Introduction
The term shock first appeared in the English medical literature in a translation by John Clarke of a French treatise on gunshot wounds by Henry LeDran in 1740, Traité ou Reflexions Tirées de la Pratique sur les Playes d’armes à feu. In his translation, he used the English “shock” to translate the French word saisissement , which at that time might have meant “fright” or “violent emotion.” The description only slowly gained acceptance and described more the neurologic reaction, either torpor or agitation, to the trauma of violent injury rather than a physiologic response. The battlefield surgeons of the American Civil War were well acquainted with the condition, “Although the nervous shock accompanies the most serious wounds…. It is recognized by the sufferer becoming cold, faint and pale, with the surface bedewed with a cold sweat; the pulse is small and flickering; there is anxiety, mental depression, with at times incoherence of speech.” The measurement of blood pressure, at first invasively and then noninvasively, in the later part of the 19th century added reduced blood pressure to the syndrome.
In the late 19th and early 20th centuries, the etiology of shock was thought to be a neurologic reflex or a result of abnormal blood pooling in the mesenteric vessels. World War I led to an intensification of medical interest on the shock syndrome, with insights added from animal models used to scientifically test models for the initiation of shock.
In August 1917, George Crile led the Lakeside Unit from Cleveland into the war. These were the first US Army troops to enter the conflict. A base hospital was established to treat the wounded troops along the German-Allied lines near Rouen, France, and in Belgium’s Flanders Field. Several other units from academic medical centers were assembled, including the Harvard Unit, led by Harvey Cushing. Prior to the war, Crile developed an interest in hemorrhagic shock, developing during surgical procedures. He created a number of approaches to blood transfusion after visiting the labs of Alexis Carrel in 1902 and is sometimes credited with the first direct human blood transfusion. A poignant event is described in his autobiography when he was called by his dear friend Harvey Cushing to his outpost, also serving as a forward base hospital in the war. William Osler’s only child had been mortally wounded and Crile was called to assist with surgery and to arrange for blood transfusions in a desperate attempt to save his life. Sadly, Revere Osler died despite efforts to ameliorate his shock state, which was multifactorial in nature. Crile’s work subsequently led to development of “shock trousers,” which were used in the operating room when shock developed. It was also learned during this time that shock from blood loss could be reversed with lactated Ringer’s solution.
The current understanding, still incomplete, of cardiogenic shock moved forward in 1927, when Alfred Blalock, prior to the creation of his eponymous shunt with Vivien Thomas and Helen Taussig, began pivotal research on the origins and classification of shock. He was able to show experimentally that it often was not neurologically driven. He also classified its presentation into five clinical syndromes, which form the foundation for approaching shock today, including cardiogenic shock.
- 1.
Shock due to volume loss
- 2.
Neurogenic shock
- 3.
Vasogenic shock, which includes sepsis and anaphylaxis
- 4.
Cardiogenic shock
- 5.
Unclassified conditions
What is described in the following is a current understanding of the pathophysiology of cardiogenic shock. This is by no means to suggest that cardiogenic shock is “understood,” a point that is underscored by the persistently high mortality of cardiogenic shock. We are standing on the shoulders of giants, but our vision is still woefully incomplete ( Table 2.1 ).
| Category | Profile | Shorthand Jargon | |
|---|---|---|---|
| INTERMACS Level 1 | Critical cardiogenic shock | “Crash and burn” | |
| INTERMACS Level 2 | Progressive decline | “Sliding fast on inotropes” | |
| INTERMACS Level 3 | Stable/inotrope dependent | “Inpatient/outpatient inotropes” | |
| INTERMACS Level 4 | Recurrent severe CHF | “Symptoms on oral Rx at home” | |
| INTERMACS Level 5 | Exertion Intolerant | “Housebound and sx with ADL” | |
| INTERMACS Level 6 | Exertion limited | “Walking wounded” | |
| INTERMACS Level 7 | NYHA Class IIIb | Advanced/not critical CHF |
Definition
Shock is a clinical syndrome, much like heart failure, that is characterized by signs and symptoms recognized by the clinician. These can be horribly apparent, as when cardiac arrest initiates cardiogenic shock with complete absence of vital signs ( Fig. 2.1 ) or so subtle that the patient drifts into shock over the course of weeks or months and even skilled clinicians miss the transition (gradual-onset cardiogenic shock). In general, contemporary definitions of cardiogenic shock are eerily similar to battlefield depictions of severe trauma in the American Civil War, but with the addition of quantitative parameters of reduced urine output and blood pressure. Cardiogenic shock was defined in a recent trial evaluating percutaneous intervention in shock as “a systolic blood pressure of less than 90 mm Hg for longer than 30 minutes or the use of catecholamine therapy to maintain a systolic pressure of at least 90 mm Hg, clinical signs of pulmonary congestion, and signs of impaired organ perfusion with at least one of the following manifestations: altered mental status, cold and clammy skin and limbs, oliguria with a urine output of less than 30 mL per hour, or an arterial lactate level of more than 2.0 mm per liter.”
Etiology of cardiogenic shock
Acute myocardial infarction is a common, but by no means the only, cause of cardiogenic shock ( Box 2.1 ), and the infarction can result in shock in a number of ways. It can be the result of a catastrophically large infarct or a relatively small infarction in the setting of an ischemic cardiomyopathy. Infarction of the right ventricle with relative sparing of the left ventricle has unique clinical features, including shock. Severe ischemia even in the absence of myocardial injury can reduce cardiac output substantially with reduced blood pressure. Finally, infarction with tissue necrosis can result in papillary muscle rupture, acute ventricular septal defect, or free wall rupture with severe, often fatal, shock.
Ischemic
Acute myocardial infarction
Unstable angina with global ischemia
Right ventricular infarction
Complications of ischemic heart disease
Papillary muscle rupture
Acute ventricular septal defect
Myocardial rupture
Valvular
Severe aortic stenosis or insufficiency
Severe mitral regurgitation or stenosis
Severe pulmonic stenosis or regurgitation
Severe tricuspid regurgitation or stenosis
Myocardial disease/unknown
Acute myocarditis
Giant cell myocarditis
Takotsubo stress myocarditis
Substance abuse
Toxins
Chemotherapeutic agents
End-stage ischemic or nonischemic cardiomyopathy
Extracardiac
Cardiac tamponade
Acute aortic dissection with aortic insufficiency, tamponade, or rupture
Large pulmonary embolism
End-stage congenital heart disease
In the absence of coronary artery disease, acute myocarditis and especially giant cell myocarditis can result in profound cardiogenic shock such that almost cessation of myocardial contraction can be seen and/or incessant malignant arrhythmias requiring ECMO support. Takotsubo cardiomyopathy can mimic acute myocardial infarction in the emergency room and has a reported incidence of cardiogenic shock of 9%. Long-standing heart failure that has been stable for decades can devolve rapidly or insidiously into end-stage heart failure with hypotension and multiorgan dysfunction. Similarly, chronic valvular abnormalities, when they become severe, can profoundly impair hemodynamics and become life-threatening. Patients with adult congenital heart disease can sink later in life into a shock state with multiorgan failure after years of relatively normal cardiovascular status following early palliative surgery. Large pulmonary emboli can present with syncope and cardiogenic shock from right heart failure, as can end-stage pulmonary arterial hypertension. Finally, long-standing alcohol abuse and illicit drug use with methamphetamines or other sympathomimetic drugs can be responsible for profound cardiac dysfunction.
Hemodynamic effects of cardiogenic shock
Reduced Cardiac Output
In general, cardiac output is reduced in cardiogenic shock, although not universally so. Cardiac output is a continuum, so there is not an absolute number below which a patient is in cardiogenic shock. The shock state exists when the output is not sufficient to meet the metabolic needs of the principle organ systems, including the kidneys, liver, central nervous system, and digestive tract. In terms of cardiac output, shock has been defined as a cardiac index less than 1.8 to 2.2 L/min/m 2 . That said, not all patients with this reduction in cardiac index are in shock, but it does indicate significant derangement in cardiac function.
Unfortunately, cardiac output requires invasive measurements, and so there are often delays in obtaining this important determinate of shock. Beyond thermodilution estimation of cardiac output, mixed venous saturation can be an important indicator of low output states when corrected for anemia. Mixed venous saturations below 50% or, more frequently, less than 40% are indicative of cardiogenic shock. Echocardiographic determination of the left ventricular outflow time velocity integral can be used to calculate stroke volume and, hence, cardiac output, and extremely low values are associated with poor outcome. Stroke volume can also be estimated by arterial waveform analysis, although this may be less accurate in severe vasodilation or vasoconstriction states.
In some instances of cardiogenic shock, cardiac output may be nearly normal but is associated with profound vasodilation. Vasodilatory shock or systemic inflammatory response, which will be discussed further in the chapter, can develop quickly or during later stages of cardiogenic shock. Calculation of systemic vascular resistance can quickly differentiate between vasodilatory or vasoconstrictive shock versus shock presenting with a normal or increased vascular resistance. These distinctions are vital because the pharmacologic and mechanical support approaches are quite different and initial errors in management can prolong tissue hypoperfusion. Judicious use of vasodilators can result in marked improvement of cardiac output in vasoconstriction, whereas they are absolutely contraindicated in vasodilatory states where vasopressin may be beneficial because of vasopressin depletion.
Hypotension
The maintenance of normal blood pressure and primarily to prevent hypotension during changes in posture and abnormal physiologic states (dehydration, hemorrhage) is a critical physiologic function in humans. In common parlance, shock and hypotension are so closely associated that they are often felt to be synonymous. When hypotension is detected by the carotid baroreceptors, this sets off a cascade of neural and hormonal responses that seek to increase cardiac output by increasing heart rate, normalize blood pressure by intense vasoconstriction, and preserve volume by changes in renal handling of salt and water.
The degree and duration of hypotension are critical in both the ongoing pathophysiology of cardiogenic shock and its prognosis. Catastrophic shock associated with cardiac arrest must be corrected or at least ameliorated within minutes to prevent cerebral anoxic injury. Severe hypotension, that is, mean blood pressure < 50 mm Hg, may not immediately cause severe brain injury but can result in acute tubular necrosis and liver injury; organ failure at this level may be survivable but complicates and exacerbates shock with poorer outcomes. Milder degrees of hypotension may be present for weeks or even months in chronic heart failure, but frequently lead to more extreme derangement.
Increased Filling Pressures
As cardiogenic shock progresses, filling pressures usually rise. If the genesis of the shock is ischemic, then ischemia itself increases diastolic stiffness by interfering with calcium reuptake in the sarcoplasmic reticulum. When myocardial systolic performance is reduced, then systolic emptying falls and filling pressures rise. An increase in filling pressures may actually be salutary in that they increase cardiac output by the Frank Starling mechanism but, very quickly, the pressures rise to levels that are detrimental. Neurohormonal activation causes increased sodium reabsorption and decreased excretion of free water. Severe prolonged hypotension can result in acute tubular necrosis, so urine output may actually stop, which exacerbates fluid retention. Fluid can shift from the mesenteric bed to the central circulation, further increasing filling pressures. As left atrial pressure rises, fluid moves into the lungs, increasing the work of breathing and reducing gas exchange so that ischemia may be compounded. In primarily right-sided cardiogenic shock, left-sided filling pressures are usually low and may exacerbate systemic hypotension due to inadequate left ventricular preload.
Neurohormonal response to cardiogenic shock
There is a marked activation of the sympathetic nervous system in response to the reduced systemic blood pressure, which is a hallmark of cardiogenic shock. This response is mainly through arterial baroreceptors located in the carotid sinus and the aortic arch. Indeed, many of the classic clinical signs of shock are mediated via profound activation of this system, whose key neurotransmitter is norepinephrine. Classical physical signs of shock, such as tachycardia, peripheral vasoconstriction, and cool, clammy skin, are the direct results of norephedrine’s effect on the sinus node, vasoconstriction of epithelial arteries near the surface of the skin, and direct effects of the sweat glands. Norepinephrine levels are elevated both in heart failure and in acute myocardial infarction, but the levels are higher and persist longer when cardiogenic shock intervenes. The increases in norepinephrine level are important systemic compensatory mechanisms to both protect blood pressure and increase cardiac output via heart rate increase and myocardial contractility, but this can come at the cost of exacerbating myocardial ischemia and promoting further myocardial cell death via the toxic effect of very high levels of norepinephrine on cardiac myocytes via apotosis.
Plasma renin levels are also elevated with myocardial infarction and acute decompensated heart failure. These levels are especially elevated when blood pressure is significantly reduced. Elevated renin produces secondary increases in angiotensin II and aldosterone, whose effects include maintenance of blood pressure and sodium retention. Aldosterone levels are elevated in septic shock but have not been reported so in cardiogenic shock, although higher aldosterone levels are associated with worse long-term prognosis following myocardial infarction. NT proBNP levels may also increase after myocardial infarction, especially if shock intervenes. Extremely high levels of NT proBNP > 12,000 are associated with very poor prognosis in cardiogenic shock, especially when coupled with high interleukin 6 (IL-6) levels. Although angiotensin II levels are elevated in severe heart failure, a recent trial suggests that pharmacologic doses of angiotensin II may improve outcome in vasodilatory shock. In late 2017, this formulation of angiotensin II was approved for clinical use.
Lactic Acidosis
As a consequence of decreased oxygen delivery to tissue due to hypotension and reduced cardiac output, mitochondrial production of adenosine triphosphate (ATP) is impaired and pyruvate levels increase, resulting in increased levels of lactate, a strong acid ( Fig. 2.2 ). A reduction in intracellular and extracellular pH has important physiologic consequences that exacerbate the shock state. Reduced intracellular pH has negative effects on cardiac function by decreasing myofilament sensitivity to Ca ++ and to adrenergic agonists. In addition, it interferes with depolarization by enhancing K + egress from the cell, resulting in hyperpolization. Lactic acidosis also causes adrenoreceptor internalization so that sensitivity to norepinephrine is reduced. Finally, low intracellular PH stimulates BNIP23, which promotes apoptosis and induces nitric oxide (NO) production, which has detrimental effects.
