is that the most appropriate way to feed ICU patients with CS is a combination of EN and PN, and that careful continuous monitoring of splanchnic blood flow is particularly useful in these patients. Thus, clinical trials that can confirm these crucial concepts are warranted.
MISCONCEPTION 5: CARDIAC FUNCTION IS THE KEY SURVIVAL PREDICTOR IN CS PATIENTS Misconception 5 is the perception that the prognosis of CS patients may be primarily dependent on cardiac reserve.43 Indeed, it has been shown that the cardiac index and cardiac power index are significantly associated with 28-day mortality in several previous studies.44,45 However, it has also been shown that 45% of nonsurvivors of CS die with a satisfactory cardiac index (ie, >2.2 L/min/m2) and a high Mixed venous oxygen saturation (SvO2), value, indicating that optimization of cardiac function alone may fail to save a patient.16 Recognizing these underlying principles leads to a shift in the paradigm of CS from being only a cardiac problem to being an overall global disease related to systemic inflammatory response syndrome and, through the release of proinflammatory cytokines and neurohormones, multiorgan failure.34,44 The present misconception of a rational concept is related to the fact that major hemodynamic studies have focused on cardiac performance to predict prognosis, without assessing the role of the macrocirculation. Given this background, reliable central hemodynamic parameters that predict the outcome of patients with CS are conceivable. However, few attempts have been made to evaluate other hemodynamic variables as possible prognostic indicators of mortality due to CS, and the reports have been inconclusive. The final consequence of cardiac output is tissue perfusion because the stroke volume must be distributed to organs via the capillaries and the microcirculation.34 Recently, we have retrospectively studied our CS registry in a preliminary attempt to evaluate the prognostic importance of systemic arterial circulatory parameters to predict the survival of patients presenting with CS. We found that diastolic arterial pressure could be used to unambiguously distinguish nonsurvivors from survivors, whereas prognosis was indistinguishable based on baseline cardiac hemodynamic criteria.46 The present results were in line with findings based on the SHOCK trial registry, which demonstrated that vascular tone can be very low in patients with CS.47 Moreover, Lim and colleagues16 have already demonstrated that CS nonsurvivors may have a low systemic vascular resistance index, suggesting a distributive component during this shock. There is considerable confusion about the pathophysiology of CS because of the popular notion that its prognosis is only related to cardiac function. However, advanced cardiac output measurements inside the ICU, which could affect prognosis, have not influenced CS mortality over the past decades,48 even while therapy for heart failure has improved. For the first time, our recent investigation showed that diastolic arterial pressure is an objective criterion for predicting outcome in individual patients with CS. The availability of such a prognostic indicator will be very valuable in formulating management plans for these ICU patients. From a pathophysiological perspective, changes in the mean diastolic arterial pressure are believed to mainly reflect changes in the peripheral circulation, with a lower diastolic 244 | www.cardiologyinreview.com
arterial pressure corresponding to decreased arterial tone.46 Thus, 70 years after the seminal description of the systemic manifestations of CS,49 it is now a fact that the outcome of CS patients may depend on both cardiac reserve and an underlying systemic illness, such as inflammation or systemic inflammatory response syndrome.50 This fact also explains why 45% of CS nonsurvivors have been shown to die, despite a normal cardiac index.16 Several inflammatory cytokines have been demonstrated to be elevated in acute myocardial infarction complicated by CS.51 Moreover, the transmigration of bacteria related to intestinal ischemia and low flow could induce sepsis, as demonstrated in the SHOCK trial registry, in which 74% of patients developed positive bacterial cultures.47 Alternatively, a decrease in diastolic arterial pressure and arterial tone could be related to the accumulation of oxygen free radicals and increased nitric oxide synthesis related to ischemia–reperfusion syndrome, as already observed in CS.51 All these speculations are in accordance with the SHOCK trial registry, in which arterial tone was demonstrated to be highly variable in patients with CS.52 Hence, over the last decades, the clinician’s recurrent misconception when managing CS was that an adequate cardiac index associated with low arterial tone (low afterload) is a suitable event.
CONCLUSIONS It is generally accepted that numerous critically ill patients’ conditions are complex and can be difficult to communicate through simple reviews, lectures, and textbooks. Consequently, the pedagogical proposal of the present article was to highlight common misconceptions when managing CS, with a small number of unproven thoughts having a defensible rationale but unverified worth. As long as the common reluctance to accept new findings persists, many challenges will remain in correcting medical misconceptions through scientific clinical investigations. REFERENCES 1. Cheng JM, den Uil CA, Hoeks SE, et al. Percutaneous left ventricular assist devices vs. intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials. Eur Heart J. 2009;30:2102–2108. 2. Hooper MH, Girard TD. Sedation and weaning from mechanical ventilation: linking spontaneous awakening trials and spontaneous breathing trials to improve patient outcomes. Crit Care Clin. 2009;25:515–25, viii. 3. Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114:541–548. 4. Kress JP, Pohlman AS, O’Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471–1477. 5. Rello J, Diaz E, Roque M, et al. Risk factors for developing pneumonia within 48 hours of intubation. Am J Respir Crit Care Med. 1999;159:1742–1746. 6. Kontoyannis DA, Nanas JN, Kontoyannis SA, et al. Mechanical ventilation in conjunction with the intra-aortic balloon pump improves the outcome of patients in profound cardiogenic shock. Intensive Care Med. 1999;25:835–838. 7. Field S, Kelly SM, Macklem PT. The oxygen cost of breathing in patients with cardiorespiratory disease. Am Rev Respir Dis. 1982;126:9–13. 8. Aubier M, Viires N, Syllie G, et al. Respiratory muscle contribution to lactic acidosis in low cardiac output. Am Rev Respir Dis. 1982;126:648–652. 9. Roussos C, Macklem PT. The respiratory muscles. N Engl J Med. 1982;307:786–797. 10. Wiesen J, Ornstein M, Tonelli AR, et al. State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock. Heart. 2013;99:1812–1817. 11. Marini JJ, Vincent JL, Wischmeyer P, et al. Our favorite unproven ideas for future critical care. Crit Care. 2013;17(suppl 1):S9. 12. Zobel C, Adler C, Kranz A, et al. Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med. 2012;40:1715–1723.
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13. Schmidt-Schweda S, Ohler A, Post H, et al. Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II). Resuscitation. 2013;84:319–325. 14. Stegman BM, Newby LK, Hochman JS, et al. Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility? J Am Coll Cardiol. 2012;59:644–647. 15. Scott JB, Hardin RA, Haddy FJ. The effect of local cooling upon small and large vessel pressures and resistances in the dog forelimb. Rep US Army Med Res Lab. 1960;430:1–12. 16. Lim N, Dubois MJ, De Backer D, et al. Do all nonsurvivors of cardiogenic shock die with a low cardiac index? Chest. 2003;124:1885–1891. 17. Kleber FX. Intraaortic balloon support for cardiogenic shock. N Engl J Med. 2013;368:80. 18. Boeken U, Feindt P, Litmathe J, et al. Intraaortic balloon pumping in patients with right ventricular insufficiency after cardiac surgery: parameters to predict failure of IABP Support. Thorac Cardiovasc Surg. 2009;57:324–328. 19. Kopman EA, Ramirez-Inawat RC. Intra-aortic balloon counterpulsation for right heart failure. Anesth Analg. 1980;59:74–76. 20. Darrah WC, Sharpe MD, Guiraudon GM, et al. Intraaortic balloon counterpulsation improves right ventricular failure resulting from pressure overload. Ann Thorac Surg. 1997;64:1718–1723; discussion 1723. 21. Liakopoulos OJ, Ho JK, Yezbick AB, et al. Right ventricular failure resulting from pressure overload: role of intra-aortic balloon counterpulsation and vasopressor therapy. J Surg Res. 2010;164:58–66. 22. Haddad F, Doyle R, Murphy DJ, et al. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008;117:1717–1731. 23. Vlahakes GJ, Turley K, Hoffman JI. The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations. Circulation. 1981;63:87–95. 24. Belenkie I, Horne SG, Dani R, et al. Effects of aortic constriction during experimental acute right ventricular pressure loading. Further insights into diastolic and systolic ventricular interaction. Circulation. 1995;92:546–554. 25. Buckberg GD. The ventricular septum: the lion of right ventricular function, and its impact on right ventricular restoration. Eur J Cardiothorac Surg. 2006;29(suppl 1):S272–S278. 26. Arafa OE, Geiran OR, Andersen K, et al. Intraaortic balloon pumping for predominantly right ventricular failure after heart transplantation. Ann Thorac Surg. 2000;70:1587–1593. 27. Thiele H, Zeymer U, Neumann FJ, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABPSHOCK II): final 12 month results of a randomised, open-label trial. Lancet. 2013;382:1638–1645. 28. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287–1296. 29. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail. 2008;10:933–989. 30. Reilly PM, Wilkins KB, Fuh KC, et al. The mesenteric hemodynamic response to circulatory shock: an overview. Shock. 2001;15:329–343. 31. Melis M, Fichera A, Ferguson MK. Bowel necrosis associated with early jejunal tube feeding: A complication of postoperative enteral nutrition. Arch Surg. 2006;141:701–704.
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32. Chaudhuri N, James J, Sheikh A, et al. Intestinal ischaemia following cardiac surgery: a multivariate risk model. Eur J Cardiothorac Surg. 2006;29:971–977. 33. Carrico CJ, Meakins JL, Marshall JC, et al. Multiple-organ-failure syndrome. Arch Surg. 1986;121:196–208. 34. De Backer D, Creteur J, Dubois MJ, et al. Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J. 2004;147:91–99. 35. Thibault R, Pichard C, Wernerman J, et al. Cardiogenic shock and nutrition: safe? Intensive Care Med. 2011;37:35–45. 36. Osuka A, Shimizu K, Ogura H, et al. Prognostic impact of fecal pH in critically ill patients. Crit Care. 2012;16:R119. 37. Berger MM, Revelly JP, Cayeux MC, et al. Enteral nutrition in critically ill patients with severe hemodynamic failure after cardiopulmonary bypass. Clin Nutr. 2005;24:124–132. 38. Villet S, Chiolero RL, Bollmann MD, et al. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clin Nutr. 2005;24:502–509. 39. Mentec H, Dupont H, Bocchetti M, et al. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med. 2001;29:1955–1961. 40. Heidegger CP, Berger MM, Graf S, et al. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013;381:385–393. 41. Gatt M, MacFie J, Anderson AD, et al. Changes in superior mesenteric artery blood flow after oral, enteral, and parenteral feeding in humans. Crit Care Med. 2009;37:171–176. 42. Zaloga GP, Roberts PR, Marik P. Feeding the hemodynamically unstable patient: a critical evaluation of the evidence. Nutr Clin Pract. 2003;18:285–293. 43. Jeger RV, Lowe AM, Buller CE, et al. Hemodynamic parameters are prognostically important in cardiogenic shock but similar following early revascularization or initial medical stabilization: a report from the SHOCK trial. Chest. 2007;132:1794–1803. 44. Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving outcomes. Circulation. 2008;117:686–697. 45. Tan LB, Littler WA. Measurement of cardiac reserve in cardiogenic shock: implications for prognosis and management. Br Heart J. 1990;64:121–128. 46. Rigamonti F, Graf G, Merlani P, et al. The short-term prognosis of cardiogenic shock can be determined using hemodynamic variables: a retrospective cohort study*. Crit Care Med. 2013;41:2484–2491. 47. Kohsaka S, Menon V, Iwata K, et al. Microbiological profile of septic complication in patients with cardiogenic shock following acute myocardial infarction (from the SHOCK study). Am J Cardiol. 2007;99:802–804. 48. Zobel C, Dörpinghaus M, Reuter H, et al. Mortality in a cardiac intensive care unit. Clin Res Cardiol. 2012;101:521–524. 49. Stead EA, Ebert RV. Shock syndrome produced by failure of the heart. Arch Intern Med. 1942;69:369–383. 50. Stegman BM, Newby LK, Hochman JS, et al. Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility? J Am Coll Cardiol. 2012;59:644–647. 51. Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53:31–47. 52. Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation. 2003;107:2998–3002.
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Five Recurrent Misconceptions Regarding Cardiogenic Shock Management Karim Bendjelid, MD, PhD
Abstract: Medical therapeutic knowledge advances by continual action and reaction between retrospective and prospective evaluation on the one hand and clinical real-life observation and assessment on the other. In this regard, our goal is to articulate and demystify certain myths and misconceptions that impede the optimal management of patients with circulatory failure related to acute cardiac diseases. More specifically, we outline 5 statements that represent misconceptions about cardiogenic shock management that we have frequently faced throughout years of caring for critically ill patients. Moreover, for each statement, we suggest concise, corrective responses. Key Words: cardiogenic shock, shift, paradigms (Cardiology in Review 2014;22: 241–245)
I
n clinical medicine, physicians frequently accept paradigms or ideas that have been passed from one generation of doctors to another as being correct, although such ideas have never been subject to scientific examination. Generally, in the absence of evidence-based medicine, these concepts are derived from experience and frequently take on a power of their own. In many situations, the concepts are correct, but this may not always be the case. The present review is written in the context of ongoing efforts to dispel misunderstandings about cardiogenic shock (CS) management in the intensive care unit (ICU). CS is characterized by low cardiac output, with a marked reduction in stroke volume, increased venous pressure, and signs of low organ perfusion. CS mortality remains unacceptably high (40–75%) and has not improved significantly, despite the use of readily available advanced hemodynamic monitoring devices and therapeutic modalities for heart failure.1 Our goal is to articulate and demystify certain myths and misconceptions that impede the optimal management of patients with circulatory failure related to acute cardiac diseases. More specifically, we outline 5 statements that represent misconceptions about CS management that we have frequently faced throughout years of caring for critically ill patients. Moreover, for each statement, we suggest concise, corrective responses.
MISCONCEPTION 1: FAST WEANING FROM SEDATION AND MECHANICAL VENTILATION IS VITAL FOR PATIENTS WITH CS Misconception 1 is the perception that a deeply sedated, mechanically ventilated patient with CS related to acute heart diseases (eg, myocardial infarction, tamponade, and electrical storm)
From the Intensive Care Service, Geneva University Hospitals, the Faculty of Medicine, University of Geneva, and the Geneva Hemodynamic Research Group, Geneva, Switzerland. Disclosure: The author has no conflicts of interest to report. Correspondence: Karim Bendjelid, MD, PhD, Médecin Adjoint Agrégé, Intensive Care Service, Geneva University Hospitals, 4 Rue Gabrielle Perret-Gentil, CH-1211 Geneva 14, Switzerland. E-mail: [email protected]. Copyright © 2014 Lippincott Williams & Wilkins ISSN: 1061-5377/14/2205-0241 DOI: 10.1097/CRD.0000000000000019
should be weaned from sedation and mechanical ventilation (MV) once the cardiac disease triggering CS has been successfully treated. The present misconception is the result of the correct thought that weaning from sedation and MV is vital in the management of many critically ill patients.2 The present strategy is also the result of current guideline recommendations, which advocate early liberation from the ventilator for ICU patients. Indeed, in the past 20 years, concern over the deleterious effects of oversedation has prompted the investigation of ways to safely deliver the appropriate level of sedation to patients without delaying extubation.3,4 Moreover, observational studies and randomized trials have suggested that in contrast to intermittent infusion, a continuous infusion of sedatives increases the risk of developing pneumonia and requiring prolonged MV.5 However, there is also no evidence that justifies early cessation of the use of sedation and MV in patients enduring CS, especially during the first 48 hours following the shock. Indeed, MV with postive end-expiratory pressure (PEEP) has been associated with not only improved hemodynamic measurements but also superior clinical end points. A small study of 18 patients with CS necessitating intra-aortic balloon pump (IABP) placement found that the patients randomized to receive elective MV with 10 cm H2O of PEEP were more likely to be weaned off the IABP and to survive to discharge than patients without MV.6 Thus, an attempt to minimize the duration of sedation and MV to reduce other probable outcomes is at risk of increasing oxygen consumption (VO2) in a patient exhibiting nonoptimal cardiac function (low oxygenated blood flow, ie, DO2) and recent energy debt and organ failure. Because the goal of tissue resuscitation is only to re-equilibrate the DO2/VO2 ratio, attenuating or avoiding hyperadrenergic stress responses via intravenous sedation of patients with CS until the re-establishment of the most important organs’ function is of great interest. VO2 mainly depends on cellular metabolism and could be increased by a rise in this metabolism (eg, agitation, temperature, and muscular activity). Moreover, the energetic cost of spontaneous breathing in patients with CS could be very significant, as Field et al7 estimated the cost of breathing in patients with cardiorespiratory disease to be approximately 24% of the total VO2, with higher values in certain patients.8,9 Therefore, a decrease in VO2 by respiratory support may allow the re-equilibration of the DO2/VO2 ratio until cardiac output and the related DO2 value can improve. This concept is especially important in patients in whom refractory low cardiac output limits DO2. In this regard, several studies demonstrated that a moderate level of PEEP is safe to use in CS and may also provide hemodynamic benefits in left ventricular (LV) failure, which exhibits afterload-sensitive physiology.10 Additionally, patients with coronary artery disease who are receiving MV commonly present electrocardiographic evidence of myocardial ischemia during trials of weaning from ventilation. Thus, intensivists should wonder what effect a sudden withdrawal of sedation might have on the myocardial VO2 balance in CS patients who are at risk of cardiac disease. In this situation, the increased cost of breathing during early weaning from MV can be associated with the apparition of a DO2/VO2 imbalance, resulting in cellular hypoxia. Accordingly, it is our opinion that advice against the withdrawal of deep sedation and MV during the first 48 hours post-CS remains warranted. The present thinking emphasizes minimizing a patient’s
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oxygen needs, providing full respiratory muscle support and gentle transitions, and assuming physiological control.11
MISCONCEPTION 2: THE OPTIMAL BODY TEMPERATURE VALUE IS 37°C IN PATIENTS WITH CS From an analogous perspective regarding sedation and MV in patients with CS, a recent study reported that following out-of-hospital cardiac arrest, therapeutic hypothermia (TH) improves the hemodynamic status,12 despite a significant reduction in the cumulative doses of vasopressors and inotropes, in comparison with matched historical controls without TH. Moreover, recently, TH has been shown to improve cardiac function, suggesting that TH might be considered as a positive inotropic intervention.13 Thus, similar to deep sedation and MV, TH decreases VO2 and allows the re-equilibration of the DO2/VO2 ratio until cardiac output and the related DO2 value can improve (Fig. 1). TH also has other potentially beneficial physiologic effects in patients with CS: as the potential to improve the force development of the human myocardium and hemodynamics, to decrease myocardial damage, and to reduce end-organ injury from prolonged hypoperfusion. This concept is based on robust pathophysiological data from animal models of CS and small case series of human patients with CS, which have demonstrated the positive inotropic effect of low blood temperature on heart failure.14 Moreover, it is well-known that local cooling affects smalland large-vessel pressure and resistance.15 This concept is of great interest when CS patients have been well resuscitated and present ischemia–reperfusion syndrome associated with an inflammatory process and vasoplegia. In this regard, Lim and colleagues16 have already demonstrated that CS nonsurvivors may have low vascular tone, suggesting a distributive component during shock. In the present setting, the use of TH can increase vascular tone and decrease the requirement for vasopressor drugs. Thus, a very important key point when managing patients with CS is to disregard body temperature as a therapeutic target value, a recommendation that promises to be a potential salutary strategy in the near future.
MISCONCEPTION 3: AN INTRA-AORTIC BALLOON PUMP IS USELESS IN PATIENTS WITH CS RELATED TO RIGHT VENTRICULAR FAILURE The third false impression when treating patients with CS is that the impact of an IABP on hemodynamic optimization in the case of right ventricular (RV) failure is not important. Indeed, even if an IABP is the first choice for mechanical circulatory support of the LV, the indications for IABP use in the case of a failing RV are still
FIGURE 1. Evolution of oxygen consumption/O2-delivery relationship at various blood temperatures. Note the drop in the critical O2-delivery point associated with the decrease in temperature. 242 | www.cardiologyinreview.com
controversial.17,18 Indeed, only a few studies have concentrated on the use of an IABP in RV failure.19–21 Several mechanisms have been hypothesized to account for the hemodynamic decompensation of RV failure, including decreased RV cardiac output (series circulatory connection) and altered RV–LV interactions mediated by pericardial constraint and leftward septal shift (ventricular interdependence).22 Because little blood is being pumped to the LV, its filling is compromised, contributing to impaired LV output and systemic pressure, although the left side of the heart itself is normal. Additionally, ischemia has been demonstrated to be an important contributing factor for right heart failure in RV pressure overload.22 Indeed, in the case of high RV hypertension, an increase in central venous pressure and RV end-diastolic volume and pressure augments oxygen demand because of Laplace’s law and reduces coronary driving pressure because of a decrease in the endoepicardial (transmural) free-wall pressure gradient. All these phenomena occur in the presence of systemic hypotension and low coronary pressure. Thus, therapeutic strategies for treating pressure-induced RV failure aim to restore ventricular interactions and reverse RV ischemia. Experimentally, systemic hypertension after aortic constriction or vasopressor use has been reported to increase RV performance by reorganizing ventricular interactions and increasing RV coronary driving pressure.23,24 More notably, the clinical application of these strategies is limited in cases in which vasopressor infusion results in substantial increases in LV afterload, which ultimately causes LV dysfunction. In the present setting, an IABP seems to be a promising addition to systemic vasopressors, as this device unloads the LV and augments both systemic and coronary driving pressure (Fig. 2). Encouraging data reporting the use of an IABP to support a failing RV appear in 2 reports demonstrating beneficial hemodynamic effects on cardiac output and systemic pressure.19–21 These results are logical, as an IABP decreases LV afterload, reduces oxygen consumption, and at the same time increases coronary artery blood flow and oxygen supply to the myocardium by diastolic inflation. The significant improvement in coronary perfusion after IABP use could account for the improvement in both LV and RV function. Indeed, as the RV is contiguous to the LV through the septum, and as RV contractility is assisted by the LV, the latter is considered as the “lion of RV function.”25 Effectively, when the septum is ischemic, not only is the LV function curve impaired but also the RV function curve. The improved myocardial perfusion will then restore RV function both directly and indirectly. Several studies have demonstrated that the LV may contribute to >50% of RV function through ventricular interdependence-related mechanisms.25 In this regard, a previous report demonstrated that low output syndrome predominantly caused by RV allograft failure after heart transplantation may benefit from IABP use.26 Based on the results of a recent, randomized, controlled trial demonstrating that the use of an IABP in patients with CS did not significantly reduce 12-month all-cause mortality,27,28 the European Society of Cardiology has downgraded the recommendation for the use of an IABP in such patients from IC to IIB, while leaving the recommendation for the use of catecholamines at guideline IIA. From a pathophysiological perspective, the present recommendations have to be considered with caution, as IABP use has already proven efficient in low cardiac output syndromes. To date, the present form of hemodynamic support is the only form able to concomitantly decrease RV and LV afterloads and improve coronary and systemic tissue perfusion. In this way, the method reduces the need for inotropic and vasopressor drugs, whose potential benefits must be weighed against possible complications (eg, arrhythmias and high afterload). Therefore, the view that an IABP is useful in patients with CS related to both RV and LV failure is evident for clinicians, who look at the physiology of circulation. © 2014 Lippincott Williams & Wilkins
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FIGURE 2. Electrocardiographic (EKG) and aortic pressure curve of a patient with cardiogenic shock and under an intra-aortic balloon pump (IABP) programmed to assist 1 beat/2. Of note, please see the impact of IABP function on left ventricular performance. Immediately after balloon deflation, the time required for the left ventricle to eject (Δt1) is lower than in absence of IABP function (Δt2) [augmentation of the rate of rise of aortic pressure (Slope ΔP1/Δt1 > Slope ΔP2/Δt2)].
MISCONCEPTION 4: TOTAL ENTERAL NUTRITION IS SAFE IN PATIENTS WITH CS There is an irony in the enthusiasm of physicians, and mainly intensivists and nutritionists, about enteral nutrition (EN) use to improve the outcome of all types of critically ill patients. Even if the present experts’ opinion is correct for most ICU patients, EN could increase the risk of mesenteric ischemia and sepsis in CS patients. Indeed, the use of EN increases mesenteric arterial output, and patients with CS are characterized by a decrease in arterial flow delivery to organs such as the liver, intestine, and kidney.29 In fact, mesenteric blood flow accounts for 15–30% of cardiac output under fasting conditions, and the gut mucosa is a tissue that is particularly sensitive to alterations in its perfusion and oxygen status.30 It is right that patients experiencing heart failure are at a high risk of undernutrition and lean tissue losses. Thus, early optimal nutritional support could be a key point in the management of CS patients to prevent a protein-energy deficit. However, although early EN is usually recommended for most ICU patients, the present way of feeding is not necessarily the most suitable nutritional approach in patients presenting CS. Indeed, parenteral nutrition (PN) administration is associated with a reduction in mesenteric arterial output that could prevent ischemia in the liver and intestine of patients with CS. It is well-known that hypoperfusion in the splanchnic (mesenteric and hepatic) area secondary to CS could affect EN tolerance and intestinal absorption. Severe digestive complications associated with a low mesenteric arterial supply have been reported in ICU patients receiving EN.31 Thus, EN during CS may be associated with an increased risk of mesenteric ischemia, bacterial translocation, and sepsis. Indeed, one of the supposed complications of EN during low-flow states is claimed to be bowel infarction. The mechanism proposed is a decrease in mesenteric blood flow while an increase in splanchnic oxygen demand, triggered by EN, occurs. By examining more than 10,000 consecutive cardiac surgery patients, Chaudhuri et al32 identified one of the predictors of postoperative intestinal ischemia: postoperative atrial fibrillation. Therefore, the early identification of mesenteric ischemia in patients with CS is of great importance, especially because the gastrointestinal tract has been identified as the “motor” of multiple organ failure in ICU patients.33 © 2014 Lippincott Williams & Wilkins
Several studies have investigated human mesenteric circulation during CS. Measuring sublingual microcirculation using orthogonal polarization spectral imaging, De Backer et al34 reported a decreased proportion of functional capillaries in patients with CS compared with healthy controls. In addition, these alterations in the microcirculatory blood flow of the sublingual mucosa (which shares a similar embryologic origin with the digestive mucosa) was correlated with ICU mortality.34 These data suggest that human splanchnic microcirculation may be altered during CS.34 Several other methods of measurement of regional splanchnic blood flow have been evaluated in the ICU setting,35 but validation is problematic because a gold standard does not exist. Recently, measuring fecal pH changes related to altered gut flora have been shown to be a way to monitor intestinal failure and to clarify the significance of microbiota as a marker of splanchnic hypoperfusion.36 This type of elegant functional monitoring could be of interest for critically ill patients experiencing low-flow states, such as CS. Practically, the use of vasoactive drugs is positively correlated with muscle catabolism and negatively correlated with enteral energy intake.37 Thus, vasoactive drugs are also possibly involved in the risk of energy deficit in and undernutrition of CS patients. Additionally, data suggest that continuous EN at a low flow rate of 20 ml/h reduces the risk of severe intestinal complications in CS patients but leads to a negative energy balance that is responsible for infectious or noninfectious complications.38 Effectively, in ICU patients with CS, EN is frequently insufficient to obtain sufficient optimal energy delivery.37 This phenomenon may be related to the fact that catecholamine drugs are independent risk factors for a high gastric aspirate volume and gastrointestinal intolerance.39 In the present setting, associated PN could reduce mesenteric arterial output and its associated risk of mesenteric ischemia. Indeed, either form of nutrition and association is preferable to no nutrition at all. In this regard, recent randomized studies suggest that in patients with insufficient EN, supplementary PN could prevent the worsening of energy deficit and decrease the proportion of infected patients and the duration of MV.40 In conclusion, even if the supposed deleterious effect of EN on ICU patients with CS has never been demonstrated, from a pathophysiological perspective, we can anticipate that a total enteral feeding approach increases mesenteric arterial blood flow and ATP consumption, and may thus induce gut tissue hypoxia in CS patients.41 www.cardiologyinreview.com | 243
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Indeed, certain clinical reports suggest that early EN could be associated with gut ischemia due to alterations in splanchnic blood flow in patients with severe circulatory failure.31,42 The author of the present study agrees that EN cannot be systematically contraindicated in patients with CS, as it cannot be excluded that a slight increase in splanchnic blood flow related to limited EN could be beneficial, reinforcing the intestinal epithelial barrier. However, the evidence seems sufficient to make the statement that supplemental PN may decrease the inadequate hemodynamic response related to total EN in patients with CS. Clearly, the final undercurrent of this discourse is that the most appropriate way to feed ICU patients with CS is a combination of EN and PN, and that careful continuous monitoring of splanchnic blood flow is particularly useful in these patients. Thus, clinical trials that can confirm these crucial concepts are warranted.
MISCONCEPTION 5: CARDIAC FUNCTION IS THE KEY SURVIVAL PREDICTOR IN CS PATIENTS Misconception 5 is the perception that the prognosis of CS patients may be primarily dependent on cardiac reserve.43 Indeed, it has been shown that the cardiac index and cardiac power index are significantly associated with 28-day mortality in several previous studies.44,45 However, it has also been shown that 45% of nonsurvivors of CS die with a satisfactory cardiac index (ie, >2.2 L/min/m2) and a high Mixed venous oxygen saturation (SvO2), value, indicating that optimization of cardiac function alone may fail to save a patient.16 Recognizing these underlying principles leads to a shift in the paradigm of CS from being only a cardiac problem to being an overall global disease related to systemic inflammatory response syndrome and, through the release of proinflammatory cytokines and neurohormones, multiorgan failure.34,44 The present misconception of a rational concept is related to the fact that major hemodynamic studies have focused on cardiac performance to predict prognosis, without assessing the role of the macrocirculation. Given this background, reliable central hemodynamic parameters that predict the outcome of patients with CS are conceivable. However, few attempts have been made to evaluate other hemodynamic variables as possible prognostic indicators of mortality due to CS, and the reports have been inconclusive. The final consequence of cardiac output is tissue perfusion because the stroke volume must be distributed to organs via the capillaries and the microcirculation.34 Recently, we have retrospectively studied our CS registry in a preliminary attempt to evaluate the prognostic importance of systemic arterial circulatory parameters to predict the survival of patients presenting with CS. We found that diastolic arterial pressure could be used to unambiguously distinguish nonsurvivors from survivors, whereas prognosis was indistinguishable based on baseline cardiac hemodynamic criteria.46 The present results were in line with findings based on the SHOCK trial registry, which demonstrated that vascular tone can be very low in patients with CS.47 Moreover, Lim and colleagues16 have already demonstrated that CS nonsurvivors may have a low systemic vascular resistance index, suggesting a distributive component during this shock. There is considerable confusion about the pathophysiology of CS because of the popular notion that its prognosis is only related to cardiac function. However, advanced cardiac output measurements inside the ICU, which could affect prognosis, have not influenced CS mortality over the past decades,48 even while therapy for heart failure has improved. For the first time, our recent investigation showed that diastolic arterial pressure is an objective criterion for predicting outcome in individual patients with CS. The availability of such a prognostic indicator will be very valuable in formulating management plans for these ICU patients. From a pathophysiological perspective, changes in the mean diastolic arterial pressure are believed to mainly reflect changes in the peripheral circulation, with a lower diastolic 244 | www.cardiologyinreview.com
arterial pressure corresponding to decreased arterial tone.46 Thus, 70 years after the seminal description of the systemic manifestations of CS,49 it is now a fact that the outcome of CS patients may depend on both cardiac reserve and an underlying systemic illness, such as inflammation or systemic inflammatory response syndrome.50 This fact also explains why 45% of CS nonsurvivors have been shown to die, despite a normal cardiac index.16 Several inflammatory cytokines have been demonstrated to be elevated in acute myocardial infarction complicated by CS.51 Moreover, the transmigration of bacteria related to intestinal ischemia and low flow could induce sepsis, as demonstrated in the SHOCK trial registry, in which 74% of patients developed positive bacterial cultures.47 Alternatively, a decrease in diastolic arterial pressure and arterial tone could be related to the accumulation of oxygen free radicals and increased nitric oxide synthesis related to ischemia–reperfusion syndrome, as already observed in CS.51 All these speculations are in accordance with the SHOCK trial registry, in which arterial tone was demonstrated to be highly variable in patients with CS.52 Hence, over the last decades, the clinician’s recurrent misconception when managing CS was that an adequate cardiac index associated with low arterial tone (low afterload) is a suitable event.
CONCLUSIONS It is generally accepted that numerous critically ill patients’ conditions are complex and can be difficult to communicate through simple reviews, lectures, and textbooks. Consequently, the pedagogical proposal of the present article was to highlight common misconceptions when managing CS, with a small number of unproven thoughts having a defensible rationale but unverified worth. As long as the common reluctance to accept new findings persists, many challenges will remain in correcting medical misconceptions through scientific clinical investigations. REFERENCES 1. Cheng JM, den Uil CA, Hoeks SE, et al. Percutaneous left ventricular assist devices vs. intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials. Eur Heart J. 2009;30:2102–2108. 2. Hooper MH, Girard TD. Sedation and weaning from mechanical ventilation: linking spontaneous awakening trials and spontaneous breathing trials to improve patient outcomes. Crit Care Clin. 2009;25:515–25, viii. 3. Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114:541–548. 4. Kress JP, Pohlman AS, O’Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471–1477. 5. Rello J, Diaz E, Roque M, et al. Risk factors for developing pneumonia within 48 hours of intubation. Am J Respir Crit Care Med. 1999;159:1742–1746. 6. Kontoyannis DA, Nanas JN, Kontoyannis SA, et al. Mechanical ventilation in conjunction with the intra-aortic balloon pump improves the outcome of patients in profound cardiogenic shock. Intensive Care Med. 1999;25:835–838. 7. Field S, Kelly SM, Macklem PT. The oxygen cost of breathing in patients with cardiorespiratory disease. Am Rev Respir Dis. 1982;126:9–13. 8. Aubier M, Viires N, Syllie G, et al. Respiratory muscle contribution to lactic acidosis in low cardiac output. Am Rev Respir Dis. 1982;126:648–652. 9. Roussos C, Macklem PT. The respiratory muscles. N Engl J Med. 1982;307:786–797. 10. Wiesen J, Ornstein M, Tonelli AR, et al. State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock. Heart. 2013;99:1812–1817. 11. Marini JJ, Vincent JL, Wischmeyer P, et al. Our favorite unproven ideas for future critical care. Crit Care. 2013;17(suppl 1):S9. 12. Zobel C, Adler C, Kranz A, et al. Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med. 2012;40:1715–1723.
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