Management of cardiogenic shock after acute coronary syndromes

Key points•Cardiogenic shock is the most common cause of in-hospital death after acute coronary syndromes.•Myocardial dysfunction triggers a compensatory systemic vascular response.•The key to diagnosis is demonstration of end-organ hypoperfusion.•Myocardial revascularisation by percutaneous coronary intervention is the only evidence-based treatment shown definitively to improve outcome.•Pharmacological and mechanical circulatory support enables revascularisation, advanced therapies and recovery.Learning objectivesBy reading this article you should be able to.•Define cardiogenic shock and understand its pathophysiology after acute coronary syndromes (ACS).•Assess the patient with, or at risk of cardiogenic shock after ACS.•Discuss the key therapeutic and supportive steps in managing patients with cardiogenic shock after ACS. •Cardiogenic shock is the most common cause of in-hospital death after acute coronary syndromes.•Myocardial dysfunction triggers a compensatory systemic vascular response.•The key to diagnosis is demonstration of end-organ hypoperfusion.•Myocardial revascularisation by percutaneous coronary intervention is the only evidence-based treatment shown definitively to improve outcome.•Pharmacological and mechanical circulatory support enables revascularisation, advanced therapies and recovery. By reading this article you should be able to.•Define cardiogenic shock and understand its pathophysiology after acute coronary syndromes (ACS).•Assess the patient with, or at risk of cardiogenic shock after ACS.•Discuss the key therapeutic and supportive steps in managing patients with cardiogenic shock after ACS. Cardiogenic shock (CS) represents a spectrum of potential clinical presentations characterised by end-organ hypoperfusion and tissue hypoxia caused by primary cardiac dysfunction, which can result in multiorgan failure and death.1Reynolds H.R. Hochman J.S. Cardiogenic shock: current concepts and improving outcomes.Circulation. 2008; 117: 686-697Crossref PubMed Scopus (565) Google Scholar, 2van Diepen S. Katz J.N. Albert N.M. et al.Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.Circulation. 2017; 136: e232-e268Crossref PubMed Scopus (833) Google Scholar, 3Thiele H. Ohman E.M. de Waha-Thiele S. Zeymer U. Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019.Eur Heart J. 2019; 40: 2671-2683Crossref PubMed Scopus (259) Google Scholar It is the most common cause of in-hospital death after acute coronary syndromes (ACS) (CS after acute myocardial infarction [AMI]; CS-AMI) with a mortality rate of 40–70%.3Thiele H. Ohman E.M. de Waha-Thiele S. Zeymer U. Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019.Eur Heart J. 2019; 40: 2671-2683Crossref PubMed Scopus (259) Google Scholar,4Rathod K.S. Koganti S. Iqbal M.B. et al.Contemporary trends in cardiogenic shock: incidence, intra-aortic balloon pump utilisation and outcomes from the London Heart Attack Group.Eur Heart J Acute Cardiovasc Care. 2018; 7: 16-27Crossref PubMed Scopus (72) Google Scholar Traditionally, CS has been defined by haemodynamic criteria derived from invasive monitoring, but recent definitions describe a recognisable clinical phenotype (Table 1).1Reynolds H.R. Hochman J.S. Cardiogenic shock: current concepts and improving outcomes.Circulation. 2008; 117: 686-697Crossref PubMed Scopus (565) Google Scholar,3Thiele H. Ohman E.M. de Waha-Thiele S. Zeymer U. Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019.Eur Heart J. 2019; 40: 2671-2683Crossref PubMed Scopus (259) Google Scholar However, oversimplistic classifications with arbitrary systolic arterial pressure (SAP) thresholds have inherent weaknesses, with a wide interpatient variability as to the SAP at which hypoperfusion develops. Furthermore, compensatory vasoconstriction may result in a spuriously reassuring SAP despite clinically obvious peripheral hypoperfusion. Versatile clinical and diagnostic skills are therefore required when assessing such patients.Table 1Haemodynamic and clinical definitions of cardiogenic shock. LVEDP, left ventricular end-diastolic pressure; RVEDP, right ventricular end-diastolic pressure; SAP, systolic arterial pressure. Haemodynamic definition – Reynolds and Hochman1Reynolds H.R. Hochman J.S. Cardiogenic shock: current concepts and improving outcomes.Circulation. 2008; 117: 686-697Crossref PubMed Scopus (565) Google Scholar; clinical definition – Thiele and colleagues3Thiele H. Ohman E.M. de Waha-Thiele S. Zeymer U. Desch S. Management of cardiogenic shock complicating myocardial infarction: an update 2019.Eur Heart J. 2019; 40: 2671-2683Crossref PubMed Scopus (259) Google ScholarHaemodynamic definitionClinical definitionPersistent hypotension (SAP <80–90 mmHg, or MAP 30 mmHg below baseline) with:Cardiac index (<1.8 L min−1 m−2 unsupported, or <2.0–2.2 L min−1 m−2 with support)and: Adequate/elevated filling pressures (LVEDP >18 mmHg or RVEDP >10–15 mmHgSAP <90 mmHg with adequate volume and:Clinical signs of hypoperfusionCool peripheriesOliguriaImpaired mentationNarrow pulse pressureLaboratory signs of hypoperfusionMetabolic acidaemiaIncreased serum lactateIncreased serum creatinine Open table in a new tab Acute myocardial infarction with subsequent left ventricular (LV) dysfunction accounts for most cases of CS, and recent UK registry data reveal that 8.9% of patients with ST-elevation myocardial infarction (STEMI) develop CS-AMI.2van Diepen S. Katz J.N. Albert N.M. et al.Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.Circulation. 2017; 136: e232-e268Crossref PubMed Scopus (833) Google Scholar,4Rathod K.S. Koganti S. Iqbal M.B. et al.Contemporary trends in cardiogenic shock: incidence, intra-aortic balloon pump utilisation and outcomes from the London Heart Attack Group.Eur Heart J Acute Cardiovasc Care. 2018; 7: 16-27Crossref PubMed Scopus (72) Google Scholar At coronary angiography in the Culprit Lesion Only PCI vs Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) study, 42% of patients had left anterior descending (LAD) artery lesions, with left circumflex (LCx) artery (21%), left mainstem (LMS) artery (8%) and right coronary artery (RCA) (28%) representing the majority of other causative lesions. The majority of patients (63%) had triple-vessel disease, whereas 23% had at least one chronic total occlusion.5Thiele H. Akin I. Sandri M. et al.PCI strategies in patients with acute myocardial infarction and cardiogenic shock.N Engl J Med. 2017; 377: 2419-2432Crossref PubMed Scopus (568) Google Scholar Thrombotic total or subtotal occlusion of an epicardial coronary artery obstructs, or restricts, perfusion to a region of myocardium. Ischaemia and infarction ensue, characterised by myocyte necrosis and acute myocardial dysfunction.6Samsky M.D. Morrow D.A. Proudfoot A.G. Hochman J.S. Thiele H. Rao S.V. Cardiogenic shock after acute myocardial infarction: a review.JAMA. 2021; 326: 1840-1850Crossref PubMed Scopus (53) Google Scholar Reduced contractility may result in declining cardiac output (CO) and arterial pressure, and elevated LV filling pressures (Fig 1). High LV end-diastolic pressure (LVEDP) reduces coronary perfusion pressure (CPP), further exacerbating myocardial ischaemia, and causes pulmonary congestion with resultant worsening hypoxaemia and ischaemia.1Reynolds H.R. Hochman J.S. Cardiogenic shock: current concepts and improving outcomes.Circulation. 2008; 117: 686-697Crossref PubMed Scopus (565) Google Scholar The pathophysiology of CS extends beyond a state of simple ‘pump failure’ and is characterised by multisystem dysfunction, which promotes its development and progression. Reduced CO is detected by carotid arterial baroreceptors and the renal juxtaglomerular apparatus, with consequent activation of the renin–angiotensin–aldosterone and sympathetic nervous systems. The sequelae are intense peripheral vasoconstriction and avid sodium and water retention, resulting in a clinical syndrome of hypoperfusion with cool extremities, rising lactate and, usually, fluid overload with high filling pressures and congestion (‘cold and wet’ phenotype; Table 2).2van Diepen S. Katz J.N. Albert N.M. et al.Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association.Circulation. 2017; 136: e232-e268Crossref PubMed Scopus (833) Google Scholar,7Hochman J.S. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm.Circulation. 2003; 107: 2998-3002Crossref PubMed Scopus (471) Google Scholar Acidosis, hypoperfusion and congestion exacerbate myocardial dysfunction with resultant augmentation of adverse neurohormonal activation resulting in a self-perpetuating spiral of reduced CPP, increased myocardial ischaemia, worsening cardiac function and circulatory collapse.6Samsky M.D. Morrow D.A. Proudfoot A.G. Hochman J.S. Thiele H. Rao S.V. Cardiogenic shock after acute myocardial infarction: a review.JAMA. 2021; 326: 1840-1850Crossref PubMed Scopus (53) Google ScholarTable 2Physiological characteristics of cardiogenic shock phenotypes. Alternative shock phenotypes, include normotensive cardiogenic shock (CS) (likely a compensatory pre-shock phase) and isolated right ventricular CSPhenotypeCardiac indexSystemic vascular resistancePulmonary capillary wedge pressureNotes‘Cold and wet’ReducedIncreasedIncreasedThe predominant (‘classic’) phenotypePeripheral vasoconstriction and intravascularly replete‘Cold and dry’ReducedIncreasedNormalMinority of patientsEuvolaemic‘Wet and warm’ReducedReduced/normalIncreasedMinority of patientsMyocardial injury causes a predominate systemic inflammatory response. Inflammatory mediators cause vasodilation, impair mitochondrial function, depress myocardial contractility and reduce catecholamine sensitivity Open table in a new tab Deciphering the temporal relationship between the onset of a recognisable shocked state and the ischaemic precipitant is complex. For example, patients with LMS or proximal LAD disease may present in profound shock, pulmonary oedema or cardiac arrest. Similarly, proximal RCA disease can drive a shock presentation secondary to high-grade atrioventricular block. Other patients may present with ischaemic chest pain, which can be insidious and protracted, before developing CS. A high degree of vigilance is thus required, to consider an ischaemic cause in the patient with shock, and to prepare for potential CS in the patient with more classical symptoms of ACS, especially those with ECG evidence of a proximal LAD or LMS lesion. Routine initial assessment of the CS-AMI patient should include a focused clinical history, if possible, and examination, which alone may enable diagnosis by demonstration of significant hypotension, clinical signs of inadequate end-organ perfusion, or both (Table 1). Echocardiography will help confirm suspected myocardial ischaemia, indicate the region involved and can guide prediction of LV recovery or the need for advanced heart failure therapies by the development of Q waves (i.e. transmural irreversible infarction) in the affected coronary territory. Echocardiography is essential to assess for regional wall motion abnormalities; evaluate the extent of LV dysfunction, right ventricular (RV) dysfunction, or both; screen for mechanical complications (including ischaemic mitral regurgitation [MR] and ventricular septal rupture [VSR]) and for pericardial or pleural effusions, which may contribute to cardiorespiratory impairment. Arterial (ABG) or venous blood-gas analysis is required to assess the extent of hypoperfusion and shock severity, by demonstration of a metabolic acidaemia and hyperlactataemia. Laboratory blood tests should include renal and liver function tests (LFTs), which may provide further evidence of end-organ hypoperfusion, and serum troponin, for diagnostic purposes, and to indicate degree of cardiac muscle loss. Pulmonary artery catheterisation (PAC) can assist initial diagnosis, yielding highly useful quantitative information with increasing value for increasing severity of illness, but should not delay primary revascularisation.8Henry T.D. Tomey M.I. Tamis-Holland J.E. et al.Invasive management of acute myocardial infarction complicated by cardiogenic shock: a scientific statement from the American Heart Association.Circulation. 2021; 143: e815-e829Crossref PubMed Scopus (55) Google Scholar A readily applicable classification tool has been proposed for patients across the risk/severity spectrum, with increasing class associated with increasing mortality (Table 3).9Naidu S.S. Baran D.A. Jentzer J.C. et al.SCAI SHOCK stage classification expert consensus update: a review and incorporation of validation studies: this statement was endorsed by the American College of cardiology (ACC), American College of emergency physicians (ACEP), American heart association (AHA), European society of cardiology (ESC) association for acute cardiovascular care (ACVC), international society for heart and lung transplantation (ISHLT), society of critical care medicine (SCCM), and society of thoracic surgeons (STS) in december 2021.J Am Coll Cardiol. 2022; 79: 933-946Crossref PubMed Scopus (73) Google ScholarTable 3Society for Cardiovascular Angiography & Interventions cardiogenic shock stages. Features typical for stage are in bold. CI, cardiac index; CHF, chronic heart failure; CPR, cardiopulmonary resuscitation; CRT, capillary refill time; CS, cardiogenic shock; GCS, Glasgow coma scale; JVP, jugular venous pressure; MCS, mechanical circulatory support; MI, myocardial infarction; NT-proBNP, N-terminal pro-brain natriuretic peptide; PCWP, pulmonary capillary wedge pressure; SAP, systolic arterial pressure; UO, urine output. Adapted with permission from Naidu and colleagues9Naidu S.S. Baran D.A. Jentzer J.C. et al.SCAI SHOCK stage classification expert consensus update: a review and incorporation of validation studies: this statement was endorsed by the American College of cardiology (ACC), American College of emergency physicians (ACEP), American heart association (AHA), European society of cardiology (ESC) association for acute cardiovascular care (ACVC), international society for heart and lung transplantation (ISHLT), society of critical care medicine (SCCM), and society of thoracic surgeons (STS) in december 2021.J Am Coll Cardiol. 2022; 79: 933-946Crossref PubMed Scopus (73) Google ScholarStageDescriptionClinical findingsAAt riskAt risk of developing CS, but without current signs or symptoms, e.g. large acute MI, or new MI with prior infarction/CHFNormal JVPWarm and well perfusedSerum lactate <2.0 mmol L−1SAP ≥100 mmHgReassuring invasive haemodynamicsBBeginning CSEvidence of haemodynamic instability (i.e. hypotension or tachycardia) without hypoperfusionIncreased JVPWarm and well-perfusedMay have crepitationsSerum lactate <2.0 mmol L−1SAP <90 mmHg/MAP <60 mmHg/>30 mmHg decrease from baselineHeart rate ≥ 100 beats min−1CClassic CSEvidence of hypoperfusion requiring single intervention (beyond fluid resuscitation)Volume overloadAltered GCS, cool extremities, delayed CRT, UO <30 ml h−1Extensive crepitationsLactate ≥ 2.0 mmol L−1Deranged renal/liver functionIncreased NT-proBNPCI <2.2 L min−1 m−2PCWP >15 mmHgDDeterioratingFailure of initial intervention to restore perfusionDeteriorating signs/symptoms of hypoperfusion (as in C)Increasing serum lactateDeteriorating renal/liver functionEscalating doses/number of vasoactive therapies/use of MCS deviceEExtremis (A) Modifier – cardiac arrest with suspected hypoxic brain injuryCirculatory collapse (actual or impending)UnconsciousWeak pulseProfound hypotension despite maximal supportRequiring multiple defibrillations/CPRSerum lactate ≥8 mmol L−1 pH <7.2 Open table in a new tab Myocardial revascularisation is the only evidence-based intervention to reduce mortality in CS-AMI with the consensus backing of numerous international guidelines. Therefore, emergent angiography must be prioritised in any shocked patient with evidence of myocardial ischaemia on ECG. Immediate revascularisation has been shown to significantly reduce mortality at 6, 12 and 72 months, compared with initial medical management, whereas delayed revascularisation adversely affects outcomes.10Hochman J.S. Sleeper L.A. Webb J.G. et al.Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction.JAMA. 2006; 295: 2511-2515Crossref PubMed Scopus (512) Google Scholar,11Scholz K.H. Maier S.K.G. Maier L.S. et al.Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.Eur Heart J. 2018; 39: 1065-1074Crossref PubMed Scopus (199) Google Scholar Subsequent RCT evidence favours the prioritisation of immediate revascularisation by percutaneous coronary intervention (PCI) of the culprit lesion only in CS-AMI, with reduced all-cause mortality at 30 days and 1 yr.5Thiele H. Akin I. Sandri M. et al.PCI strategies in patients with acute myocardial infarction and cardiogenic shock.N Engl J Med. 2017; 377: 2419-2432Crossref PubMed Scopus (568) Google Scholar Patients with multi-vessel disease should thus receive a staged revascularisation strategy. In the UK, angiography with follow-on primary PCI is performed for STEMI patients if presenting within 12 h of symptoms (if deliverable within 120 min), or if presenting more than 12 h after symptom onset with continuing myocardial ischaemia or CS-AMI. Similarly, although PCI for non-STEMI (NSTEMI) is usually guided by risk-stratification tools, immediate angiography is offered in CS-AMI.12National Institute for Health and Care Excellence. Acute coronary syndromes [NG185]. 2020. Available from https://www.nice.org.uk/guidance/ng185.Google Scholar Immediate angiography and follow-on PCI is also indicated in patients resuscitated from out-of-hospital cardiac arrest and ST elevation on ECG; or with no ST elevation but a high probability of acute coronary occlusion (usually evidenced by haemodynamic or electrical instability).13Nolan J.P. Sandroni C. Böttiger B.W. et al.European resuscitation council and European society of intensive care medicine guidelines 2021: post-resuscitation care.Intensive Care Med. 2021; 47: 369-421Crossref PubMed Scopus (245) Google Scholar Surgical revascularisation is largely reserved for patients in whom PCI is not possible or there has been a procedural complication such as coronary dissection or tamponade not amenable to percutaneous drainage. Such intervention in a patient with CS-AMI is clearly extremely high-risk and requires careful individualised consideration. Surgery is the primary therapy for mechanical complications of AMI such as acute severe ischaemic MR or VSR. Without intervention, these complications are associated with a dire prognosis. Where possible, it is current practice to attempt to stabilise patients with short-term mechanical circulatory support (MCS) such as an intra-aortic balloon pump (IABP) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) before surgery. This allows resolution of end-organ dysfunction and for friable areas of necrotic myocardium to fibrose before subsequent surgical manipulation, which increases the chances of successful repair. Patients with emerging or evolving CS-AMI are likely to require invasive ventilation, owing to altered mentation, haemodynamic instability, impaired gas exchange and, potentially, to facilitate PCI. Use of non-invasive continuous positive airway pressure (CPAP) can be considered in patients not appropriate for invasive ventilation, or those with less severe shock state, but for this latter group preparation should be made for emergent tracheal intubation. Mechanical ventilation should adhere to lung protective principles, including low pressure and low tidal volume ventilation, to reduce the release of inflammatory mediators, reduce the burden of superimposed iatrogenic lung injury and optimise pulmonary blood flow.14Vahdatpour C. Collins D. Goldberg S. Cardiogenic shock.J Am Heart Assoc. 2019; 8e011991Crossref PubMed Scopus (151) Google Scholar The benefits of positive pressure ventilation should be considered (improved oxygenation, reduced LV afterload and work of breathing), alongside the detrimental effects (reduced venous return and therefore preload, reduced RV output and CO), in the context of the anatomical region of AMI. Lung protective ventilation should be used with careful selection of appropriate PEEP. This is particularly important in isolated RV failure because of the harmful effect on RV afterload of increased intrathoracic pressure. The aim of management in perioperative and intensive care is to restore haemodynamic stability by reversing the pathophysiological spiral described and providing end-organ support where necessary. No robust evidence exists for any specific agent, and choice is guided by the clinician's familiarity and the presence of significant renal impairment. The potential for all vasopressor and inotropic drugs to cause arrhythmias needs to be considered, especially if shock has already been associated with significant arrhythmias. Hypotension is a common clinical feature requiring intensive care input. Assessment of fluid status can be challenging, especially in younger patients when the typical clinical signs of congestion seen in older patients will be absent owing to more effective compensatory mechanisms. The pathophysiological mechanisms of CS-AMI do not leave the patient volume deplete, doing the opposite, and so pursuing fluid resuscitation is potentially hazardous. Furthermore, pharmacological management of hypotension often commences with noradrenaline (norepinephrine) infusion. However, this is contentious as CS-AMI is overwhelmingly associated with intense intrinsic vasoconstriction and high systemic vascular resistance (SVR). Extremely careful titration is required, with invasive monitoring, to avoid a clinically significant increase in LV afterload secondary to a predominant vasopressor effect. In contrast, inodilation can be beneficial in reducing LV afterload, imposed by the adverse neurohormonal activation of the CS-AMI syndrome. Commonly used vasopressors and inotropes are compared in Table 4.Table 4Comparison of vasopressor and inotropic drugs commonly used in CS-AMI. AF, atrial fibrillation; AS, aortic stenosis; AV, atrioventricular; cAMP, cyclic adenosine monophosphate; CBF, coronary blood flow; CO, cardiac output; COMT, catechol-O-methyltransferase; CS, cardiogenic shock; MAO, monoamine oxidase; PCWP, pulmonary capillary wedge pressure; PDE, phosphodiesterase; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; t1/2, half-lifeClassDrugSite of actionUsual doseMetabolismMechanism of actionBeneficial effectsAdverse effectsCatecholaminesDobutamineβ1 agonism (β1>β2)Infusion: 0.5–20 μg kg−1 min−1t1/2: 2 minMetabolised by COMTInactive metabolitesRenal excretionSynthetic catecholamineIncreases cAMP production, increasing myocardial contractilityOverall effect counteracts pathophysiology of CS: increases myocardial performance and reduces vasoconstrictionIncreased COReduced PCWPReduced SVR/PVRIncreases myocardial oxygen consumptionIncreased AV conduction may cause tachycardia or proarrhythmic effect, therefore caution with AFCaution with use in fixed cardiac outflow obstruction (e.g. AS)Caution with vasoconstriction at higher dosesDopamineβ1 agonism (Lower dose: D1/D2 Agonism; Higher dose range: α1 agonismβ1: 5–10 μg kg−1 min−1D1/D2: <5 μg kg−1 min−1α1: >10 μg kg−1 min−1t1/2: 3 minMetabolised by MAO and COMT in liver, kidneys and plasmaInactive metabolitesRenal excretionEndogenous precursor of noradrenalinePredominant β1 agonism increases cAMP, increasing myocardial contractilityIncreased CO and CBFDebated effect of low dose infusion to increase renal perfusion (via vasodilation of splanchnic vessels) – effect may relate to improved CO and enhanced natriuresis owing to inhibition of proximal tubule sodium reabsorptionIncreased myocardial oxygen consumption, tachycardia, proarrhythmicHigher doses can cause systemic and pulmonary vasoconstrictionIncreases endogenous noradrenaline release, which may increase SVR, independent of α-agonismAdrenalineβ1 agonism (<0.1 μg kg−1 min−1)Higher dose: α1 agonism0.05–0.5 μg kg−1 min−1t1/2: 2 minMetabolised by COMT and MAOInactive metabolitesRenal excretionEndogenous catecholamineβ1 Agonism increases cAMP production, increasing myocardial contractility, and coronary artery dilationα1 Agonism increases availability of intracellular calcium, increasing SVRIncreased CO and coronary artery dilatationIncreased myocardial oxygen consumption, proarrhythmic, tachycardia. Increased SVR and PVR at higher dosesIncreased plasma glucose and lactate, and ketogenesisNoradrenalineMainly α1 agonism, with some β1 agonism0.01–1.0 μg kg−1 min−1t1/2: 2 minMetabolised by COMTInactive metabolitesRenal excretionEndogenous catecholamineα1 Agonism increases intracellular calcium availabilityPeripheral vasoconstrictionMinimal impact on myocardial contraction, in the context of markedly increased systemic vascular resistanceVenoconstriction can increase venous returnCoronary artery dilatationIncreases myocardial oxygen consumption, but CO likely to decrease owing to increased SVR/PVRReflex bradycardia, proarrhythmicReduced splanchnic blood flowPDE III inhibitorsMilrinoneNon-receptor- mediated inhibition of PDE IIISlow bolus 25–75 μg kg−1, infusion 0.375–0.75 μg kg−1 min−1t1/2: 1–2 hRenal excretion (unchanged, so adjust dose in renal failure)Bipyridine derivativeIncreased intracellular cAMP, increasing calcium for contractilityIncreased CO by increased myocardial contractility, with vasodilation (pulmonary and systemic) owing to effect on vascular smooth muscleImproved myocardial oxygen balance owing to reduced ventricular wall tension and enhanced CBFReduces myocardial refractory period, causing tachycardia and is proarrhythmicEffect on vascular smooth muscle can cause hypotensionEnoximoneNon-receptor- mediated inhibition of PDE IIISlow bolus 0.5–1.0 mg kg−1, Infusion 5–20 μg kg−1 min−1t1/2: 7.5 hHepatic metabolismActive metaboliteRenal excretion (reduce dose in renal failure)Imidazole derivativeIncreased intracellular cAMP, increasing calcium for contractilityAs for milrinoneAs for milrinoneCalcium SensitisersLevosimendanNon-receptor- mediated increase in calcium sensitivityOptional slow bolus: 12 μg kg−1Infusion: 0.1 μg kg−1 min−1 (decrease to 0.05 or increase to 0.2 if required)t1/2: 80 hHepatic metabolismActive metabolitesRenal excretionPyridazoline–dinitrile derivativeIncreases sensitivity of troponin C to calcium, increasing myocardial contractilityIncreased CBFIncreases CO by increased myocardial contractility, without increasing myocardial oxygen demandReduced PVR and SVR owing to action on vascular smooth muscleReduces PCWPIncreased CBFRisks of hypotension and proarrhythmicProlonged t1/2 means that adverse effects can persist Open table in a new tab Vasoactive management should be guided by invasive monitoring, including an arterial catheter, and although there is little in the way of specific evidence, a MAP between 60 and 65 mmHg is commonly targeted. Vascular access via the radial artery is preferred for PCI, which should be considered when siting arterial catheters or ABG sampling if the patient has yet to undergo cardiac catheterisation. Arterial blood-gas monitoring, including serial lactate concentrations, can guide resuscitation. A central venous catheter (CVC) may yield some relevant information if there is an abnormal central venous waveform or grossly increased central venous pressure. Echocardiography can also be used as a haemodynamic monitor in the ICU, guiding drug therapy, by assessment of trends in intracardiac pressures and individual ventricular function in response to drug titration. It can also inform ventilator management, particularly PEEP titration for optimal RV function. Pulmonary artery catheterisation provides a large amount of crucial data. Left and right heart filling pressures, CO/cardiac index (CI), SVR and pulmonary artery (PA) oxygen saturation can be monitored continuously. This allows titration of vasopressor, inodilator, diuretic drugs and MCS. In contrast, minimally invasive CO monitors based on arterial waveform analysis have limited use in CS-AMI, because of intense peripheral vasoconstriction and possible concomitant use of IABP. Adequate sedation to enable optimal ventilation, reduce oxygen consumption and avoid psychological harm must be ensured, whilst minimising possible adverse effects from the sedative agents. There is no robust evidence for or against the use of specific drugs. The agents chosen should be used within the context of the haemodynamic status of the patient and taking care to avoid the harms of oversedation.15Zeymer U. Bueno H. Granger C.B. et al.Acute Cardiovascular Care Association position statement for the diagnosis and treatment of patients with acute myocardial infarction complicated by cardiogenic shock: a document of the Acute Cardiovascular Care Association of the European Society of Cardiology.Eur Heart J Acute Cardiovasc Care. 2020; 9: 183-197PubMed Google Scholar More than one third of patients with CS-AMI will develop acute kidney injury (AKI).16Singh S. Kanwar A. Sundaragiri P.R. et al.Acute kidney injury in cardiogenic shock: an updated narrative review.J Cardiovasc Dev Dis. 2021; 8: 88Cross