Shock is defined as the failure of the cardiovascular system to supply adequate tissue perfusion, which results in insufficient cellular oxygen utilization.1,2 It is crucial that treatment of a patient in shock is started immediately because shock is associated with high mortality and morbidity.3
Clinical manifestations of shock
When diagnosing shock, it is important to note that shock is based on three parameters that include clinical, hemodynamic, and biochemical signs.2 First, systemic arterial hypotension (defined as a mean arterial pressure [MAP] of less than 70 mm Hg) and tachycardia are generally present. Second, clinical signs of tissue hypoperfusion will be seen.2 The patient's skin will be cold and clammy, and the nurse will see decreased capillary refill of the nail beds because the body is in a vasoconstrictive state.2,3 Urine output will decrease to less than 0.5 mL/kg/h (oliguria), and altered mental status, disorientation, and confusion will be present because the brain is not being adequately perfused.2,3 Last, one biochemical marker that indicates atypical cellular oxygen metabolism, lactate, is generally elevated (over 1.5 mmol/L) in shock and should be monitored throughout the treatment course to determine whether interventions are successful.2
Four different forms of shock exist, and it is crucial to identify which type of shock the patient is experiencing to determine the best course of treatment. Hypovolemic shock is excess loss of plasma or blood volume that is initially compensated by increases in heart rate (HR) and systemic vascular resistance (SVR) but typically requires resuscitation.2,4
Cardiogenic shock is a low-cardiac-output state with abnormal myocardial contractility caused by myocardial infarction (MI), dysrhythmias, valvular disease, end-stage cardiomyopathy, and conduction defects and appears clinically similar to hypovolemic shock. However, compared with hypovolemic shock, patients with cardiogenic shock generally present with pulmonary edema and jugular venous distension.2,4
Obstructive shock is an extracardiac process cutting off circulatory flow that can be caused by tension pneumothorax, cardiac tamponade, or massive pulmonary embolus. Clinically, because cardiac output is decreased in obstructive shock, signs and symptoms resemble hypovolemic and cardiogenic shock.2,4
Distributive shock (which includes septic shock) initially presents as elevated cardiac output and decreased SVR, as the peripheral vasculature is vasodilated after an inflammatory response.2,4
Once a patient has been diagnosed with shock, resuscitation should be initiated immediately to prevent progression of organ dysfunction or failure.2 Using a mnemonic known as the “VIP rule” can help determine how to proceed with resuscitation: Ventilate (administer oxygen), Infuse (fluid resuscitation including crystalloids or blood products), and Pump (administer vasoactive agents).2
Ventilatory support with oxygen should begin immediately to increase oxygen delivery.2 Depending on the patient's status, ventilatory support can be achieved noninvasively through a mask or invasively with mechanical ventilation.2
Next, fluids are infused to improve blood flow to the microvasculature and to increase cardiac output.2 For example, crystalloid fluids, such as 0.9% sodium chloride (normal saline), should be infused quickly (at a volume of at least 30 mL/kg) for distributive shock.2,5 In a patient with hemorrhagic shock (hypovolemic shock from rapid blood loss), crystalloid fluids and blood products would be used to resuscitate the patient. However, the treatment of shock including the amount of fluid given to the patient must be carefully chosen based on the type of shock.2
Adverse reactions such as fluid overload can occur, and the patient should be monitored closely.2 If hypotension persists after fluid resuscitation, the administration of vasoactive agents is required.2 Hypovolemia should be corrected before the administration of any vasoactive agents.2
This article reviews the following vasopressors and inotropes that may be administered to treat shock: epinephrine, norepinephrine, vasopressin, phenylephrine, dopamine, dobutamine, and milrinone (see Overview of vasopressors and inotropic agents).
Epinephrine. A potent alpha- and beta-adrenergic agonist, epinephrine increases MAP by increasing cardiac output and vascular tone.6 At low weight-based doses, epinephrine heavily stimulates the beta1 and beta2 receptors, increasing cardiac output and HR; at higher doses, epinephrine heavily stimulates the alpha receptors, leading to vasoconstriction and an inotropic effect.1 Epinephrine has a quick onset of less than 5 minutes and a half-life of less than 5 minutes.7
Although epinephrine is an effective vasopressor, it may lead to detrimental adverse reactions. Epinephrine has been shown to decrease blood flow to the splanchnic circulation and may increase lactate levels.5 At high doses and prolonged infusion administration of epinephrine, direct cardiac toxicity can occur through damage to arterial walls by cardiac myocyte necrosis and apoptosis.8 Epinephrine, along with other vasopressors, can cause significant tissue damage, skin sloughing, and dermal necrosis. If extravasation occurs, the I.V. infusion must be changed to another site and the area of necrosis treated with phentolamine, an alpha-receptor antagonist, which is injected into the area of necrosis and reverses ischemic changes.9 To prevent extravasation, vasopressors should be infused through a central venous catheter using an infusion pump.10 Additional adverse reactions of epinephrine include hyperglycemia from the beta1 receptor stimulation and tachycardia.7
Despite the adverse reactions, epinephrine remains an effective vasopressor that is generally reserved for second-line treatment and is the preferred vasopressor for refractory shock.1,5
Norepinephrine. The mediator of the sympathetic nervous system, norepinephrine is a potent alpha1- and alpha2-receptor agonist with beta1-adrenergic agonist effects and no beta2 effects, which leads to robust vasoconstriction with little to no inotropic effects.10 Through the stimulation of alpha1 and alpha2 receptors and limited beta-adrenergic receptors, norepinephrine increases MAP by increasing BP and SVR with a slight impact on cardiac output.1,8,10 Norepinephrine has a rapid onset of action, within 1 to 2 minutes, and has a duration of 1 to 2 minutes.11 Currently, norepinephrine is the recommended first-line vasopressor by the Society of Critical Care Medicine Guidelines for Management of Sepsis and Septic Shock.5
Although norepinephrine is considered a first-line vasopressor for shock, a variety of precautions, warnings, contraindications, and adverse reactions should be taken into consideration when administering.2 Prolonged administration of norepinephrine could result in myocardial ischemia because of cardiotoxic effects on the cardiac myocytes.8 Like epinephrine, norepinephrine can cause significant tissue damage, skin sloughing, and dermal necrosis that is treated with phentolamine. Administration of norepinephrine through a larger, central vein, diluted at an appropriate concentration, will also help prevent extravasation.9,10 Norepinephrine should be used cautiously in patients taking antidepressants (such as monoamine oxidase inhibitors [MAOIs], tricyclic antidepressants [TCAs], or imipramine type antidepressants) because concomitant administration has been shown to lead to severe, prolonged hypertension.12
Contraindications to norepinephrine treatment include concomitant use with inhaled anesthetics such as cyclopropane (no longer used in the United States) and halothane because it can increase cardiac autonomic irritability, leading to ventricular tachycardia and fibrillation. Avoid the use of norepinephrine in patients with mesenteric or peripheral vascular thrombosis, and those who are hypotensive from blood volume deficits, except for emergency therapy to maintain perfusion until blood replacement therapy can be administered.12 Adverse reactions to norepinephrine include ischemic injury from tissue hypoxia, brady- or tachydysrhythmias, anxiety, transient headaches, dyspnea, nausea/vomiting, and extreme hypertension.10,12
Vasopressin. Also known as antidiuretic hormone, vasopressin is a hormone that is naturally released by the posterior pituitary gland in response to decreased blood volume and increased plasma osmolality that leads to vasoconstriction.10 Vasopressin acts via the V1 receptor, which leads to constriction of the vascular smooth muscle and the V2 receptor. This leads to enhanced water reabsorption in the renal collecting duct, resulting in an increase in SVR and little to no impact on cardiac output.8
Vasopressin has a rapid onset of action, with a peak effect occurring within 15 minutes and a half-life of 10 minutes or less.13 Currently, vasopressin is recommended as an adjunct therapy to norepinephrine when monotherapy with norepinephrine does not achieve the target MAP over 65 mm Hg.5
Although vasopressin is an endogenous hormone, many warnings, precautions, adverse reactions, and interactions should be taken into consideration before administration. Vasopressin has been reported to cause dysrhythmias, chest pain, MI, and asystole.10 Although uncommon, vasopressin also has been shown to cause extravasation when administered through a peripheral line; administration of vasopressin through a central line could avoid this complication.9 Vasopressin should be cautiously used in patients who are taking medications that may cause the syndrome of inappropriate antidiuretic hormone secretion such as TCAs, selective serotonin reuptake inhibitors, haloperidol, enalapril, methyldopa, and pentamidine, because concomitant use may increase the pressor and antidiuretic effect of vasopressin.13 Patients who are taking medications that could cause diabetes insipidus (such as demeclocycline, lithium, foscarnet, and clozapine) could experience a decreased pressor effect of vasopressin.13 Adverse reactions of vasopressin include gastrointestinal disorders (mesenteric ischemia), increased bilirubin, acute kidney insufficiency, hyponatremia, bronchial constriction, and diaphoresis.10,13
Phenylephrine. A pure alpha1-adrenergic agonist, phenylephrine causes rapid peripheral vasoconstriction resulting in increased BP. It has minimal beta-adrenergic activity, and therefore minimal chronotropic or inotropic activity.10
Phenylephrine has a rapid onset that typically occurs within minutes and has a half-life of approximately 5 minutes.14 Currently, little to no clinical data exist on phenylephrine use in sepsis and its use in patients with sepsis should be limited.5
Although phenylephrine is an effective vasoconstrictor, many warnings and precautions, adverse reactions, and interactions should be taken into consideration before administration. Phenylephrine has been linked to severe bradycardia and decreased cardiac output, which could be detrimental in a patient with shock.14 Like other vasopressors, phenylephrine causes significant tissue damage, skin sloughing, and dermal necrosis that could be treated with phentolamine. However, this adverse reaction can be avoided by administering phenylephrine through a larger, central vein, diluted to an appropriate concentration.9,10 I.V. phenylephrine contains sodium metabisulfite, which could lead to life-threatening anaphylactic symptoms in individuals with sulfite sensitivity. However, according to the package insert, the prevalence of sulfite sensitivity is unknown and is probably low.14 Next, oxytocic drugs, such as oxytocin, increase the pressor effect of phenylephrine and could potentially lead to hemorrhagic stroke; BP should be monitored closely in patients receiving both drugs.14 Phenylephrine has been shown to cause renal toxicity; renal function should be monitored closely.14
Adverse reactions to phenylephrine include bradycardia, atrioventricular (AV) block, myocardial ischemia, nausea, vomiting, chest pain, headache, excitability, nervousness, and tremor.14 Phenylephrine has many drug interactions that should be taken into consideration; for example, MAOIs, TCAs, centrally acting sympatholytic agents (such as guanfacine), alpha2-adrenergic agonists (such as clonidine), steroids, and atropine increase the pressor effect of phenylephrine. Adversely, phenylephrine can block medications such as alpha-adrenergic antagonists.14
Dopamine. A naturally occurring precursor to norepinephrine, dopamine is a potent vasoconstrictor that has many different dose-dependent effects on the systemic vasculature.15 At very low doses, once known as renal doses, dopamine primarily activates dopaminergic receptors, leading to vasodilation in the renal, splanchnic, mesenteric, and coronary vasculature.1 Administering dopamine at a higher rate for renal protection is not recommended because there are no available data to support this treatment solely to maintain kidney function.5 At moderate (inotropic) doses, dopamine primarily activates the beta1-adrenergic receptors, leading to an increase in MAP, HR, stroke volume, and cardiac output.1 At high doses, dopamine begins to stimulate the alpha1-adrenergic receptors, increasing MAP.1
Dopamine has a quick onset of action that occurs within 5 minutes and has a short half-life of 2 minutes.15 Norepinephrine is a more potent vasopressor than dopamine to correct hypotension in patients with shock, but dopamine could be an acceptable alternative to norepinephrine in patients with a low risk of tachydysrhythmias and absolute or relative bradycardia.5
Although dopamine is an acceptable alternative to norepinephrine, many contraindications, warnings and precautions, adverse reactions, and interactions must be taken into consideration. Dopamine is contraindicated in patients with pheochromocytoma (a rare neuroendocrine tumor that originates in the adrenal gland) and should not be administered to patients with tachydysrhythmias because infusion of dopamine may worsen these conditions. Sodium metabisulfite is embedded within the drug and could lead to life-threatening anaphylactic reactions.15
Precautions should be taken into consideration with administration of dopamine. When titrating the infusion during discontinuation, hypotension can occur. To avoid this problem, consider coadministering I.V. fluids to expand the patient's intravascular volume.15 Like other vasopressors, dopamine has been known to cause extravasation, which can be prevented by administering dopamine through a larger, central vein; if extravasation occurs, it can be treated with phentolamine.9,15 Adverse reactions of dopamine include ventricular dysrhythmias, atrial fibrillation, ectopic beats, tachycardia, hyper/hypotension, headache, and nausea/vomiting and should be monitored for and treated appropriately.15
Many medications interact with dopamine. Because dopamine is metabolized by monoamine oxidase, MAOIs could potentiate the effects of dopamine, and patients taking MAOIs should receive no more than one-tenth of the usual initial dose of dopamine.15 Coadministration with dopamine and cyclopropane (no longer used in the United States) or halogenated hydrocarbon inhaled anesthetics can increase the risk of ventricular dysrhythmias and should be coadministered with extreme caution. Medications such as TCAs and oxytocin could lead to extreme hypertension, and haloperidol could block the dopaminergic effect.15
Dobutamine. A synthetic catecholamine, dobutamine is a potent inotrope that increases cardiac output by strongly stimulating the beta1-adrenergic receptor, and mild-to-moderate stimulation of the beta2-adrenergic and alpha1-adrenergic receptors.1 At low doses, dobutamine has been shown to increase stroke volume without significant tachycardia; with high doses, tachycardia worsens, leading to decreased diastolic filling time, which results in smaller increases in cardiac output.1
Dobutamine's onset of action occurs within 1 to 2 minutes and has a half-life of 2 minutes.16 This makes dobutamine the preferred inotrope in unstable patients with cardiogenic shock, and it is recommended in patients with hypoperfusion in septic shock when appropriate fluid loading and vasopressors do not achieve normal end-organ function.1,5
Although dobutamine is an effective inotropic agent, many contraindications, precautions and warnings, interactions, and adverse reactions exist. Dobutamine is contraindicated in patients with idiopathic hypertrophic subaortic stenosis. Because dobutamine promotes conduction, patients with atrial fibrillation are at increased risk of developing rapid ventricular response, and patients with hypertension are at increased risk of an increased pressor effect. Dobutamine could precipitate or exacerbate ventricular ectopic activity and hypersensitivity reaction, and elicit an anaphylactic reaction from patients who have a sulfite sensitivity. In animal studies, the concomitant use of a beta-antagonistic medication led to a lesser dobutamine effect. Hypotension can also be a result of dobutamine administration, but is mainly seen when titrating the agent down or off.16 Adverse reactions of dobutamine include nausea, angina, dyspnea, headache, decreases in serum potassium, and phlebitis.16
Milrinone. A selective phosphodiesterase-3 inhibitor, milrinone is a potent inotrope and vasodilator that increases intracellular calcium and myocardial contractions, and relaxes the pulmonary and systemic vasculature, lowering SVR and pulmonary vascular resistance.1,17 Milrinone is indicated for short-term management of patients with acute decompensated heart failure.17 When infused I.V., milrinone peaks within 2 minutes and has a half-life of 1 to 3 hours.11
Although milrinone has a different mechanism of action than dobutamine, there are many contraindications, precautions and warnings, interactions, and adverse reactions that must be taken into consideration. Milrinone is contraindicated in patients with severe obstructive aortic or pulmonary vascular disease or hypertrophic subaortic stenosis. Because milrinone, like dobutamine, increases myocardial contractions, supraventricular and ventricular dysrhythmias may occur, and patients should be closely monitored during infusions. Milrinone also slightly shortens the AV node conduction time, and patients with atrial fibrillation or flutter may experience an increased ventricular response rate. It should be used with caution in patients with hypotension. Patients with kidney impairment (creatinine clearance of 50 mL/min/1.73 m2 or less) will require a renal dose adjustment.17 Few interactions with milrinone exist, but it can form a precipitate with furosemide and bumetanide when administered into the same I.V. line; therefore, coadministration of these medications should be avoided. Adverse reactions of milrinone include ventricular dysrhythmias, ventricular ectopic activity, hypotension, angina, headache, hypokalemia, and tremor.17
Patients presenting to EDs or ICUs with hemodynamic compromise related to any form of shock are considered high-acuity patients. Critical care nurses must know the probable medications used to treat these patients and any invasive or noninvasive monitoring that may be required. Nurses are responsible for knowing the adverse reactions of each vasoactive medication. Lack of understanding of vasoactive medications may lead to patient compromise and possibly a sentinel event.
Appropriate and accurate monitoring of hemodynamic parameters is required when titrating continuous infusions of vasoactive medications. Patients need an arterial line for continuous BP monitoring.18 An arterial line allows for optimal titration of medications with close observation of patient responsiveness in real time.
Nurses must monitor the arterial line waveform to ensure accurate readings are obtained. The accurate recording of intra-arterial pressure depends upon an appropriate dynamic response of the monitoring system.
The rapid-flush (square wave) test is the clinical test of choice. This will determine if the arterial waveform has overdamped or underdamped characteristics. If the waveform is overdamped, mainly caused by air bubbles in the tubing, the systolic BP has been underestimated. If the waveform is underdamped, the systolic BP has been overestimated. This can be caused by patient factors, excessive tubing length, or connecting tubing with stopcocks. If the arterial line waveform is inaccurate, nurses should use noninvasive BP cuff readings for titration of medications until a new arterial line can be placed. When utilizing a noninvasive BP cuff for titration of vasoactive medications, obtain readings at least every 15 minutes, and more frequently if readings reveal hypotension.18
Inotropes affect cardiac contractility as well as preload and afterload. Inotropic medications require further invasive monitoring of cardiac output along with preload and afterload. The gold standard for this monitoring has been a pulmonary artery (PA) catheter.19 Based on recent consensus statements on circulatory shock and hemodynamic monitoring, PA catheters should only be used in complex shock patients to determine the type of shock, refractory shock patients, or patients with severe shock. PA catheters are not recommended for routine use in patients with shock.19 However, noninvasive devices that calculate these values have been developed and can be used as a substitute for PA catheters with fewer complications for the patient.
Appropriate education is required to understand the hemodynamic parameters and titration of vasoactive and inotropic medications based on hemodynamic measurements. Vasopressors and inotropic medications are caustic to veins. Vasoactive medication should not be administered for a prolonged period of time through a peripheral I.V. catheter because of the possibility of serious tissue injury by extravasation.20 A central venous catheter placed in the subclavian vein, internal jugular vein, or femoral vein is appropriate for vasoactive medication infusions. In emergent, life-threatening situations, a brief period of infusion through a peripheral catheter is acceptable. Whenever a vasoactive medication infusion is started, use an infusion pump to control the rate of infusion.21 Nurses need to be familiar with the infusion pumps at their facilities and how to titrate the medications on specific infusion pumps.
Once a patient has been diagnosed with shock, resuscitation should be initiated immediately, which may require the administration of vasoactive agents once the patient has been volume resuscitated. Each vasoactive agent exerts its effects differently, and it is important to select the correct vasoactive agent for the type of shock the patient has. Once the patient has been initiated on a vasoactive agent, appropriate and accurate monitoring should be enforced to prevent adverse outcomes.