Phlebitis in Amiodarone Administration
Phlebitis in Amiodarone Administration
Amiodarone-induced thrombophlebitis was initially described in case reports. The graphic descriptions of marked tissue injury in these early reports gave reason for further evaluation of the incidence and clinical significance of thrombophlebitis. In a prospective study of 20 patients receiving amiodarone for recent-onset atrial fibrillation, Kreiss et al found that thrombophlebitis was the most common side effect, occurring in 5 of the 20 patients (25%). Thrombophlebitis was the most common adverse reaction associated with intravenous amiodarone, at a rate of 8% among 550 patients, in a metaanalysis of 18 random-controlled trials of patients with atrial fibrillation who received intravenous amiodarone. In a retrospective review by Mowry and Hartman of 339 hospitalized patients who had received intravenous amiodarone, the incidence of thrombophlebitis was 10.6%.
Phlebitis (or thrombophlebitis) is an inflammation of the vein wall characterized by pain, tenderness, edema, erythema, and an increase in local temperature (Figure 1). In a descriptive study of 355 patients treated in an inpatient unit during a 3.5-month period, pain was the first symptom of phlebitis. Other signs and symptoms included redness, tenderness, swelling, and warmth at the intravenous site. Uslusoy and Mete also noted that phlebitis can cause sepsis, which requires additional diagnostic interventions and treatments, increases hospital length of stay, and increases stress and costs for patients.
(Enlarge Image)
Figure 1.
Phlebitis of the right hand.
Amiodarone-induced phlebitis has been attributed to the mechanical and chemical effects of the particulate matter introduced during injection. Amiodarone may break down into particles during storage because of the drug's physical instability, poor quality control, or poor compounding processes. Crystallization of amiodarone may occur at the time of administration if the solubility limits of the drug are approached during dilution and mixing in the bloodstream.
Ward et al and Ward and Yalkowsky examined amiodarone-induced phlebitis with thermal measurement to distinguish rates of infusion and the consequences. They found that rapid dilution of the formulation is an important variable in the determination of phlebitis. A slow injection into a constantly flowing bloodstream or a slow injection rate into a large blood volume both produce a rapid dilution. A very slow injection (especially if into a large vessel such as the femoral vein) will eliminate precipitation because the drug becomes soluble before nucleation can occur. Similarly, injection into small veins (such as those of the wrist) should be avoided because the low rate of blood flow would result in a high local venous concentration of drug and an increased likelihood of precipitation and purulence.
Using a rabbit ear model and a thermographic camera, Ward and Yalkowsky and Ward et al were able to detect temperature changes during infusion of amiodarone. Despite the use of a filter, precipitation within the vessel depended on the ratio of the rate of injection to the rate of blood flow. Precipitation was directly correlated with phlebitis.
Yalkowsky et al found a relatively high incidence of adverse reactions at the infusion site in patients receiving a continuous infusion and paradoxically found that a single dose seemed to be better tolerated than a lower dose given over several hours.
The research by Ward, Yalkowsky and their colleagues also showed that amiodarone may be a direct irritant to the vessel wall, because it can leach out plasticizers in polyvinyl chloride tubing. Leaching increases at higher concentrations and lower flow rates. Their findings clearly indicate the link between the time of amiodarone administration and the clinical findings of inflammation, redness, tenderness, pain, increased temperature, edema, swelling, and a palpable cord and vein. Most important, phlebitis can lead to thrombus formation and even death.
Thrombophlebitis is a common complication of intravenous therapy; it can cause marked pain, swelling, fever, and tissue loss and may increase hospital costs by increasing length of stay. The range of reported rates of occurrence and contributing factors related to thrombophlebitis is wide. Contributing factors include the material, length, and lumen size of the cannula; the skill of the person inserting the cannula; the character of the material infused; the frequency of changes of intravenous dressings; and host factors, such as age, sex, and underlying disease.
The wide variations in amiodarone-induced phlebitis most likely are due to the varied populations of patients studied, the small sample sizes of most of the studies, and different methods and practices of drug administration. Understanding the mechanisms and pathophysiology of the development of amiodarone-induced phlebitis and the changes in the drug solution and its delivery methods and technology (cannulas, intravenous containers) have not altered the occurrence of the complication to date. Understanding when phlebitis occurs and its relationship to dosage and concentration of amiodarone is needed to devise improved practice guidelines.
Thrombophlebitis and Amiodarone
Amiodarone-induced thrombophlebitis was initially described in case reports. The graphic descriptions of marked tissue injury in these early reports gave reason for further evaluation of the incidence and clinical significance of thrombophlebitis. In a prospective study of 20 patients receiving amiodarone for recent-onset atrial fibrillation, Kreiss et al found that thrombophlebitis was the most common side effect, occurring in 5 of the 20 patients (25%). Thrombophlebitis was the most common adverse reaction associated with intravenous amiodarone, at a rate of 8% among 550 patients, in a metaanalysis of 18 random-controlled trials of patients with atrial fibrillation who received intravenous amiodarone. In a retrospective review by Mowry and Hartman of 339 hospitalized patients who had received intravenous amiodarone, the incidence of thrombophlebitis was 10.6%.
Phlebitis (or thrombophlebitis) is an inflammation of the vein wall characterized by pain, tenderness, edema, erythema, and an increase in local temperature (Figure 1). In a descriptive study of 355 patients treated in an inpatient unit during a 3.5-month period, pain was the first symptom of phlebitis. Other signs and symptoms included redness, tenderness, swelling, and warmth at the intravenous site. Uslusoy and Mete also noted that phlebitis can cause sepsis, which requires additional diagnostic interventions and treatments, increases hospital length of stay, and increases stress and costs for patients.
(Enlarge Image)
Figure 1.
Phlebitis of the right hand.
Amiodarone-induced phlebitis has been attributed to the mechanical and chemical effects of the particulate matter introduced during injection. Amiodarone may break down into particles during storage because of the drug's physical instability, poor quality control, or poor compounding processes. Crystallization of amiodarone may occur at the time of administration if the solubility limits of the drug are approached during dilution and mixing in the bloodstream.
Ward et al and Ward and Yalkowsky examined amiodarone-induced phlebitis with thermal measurement to distinguish rates of infusion and the consequences. They found that rapid dilution of the formulation is an important variable in the determination of phlebitis. A slow injection into a constantly flowing bloodstream or a slow injection rate into a large blood volume both produce a rapid dilution. A very slow injection (especially if into a large vessel such as the femoral vein) will eliminate precipitation because the drug becomes soluble before nucleation can occur. Similarly, injection into small veins (such as those of the wrist) should be avoided because the low rate of blood flow would result in a high local venous concentration of drug and an increased likelihood of precipitation and purulence.
Using a rabbit ear model and a thermographic camera, Ward and Yalkowsky and Ward et al were able to detect temperature changes during infusion of amiodarone. Despite the use of a filter, precipitation within the vessel depended on the ratio of the rate of injection to the rate of blood flow. Precipitation was directly correlated with phlebitis.
Yalkowsky et al found a relatively high incidence of adverse reactions at the infusion site in patients receiving a continuous infusion and paradoxically found that a single dose seemed to be better tolerated than a lower dose given over several hours.
The research by Ward, Yalkowsky and their colleagues also showed that amiodarone may be a direct irritant to the vessel wall, because it can leach out plasticizers in polyvinyl chloride tubing. Leaching increases at higher concentrations and lower flow rates. Their findings clearly indicate the link between the time of amiodarone administration and the clinical findings of inflammation, redness, tenderness, pain, increased temperature, edema, swelling, and a palpable cord and vein. Most important, phlebitis can lead to thrombus formation and even death.
Thrombophlebitis is a common complication of intravenous therapy; it can cause marked pain, swelling, fever, and tissue loss and may increase hospital costs by increasing length of stay. The range of reported rates of occurrence and contributing factors related to thrombophlebitis is wide. Contributing factors include the material, length, and lumen size of the cannula; the skill of the person inserting the cannula; the character of the material infused; the frequency of changes of intravenous dressings; and host factors, such as age, sex, and underlying disease.
The wide variations in amiodarone-induced phlebitis most likely are due to the varied populations of patients studied, the small sample sizes of most of the studies, and different methods and practices of drug administration. Understanding the mechanisms and pathophysiology of the development of amiodarone-induced phlebitis and the changes in the drug solution and its delivery methods and technology (cannulas, intravenous containers) have not altered the occurrence of the complication to date. Understanding when phlebitis occurs and its relationship to dosage and concentration of amiodarone is needed to devise improved practice guidelines.
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