Signs of Digitalis Toxicity
Initial signs of digitalis toxicity include bradycardia, as well as nausea and diarrhea. The latter symptoms of abdominal distress, visual changes, and general malaise may be misinterpreted by the patient as flu-like symptoms and ignored by the patient. The combination of the losses of potassium from both diarrhea and vomiting only serve to worsen the situation and lead to more nausea, vomiting, and diarrhea.
As the intoxication continues, the patient may experience confusion, which may be misinterpreted as dementia or depression in the elderly. The patient may also complain of seeing yellow-green halos around lights. At this point, significant cardiac manifestations typically occur, including tachycardia-induced syncope.
Overt digitalis overdose, either accidental or otherwise, may be treated emergently with digitalis-specific antibody fragments (digoxin immune fab). Otherwise, treatments focus on the cause of the toxicity: reversing hypoperfusion leading to kidney failure, withdrawal of the numerous drugs which interact negatively with digitalis, or correcting hypokalemia. If the patient is hypokalemic, then potassium replacement is provided. Phenytoin has been found useful in treating digitalis-induced dysrhythmia because of its anticholinergic effects.123 Administration of magnesium as a competitive ion may be helpful in reducing ventricular ectopy, including ventricular tachycardia/flutter.
Acute Heart Failure
Acute heart failure is a medical emergency that, if untreated, can quickly culminate in death. Acute heart failure can present in several ways. The first syndrome is forward failure, a loss of cardiac output that results in hypotension and rapidly progresses to end-organ failure. The other syndrome is backward failure, a backup of pressures into the low-pressure lung fields which produces acute pulmonary edema. Acute pulmonary edema literally suffocates the lungs, leading to hypoxia and respiratory acidosis.
Backward Failure
The goal of treating backward failure, manifested by acute pulmonary edema, is to quickly reduce the preload. Treatment with diuretics can provide rapid symptomatic relief but can also lead to rebound edema later in the course of the patient’s care. This rebound edema is the result of activation of the renin-angiotensin-aldosterone mechanism by the diuresis.
In many cases, these patients are already on diuretics and are not "fluid-overloaded." More correctly, these patients are fluid "maldistributed" and only need temporary relief from excessive preload. Patients at particular risk are those with restrictive cardiomyopathy, early phase acute myocardial infarction, and mild chronic heart failure.
Repeated doses of nitrates may be more effective in these cases. Nitrates will cause immediate venodilation, increasing the volume within the venous pool, and effectively create an internal phlebotomy. That is to say, a portion of blood volume will be temporarily warehoused in the venous circulation (which has a large capacitance) and taken out of the core circulation until the heart can recover.
Forward Failure
Acute forward failure, or cardiogenic shock, is a failure of the heart as a pump. Regardless of the underlying cause of the pump’s failure, it is imperative to increase the heart’s cardiac output (blood pressure).
The body’s own compensatory mechanisms depend on the hormone epinephrine (a catecholamine) to increase the heart rate (positive chronotropy), speed of conduction (dromotropy), and most importantly, the strength of contraction (inotropy). Supporting the body’s own compensatory mechanisms, Paramedics can infuse additional sympathomimetics classified as catecholamines: three naturally occurring catecholamines—dopamine, epinephrine, and norepinephrine—plus two synthetic catecholamines— dobutamine and isoproterenol.
These vasopressors, drugs which affect blood vessels directly, increase blood flow to vital organs. However, some are associated with significant side effects and should be used carefully in the patient with acute heart failure.
STREET SMART
Before starting any catecholamine infusion, it is important to rule out hypovolemia as a cause of hypotension. Failure to do so may compromise already ischemic tissue. "Squeezing dry pipes" with vasopressors will not improve blood pressure significantly.
Catecholamines
All catecholamines interact directly with sympathetic receptors throughout the body. Alpha-receptor stimulation will increase vasoconstriction of peripheral capillary beds, increasing blood in the core circulation while also increasing the peripheral vascular resistance the heart must overcome.
Beta-receptors in the heart will both increase the speed of the heart (positive chronotropy) as well as the strength of contraction (positive inotropy) and dilate the bronchial smooth muscle, thereby improving oxygen delivery. However, this comes at a cost of increased work of the heart.
Precautions
Catecholamines are potent medications, so potent that the dose is measured in micrograms (mcg) instead of milligrams (mg). Typically infused intravenously, catecholamines are carefully titrated to a dose of micrograms per kilogram of patient weight per minute of infusion (mcg/kg/min) and often infused via an intravenous pump which can ensure precise delivery.
The patient receiving a catecholamine infusion, in order to sustain an adequate perfusing blood pressure, may be drug-dependent. A sudden interruption in the infusion, for any reason, can result in a precipitous fall in blood pressure. For this reason, most providers ensure the presence of a second intravenous access site for use if the first intravenous access is lost.
Inadvertent infiltration of a catecholamine into subcutaneous tissue, secondary to a dislodged or misplaced catheter, can result in localized ischemia and necrosis of the tissue. Phentolamine, an alpha-adrenergic blocking agent, injected subcutaneously around the catecholamine infiltration may help prevent tissue necrosis, but special care should be taken to assure IV patency prior to and during administration of catecholamines.
STREET SMART
Commercially prepared catecholamines contain a preservative (sulfite) which helps maintain potency. Some patients are sensitive to sulfites and may have an allergic reaction to the drug, compounding the severity of the situation instead of improving it.
Epinephrine
Epinephrine, the original catecholamine, is available for injection, inhalation, and infusion. Epinephrine is a powerful direct-acting synthetic catecholamine. In small doses, epinephrine is used to treat severe asthma exacerbation and serves as an adjunct to local anesthetics to control bleeding during wound repair (sutures). In larger doses, epinephrine can reverse cardiovascular collapse secondary to anaphy-laxis or coarsen ventricular fibrillation for more effective defibrillation.
Epinephrine’s rapid onset of action (three to five minutes by subcutaneous injection) makes it useful in an emergency.
Occasionally, after a subcutaneous injection or intravenous bolus, it is necessary to continuously infuse epinephrine to maintain blood pressure, particularly in cases of distributive shock, such as septic shock and anaphylactic shock.
Dopamine
Dopamine, a naturally occurring catecholamine, is the precursor to epinephrine and has effects similar to epinephrine. At lower doses, one-half to two micrograms per kilogram per minute infusion (0.5 to 2 mcg/kg/min), dopamine dilates renal arteries, increasing blood flow and subsequent production of urine.
At higher doses, up to 10 micrograms per kilogram per minute infusion (10 mcg/kg/min), dopamine stimulates the beta-receptors of the heart, increasing heart rate and force of contraction. At the highest doses, 10 to 20 micrograms per kilogram per minute infusion, alpha-adrenergic receptors are increasingly stimulated.
Alpha-adrenergic receptor stimulation leads to peripheral vasoconstriction, an increase in peripheral vascular resistance (afterload), and more work for the heart, while elevating the blood pressure via increased venous return (preload). The trade-off, a perfusing blood pressure for increased work of the heart, may induce an acute myocardial infarction and renal ischemia.124 For those reasons, high dose dopamine is reserved for severe hemodynamic imbalance.
STREET SMART
While dopamine at 4 to 20 mcg/kg/min can increase blood pressure, dopamine 3 mcg/kg/minute or less can actually lower the blood pressure. These lower, or renal, doses of dopamine also cause a vasodilation of the mesenteric vessels resulting in venous pooling. Therefore, dopamine infusions should always be started at more than 5 mcg/kg/min in the field.
Dobutamine
Dobutamine is the synthetic analog of dopamine but is more beta-selective than dopamine. This quality makes it less desirable in cases of distributive shock (e.g., septic shock), but very desirable for cardiogenic shock.
Dobutamine is a potent inotropic agent and a weak chro-notropic agent. Therefore, dobutamine does not significantly increase the oxygen demands of the heart but can improve cardiac output. This makes it attractive for use in cardiogenic shock secondary to pump failure.
Dobutamine is very effective for patients in cardiogenic shock who have an elevated left ventricular filling pressure, often manifested by elevated jugular venous distention (JVD), but who are not remarkably hypotensive (systolic B/P greater than 90 mmHg). These patients, on the border of severe car-diogenic shock, often benefit from a combination of dobu-tamine (to maintain blood pressure) and dopamine at renal doses (for diuresis).
As an added bonus, dopamine and dobutamine are compatible and may be infused together via the same intravenous access. This approach is often preferable, especially in patients with potential for hypokalemia, because of a decreased risk of tachydysrhythmia.
Norepinephrine
Norepinephrine, in contrast to dobutamine, has a high affinity for alpha-adrenergic receptors. Norepinephrine is a powerful peripheral vasoconstrictor which is effective in treating cardiovascular collapse secondary to distributive shock (e.g., advanced septic shock).
The use of norepinephrine in patients in cardiogenic shock is questionable, as the increased peripheral vascular resistance (afterload) translates to increased work for the heart and offsets any advantage obtained by increasing the blood pressure. In fact, imprudent administration of norepi-nephrine can lead to acute myocardial infarction in patients with pre-existing coronary artery disease.
STREET SMART
Monoamine oxidase oxidizes catecholamines, like dopamine and norepinephrine, into inactive metabolites. Monoamine oxidase inhibitors (MAO inhibitors), a class of antidepressant medications, prevents the breakdown of these catecholamines. Routine doses of dopamine administered to a patient who has prescribed MAO inhibitors can result in serum dopamine levels that are increased ten-fold and lead to acute hypertensive crisis.
Conclusion
Two of the most common chief complaints of patients are chest pain and shortness of breath. By understanding the underlying cardiopulmonary physiology and pathophysiology, Paramedics can establish effective therapeutic interventions earlier in the course of the patient’s illness. Early intervention can translate directly into decreased morbidity and mortality.
key points:
• The central nervous system consists of the brain and spinal cord.
• The peripheral nervous system consists of the cranial, nervous, and spinal nerves.
• The autonomic nervous system is that portion of the peripheral system that controls involuntary functions.
• The autonomic nervous system consists of two branches: the sympathetic division, which serves to accelerate organs, and the parasympathetic division, which controls vegetative functions.
• The vagus nerve is the primary parasympathetic nerve.
• Messengers which relay signals from nerve to organ are called neurotransmitters.
• Neurotransmitters attach to a receptor.
• Agonist drugs increase the neurotransmitters’ ability to stimulate the receptor.
• Antagonist drugs block stimulation of the receptor.
• Parasympathetic receptors are classified as cholinergic (responding to acetylcholine), i.e., muscarinic, or nicotinic receptors.
• Muscarinic receptors are found in organs, whereas nicotinic receptors are located in the adrenal medulla, CNS, and skeletal muscles.
• Cholinergic agents are agonists which stimulate a parasympathetic response.
• Anticholinergic agents would slow or stop parasympathetic responses.
• Blocking nicotinic receptors causes paralysis. Depolarizing agents cause fasciculations before paralysis while non-depolarizing agents lead directly to paralysis.
• Adrenergic agents directly or indirectly stimulate a sympathetic response.
• Adrenergic blockers would prevent a sympathetic response.
• Alpha-adrenergic agents or blockers primarily affect the vessels.
• Beta-adrenergic agents or blockers affect the heart or lungs.
• Drugs used to treat pulmonary diseases usually target one of the three S’s: spasms, swelling, or secretions.
• Beta-adrenergic agonists, xanthine derivatives, and cholinergic antagonists prevent or reduce spasms.
• Corticosteroids, leukotriene antagonists, and mast cell inhibitors reduce swelling.
• Mucolytics liquefy mucus.
• Drugs used to treat coronary artery disease usually target vessels, platelets, coagulation cascade, or lipids.
• Antilipidemic drugs either prevent absorption of cholesterol, sequester in the bile for elimination, or prevent the liver from making cholesterol.
• Anticoagulant drugs interfere in the clotting cascade, preventing the formation of a fibrin clot.
• Antiplatelet drugs alter platelet membranes, preventing aggregation, adherence, and vasoconstriction.
• Fibrinolytics disassemble the fibrin clot.
• Nitrates dilate the venous system (reducing blood return to the heart), dilate the arterial system (reducing workload of the heart), and may dilate coronary vessels (increasing blood flow to the myocardium).
• Dysrhythmias are an alteration in the heart’s rate or rhythm. Not all dysrhythmias require treatment.
• The goal of dysrhythmic treatment is to alleviate symptoms. Antidysrhythmic drugs can cause other dysrhythmias and are proarrythmic.
• Drugs used to treat dysrhythmias affect the transition of the ionic channels from resting to open/active or inactive.
• The cations of the heart’s action potential are sodium, potassium, and calcium. The Vaughn-Williams classification system divides drugs according to the ion affected.
• Class I drugs affect sodium influx. Class I drugs are subcategorized as IA, IB, or IC, depending upon where in the sodium influx stage they act.
• Class II drugs are beta-blockers. They affect the chemical which opens the calcium channels. They also reduce myocardial infarct size by decreasing heart rate and thus allow a longer diastole and increased coronary blood flow. By also dilating peripheral vessels, they decrease myocardial oxygen demand.
• Class III drugs block potassium movement from the cell, lengthening the period of time in which the cell cannot respond to another stimulus.
• Class IV drugs block the movement of calcium into heart cells, reducing the rate of depolarization or the mechanical initiation of contraction.
• Class V drugs have miscellaneous effects and include the cardiac glycoside digitalis and the antiarrythmic adenosine.
• An indirectly acting drug which allows the heart rate to increase is the cholinergic blocker called atropine.
• When underperfused, the kidneys release a substance called renin. Through several steps, renin is converted to angiotensin, which affects vessel dilation and the movement of water and sodium from the kidney.
• The conversion of renin to angiotensin requires an enzyme. Inhibiting the enzyme (with an angiotensin-converting enzyme inhibitor or ACE inhibitor) prevents an increase in blood pressure through constriction and increased volume.
• Diuretics affect the release of water and other ions from the kidney. Depending upon the exact location of action, more or less water is released and potassium may be excreted or retained.
• Vasodilators usually cause dilation of the venous side and reduction of blood return to the heart. Those that cause arterial dilation decrease diastolic pressure, peripheral vascular resistance, and afterload.
• Digitalis, a cardiac glycoside, slows electrical conduction and increases the strength of contraction. It is both an antidysrhythmic and a treatment for heart failure.
• Digitalis has a narrow therapeutic range and can rapidly lead to toxicity.
• Catecholamines act with sympathetic receptors. They are indicated for vascular support.
