Chapter 56: Cardiovascular Failure

Cardiovascular failure is deterioration of cardiac function or vascular tone that results in impairment in end-organ perfusion. Collapse of the cardiovascular system can be either the end result of multisystem organ failure (MOF) or a manifestation of impaired cardiac function. In the acute phase of trauma, most shock is due to hemorrhage. Hemorrhagic shock leads to decreased preload or decreased right heart filling volumes, which is compensated by tachycardia and then may progress to hypotension and end-organ hypoperfusion. Cardiogenic shock alone stems from impaired myocardial contractility resulting in impairment of end organ perfusion with elevated cardiac filling pressures and low cardiac output.¹ Unlike hemorrhagic shock, cardiogenic shock often does not respond simply to volume/blood product resuscitation and control of hemorrhage.^2,3 Cardiogenic shock solely from impaired contractility is most often due to an acute myocardial infarction or acute on chronic heart failure.⁴ Therapy to support the failing cardiovascular system is directed at the etiology of the shock state and includes fluid resuscitation (preload) as well as pharmacologic modulation of vascular tone (afterload), contractility (with inotropes), and heart rate (with chronotropes). This chapter will explain the physiologic components of cardiovascular failure, assessment of patients with cardiovascular failure, treatment and monitoring (Fig. 56-1).⁵

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 therapies for augmenting cardiac output aim to restore filling pressures and support ineffective contractility.

Typically, 5.6 L/min is considered a normal resting cardiac output as measured in young, healthy males. However, cardiac output varies with activity, and is influenced by level of metabolism, exercise state, age, size of the individual, and other factors. 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, cardiac index (defined as cardiac output divided by body surface area in m²) is employed.⁶

Preload

Preload is the force that stretches the myocardium prior to contraction and most commonly is fluid dependent. The Frank–Starling relationship shows that as cardiac sarcomere length increases so will the force of contraction, until the sarcomere is stretched beyond its maximal length at which time the force decreases. 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, or contraction of the intravascular space due to internal sequestration as edema or third-space losses. Taken together, intravascular volume and venous return determine left ventricular end-diastolic volume (LVEDV), which in turn determines the force of ventricular contraction. The pulmonary artery catheter (PAC) 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, and myocardial edema 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. Therefore, multiple measures of cardiovascular function including the pulmonary artery pressure, CVP, IVC filling, clinical scenario, and response to fluid challenge all should be used to gauge preload when caring for these complex patients.

Besides changes in venous capacitance, venous return to the heart can be compromised by increased intra-thoracic or intra-abdominal pressure. This is most evident with tension pneumothorax, when the shock state is immediately reversed by decompression of the pleural space. Decreased venous return is also seen with abdominal compartment syndrome and pregnancy, of which the former can lead to dramatic hypotension following intra-abdominal trauma.

Afterload

Cardiovascular failure due to a reduction in afterload is referred to as distributive shock, and has multiple etiologies: sepsis, neurologic deficit, and anaphylaxis. In trauma patients, distributive shock may develop from sepsis later in the post-trauma recovery period and is unlikely to be the source of shock in the immediate post-trauma period unless there is severe CNS injury. Afterload is the force that opposes ventricular contraction. Afterload is estimated with systemic vascular resistance. 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 PAC 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 CO with fluid administration to maximize preload, which will serve to increase CO and decrease SVR.

Contractility

Contractility, also known as inotropy, 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.

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 is readily appreciated under this model, as increasing afterload at a given stroke volume results in increased external work performed by the heart.

Heart Rate

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 which leads to higher 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. Therefore, rate control becomes paramount in ensuring matched oxygen delivery and utilization in patients with risk for myocardial ischemia.

Myocardial dysfunction can be defined on the basis of perturbed preload, afterload, contractility, or heart rate. Systemic hypovolemia (eg, inadequate preload), secondary to hemorrhage or third-space losses, is the most common etiology in the postsurgical or trauma patient. Other causes of decreased cardiac output may arise from failing or decreased contractile function of the heart. Evolving ischemia can lead to areas of heart muscle that lose their ability to contract, leading to decreased cardiac output. The contractility of heart muscle can also become altered following any insult that results in intrinsic metabolic derangements at the cellular level. This typically occurs in the settings of sepsis, postcardiac arrest, or postcardiopulmonary bypass. Direct physical injury to the myocardium, as occurs following blunt chest injury, may produce contused cardiac muscle, which can lead to contractile dysfunction and decreased cardiac output.

Right Heart Failure

One of the more difficult scenarios to diagnose and manage is right ventricular dysfunction following inferior wall myocardial infarction. Although cardiogenic shock results from right ventricular infarction infrequently, mortality from right ventricular infarction is high (23–53%).^7,8 In addition, patients with inferior MI have much higher rates of arrhythmias including atrial fibrillation, ventricular fibrillation and tachycardia and second/third degree AV block.⁹ The mainstays of treatment include maintaining adequate intravascular volume while supporting a remodeling right ventricle with inotropes.

Pulmonary hypertension may develop after blunt cardiac injury. Most often, this is due to either an acute valvular or papillary disruption, formation of a ventricular septal defect,¹⁰ or myocardial damage to the right ventricle. Pulmonary hypertension and right heart failure are difficult to diagnose as there is no particular lab value or routine monitoring that will signal this pathology. Therefore, physical examination findings (new and worsening JVD, a new murmur, unexplained hypotension or hepatic failure, a new arrhythmia, etc) in the proper traumatic setting should prompt further testing with echocardiography. In fact, as many as 27% of major chest trauma patients may have pulmonary hypertension identified on transthoracic echocardiography.¹¹ If this pulmonary hypertension persists beyond the acute traumatic period, it is possible to lead to right heart strain that is also difficult to assess for or make the diagnosis without echocardiography.

Valvular Pathology

Acute traumatic injury to a cardiac valve is rare and is discussed elsewhere (see Chapter 26). Knowledge of common valvular pathology and the impact on trauma resuscitation is important as valve abnormalities can significantly impact the response to fluids, vasopressors and inotropes. Three of the more common valve disorders (aortic stenosis, mitral regurgitation, and tricuspid regurgitation) will be discussed in this section. In aortic stenosis, narrowing of the aortic valve most often leads to symptoms of heart failure with patients complaining of dyspnea on exertion, angina, lightheadedness, or syncope. Persistent and excessive fluid resuscitation and failure of diuresis during recovery may exacerbate the symptoms associated with aortic stenosis. Patients with known aortic stenosis undergoing induction of anesthesia must be ensured adequate preload as rapid hypotension is poorly tolerated due to inadequate compliance of the left ventricle. In addition, similar acute periods of hypotension should be avoided if epidural catheter placement is necessary. Chronic mitral regurgitation may eventually lead to decompensated left ventricular failure. Often, due to left atrial enlargement, these patients suffer from atrial fibrillation. In patients with worsened cardiac function following trauma, offloading the left ventricle by maintaining normotension in patients with mitral regurgitation is key. In addition, responsible fluid management in these patients is necessary as they may also have pulmonary hypertension with excessive fluid resuscitation, leading to the development of pulmonary edema and right heart failure. Acute mitral regurgitation can result from either acute MI or trauma with the rapid development of cardiogenic shock, pulmonary edema, and hemodynamic instability. Given the failure of the mitral valve, the pressures within the left atrium and ventricle will equalize. Treatment includes afterload reduction and emergent surgical repair.¹² Tricuspid regurgitation is common but infrequently symptomatic. As with mitral regurgitation, in patients symptomatic (elevated JVD, kidney, and liver dysfunction) from tricuspid regurgitation, fluid overload will lead to right heart failure, then left heart failure and finally, impaired cardiac output with deficits in end organ perfusion.

Unstable Arrhythmias

Due to elevated catecholamines, fluctuations in intravascular volume, electrolyte disturbances, and inflammatory states, critically ill patients are at high risk for the development of arrhythmias.¹³ The development of an arrhythmia in the ICU is associated with increased mortality with a recent study showing a 17% in-hospital mortality for patients without the development of an arrhythmia, 29% for those who developed a supraventricular arrhythmia, and 73% for those with a ventricular arrhythmia.¹⁴ New onset of an arrhythmia in the ICU also leads to increased length of stay by up to 33%.¹⁵ The development of any arrhythmia should prompt an evaluation of electrolyte levels, assessment of the rhythm with an ECG and patient assessment for hypotension or signs of impaired perfusion (mental status changes). The management of arrhythmias follows the most recent ACLS guidelines.¹⁶

The most common tachyarrhythmia in the critically ill patient is atrial fibrillation.¹⁷ If the patient is hemodynamically unstable as evidenced by hypotension and mental status changes, electrical cardioversion is indicated. Medical therapy with β-blockade, calcium channel blockers, or amiodarone can be used to prevent recurrence once the patient has been stabilized. Amiodarone is the preferred agent in patients with hypotension or heart failure.¹⁸

Bradyarrhythmias in the critically ill patient can be life-threatening and can be treated with atropine or transcuteneous pacing if there is evidence of hypoperfusion. Most commonly, bradyarrhythmias are caused by elevated intracranial pressure, exaggerated vagal activity, hypothermia, electrolyte abnormalities, and medications (β-blockers, calcium-channel blockers, clonidine, opioids, and dexmedetomidine).⁸

Cytopathic Hypoxia

During the acute resuscitative phase of care, cardiovascular failure in trauma patients is the result of hemorrhage and reversal of this failure occurs only with control of hemorrhage and transfusion of blood products. However, some patients remain in cardiovascular failure despite hemorrhage control and adequate blood product resuscitation. These patients often remain acidotic with large base deficits. The underlying derangement in this circumstance may be cytopathic hypoxia.^19,20 Although an infrequent cause of CV failure, it should be considered in the adequately resuscitated but hypotensive and acidotic patient. In fact, cytopathic hypoxia may manifest as profound vasoplegia (see further) with potential etiologies being mitochondrial dysfunction, problems with nitric oxide metabolism, and alterations in hypoxia-induced pathways. Although no specific therapy is available, treatment must be systemic and target all cells (methylene blue, ubiquitin, therapeutic hypothermia, etc).

Preload Augmentation

Myocardial dysfunction secondary to hypovolemia may be caused by hemorrhage or other causes of intravascular volume loss. Prior to the development of hypotension, most adult patients will demonstrate a decrease in urine output, indicative of end-organ hypoperfusion. Augmentation of preload, or restoration of intravascular volume, will reverse this dysfunction if instituted promptly. Normalization of heart rate and blood pressure, along with adequate urine output are simple and effective measurements of adequate volume restoration.

Methods of Support

Vasopressors

The use of vasopressors during acute, severe traumatic injury resuscitation should be avoided if possible as hemorrhage is the source of almost all shock in the immediate post-injury period (Table 56-1).

Norepinephrine

Norepinephrine is an endogenous sympathetic neurotransmitter with α- and β-adrenergic effects. At high doses, α-adrenergic effects predominate, and increased SVR and increased blood pressure result. Specifically, in the setting of right ventricular failure, low-dose norepinephrine improves cardiac function without adversely affecting visceral perfusion.²¹ Norepinephrine is typically the vasopressor of first choice during or after fluid resuscitation²² and in the setting of sepsis.²³ In cardiogenic shock, norepinephrine, when compared to dopamine, is associated with decreased mortality and rates of arrhythmia.²⁴ Norepinephrine is widely used in the care of the head-injured patient in shock because its vasoconstrictive effects do not extend to the cerebral vasculature, making it an ideal agent for maintaining cerebral perfusion pressure.

Vasopressin

Vasopressin is a natural hormone produced by the posterior pituitary that acts as a potent vasoconstrictor. Vasopressin is recommended as the second vasopressor during septic shock that is refractory to norepinephrine according to the Surviving Sepsis Campaign.²³ When vasopressin is combined with norepinephrine, outcomes in the treatment of catecholamine resistant cardiovascular failure in septic shock are superior to therapy with norepinephrine alone.

Vasopressin has also emerged as a therapy for cardiac arrest and acute resuscitation. Improved neurologic outcomes following cardiac arrest have been shown with the use of vasopressin and steroids in addition to epinephrine in comparison to epinephrine alone.²⁵ In the postoperative cardiotomy patient, vasopressin significantly reduces the need for both pressor and inotropic support, and the development of arrhythmias.²⁶

Phenylephrine

Phenylephrine is a pure α-agonist and is without any β activity. Phenylephrine is often administered in the bolus form for acute hypotension but may also be infused in patients with hypotension and serious arrhythmias that may be triggered by other vasopressors with β activity.¹⁹ Phenylephrine has a duration of action of up to 20 minutes.²⁷ In the setting of cardiogenic shock, phenylephrine is rarely used. At high doses, phenylephrine administration may lead to bradycardia²⁸ and visceral hypoperfusion.

Methylene blue for profound vasoplegia

Profound vasoplegia occurs when hypotension and inadequate end organ perfusion persist despite adequate fluid resuscitation, high cardiac output, and the use of multiple vasopressors.²⁹ The exact physiologic mechanism of profound vasoplegia is poorly understood. This profound vasoplegia is most commonly encountered in cardiac surgery patients, especially those who have required cardiopulmonary bypass. Mortality rates, wound infections, days on mechanical ventilation, and lengths of stay are all increased in cardiac patients who have profound vasoplegia.³⁰ Profound vasoplegia may occur in the trauma and postoperative surgical patient as well. Unfortunately, additional treatment modalities for profound vasoplegia are limited. Methylene blue has been used with some success to help to reverse profound vasoplegia. Methylene blue inhibits nitric oxide-mediated vasodilation and can be administered as a slow infusion (2 mg/kg over 20 minutes) for this purpose. Outside of cardiac surgery, methylene blue has been used to reverse vasoplegia in burn patients,³¹ following liver transplant³² and for septic shock.³³ While it should not be considered standard of care, methylene blue may be used in a trauma patient with profound shock unresponsive to fluids or vasopressors as a last resort.

Inotropy

Dobutamine

Dobutamine is a synthetic catecholamine with primarily β-adrenegic effects, although it does possess some α₁-adrenergic properties. It is primarily an inotrope, increasing contractility, with minimal chronotropic effects. Dobutamine also possesses mild β₂-adrenoreceptor activity, producing peripheral vasodilatation. This combination of increased contractility and reduced afterload results in improved cardiac output. Importantly, the increase in cardiac output occurs without an increase in myocardial oxygen consumption.³⁴ Dobutamine may also increase capillary perfusion in septic shock independent of overall hemodynamic effects.³⁵ Because of the vasodilatory effects, dobutamine may reduce blood pressure and is ideally suited for use in low-output cardiac states. For these reasons, dobutamine should be considered the first-choice inotrope for patients with low cardiac output in the presence of adequate preload.³⁶ In addition, dobutamine may be added in the setting of septic shock if cardiac dysfunction is considered to be a contributor to the shock state.

Epinephrine

Epinephrine is an endogenous catecholamine with α- and β-adrenergic activity. At low doses, epinephrine exerts primarily β-adrenergic effects, increasing contractility and reducing SVR. Despite this, there is little evidence that epinephrine is superior to dobutamine in the treatment of low-output states. The increases in stroke volume and cardiac output seen with epinephrine have the potential of decreasing blood pressure in patients with inadequate preload. In patients with septic shock that have been adequately fluid resuscitated, epinephrine increases heart rate and stroke volume (and therefore cardiac output) and systemic oxygen delivery without altering vascular tone. Care must be taken when using epinephrine, as renal vasoconstriction, cardiac arrhythmias and splanchnic blood flow,³⁷ and increased myocardial oxygen consumption and demand may result.³⁸ Additionally, metabolic abnormalities are common, including dyskalemias, hyperglycemia, and ketoacidosis.³⁹

Milrinone

Milrinone selectively inhibits phosphodiesterase-3 that leads to increased cAMP and increased calcium intracellularly to promote more efficient contractility. Overall, milrinone administration leads to pulmonary and systemic vasodilation with increased inotropy. Milrinone is used more frequently in the patient with well-established cardiac failure as the half-life is long (2.5 hours) and is not a rapidly titratable medication, unlike dobutamine or epinephrine. As with dobutamine, hypotension may result from either bolus or excessive milrinone use especially in patients who are hypovolemic. In addition, risk of arrhythmia is increased with use of milrinone or dobutamine.

Dopamine

Dopamine is an endogenous catecholamine that has several cardiovascular effects, including increased heart rate, increased contractility, and peripheral vasoconstriction. It is used primarily for inotropic support in order to maintain brain, heart, and kidney perfusion. Dopamine acts on α- and β-adrenoreceptors as well as DA1 and DA2 dopamine receptors, and its actions can be classified based on dose. At doses of 1–3 μg/kg/min, dopamine acts at primarily DA1 receptors in renal, mesenteric, coronary, and cerebral vascular beds, resulting in vasodilation. At moderate doses (3–5 μg/kg/min), dopamine stimulates primarily cardiac β-adrenoreceptor, increasing contractility and thus cardiac output. At higher doses of dopamine (10 μg/kg/min), peripheral vasoconstrictive effects from stimulation of α-adrenergic receptors predominate. This can result in significant coronary vasoconstriction resulting in angina, vasospasm, and increased PAWP. Additionally, increasing afterload from vasoconstriction coupled with an increased heart rate seen at this dose, results in increased myocardial oxygen consumption and demand. Individual variation in the pharmacokinetics of dopamine due to weight-based dosing typically results in poor correlation between blood levels and administered dose. Tachycardia can occur with any dose of dopamine, particularly in the hypovolemic patient. Due to the variable effects of dopamine, the dosage ranges used to define which receptors it affects are to be used as broad guidelines only, with the awareness that low-dose dopamine may have the unwanted effects of medium- or high-dose dopamine on an individual patient. Low-dose dopamine is no longer used for renal protection.⁴⁰

Mechanical

Intra-Aortic Balloon Pump Counterpulsation

Until recently, when myocardial failure had an underlying, surgically correctable, anatomic cause, and pharmacologic methods were ineffective in augmenting cardiac output, the use of intra-aortic balloon counterpulsation (IABP) was quite common.⁴¹ However, recent studies including the IABP-SHOCK II trial showed no benefit in mortality for IABP use in patients in cardiogenic shock.⁴² In fact, the current American College of Cardiology Foundation and American Heart Association guidelines on post STEMI care have downgraded the recommendation for use of IABP.⁴³ However, the intensivist should be familiar with its use and function. IABP involves placement of a balloon catheter into the proximal descending aorta (distal to the origin of the left subclavian artery) via the femoral artery. The balloon catheter is connected to a pumping device that, in synchrony with the electrocardiogram, inflates the balloon during cardiac diastole and deflates it during systole. By filling during diastole, the balloon displaces approximately 40 mL of blood retrograde into the coronary arterial circulation and antegrade into the descending aorta. The balloon is abruptly deflated at the beginning of systole, allowing the left ventricle to eject its stroke volume. These dual functions augment coronary arterial flow while decreasing afterload, thereby reducing myocardial oxygen consumption.

Other methods of providing direct inotropic support to the acutely failing heart include the Impella and Tandem Heart devices. Both devices are inserted percutaneously and deposited into the left heart to provide circulatory support for a failing left ventricle.⁴⁴ Both devices are used to bridge the patient until more appropriate, longer term therapy is available. However, both require systemic anticoagulation which may limit use in the trauma patient.

Extracorporeal Membranous Oxygenation

Extracorporeal membranous oxygenation (ECMO) can provide temporary cardiac and/or respiratory support as the last step in resuscitation.⁴⁵ Essentially, ECMO can provide the necessary flow to maintain oxygen delivery to the brain and end organs while also oxygenating and removing CO₂ from the blood if the lungs are unable to adequately do so. Traditionally, ECMO is run with an anticoagulant as the ECMO circuit is thrombogenic and a common complication of ECMO being intracranial, surgical, gastrointestinal or pulmonary bleeding.⁴⁶ Given the need for anticoagulation, the use of ECMO in trauma patients who often have injuries that prevent anticoagulation has been limited. However, recent reports have suggested that ECMO with or without anticoagulation⁴⁷ can safely and successfully be performed in trauma patients.^48,49 With this in mind though, the use of ECMO in trauma patients should be reserved for centers well experienced in the delivery of ECMO.

Management of Hypertension

The shock state precludes vasodilation. However, in acute heart failure without shock, afterload reduction with vasodilators may be advantageous to global perfusion while a rapid reduction in preload should help with a heart that cannot handle wholebody fluid demands. The most commonly used agents in the critically ill include nitroprusside, nitroglycerin, and nesiritide.²

Nitroprusside acts primarily on arteriolar smooth muscle, reducing afterload. The onset of action of nitroprusside is rapid, and its effects cease within minutes once the infusion is discontinued. When titrating the dose of nitroprusside, SVR should be decreased with a concomitant increase in cardiac output, thereby maintaining a relatively constant systemic arterial pressure. Although the effects of nitroprusside favor arterial dilatation, it does have mild venous dilatory effects that can lead to an increase in venous capacitance and decreased preload. Care must be taken when using nitroprusside, as cyanide toxicity is a known side effect. This is generally seen with infusion rates in excess of 10 μg/kg/min, with prolonged therapy (several days) or in the setting of renal or hepatic dysfunction. Treatment is with sodium nitrite and is aimed at providing an alternate substrate for the cyanide ion. Sodium nitrite also converts hemoglobin to methemoglobin, producing a ferric ion that competes with the ferric ion in the cytochrome system for the cyanide ion. Methylene blue can be administered to treat the methemoglobinemia that results from sodium nitrite treatment.

Nitroglycerin, a potent arteriolar and venous smooth muscle dilator, is a useful agent when both preload and afterload are elevated. The cardiovascular effects are dose-dependent, with low doses (5–20 μg/min) primarily increasing venous capacitance and higher doses (>20 μg/min) relaxing arterial tone. Side effects are generally the result of an overly rapid reduction in venous or arterial tone, and are readily reversed by cessation of the medication.

Nesiritide is recombinant, human brain type natriuretic peptide that is normally produced in the ventricular myocardium in response to wall stress, hypertrophy, or volume overload.⁵⁰ Nesiritide infusion leads to arterial and venous dilation, diuresis, and activation of the renin–angiotensin–aldosterone system.⁵¹ Fundamentally, nesiritide would appear to be an ideal treatment in acute heart failure. However, nesiritide may be associated with increased mortality^52,53 and with the development of worsened renal function and hypotension.⁵⁴ As a result, nesiritide use is no longer recommended for the use of acute decompensated heart failure.

Management of acute on chronic heart failure

As our population ages, the number of elderly patients in the intensive care unit (ICU) will increase. In fact, the number of elderly patients (>65 years old) is expected to double in the next three decades. With an aging population, there are age-related changes in physiology, exacerbations of chronic illnesses, and effects of therapeutic drugs, which need to be taken into consideration when caring for the traumatically injured patient. Often, these patients will present with chronic congestive heart failure. Acute on chronic heart failure in the geriatric patient, which may develop in the post-trauma period, needs to be considered in the setting of low urine output despite fluid resuscitation or worsening pulmonary edema. In this case, fluid status and medication administration needs to address both the traumatic injury and heart failure which is a difficult balancing act that requires a combination of the cardiac monitoring and management options discussed in this chapter.

Central Venous Pressure

Central venous pressure (CVP) monitoring has been used for many years as a surrogate measurement of preload. In the young trauma patient with a normal functioning heart, the CVP monitor provides an adequate assessment of right-sided filling pressure (or preload). Usually placed percutaneously into the superior vena cava, adequate assessment of volume status is achieved, and fluid resuscitation guided. Normal CVP is between 0 and 4 mm Hg; however, response to fluid is more useful than an absolute number. A low CVP usually indicates hypovolemia, whereas an elevated CVP may be evidence of volume overload. Increases or decreases in cardiac output/index may be further used in conjunction with CVP to assess volume status as evidenced by the Frank–Starling curve. CVP and PAWP correlate well in the normal functioning heart (EF >50%), but this correlation is not maintained in patients with cardiac impairment (EF <40%).⁵⁵ CVP measurement has its limitations and is affected by multiple variables, which may cause an inadequate assessment of true volume status. Misplacement of the catheter, congestive heart failure (CHF; right or left sided), pneumothorax, lung recruitment techniques or high PEEP, pulmonary embolus, cardiac tamponade, increased intrathoracic, and/or increased intra-abdominal pressure may all lead to increases in CVP measurements, which do not reflect the true overall volume status. Marik et al recommends alternative measurements of fluid status to guide resuscitation.⁵⁶ Magder cautions the use of CVP alone without other measurements of fluid status such as cardiac output, pulse pressure variation, or stroke volume variation.⁵⁷ These will be discussed later.

Pulmonary Artery Catheters

Pulmonary artery catheters (PAC), first introduced for human use in 1970, have been widely accepted as the standard for invasive monitoring of not only volume status but also of cardiac function by measurement and approximation of left-sided cardiac pressures. Continuous monitoring of cardiac output/index along with other information provided by newer PACs may help identify cardiovascular failure early and allow treatment to be adjusted accordingly. Measurement of the PAWP is used as an indirect measurement of LVEDP and LVEDV; however, these measurements often show poor correlation and can be altered by myocardial ischemia, ventricular outflow obstruction, mitral regurgitation, vasodilator therapy, or severe heart failure.⁵⁸ Similar to CVP, PAWP can be affected by decreased pulmonary compliance and high PEEP (as seen in lung recruitment strategies). Commercially available PACs currently incorporate multiple calculations to derive other indices of cardiac function and tissue perfusion such as mixed venous oxygen saturation (SvO₂), systemic vascular resistance (SVR), oxygen delivery (DO₂), and oxygen consumption (VO₂).⁵⁹ However, a large National Heart, Lung and Blood Institute randomized clinical trial reported that PAC-guided treatment was not superior to that of CV catheter-guided treatment; mortality and ICU length of stay (LOS) were similar but the PAC group had a higher rate of complications.⁶⁰ A 2013 Cochrane Review analyzing 13 studies found no difference in mortality, hospital, or ICU LOS with the routine use of PAC, and that PAC use was associated with higher costs.⁶¹ While routine use of PAC may not be indicated in trauma patients, its use should be considered in certain situations: ongoing hemodynamic instability of unclear etiology, in patients with a history of congestive heart failure or pulmonary hypertension, and in those with suspected hemodynamic changes from blunt cardiac injury.

Echocardiography

Echocardiography, either transthoracic or transesophageal, has gained wide acceptance in the monitoring of cardiac function and has emerged as an effective tool in the ICU as a guide to resuscitation and fluid status monitoring. In addition, information about structural abnormalities of the heart, aorta, and main pulmonary arteries can be obtained by this method, along with assessment of ventricular dysfunction, ventricular filling, valvular abnormalities, ventricular hypertrophy, and pulmonary embolus. Continuous transesophageal echocardiography (TEE) can give accurate measurements of both right- and left-sided filling volumes of the heart and may provide a better assessment of myocardial preload when compared to CVP or PAC measurements.⁶² Placed in the esophagus, Doppler probes can accurately predict cardiac output using the diameter of the aorta and measurements of blood flow velocity. The finding of short mitral deceleration time (≤140 ms) is highly predictive of pulmonary capillary wedge pressure of ≥20 mm Hg, which is consistent with cardiogenic shock.⁶³ A prospective, multicentered study in 2013 demonstrated that the performance of at least 31 supervised examinations over a 6-month period was required to achieve competence in TEE-driven hemodynamic evaluation of a critically ill patient.⁶⁴ TEE has been found to be a safe procedure that can be done at the bedside by intensivists, and has been found to affect management of the critically ill patient in up to 80% of patients.⁶⁵

Inferior Vena Caval Ultrasound

Ultrasound evaluation of the inferior vena cava (IVC) can give an estimate of the volume status of the patient and can reasonably predict a beneficial response to fluid. An IVC diameter of less than 1.5 cm with complete inspiratory collapse is associated with a low CVP (<5), and a beneficial response to fluid bolus and volume loading. An IVC diameter of 2.5 cm with no inspiratory collapse represents a high CVP and the patient is unlikely to benefit from further fluid loading. In those patients on mechanical ventilation, the IVC will expand with inspiration. The need for fluid loading can be gauged by calculating the difference between the inspiratory and expiratory size of the IVC. However, the patients must be sedated enough to not be taking spontaneous breaths during the time of measurement, and the ventilator should deliver 10 mg/kg of tidal volume (for the time of the measurement only, ~30 second). A delta IVC greater than 12% corresponded to a greater than 15% increase in cardiac output in one study while a delta IVC greater than 18% corresponded to fluid responsiveness (with 90% specificity and sensitivity) in another. Multiple studies have demonstrated that ultrasound of the IVC can be a useful noninvasive technique for volume status measurement and fluid responsiveness.^66,67

Stroke Volume Variation and Preload Assessment

As discussed above, with CVP validity in question, other measurements of fluid status should be utilized. Another useful adjunct in the evaluation of a trauma patient’s fluid status and heart function is by use of monitoring through an arterial catheter (ie, FloTrac monitor, Edwards Lifesciences, Irvine, CA). Such devices can monitor trends in cardiac output and cardiac index, in addition to providing information regarding evaluation of a patient’s volume status, via monitoring of the pulse pressure variation (PPV) and stroke volume variation (SVV). Excessive variations in arterial blood pressure caused by the specific interactions of the heart and lungs under mechanical ventilation are a clinically well-known sign of hypovolemia.⁶⁸ Variations in PPV are exaggerated when the left ventricle (LV) is on the steep portion of the Frank–Starling curve; small preload changes cause large stroke volume changes. PPV does not measure preload but rather the responsiveness to fluid in mechanically ventilated patients. PPV greater than 11% is indicative of fluid responsiveness.⁶⁹ PPV is a surrogate of SVV.⁷⁰ PPV is proportional to stroke volume and inversely related to aortic compliance. Therefore, PPV may be more affected by changes in vasomotor tone. In contrast, stroke volume is a volume, not a pressure, measurement. Therefore, SVV may be more accurate than PPV. Multiple studies of SVV have shown improved prediction of fluid responsiveness over CVP and PAWP, and have validated SVV and PPV as helpful adjuncts used to improve cardiac output.^71,72 Arterial pulse contour analysis has also been clinically validated for continuous CO measurement and is now available for the real-time quantification of left ventricular stroke volume variation and cardiac output. Despite the promise of encouraging initial results in intraoperative patients, the use of stroke volume variation has its limitations, due to questions of validity at high respiratory rates, with tachycardia, in the presence of β-adrenergic blockade, as well as in the presence of an over- or under-dampened arterial curve.⁷³

An additional noninvasive method of preload assessment is via passive leg raise (PLR); in this method, the legs are passively raised with the patient in a semirecumbent position. By transferring approximately 300 mL of fluid from the lower body to the right heart, PLR simulates a fluid challenge but with only transient hemodynamic effects, thus avoiding volume overload. The effects on cardiac output, PPV, or aortic blood flow should be assessed, with measurements done both before and after PLR is performed. While some studies have demonstrated PLR to be an accurate predictor of fluid responsiveness, this finding has not been corroborated in subsequent studies.⁷⁴

Mixed Venous Oxygen Saturation

Mixed venous oxygen saturation (SvO₂) is a measurement of the oxygen saturation in the venous return to the heart, and therefore an indirect measurement of oxygen utilization by the end organs. Normal values are approximately 75–80% and are calculated by taking the difference between measured oxygen delivery and oxygen consumption. During the septic state, the cell’s inability to utilize delivered oxygen may increase SvO₂. Cellular destruction from prolonged ischemia or cellular metabolic poisoning following carbon monoxide inhalation often yield normal or increased SvO₂ despite inadequate end-organ perfusion, because of an inability to utilize the oxygen delivered.

Lactate and Base Deficit

Elevated serum lactate, or lactic acidosis, can be an indicator of cellular hypoxia or shock. When cells can no longer function normally due to hypoxia or decreased blood flow, the normal mechanism of ATP generation by aerobic metabolism is shifted to anaerobic metabolism. This inefficient method of ATP production yields increased amounts of pyruvate, which is converted to lactate. Therefore, increased levels of lactate may be a reflection of ongoing tissue hypoxia. Hepatic dysfunction may increase serum lactate levels due to inability of the liver to metabolize lactate to carbon dioxide. The use of serum lactate measurements as a guide to resuscitation is limited due to the time necessary for laboratory results to return. However, in critically ill patients past the acute resuscitation phase of treatment, serum lactate levels may be useful in determining the onset of organ dysfunction. In clinical practice, multiple other factors may also affect lactate production. Following severe injury, increased circulating epinephrine may cause an increase in lactate production by aerobic glycolysis in response to increased activity of the Na⁺/K¹⁺-ATPase, despite adequate tissue perfusion.⁷⁵

The base deficit is the difference between the standard value of 24 mEq/L and the serum bicarbonate level. This value is typically negative in hypovolemic shock, and therefore the term base deficit is widely used. The magnitude of the base deficit has been used to quantify the magnitude of acidosis, with mild acidosis having a base deficit of –3 to –5 mEq/L, moderate acidosis –6 to –10 mEq/L, and severe acidosis less than 10 mEq/L. As the magnitude of the base deficit increases, the resuscitation volumes of both blood and fluid increases, as does mortality.⁷⁶ Patients who are able to clear their base deficits in less than 48 hours have decreased mortality when compared to patients whose base deficits persist beyond this time frame. Persistent base deficits despite normal vital signs may be a signal of compensated shock requiring further resuscitation, and if left untreated may lead to multiorgan failure, and increased morbidity and mortality. New-onset lactic acidosis and increasing base deficit in the critically ill patient may be early signs of a low flow state, cellular hypoxia, and/or end-organ injury; therefore, every effort should be made to find the cause and address it as quickly as possible.

Capnography

Defined as the measurement of carbon dioxide, capnography is most commonly used during endotracheal intubation to ensure proper placement of the endotracheal tube. Other studies have reported its use to predict prognosis following cardiopulmonary arrest, to assess resuscitation efforts, to detect alveolar dead space changes, and to monitor sedation and paralytic therapy.^76,77 Under normal conditions, exhaled carbon dioxide closely correlates with arterial blood CO₂ levels. Due to unmatched areas of ventilation and perfusion in the lungs, the arterial PaCO₂ will usually be slightly higher than the exhaled CO₂.

End-tidal CO₂ has been shown to predict resuscitation efforts during cardiopulmonary arrest.⁷⁷ Higher EtCO₂ levels correlate with increased survival after cardiac arrest. Nonsurvivors with prehospital arrests after 20 minutes of ACLS were found to have an average EtCO₂ of 3.9 mm Hg, whereas survivors had EtCO₂ values of 31 mm Hg.⁷⁸ An EtCO₂ value of 10 mm Hg has been determined to provide a 100% sensitivity to predict return of spontaneous circulation.⁷⁹

Measuring tissue pH to study the adequacy of perfusion is an extremely attractive concept. Tonometric determination of mucosal carbon dioxide tension can be used to calculate pH by use of the Henderson–Hasselbalch equation. Although gastric tonometry and measurement of submucosal pH has its merits in determining ongoing tissue hypoxia in the ICU setting, it has not gained wide use in the initial assessment of patients due to the need for serum HCO₃ measurement with each tonometric reading. Gastric pH has proven to be a remarkable reliable predictor of outcome in critically ill individuals: general medical ICU patients, multiply injured trauma patients, patients with sepsis, and patients undergoing major surgical procedures. Studies have shown that sublingual CO₂ (SLCO₂) yielded measurements equivalent with gastric tonometry and is a reliable marker of tissue perfusion, with impaired circulatory blood flow correlating with high levels of SLCO₂. In a prospective observational cohort study, SLCO₂ correlated with blood loss in penetrating trauma patients and may be superior to gastric tonometry in its noninvasive nature.⁸⁰

Patients at high risk for cardiac events during noncardiac surgery have been the topic of discussion for years due to the increased mortality from perioperative arrhythmias and myocardial infarction (MI). Cardiac death or MI occurs in 1–5% of unselected patients undergoing noncardiac surgery, and is the most common reason for preoperative evaluation. The pathophysiology of MI in the perioperative setting differs from that seen in nonsurgical patients. In the nonsurgical setting, MI usually follows rupture of atherosclerotic plaques in the coronary arteries leading to platelet aggregation and thrombus formation. MI in the perioperative setting is due to plaque rupture approximately 50% of the time, with the remainder resulting from myocardial ischemia from decreased myocardial oxygen supply and increased demand in the face of atherosclerotic coronary artery disease. These demands are often exacerbated by anemia, hypotension, hypoxia, hypertension, and tachycardia. Perioperative shifts in intravascular volume, withdrawal of anesthesia, and postoperative pain are all factors that may contribute to the increased demand of oxygen in the perioperative setting. Postoperative tachycardia, arrhythmias, and MI most commonly occur 3 days after an operation, when fluid shifts are at their greatest.

Until recently, reduction in the occurrence of these events has centered on preoperative risk assessment with clinical recommendations and often cancellation or postponement of procedures. Medical strategies have been proposed to reduce perioperative ischemia, as this has been linked to postoperative MI with a 21-fold increase in risk. Mixed results have been obtained in studies using intraoperative calcium channel blockers and nitroglycerin. Two randomized controlled trials have shown that β-blocker therapy reduces perioperative cardiac complications. Mangano and colleagues performed a randomized, double-blinded, placebo-controlled trial using atenolol in 200 patients with known coronary artery disease and/or risk factors for atherosclerosis who underwent noncardiac surgery. Although acute perioperative mortality did not differ between the two groups at 6 months, eight deaths occurred in the placebo group and none in the atenolol group (P < 0.001), with the difference being sustained at the 2-year follow-up period.⁸¹ In a landmark 1999 study, patients with clinical risk factors and ischemia demonstrated by dobutamine stress echo who were to undergo major vascular procedures were randomly assigned to bisoprolol or placebo.⁸² The study was terminated early when investigators noted that bisoprolol markedly reduced perioperative mortality (17% vs 3.4%; P = 0.02) and MI (17% vs 0%; P < 0.001). A 2002 meta-analysis of randomized, controlled trials concluded that β-blockade may be beneficial in preventing perioperative cardiac morbidity despite the heterogeneity of the trials.⁸³ Subsequent studies have shown that withdrawal of β-blockers increased the risk of morbidity and mortality, and that initiation of β-blockers in the preoperative setting requires titration to blood pressure and heart rate control. While perioperative β-blockade has been demonstrated to decrease perioperative cardiac morbidity, there also is an increased risk of stroke, bradycardia, hypotension, and (potentially) all causes of death. Furthermore, perioperative metoprolol has been demonstrated in multiple studies to have worse outcomes than those associated with more selective agents, such as bisoprolol or atenolol.⁸⁴ Therefore, the 2014 ACC/AHA recommendations are aimed at continuation of β-blocker therapy in the perioperative period (for those patients already taking a β-blocker).⁸⁵ The initiation of selective β-blockade should be strongly considered in patients who are undergoing high-risk surgery and have a history of coronary artery disease or evidence on stress test of reversible ischemia.

The definition of acute MI encompasses a spectrum of clinical entities ranging from non ST-segment elevation MI (also known as acute coronary syndrome [ACS] or unstable angina) to acute ST-segment elevation MI. The pathophysiology for ACS differs from that of ST-segment elevation MI, as does the treatment. Whereas ACS in nonsurgical patients is commonly due to a partial occlusion of the coronary arteries or transient ischemia (due to plaque rupture with platelet aggregation), in the surgical patient, ACS is more commonly secondary to decreased oxygen supply or increased demand due to anemia, tachycardia, intravascular fluid shifts, hypotension, or arrhythmias. Acute ST-segment elevation MI refers to complete occlusion of the coronary arteries with myocardial injury.

During workup of suspected MI, the interpretation of elevated troponins can be confounded by a variety of factors, including recent chest trauma, chest compressions, and/or demand ischemia, all of which can cause mild elevations in troponin levels. Significant troponin elevations in the presence of ECG changes should prompt evaluation by a cardiologist. Mild troponin elevation in the absence of ECG changes, especially in the presence of suspected demand ischemia, should be trended with levels checked every 6 hours. Another consideration to take into account is that troponin clearance will be prolonged in patients with renal insufficiency.

Despite marked advances in diagnosis and treatment, there is still an approximately 6.3% in-hospital mortality associated with acute MI. Reduced mortality has been shown to result from adherence to three basic tenets of treatment for acute MI: (1) prompt diagnosis, (2) immediate aspirin and oxygen therapy, and (3) rapid restitution of blood flow to the infarcted myocardium. Whereas prompt diagnosis and institution of aspirin and oxygen therapy are relatively straight forward, the re-establishment of blood flow to the affected myocardium has evolved into two primary therapies: pharmacologic therapy with thrombolytic agents, and interventional therapy with percutaneous coronary intervention (PCI). With its ease of administration, early studies on the use of thrombolytic therapy consistently showed decreased mortality and improved myocardial performance compared with placebo.⁸⁶ However, thrombolytic therapy has well-documented limitations and contraindications. Intracranial bleeding resulting in death or stroke occurs in 0.6–1.4% of patients who receive thrombolytic therapy. Thrombolytic therapy is also associated with a reocclusion rate of 30%, resulting in reinfarction of the affected area within 3 months.⁸⁶ In the multiply injured patient with an increased risk of bleeding, head injury, or multivessel disease, thrombolytic therapy is contraindicated.

PCI has been shown to result in better clinical outcomes when compared to thrombolysis.⁸⁷ In addition to improved outcomes, PCI offers direct visualization of the affected anatomy, and also gives specific hemodynamic and functional data that can be used to guide further therapy. It can also quickly identify those patients who should not undergo reperfusion therapy, which include patients with minimal residual stenosis, spontaneous reperfusion, coronary vasospasm, myocarditis, and aortic dissection involving the ostia.⁸⁸ The 2013 American College of Cardiology Foundation/American Heart guideline for the management of STEMI recommends PCI for any patient with an acute STEMI, provided that the procedure can be performed in a timely fashion; this is defined as within 90 minutes at a PCI-capable hospital or within 120 minutes for patients transferred from a non-PCI capable hospital to a PCI-capable hospital.⁸⁹ Unfortunately, PCI is not available in all medical centers and there is wide variability in the use of PCI even in those centers that are PCI capable.⁹⁰ Complications from PCI include major bleeding (7%), vascular complications that require surgical repair (2%), and renal failure (13%). The incidence of renal failure rises with increasing age, volume of contrast material, decreased baseline renal function, and hypovolemia. When comparing thrombolytic therapy to PCI, primary PCI had been found to be more effective in reducing both short- and long-term outcomes, including death. Recent trials of PCI with or without stent placement show no difference in mortality, but stented vessels had a decreased rate of restenosis and reocclusion over 6 months. The use of platelet glycoprotein (GP) IIb/IIIa inhibitors (eg, abciximab) or platelet adenosine diphosphate chemoreceptor inhibitors (eg, clopidogrel bisulfate) at the time of PCI reduces the rates of subacute thrombosis, recurrent ischemia, and need for repeat revascularization procedures during the first month after PCI with or without stents. However, clinical outcomes do not differ at 6-month follow-up. Despite the heterogeneity of these trials, including whether stents were used or not and the use of platelet inhibitors versus the various thrombolytic agents, the accumulated data appear to favor primary PCI in the treatment of acute ST-segment MI. The addition of platelet inhibitors should be based on clinical judgment in the multiply injured trauma patient with ACS.

For those patients with non ST-segment elevation MI, treatment centers on the presence or absence of hemodynamic instability. In the presence of hemodynamic instability, treatment includes aspirin (ASA) and vasopressors, and cardiac catheterization ±PCI. In those patients with no hemodynamic instability and minimal risk factors for recurrence, medical management with ASA, β-blockers, angiotensin converting enzyme inhibitors (ACE inhibitors), and statins is first line therapy. Low-dose anticoagulation may also be considered, in patients for whom anticoagulation is not contraindicated.⁹¹ While the initial results from studies regarding the initiation of statin therapy following ACS were encouraging, a 2014 Cochrane review of 18 randomized controlled trials comparing statins to placebo demonstrated no significant reduction in death or myocardial infarction after 4 months. There was, however, a reduction in unstable angina with statin administration.⁹² For those patients with multiple risk factors, cardiac catheterization may be indicated when the patient is able to be systemically anticoagulated.⁸⁵

The syndrome of CHF typically brings to mind an enlarged heart and decreased systolic function. However, when systolic function is normal or near-normal, as is the case in nearly 50% of patients diagnosed with CHF, and the other clinical manifestations of CHF exist, such as orthopnea, dyspnea, increased jugular venous pressure, and abnormal heart sounds on auscultation, the diagnosis of diastolic dysfunction (DD) or, more accurately, diastolic heart failure is made. DD is associated with hypertension (HTN), diabetes, female gender, coronary artery disease, and chronic atrial fibrillation. Aging itself has been associated with reductions in elastic properties of the great vessels, decreased ventricular filling, diminished relaxation and compliance, and decreased β-adrenergic receptor density. DD should be described as CHF with normal or preserved EF. The diagnosis of DD is generally made clinically and is often one of exclusion. Objective testing should include echocardiography or cardiac catheterization. Because the normal ejection fraction is not a standardized number, and given that systolic dysfunction often accompanies DD, the diagnosis of DD is often not clear-cut. Therefore, the diagnostic “gold standard” for DD is cardiac catheterization demonstrating increased ventricular diastolic pressure with normal systolic function and volumes. Echocardiography, being noninvasive and practical, can be used to exclude systolic dysfunction. The majority of clinical studies have been geared toward management of systolic dysfunction, with a relative paucity of information regarding the specific management of DD.

In general, the treatment principles for patients diagnosed with DD include antihypertensive therapy, reduction of volume overload, decreasing heart rate, maintenance of sinus rhythm and the reduction of ischemia.⁹³ With hypertension being the primary predisposing factor for CHF, neurohormonal regulation has been shown to play a role in CHF and DD. The renin–angiotensin system influences CHF indirectly by causing hypertension and left ventricular hypertrophy (LVH), and directly by both angiotensin II and endothelin contributing to LVH and impaired myocardial relaxation. Blockade of the renin–angiotensin system improves diastolic distensibility in both human and animal studies. Volume overload can be reduced with diuretics or renal replacement therapy in patients with renal failure. In DD, the use of β-adrenergic blockade or calcium channel blockade to reduce heart rate and increase left ventricular filling time reduces mortality.⁹⁴ Digoxin decreases hospitalization of patients with CHF with and without systolic dysfunction; however, since digoxin is a negative chronotrope the benefit may be due to the rate-lowering effect of the drug rather than to its other hemodynamic properties. While angiotensin converting enzyme-inhibitor (ACE-I) therapy is beneficial in patients with hypertensive disease and in patients with mixed systolic and diastolic dysfunction, there is no direct evidence that ACE-I reduce mortality or morbidity in patients with DD. If a patient has both DD and rate-altering arrhythmias, such as atrial flutter or atrial fibrillation, rate control will lead to increased filling times once normal sinus rhythm is restored. Myocardial ischemia can also contribute to DD; thus, patients with drug-resistant ischemic DD may benefit from PCI or coronary artery bypass grafting.⁹⁵ Aldosterone has also been shown to contribute to CHF with detrimental effects on endothelial function as well as inducing a vasculopathy. Infusion of aldosterone into healthy volunteers for 1-hour results in endothelial dysfunction with a notably reduced vascular response to acetylcholine. Patients with mild CHF treated with β-blocker therapy, ACE inhibitors, and statins show an improvement in acetylcholine-mediated endothelium-dependent vasodilatation.

Right heart dysfunction may result from pulmonary arterial hypertension (PH), defined as systolic Ppa greater than 25 mm Hg at rest. The signs and symptoms of PH are often vague, with patients presenting with dyspnea and fatigue. The initial evaluation for PH typically involves either echocardiography (transthoracic or transesophageal) or pulmonary artery catheterization, but is definitively diagnosed by right heart catheterization. Echocardiographic signs suggestive of PH include right ventricular dilation and hypertrophy, septal bowing into the left ventricle during late systole to early diastole (D-shaped left ventricle), right ventricular hypokinesis, tricuspid regurgitation, right atrial enlargement, and a dilated IVC. Other diagnostic modalities that are potentially utilized in the workup of PH are chest radiograph, ECG, pulmonary function tests, arterial blood gases, V/Q scan, high-resolution computed tomography, ultrasonography of the abdomen, and biopsy. These diagnostic modalities are used not only for the diagnosis of PH but also to determine etiology and functional impairment.⁹⁶

Primary considerations when managing a critically ill patient with PH in the ICU are contingent on promptly making the diagnosis, which then allows for specific treatment. Hemodynamic goals are to reduce the PVR, augment cardiac output, and resolve systemic hypotension while avoiding tachyarrhythmias. The cornerstones of the initial management of PH include prevention of volume overload, supplementary oxygen therapy, and anticoagulation. Prevention of fluid retention with diuretics or renal replacement therapy is essential to avoid peripheral edema and hepatic congestion.⁹⁷ Avoidance of hypoxia and hypercapnea will minimize pulmonary vasoconstriction, and thus are simple measures to avoid exacerbation of PH. Due to the increased risk of pulmonary thromboembolic disease in patients with PH, systemic therapeutic anticoagulation should be considered, unless contraindicated. For patients with acute PH secondary to pulmonary contusions, therapeutic anticoagulation is typically not necessary, since the physiological sequelae of the pulmonary contusions are transient.

More advanced therapies also exist in the treatment of PH. Milrinone significantly reduces PVR and improves right ventricular function. However, its use can be limited due to the high incidence of systemic hypotension. Phosphodiesterase type 5 inhibitors, such as sildenafil, prolong the vasodilatory effect of nitric oxide (NO), and can be helpful in the treatment of PH. The typical dose of sildenafil used for treatment of PH is 20 mg PO (or 10 mg IV) three times daily. Its onset of action is rapid, with effects seen within 1 hour; the half-life is approximately 3–4 hours. In stable patients, when it is used alone or in combination with inhaled NO, the cardiac output will increase. It is contraindicated in patients receiving nitrates because of the potential for severe systemic hypotension, and its use should be closely monitored in patients with liver dysfunction (since it undergoes hepatic metabolism). Although use of calcium channel blockers in the management of chronic PH is effective for control of heart rate, there are no studies of their use in the critically ill patient with PH. Because of their negative inotropic effects, they may precipitate fatal worsening of right ventricular failure. Other therapies, used in isolation or combination, include endothelin receptor antagonists (eg, bosentan), prostanoids (eg, epoprostenol), and guanylate cyclase stimulants.