Epinephrine cardiac effects

While epinephrine is usually well tolerated in young and healthy individuals, there may be problems in elderly patients with cardiac arrhythmia or previous myocardial infarction episodes [31-33]. Pharmacological effects of epinephrine include rapid rise in blood pressure, pallor, anxiety, tachycardia, headache and tremor as well as vertigo. Most commonly these effects occur after intravenous injection or after overdosing epinephrine. Cardiac arrhythmia or pulmonary edema may develop in serious cases [33, 34]. 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

The dose of administered epinephrine results in blood levels that may be approximately ten times endogenous levels and is close to the threshold for inducing cardiac effects in the absence of the test chemical. 

The cardiac sensitization test is based on the observation that some halocarbons make the mammalian heart abnormally sensitive to epinephrine, resulting in ectopic beats and/or ventricular fibrillation, which may result in death. Effects are monitored with electrocardiograms (EKG). The dose of administered epinephrine results in blood levels that may be approximately ten times endogenous levels and is close to the threshold for inducing cardiac effects in the absence of the test chemical. 

The cardiac effects of epinephrine are due to its action on p-adrenoceptors in the heart. The rate and contractile force of the heart are increased consequently, cardiac output is markedly increased. Because total peripheral resistance is decreased, the increase in cardiac output is largely responsible for the increase in systolic pressure. Since epinephrine causes little change in the... 

The pressor response to ephedrine is due in part to peripheral constriction and in part to myocardial stimulation. Vasoconstriction can be demonstrated by intra-arterial injection, but compared to epinephrine, ephedrine is only about one thousandth as active. This would imply that the cardiac effect is predominant in increasing the arterial pressure. This, however, is difficult to demonstrate. In perfused hearts, ephedrine produces only minor stimulation and cardiac depression appears if the drug is repeated. 

Vapors of dimethyl ether may produce eye irritation with discomfort, tearing, or blurring of vision. Inhalation exposure may be associated with nonspecific discomfort such as nausea, headache, or weakness. Signs of CNS depression may include dizziness, headache, confusion, incoordination, and loss of consciousness. Abusers of this product could show increased susceptibility to the cardiac arrhythmia effects of epinephrine (cardiac sensitization). 

Halothane is known to cause arrhythmias and it has been suggested that it may increase susceptibility to the adverse cardiac effect of beta-agonist bronchodilators, which can cause arrhythmias. Note that beta agonists such as terbutaline are sympathomimetics (see Table 24.1 , (p.879)), like adrenaline (epinephrine), which has also been shown to cause arrhythmias in the presence of halothane (see Anaesthetics, general + Inotropes and Vasopressors , p.99). 

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

Epinephrine is a nonspecific a- and P-adrenergic agonist. Epinephrine can increase cardiac index and produce significant peripheral vasoconstriction. However, it can also increase lactate levels and impair blood flow to the splanchnic system. Because of these undesirable effects, epinephrine should be reserved for patients who fail to respond to traditional therapies.24,27-28... 

Despite these potential advantages, clinical experience with vasopressin is limited and comparative trials with epinephrine have produced mixed results. Overall, these studies suggest that vasopressin is effective as part of ACLS after cardiac arrest, but its superiority to epinephrine remains questionable. 

The AEGL-2 was based on the threshold for cardiac sensitization using the dog model. Because this test is highly sensitive as the response to exogenous epinephrine is optimized, the 40,000 ppm concentration was adjusted by a single intraspecies UF of 3 to protect potentially susceptible individuals. An interspecies UF was not applied, because the dog is a reliable model for humans, and this is a highly sensitive test. Blood concentrations rapidly reach equilibrium, and the blood concentration determines the effect, so the 13,000 ppm value was used across all time periods. 

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