Cardiac output is defined as the quantity of blood ejected into the aorta by the heart each minute and is calculated as heart rate multiplied by stroke volume (CO = HR × SV). This is the quantity of blood that flows through the circulation and is responsible for oxygen and nutrient transport to the tissues. The primary determinants of cardiac output are preload (the venous return to the heart), afterload (the resistance against which the heart must pump), contractility (the extent to which the myocardial cells can contract), and heart rate. The primary determinant of cardiac output is the filling of the heart and the ability to pump that volume effectively. Accordingly, the majority of therapeutic modalities aimed at augmenting cardiac output focus on restoring filling pressures and augmenting ineffective contractility.
Multiple studies and textbooks cite 5.6 L/min as a “normal” resting cardiac output as measured in young, healthy males. However, cardiac output varies with the level of activity of the body, and is influenced by level of metabolism, exercise state, age, size of the individual, and other factors. Accordingly, cardiac output in women is generally stated as being 10–20% lower than in men. Additionally, when factoring in age, the average cardiac output for adults is approximated as 5 L/min. Laboratory and clinical research have demonstrated that cardiac output increases in proportion to increasing body surface area. Therefore, to standardize cardiac output measurements between individuals, the parameter of cardiac index (defined as cardiac output divided by body surface area in m2) is employed.4
In the discussion of cardiovascular physiology, preload is the force that stretches myocardium prior to contraction. The concept of preload is derived from laboratory experiments in which strips of muscle are stretched by small weights (preload) prior to initiating contraction. In these experiments, contraction is triggered by electrical stimulation and a transducer determines the resultant force. Both in vitro experiments and in vivo correlates have revealed that increasing sarcomere length to a maximum of 0.2 m by the addition of weights results in increased force of contraction. Once stretched beyond this length, the contractility of the muscle decreases. This relationship, the Frank–Starling relationship, was described in amphibian hearts by Otto Frank in 1884 and extended to mammalian hearts by Ernest Starling in 1914. The mechanisms linking preload and contractile force are incompletely understood. Although it was initially thought that increased myocardial stretch optimized the overlap of contractile actin and myosin leading to increased force of contraction, more recent research indicates that contractile force is also dependent on sensitivity of the myocyte to ionized calcium gradients, as determined by sarcomere length.5
The Frank–Starling relationship provides a paradigm by which the cardiovascular system and its derangements can be approached. Hypovolemia, or decreased preload, is the result of hemorrhage, contraction of the intravascular space due to external fluid losses such as diarrhea, inappropriate polyuria, or contraction of the intravascular space due to internal sequestration as edema or third-space losses. Additionally, venous return to the heart depends on the vascular tone of the venous system. As will be discussed in the pharmacology portion of this chapter, changes in venous capacitance are often unwanted side effects of pharmacologic agents used in treating the injured patient.
Taken together, intravascular volume and venous return determine left ventricular end-diastolic volume (LVEDV), which determines the force of ventricular contraction. The Swan–Ganz catheter is used to measure the pulmonary arterial wedge pressure (PAWP), which approximates left ventricular end-diastolic pressure (LVEDP). Assuming unaltered ventricular compliance, LVEDP theoretically approximates the LVEDV. Unfortunately, in the setting of critically ill patients, factors such as myocardial ischemia, heart failure, myocardial edema, endotoxemia, cardiac hypertrophy, and circulating tumor necrosis factor (TNF) can decrease ventricular compliance, rendering measurement of PAWP as a surrogate for LVEDV unreliable. In these situations, normal or elevated PAWP may not eliminate inadequate preload as a cause of low cardiac output.
Besides changes in venous capacitance, venous return to the heart can be compromised by increased intrathoracic or intra-abdominal pressure. This is most evident with tension pneumothorax, when the shock state is immediately reversed by decompression of the pleural space. Additionally, in the mechanically ventilated patient, the use of positive-pressure ventilation coupled with positive end-expiratory pressure (PEEP) may impair venous return to the heart (see Chapter 57). In this patient population, when intravascular volume is low, the adverse effects of increased intrathoracic pressure on preload predominate and cardiac output is diminished. Importantly, when an underresuscitated patient is placed on positive-pressure ventilation, this situation may lead to cardiovascular collapse. However, in the reverse scenario, patients with normal-to-high intravascular volume may benefit from the afterload-reducing effects of elevated intrathoracic pressure seen with positive-pressure ventilation. Indeed, synchronization of positive-pressure ventilation with the cardiac cycle has been described as a method of afterload reduction and cardiac output augmentation.6 In the normal heart, this decrease in afterload does not usually translate into enhanced cardiac output. However, those patients with heart failure are more sensitive to the concomitant decrease in preload. There may also be a poorly understood vasodilatory reflex and changes in sympathoadrenal function.7 It should be noted that patients in cardiogenic shock could demonstrate sudden cardiovascular collapse upon removal of ventilatory support. This change in venous return to the heart is also seen in abdominal compartment syndrome and pregnancy (see Chapter 37). It is important to note that the net result of these physiologic changes may be hard to predict in clinical practice, but a thorough knowledge of the underlying physiology is the key to prompt diagnosis and management.
Cardiovascular failure due to a reduction in afterload is referred to as distributive shock, and has multiple etiologies: septic shock, neurogenic shock, and anaphylactic shock. Afterload is the force that opposes ventricular contraction. Similar to preload, the concept of afterload is derived from in vitro experiments using strips of cardiac muscle. In these experiments, length is held constant while the muscle is given a variable load that must be moved (afterload). These studies have established that increasing afterload decreases the speed and force of contraction. Clinically, vascular input impedance appears to be the best in vivo correlate of ventricular afterload. Unfortunately, vascular input impedance is not a readily assessed clinical quantity, requiring right heart catheterization and continuous Doppler readings. Therefore, the clinician must rely on systemic vascular resistance (SVR) as a surrogate. SVR is calculated using the hemodynamic equivalent of Ohm’s law:
In this equation, MAP is the mean arterial blood pressure, CVP is the central venous pressure, and CO is the cardiac output. This equation provides an approximation of vascular impedance. Therefore, it is important to realize that the clinical practice of “measuring” afterload or SVR with data from the Swan–Ganz catheter actually provides a calculated value that assumes nonpulsatile flow and does not consider the viscosity of blood, the elastic properties of the arterial walls, or the changes in microvascular resistance. Finally, because SVR is inversely proportional to cardiac output, rather than directly treating an abnormally high SVR, one should first treat the low cardiac output with fluid administration to maximize preload, which will serve to increase CO and decrease SVR.
Contractility, also known as inotropic state, is the force with which the myocardium contracts. The inotropic state of the myocardium, and the stroke work performed, can be visualized by the construction of a left ventricular pressure–volume loop (Fig. 56-2). This loop is bounded by the four phases of the cardiac cycle: isovolemic relaxation, diastolic filling, isovolemic contraction, and systolic ejection. Stroke work is defined as the area bounded by this loop.
The relationship between left ventricular pressure and left ventricular volume during a stylized cardiac cycle.
Instantaneous pressure–volume curves also provide a method to determine both external (stroke work) and internal (loss as heat) work performed by the heart during the cardiac cycle. As described above, the area bounded by the pressure–volume loop defines the external, or stroke work performed by the myocardium. The internal work is defined as the area of the triangle determined graphically by three lines: an extrapolation of the elastance line to the x-intercept, the isovolemic relaxation portion of the pressure–volume loop, and the diastolic filling portion of the pressure–volume loop extrapolated back to its x-intercept (Fig. 56-3). Under this system, the failing heart with low contractility will demonstrate a shallow elastance line, which translates to low efficiency (more internal work performed for the same external work). Clinically, this points toward manipulation of contractility to balance myocardial oxygen demand and delivery. Finally, the strong influence of changes in afterload are readily appreciated under this model, as increasing afterload at a given stroke volume results in increased external work performed by the heart.
The effect of changes in afterload on (external) ventricular stroke work at constant stroke volume. The areas inscribed by the heavy lines represent the external stroke work performed during two representative cardiac cycles. Decreasing afterload (from A to B) decreases stroke work.
Presently, the use of pressure–volume curves in patient care is limited to centers using newer generation pulmonary artery catheters (PACs) that measure ventricular volume as well as pressure.8 More commonly, clinicians rely on Frank–Starling curves to determine myocardial performance and estimate contractility. Finally, contractility can be estimated by angiographic or echocardiographic determination of ventricular ejection fraction, but this method is highly sensitive to changes in afterload, and may be less reliable.
Heart rate is a key determinant of cardiac output. In the setting of constant stroke volume, increasing the number of cardiac ejections per unit time results in increased cardiac output. In addition, increasing the heart rate increases contractility, a phenomenon known as the Bowditch effect. This effect is due to increases in calcium concentrations. With increased heart rate, the time for reuptake of calcium decreases. The increased calcium concentrations cause upregulation of cAMP, which enhances contractility. However, in the setting of myocardial failure, it is not uncommon to observe heart rates high enough that the diastolic interval is shortened and ventricular filling is compromised, resulting in decreased cardiac output. Rapid ventricular rates that impair cardiac filling are most commonly seen in patients with preexisting or evolving myocardial ischemia. In this setting, rate control becomes paramount in ensuring matched oxygen delivery and utilization.