Critically ill patients frequently suffer circulatory disturbances necessitating the use of vasoactive medications. Records from 271 hospitals in the United States demonstrate that almost one-quarter of patients in critical care units received vasoactive infusions.1 Consequently, critical care nurses must know the actions and possible adverse reactions of vasoactive agents. More important, nurses must be able to titrate hemodynamic medications to achieve therapeutic endpoints indicating adequate perfusion.
The purpose of vasoactive infusions is to restore the delivery of oxygenated blood so cells can carry out normal aerobic metabolism. The microcirculation is comprised of approximately 10 billion capillaries,2 where oxygen and nutrient exchange occurs at the cellular level. Arterioles adjust where oxygenated blood flows based on metabolic demands of individual organs. In times of poor perfusion, precapillary sphincters dilate or constrict to shunt blood from less metabolically active tissues to the heart and brain. When the mean arterial pressure (MAP) falls below 65 mm Hg, arterioles lose the ability to autoregulate and perfusion is based solely on pressure.3 Consequently, the MAP must be preserved to maintain perfusion.
A variety of vasoactive medications are available to manage altered circulatory states. Although many medications share similar characteristics, each has a unique pharmacodynamic profile and is more suitable for a particular hemodynamic alteration. Therefore, it is essential to understand the pathophysiology of different types of shock and the actions of each medication.
Also known as sympathomimetic drugs, catecholamines stimulate adrenergic receptors, mimicking the sympathetic nervous system. Because catecholamines reach therapeutic serum levels in approximately 10 minutes, a clinical response is seen quickly, allowing for rapid titration.4 The hemodynamic effect of catecholamine drugs occurs secondary to interactions with adrenergic receptors in the heart and vascular system (see Adrenergic receptors). Alpha-1 receptors are located on blood vessels and, when stimulated, raise BP by increasing the availability of intracellular calcium, causing vasoconstriction. Beta-1 receptors are located on cardiac tissue and, when stimulated, increase cardiac contractility by releasing cyclic adenosine monophosphate (cAMP) and increasing the availability of calcium for actin and myosin binding within myocytes. Additionally, beta-1 receptor activation increases heart rate by increasing automaticity of the sinoatrial node. Vasodilation of blood vessels in skeletal muscles through the uptake of intracellular calcium occurs when beta-2 receptors are activated. Beta-2 stimulation also results in bronchodilation.
Dopaminergic receptors are located on the renal and mesenteric arteries and increase blood flow to the kidneys and gastrointestinal tract. Catecholamine medications stimulate receptors at different strengths, making the pharmacodynamics for each medication distinct (see Vasoactive agents). Consequently, each medication is better suited for a different cardiovascular abnormality. Although usual dose ranges are available, medications must be titrated to a clinical effect because patient response is highly individual (see Catecholamine medications).
Dopamine stimulates alpha-1, beta-1, and dopaminergic receptors. However, the effects of dopamine are dose dependent. At low doses, dopamine increases urine output by stimulating dopaminergic receptors and promoting natriuresis.5 Although once referred to as renal-dose dopamine, clinical studies have demonstrated that low-dose dopamine does not reduce the incidence of acute kidney injury or mortality.6,7 Kidney function may deteriorate if low-dose dopamine is administered to hypovolemic patients. At moderate doses, dopamine acts as a positive inotrope and chronotrope by stimulating beta-1 receptors. Once infused at doses higher than 10 mcg/kg/minute, dopamine primarily stimulates alpha-1 receptors, resulting in vasoconstriction. Because dopamine can induce tachycardia, ensure preload is adequate before initiating dopamine.8 Dopamine also increases myocardial oxygen consumption, sometimes exacerbating myocardial ischemia and ventricular dysrhythmias.9 At higher doses, dopamine can reduce cardiac output by increasing afterload. Higher doses of dopamine can cause poor peripheral perfusion, as well as renal and splanchnic ischemia due to vasoconstriction. Therefore, assess tissue perfusion and consider changing to another agent if signs of tissue ischemia are observed.
A catecholamine with strong affinity for beta-1 and beta-2 receptors, dobutamine results in positive inotropic and chronotropic activity. The resultant increase in heart rate and cardiac contractility raises cardiac output. Although dobutamine has mild alpha-1 properties, beta-2 activity is stronger, resulting in a net effect favoring vasodilation. The combined positive inotropic and vasodilatory effects make dobutamine a suitable choice for treatment of cardiogenic shock.10 However, increased myocardial oxygen consumption caused by dobutamine can result in ventricular dysrhythmias and myocardial ischemia. Because dobutamine is titrated to improve cardiac output, dose changes are typically made in collaboration with the prescriber.10
A potent positive inotropic and chronotropic agent, epinephrine has a strong affinity for beta-1 receptors. Additionally, epinephrine increases blood flow to skeletal muscle beds and causes bronchodilation due to strong beta-2 properties. At higher doses, intense vasoconstriction occurs with administration of epinephrine due to stimulation of alpha-1 receptors. Epinephrine is indicated for cardiogenic and distributive shock, anaphylaxis, and acute, severe asthma unresponsive to other medications. Adverse reactions include tachycardia, dysrhythmias, myocardial ischemia, and poor peripheral perfusion. Epinephrine is a stress hormone that stimulates gluconeogenesis and insulin resistance, resulting in hyperglycemia. Because of potent adverse reactions, epinephrine is reserved for use as a second-line agent when other medications have not produced desired outcomes.
Isoproterenol is a beta-agonist medication with positive chronotropic and dromotropic activity. Vasoconstriction does not occur because isoproterenol lacks alpha-agonist properties. Therefore, isoproterenol causes a marked increase in heart rate and is used as a temporizing measure for symptomatic bradycardia.4 Although isoproterenol has some positive inotropic activity, the increase in cardiac output is attenuated by a reduction in afterload. A marked increase in heart rate makes isoproterenol an unsuitable choice for cardiogenic shock. Adverse reactions include tachycardia, myocardial ischemia, and ventricular dysrhythmias.
A catecholamine agent with potent alpha-1 and mild beta-1 properties, norepinephrine has no beta-2 activity so the vasoconstrictive effects are unopposed. Consequently, norepinephrine is a potent vasopressor and weak positive inotrope. Norepinephrine is indicated for hypotension due to distributive shock states including septic and neurogenic shock.10 Adverse reactions include tachycardia, hypertension, ventricular dysrhythmias, and myocardial ischemia. Because of strong vasoconstrictive effects, high doses of norepinephrine can impede tissue perfusion, particularly of the skin, viscera, and kidneys.
A pure alpha-1 agonist, phenylephrine increases BP by causing vasoconstriction. Due to the lack of beta-agonist activity, phenylephrine has no direct effect on the myocardium. Therefore, phenylephrine is used to treat vasodilatory shock, particularly in patients at risk for developing tachydysrhythmias.10 Indications for phenylephrine include hypotension resulting from anesthesia, neurogenic shock, and vasoplegia after cardiopulmonary bypass. Increased left ventricular afterload from vasoconstriction coupled with a lack of beta-1 activity may result in a decreased cardiac output. Reflex bradycardia can occur from stimulation of baroreceptors from a higher BP.11
Vasodilators decrease arteriolar resistance and thus will reduce an elevated BP. Vasodilators also act by modulating excessive constriction of veins and arterioles.
Generating nitric oxide within vascular smooth muscle, nitroglycerin use results in vasodilation from activation of cyclic guanosine monophosphate, which facilitates calcium uptake by the sarcoplasmic reticulum. Used most commonly for acute coronary syndrome, nitroglycerin dilates coronary arteries and improves collateral blood flow to ischemic areas of the heart. At lower doses, nitroglycerin dilates veins, reducing venous return to the heart, myocardial wall tension, and oxygen consumption. At doses over 150 mcg/minute, nitroglycerin dilates arteries and reduces BP and cardiac afterload.4 Manufacturers caution that the nitroglycerin dosage is affected by the type of administration set used. The drug is absorbed in the tubing when a polyvinyl chloride administration set is used and the drug is not absorbed when a non-polyvinyl chloride administration set is used. Follow the drug manufacturer's infusion dosage recommendations based on the type of administration set used. Adverse reactions include hypotension, particularly if the patient is volume depleted. Because the right ventricle is reliant upon an adequate preload to maintain cardiac output, it is important to avoid administering nitroglycerin to individuals with a right ventricular infarction. Patients should not receive nitroglycerin within 48 hours after taking a phosphodiesterase type 5 inhibitor for erectile dysfunction because of the risk of developing severe hypotension.12 To avoid compromising coronary arterial blood flow, titrate nitroglycerin infusions carefully to prevent systolic BP from falling below 90 mm Hg.
Another nitric oxide generator, nitroprusside is a potent and rapid-acting arterial vasodilator. Consequently, nitroprusside must be titrated carefully to avoid precipitous swings in BP. Nitroprusside is indicated for hypertension and afterload reduction for heart failure when the patient is hypertensive or has mitral regurgitation.13 Consequently, it is helpful to specify the hemodynamic parameters to be used to titrate nitroprusside, given the clinical context. Nitroprusside may cause hypoxemia when pulmonary arterioles serving nonventilated areas of the lungs dilate. An I.V. bag containing nitroprusside must be protected from light because the medication is photosensitive. Cyanide is a metabolite of nitroprusside and typically is broken down and eliminated. However, at high doses or with prolonged use, cyanide toxicity may occur because the supply of rhodanese, the enzyme responsible for cyanide metabolism, is limited. Cyanide metabolites interfere with aerobic metabolism, resulting in metabolic acidosis. Although the maximum dose of nitroprusside is 10 mcg/kg/minute, it should not be administered for more than 10 minutes.14 Vigilant monitoring is warranted for doses greater than 2 mcg/kg/minute.14 Nitroprusside should not be infused for more than 9 days because thiocyanate, a neurotoxic metabolite of cyanide, can accumulate, causing confusion, hallucinations, seizures, and coma.
A dihydropyridine calcium channel blocker, nicardipine causes vasodilation by blocking the influx of calcium within arterial smooth muscle. Notably, nicardipine has substantial coronary and cerebral vasodilatory effects and does not reduce cardiac preload.15 Nicardipine is used for hypertension, particularly for patients experiencing acute hypertension after a stroke. Due to a fixed impedance, nicardipine is contraindicated for patients with advanced aortic stenosis. Adverse reactions include hypotension, tachydysrhythmias, headache, and dizziness. Nicardipine must be protected from light until it is used.
A dihydropyridine channel blocker, clevidipine, like nicardipine, reduces arterial BP by blocking calcium uptake in the smooth muscles of arteries. Whereas the initial half-life of nicardipine is 15 minutes, the effects of clevidipine are seen within 1 minute, allowing for rapid titration.16 Because clevidipine is supplied as a lipid emulsion, the medication must not be given to individuals with allergies to soybean products or eggs. Use strict sterile technique when managing the medication and change the container every 12 hours during the infusion.10 The quantity of lipids from other sources must be monitored and the total volume of clevidipine must be limited to 1,000 mL in a 24-hour period to avoid an excessive lipid load.16 Hypotension and reflex tachycardia can result when administering clevidipine, but recovery should occur within 5 to 15 minutes after discontinuing the medication.4,16
Vasopressin or antidiuretic hormone is a potent endogenous hormone that maintains water balance. At therapeutic doses, vasopressin causes vasoconstriction.
Phosphodiesterase-3 inhibitors exerts a positive inotropic effect by inhibiting the phosphodiesterase type 3 isoenzyme in cardiac myocytes. Milrinone is a noncatecholamine inotropic drug. Phosphodiesterase-3 inhibitors also have vasodilatory actions and relax arterial and venous smooth muscle.
Vasopressin stimulates V1 receptors on the arterial smooth muscle and V2 receptors located on renal tubules. When V1 receptors are stimulated, the production of nitric oxide by the vascular endothelium is blocked, resulting in vasoconstriction and elevation of BP. Stimulation of V2 receptors raises circulating blood volume by inhibiting diuresis. Vasopressin is indicated for refractory vasodilatory shock including septic and vasoplegic shock.10 Unlike catecholamine medications, vasopressin retains potency in hypoxic and acidotic states. Adverse reactions include dysrhythmias, myocardial ischemia, and decreased cardiac output due to an increased cardiac afterload.
A positive inotropic agent, milrinone blocks phosphodiesterase-3, an enzyme responsible for cAMP breakdown, and increases cardiac contractility by increasing the availability of calcium within myocytes. Milrinone improves preload by facilitating ventricular relaxation during diastole and decreases afterload by causing vasodilation. Similar to dobutamine, milrinone is referred to as an inodilator because of the combined positive inotropic and vasodilatory effects. However, the vasodilatory effects of milrinone are greater than dobutamine.17 Because the positive inotropic effects are achieved without activating the sympathetic nervous system, milrinone is useful for managing individuals with acute decompensated heart failure with beta receptor desensitization.18 Adverse reactions include hypotension, nausea, vomiting, and dysrhythmias. Due to a long half-life, loading doses are sometimes avoided for patients with a marginal BP. Additionally, titration of milrinone is often based on a specific order to change the dose.
Clinical implications for vasoactive infusions
No large, well-controlled randomized clinical trials exist to guide the selection of specific medications when treating shock. Therefore, the selection is generally based on small, often poorly controlled clinical trials, data from animal studies, and expert opinion.10 Additionally, prescriber experience figures heavily in drug selection as does matching medication pharmacodynamics with physiologic abnormalities.
Moderate doses of dopamine may be considered for individuals experiencing hypotension with an unknown etiology until further investigative studies can be completed. Because dopamine has both strong beta- and alpha-agonist activity, moderate doses of dopamine will increase cardiac output and raise BP by causing vasoconstriction. If the patient is severely hypotensive, with a systolic BP less than 70 mm Hg, a more potent alpha-agonist, such as norepinephrine, may be considered.
As an inodilator, dobutamine is the agent of choice for cardiogenic shock complicating an acute myocardial infarction. Dopamine, because of stronger alpha-agonist properties, may be a better choice for patients with a systolic BP between 70 and 100 mm Hg exhibiting signs of shock. If the patient requires high doses of either dopamine or dobutamine, a combination of both medications at moderate doses may be more effective.5 Medications with stronger alpha-agonist properties, such as norepinephrine and epinephrine, may be used for patients with cardiogenic shock unresponsive to dopamine or dobutamine.
Patients with acutely decompensated heart failure and signs of hypoperfusion and fluid overload demonstrate beneficial short-term outcomes from dobutamine or milrinone. The positive inotropic effect of both agents is enhanced by cardiac afterload reduction caused by vasodilation. However, positive inotropic agents may precipitate tachydysrhythmias and myocardial ischemia for patients with heart failure.19 Nitroglycerin or low doses of nitroprusside may be used for patients with hypertension and fluid overload in the setting of acute decompensated heart failure.13
Septic shock should initially be managed with fluid resuscitation. Subsequently, medications with strong alpha-agonist properties, such as norepinephrine, are used to restore perfusion.20 Vasopressin may be added as a second-line agent when hypotension persists with high doses of norepinephrine. Vasopressin is considered replacement therapy for a relative deficiency of antidiuretic hormone.8,21 Although epinephrine has a higher affinity for beta receptors than norepinephrine, epinephrine results in more tachydysrhythmias and myocardial ischemia and is used when an additional agent is needed to maintain perfusion.20 Due to beta-2 receptor activity, epinephrine stimulates lactic acid production in skeletal muscles, confounding efforts to use serum lactate levels as a marker for septic shock resuscitation.20 When compared with norepinephrine, dopamine is associated with a higher risk for dysrhythmias and mortality.9 Consequently, dopamine is reserved for patients with a low risk of developing tachydysrhythmias and may need to be started at a higher dose to achieve a vasopressor effect. Phenylephrine is not recommended for the treatment of septic shock except when norepinephrine is associated with serious dysrhythmias or when the cardiac output is known to be high with a persistently low BP.
Nurses administering vasoactive infusions must adhere to safe medication administration practices to protect patients from potentially deleterious effects. Use an I.V. pump and, if available, drug library and dose limit features, to deliver accurate doses of medications. Label all I.V. tubing to avoid delivering a bolus of a vasoactive medication or infusing incompatible medications in the same I.V. catheter. Catecholamines are not compatible with bicarbonate and must be infused in a separate I.V. site. Because the half-life of catecholamines is short, anticipate when the next I.V. container will be needed to avoid hemodynamic deterioration.
Vasporessors are considered a vesicant; therefore, soft-tissue extravasation can result in tissue ischemia and necrosis. Consequently, it is advisable to infuse vasoconstricting medications through a central venous catheter. If a central venous catheter is not available, vasopressors may be infused in a well-positioned peripheral I.V. catheter to reestablish perfusion in an emergent situation.22,23 However, it is important to monitor the peripheral I.V. site while the medication is infusing. Although rare, central venous catheters can also become displaced, resulting in extravasation of vasopressor medications.23 Consequently, nurses must also monitor central venous catheter sites when vasopressors are infusing and promptly administer treatment for an extravasation.22,23 If an extravasation occurs, the infusion must be moved to another I.V. site and a vasodilating agent, such as phentolamine, injected into the extravasated area.22,23 Phentolamine causes vasodilation by blocking alpha-1 receptors on blood vessels.
When initiating vasoactive medications, start at the lower end of the dose range and titrate cautiously according to the half-life of the drug. Although some patients will respond quickly, others may be more resistant to medications. Titrate one medication at a time and adjust the drug that is affecting the altered parameter. Positive inotropes are titrated to maintain cardiac output measurements; however, vasopressor doses are adjusted to achieve a target MAP. Use the lowest possible dose of any medication to avoid adverse reactions. Hypovolemia must be corrected prior to initiating catecholamine agents to avoid tachycardia.8 During emergent situations when vasopressors are initiated, previously prescribed antihypertensive agents may not be discontinued. Therefore, review the medication administration record and collaborate with the prescriber to ensure medications no longer clinically indicated are removed.
Monitor vital signs and hemodynamic parameters frequently. Because patients receiving catecholamine agents are at risk for developing atrial and ventricular dysrhythmias, assess the cardiac rhythm. Monitor the patient's MAP, even if the prescription targets a systolic BP, to ensure maintenance of circulatory autoregulation.24 Although a MAP of 65 mm Hg is recommended for most patients, target hemodynamic parameters need to be individualized for some patients. Whereas a lower MAP is advisable for individuals with uncontrolled bleeding from trauma without severe head injury,25 patients suffering neurogenic shock benefit from a MAP of 85 to 90 mm Hg.26 Perform frequent physical assessments to assess peripheral perfusion. Most hemodynamic variables reflect the macrocirculation, or blood flow through arteries and veins, and do not indicate capillary blood flow and oxygen delivery to tissues.3 Additionally, vasopressors at high doses can compromise microcirculatory perfusion, even in the setting of normal BP measurements. Signs of poor organ perfusion include altered sensorium, kidney impairment, and hepatic dysfunction. Stress ulceration and ileus can be seen with reduced splanchnic blood flow. Cool skin, delayed capillary refill, and mottling of the skin indicate compromised peripheral perfusion. An elevated serum lactate level is a marker for global hypoperfusion as is a decline in mixed venous oxygenation saturation measurements.20
When it is time to wean vasoactive medications, review the prescription and collaborate with the prescriber to formulate a weaning plan. A commonly used strategy is to wean the medication with the most adverse reactions first, typically epinephrine or vasopressin.21,27 Adjust alarm limits to promote timely weaning. For example, setting the upper MAP alarm limit to 70 mm Hg triggers timely weaning as opposed to an alarm set at 90 mm Hg.21 Although the half-life of the medication can be used as a guide to the frequency of titration, some patients require slower titration.10 Older adults and individuals with preexisting hypertension may need a higher BP to maintain cerebral perfusion.21,25 Therefore, titrate slowly and notify the prescriber if the weaning plan needs to be adjusted based on the patient's response. Once a medication is stopped, clear the I.V. catheter so the next clinician will not inadvertently administer a bolus dose of the drug.
Hemodynamically unstable patients often require vasoactive medications to restore the delivery of oxygenated blood to tissues. Identification of the underlying cardiovascular pathophysiology along with a clear understanding of the pharmacodynamics of vasoactive medications facilitates the selection of beneficial agents. Vigilant monitoring of vital signs and hemodynamic parameters along with serial physical assessments assist nurses in managing medications to achieve clinical goals. Adhering to safe medication practices is necessary for preventing avoidable medication errors.
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