The choice of vasopressor is dependent on the clinical picture and the presumed etiology of the hypotension. Specific treatments based on clinical conditions are summarized in Table 16-4. The drug is then often titrated to achieve a desired endpoint. Examples of possible endpoints include, but are not limited to, CVP 8–12 mm Hg, MAP ≥65 mm Hg, urine output ≥0.5 mL/kg/h, venous (SVO2) or central venous (SCVO2) oxygen saturation ≥70%, and improved mental status.9 It is important to note that the optimal MAP for most conditions is unknown, but a post hoc analysis of a multicenter trial of septic shock demonstrated that elevations of the MAP >70 mm Hg by augmenting the vasopressor dosage were associated with an increase in mortality.10 If the maximal dose of a drug is reached but not the desired endpoint, a second agent may be added. A critical care patient's hemodynamic status can change rapidly, and therefore it is important to frequently reevaluate the patient and determine if there is an ongoing need for vasopressor medication, titration, or a different agent. Excessive vasoconstriction can be detrimental, especially in the setting of inadequate CO and hypovolemia. When used in high doses without adequate volume or CO, these medications can lead to hypoperfusion of the kidneys, brain, and other organ systems.
No studies have been done to indicate that one vasopressor has improved mortality when compared with others when used for appropriate clinical conditions. The debate over dopamine and norepinephrine as the initial vasopressor of choice has been extensively studied. A recently published, large multicenter, randomized, blinded trial compared dopamine and norepinephrine as the initial vasopressor in the treatment of all patients presenting with shock regardless of etiology. This study concluded there was no mortality difference at 28 days when all forms of shock were examined.11 In the subset of patients with cardiogenic shock, however, dopamine was significantly associated with increased mortality. It also revealed that the use of dopamine was associated with a greater number of adverse advents, such as arrhythmias, requiring medication discontinuation.11 It seems logical that norepinephrine should be the initial vasopressor of choice, until further evidence suggests otherwise.
Prior to initiating vasopressors, it is important to ensure that the intravascular compartment has been repleted. In the case of distributive or hypovolemic shock, an adult patient should receive 2 L of crystalloid fluid before starting vasopressors. In cardiogenic shock, the patient should receive a bolus of 20 mL/kg of crystalloid if there is right ventricular involvement. Fluid therapy is discussed at length in Chapter 47. If the blood pressure fails to respond to these measures, vasopressors should be initiated. Vasopressor activity is partially, if not significantly, reduced if the patient has not been adequately volume resuscitated.12
The treatment of hypovolemic shock is initiated with crystalloid fluids, with or without colloids. Vasopressors should generally not be used since they do not address the primary problem and may lead to further hypoperfusion. If the patient is in extremis, vasopressors should be used only as a temporizing measure in the setting of hypovolemic shock while fluid resuscitation continues. The cause of hypovolemia should be identified and treated, and it is essential to distinguish between hypovolemic shock and distributive shock, which is described below. Transfusion should be considered early, particularly if the hypovolemic shock is due to blood loss. Fluid resuscitation should be continued, and the vasopressor agent should be weaned as soon as tolerated. Consider dopamine, norepinephrine, or epinephrine as a temporizing measure in this setting.
Distributive shock occurs when there is a fall in SVR secondary to significant peripheral vascular dilation. Causes of distributive shock include septic, anaphylactic, and neurogenic shock. Distributive shock is usually characterized by hypotension, low SVR, and normal to increased CO. Treatment will be discussed in the next subsections under the heading of each specific cause.
The first-line treatments of severe sepsis and septic shock are IV fluids (IVF) and antibiotics. If the patient remains hypotensive despite adequate volume resuscitation, then vasopressors should be added to the treatment regimen. Vasopressor therapy is very important in order to improve and maintain adequate tissue perfusion in an attempt to maintain life and prevent the development of multiple organ dysfunction and failure. There has been much controversy surrounding the initial vasopressor of choice in the management of patients with septic shock. For this reason, the Surviving Sepsis Campaign guidelines recommend either dopamine or norepinephrine as the initial vasopressor for patients with septic shock.9 Epinephrine versus norepinephrine plus dobutamine was found to have no mortality difference, in a large prospective, multicenter, randomized double-blind European study.13 Phenylephrine can also be helpful when tachycardia or arrhythmias preclude the use of norepinephrine or dopamine.14
Endogenous vasopressin is released in abundance in the early stages of shock but becomes depleted with prolonged resuscitation with a resulting inappropriate vasodilation. In this setting or in the clinical setting of catecholamine-resistant shock, vasopressin can be given at a dose of 0.01–0.04 U/min.15 However, in a randomized double-blind study of septic shock patients requiring vasopressor therapy, there was no mortality difference between the norepinephrine and norepinephrine plus vasopressin group, but the combination of norepinephrine and vasopressin allowed for more rapid weaning of norepinephrine while maintaining adequate MAP.16
In the patient with a persistently depressed SvO2 or ScvO2 below 70% despite adequate blood pressure response to first-line vasopressor agents and after optimizing the hematocrit to a level above 30%, dobutamine can be added. In this setting, dobutamine can significantly increase cardiac index (CI), oxygen delivery (DO2), and oxygen consumption (VO2), while decreasing MAP, pulmonary artery and wedge pressures, and systemic and pulmonary vascular resistances. Hypovolemic patients have a poor response to dobutamine when compared with euvolemic patients, so it is essential to ensure adequate fluid resuscitation prior to starting dobutamine.17,18 Dobutamine should not be used as a first-line vasopressor for septic or other forms of distributive shock.
Anaphylaxis is a hypersensitivity reaction that involves all the components of the immune system, including immunoglobulin, cytokines, leukotrienes, prostaglandins, and activation of the complement cascade. The main culprit is histamine release, which causes capillary leak resulting in hypovolemia, bronchospasm, vasospasm, and mucous gland hypersecretion.19 The treatment of anaphylaxis should be guided by the need to prevent complications and reverse the inciting process. Special attention should be paid to securing the airway, and intubation, if indicated, should be done early. This should be followed by generous volume resuscitation, vasopressor support, and ultimately treating the histamine release.
Epinephrine is the vasopressor of choice and should be given early. Epinephrine dosage is something that is easily confused, and the literature contains a multitude of dosage variations, some in milliliters and others in milligrams or micrograms. Also, recommendations vary from country to country. First, it should be recalled that epinephrine concentrations vary. The commonly used terms, 1:1,000 and 1:10,000, are not completely obvious. Strictly speaking, these terms are structured as grams:milliliters of solution. Therefore, an epinephrine solution of 1:1,000 means 1 g of medication diluted in 1,000 mL (or 1 L) of solution. When each side of the ratio is divided by 1,000, the resulting amount is 1 mg/1 mL. This is obviously more concentrated than the 1:10,000 solution that has 1 g of medication diluted in 10,000 mL (or 10 L) of solution. In this case, dividing each side by 1,000 results in 1 mg/10 mL or 0.1 mg/1 mL. Epinephrine is packaged in a number of forms. Prefilled syringes, commonly used in cardiac arrest, come as 10 mL of 1:10,000 solution. As described above, this amounts to a total of 1 mg of epinephrine for the syringe at a concentration of 0.1 mg/mL (100 μg/mL).
The current clinical guideline recommends an initial epinephrine dose of 0.3–0.5 mg (or 300–500 μg), which is the same as 0.3–0.5 mL of a 1:1,000 solution administered intramuscularly (IM) into the anterior or lateral thigh. Also, IM injection is recommended over subcutaneous (SQ) injection due to its more rapid increase in plasma and tissue concentrations of epinephrine.20 If shock is present or if symptoms are refractory to IM injection, then the epinephrine should be given by continuous IV infusion at a rate of 5–15 μg/min. This can easily be done by mixing 1 mg (1,000 μg) of either solution into a 100-mL bag of normal saline, which produces a concentration of 10 μg/mL. This solution can then be run at 1 mL/min, which provides the patient with 10 μg/min. In the event that the shock of anaphylaxis is refractory to epinephrine, norepinephrine or dopamine can be added.21
Neurogenic shock can be due to spinal cord injury or spinal anesthesia. The loss of sympathetic tone leads to increased venous capacitance, decreased venous return, decreased preload, decreased CO, and ultimately hypotension, often without a compensatory increased heart rate. Treatment of neurogenic shock includes careful IVF administration, and vasopressor support with α1 stimulation for vasoconstriction with or without β1 receptor stimulation for cardiac support. Norepinephrine and dopamine can be used for this purpose. Phenylephrine may be used as well; however, care should be taken to monitor for reflex bradycardia with this agent.
The current recommendation for blood pressure management after acute spinal injury from the American Association of Neurologic Surgeons is as follows: (1) hypotension should be avoided if possible, and if hypotension occurs, it should be corrected as soon as possible; (2) MAP goal of 85–90 mm Hg for the first 7 days following acute spinal cord injury—a MAP at this level is thought to improve spinal cord perfusion following injury. These recommendations are listed as options in the guideline as the data supporting these recommendations are limited.22
Cardiogenic shock is the result of cardiac dysfunction and is usually associated with AMI. It is defined as hypotension not reversible with fluid therapy or hypoperfusion resulting in organ dysfunction, despite adequate left ventricular filling pressure. Cardiogenic shock is generally divided into two forms: left-sided failure, mainly due to AMI, and right-sided failure, which can have several causes. The right ventricle is thin walled, compared with the left ventricle, and can handle volume overload easier than the left side that handles much higher pressures. Similarly, right ventricular function is volume dependent, whereas left ventricular function is pressure dependent.
The treatment for cardiogenic shock is based on the side primarily involved. In the clinical setting, it is reasonable to start with the electrocardiogram (EKG) in these patients. An EKG that demonstrates a left-sided AMI indicates a left ventricular cause for cardiogenic shock. This can be followed by a bedside echocardiogram. Right ventricular dilatation indicates a right-sided cause. Echocardiography can also be used to exclude a diagnosis of cardiac tamponade in these patients.
Right ventricular failure can be caused by a wide array of clinical conditions including left-sided failure, pulmonary embolism, pulmonary HTN, sepsis, and lung disease. The treatment of cardiogenic shock from right heart failure is primarily directed at volume resuscitation to ensure adequate preload and at reversing the cause of the failure. Inotropic medication may be required as well. Right ventricular overfilling in the setting of heart failure can lead to a bulging intraventricular septum. This can diminish left ventricular function and decrease coronary perfusion resulting in myocardial ischemia or infarction.23
Cardiogenic shock from left-sided failure has been extensively studied, and most guidelines are directed at treating this form of cardiogenic shock. Since it is mainly due to AMI, treatment should be aimed at early revascularization and supportive care. According to the results of the SHOCK trial, which informed the American College of Cardiology/American Heart Association guidelines, emergency revascularization should be attempted immediately for patients younger than 75 years of age with cardiogenic shock from AMI.24
The American College of Cardiology/American Heart Association guidelines for the pharmacologic treatment of cardiogenic shock complicating AMI are as follows: (1) if SBP is 70–100 mm Hg without signs and symptoms of shock, dobutamine is the first-line agent; (2) if SBP is 70–100 mm Hg and the patient has signs and symptoms of shock, dopamine is the first-line treatment. If the response to these individual agents is inadequate, they can be used in combination or norepinephrine may be used with dobutamine. Vasopressin may also be used as a second-line agent.15 A recent prospective randomized controlled trial in ICU patients revealed that the combination of norepinephrine–dobutamine appeared to be a more reliable and safer strategy than epinephrine alone.25 Epinephrine was associated with a transient lactic acidosis, higher heart rate and arrhythmia, and inadequate gastric mucosa perfusion.