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.
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).
TABLE 56-1Dosage, Mechanism, and Actions of Pharmacologic Agents Commonly Used in the Treatment of Cardiovascular Failure ||Download (.pdf) TABLE 56-1 Dosage, Mechanism, and Actions of Pharmacologic Agents Commonly Used in the Treatment of Cardiovascular Failure
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 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 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.
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 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 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 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
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 mortality52,53 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.