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Purple Glove Syndrome: A
Complication of Intravenous
Phenytoin
Debra R. Hanna
ABSTRACT: Intravenous phenytoin, available for use since 1956, has several well known adverse effects, such as hypotension, arrhythmias and toxicity. Purple glove syndrome is a less common complication that can have serious consequences. Fasciotomies, amputations and permanent disuse of the hand and forearm have been reported. The etiology of purple glove syndrome is still unknown, but possible etiologies and risk factors have been suggested. Three stages of purple glove syndrome have been identified: appearance, progression and resolution. During the second stage, progression, purple glove syndrome can be identified as either mild or severe. Mild cases may heal uneventfully when nursing measures such as elevation, application of dry, gentle heat and measures to prevent secondary injury are instituted. Severe cases may require emergency surgical intervention such as fasciotomy to relieve pressure and restore blood flow. Therapeutic nursing interventions aimed at maximizing healing and promoting comfort are essential.
Introduction
Purple glove syndrome (PGS) is a delayed, soft tissue injury of the hand and forearm which occurs after intravenous (IV) administration of phenytoin (Dilantin). Clinical signs and symptoms of pain, discoloration and edema comprise this syndrome which is frequently, but not exclusively associated with phenytoin extravasation. With early detection and intervention, mild or moderate cases of PGS may heal uneventfully, or may result in mild permanent damage. In severe cases, purple glove syndrome can lead to tissue necrosis, requiring surgical intervention such as fasciotomy or limb amputation.
Nursing concerns related to purple glove syndrome can be grouped into three categories: preventing PGS by modifying techniques of administration, maximizing healing whenever PGS occurs and using nursing measures to ease the pain associated with PGS. This article describes the 3 main stages of PGS, and delineates risk factors, preventive measures and nursing interventions to promote healing and decrease secondary damage.
Purple Glove Syndrome
Named for its characteristic appearance of a purpie, swollen hand and forearm, PGS occurs after IV administration of Rhenytoin through small, dorsal hand veins.It has three stages: appear-
Questions or comments about this article may be directed to Debra R. Hanna, RN, MSN, CNRN, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, Minnesota 55905. She is a neuroscience clinical nurse specialist.
Copyright O American Association of Neuroscience Nurses
0047-2603/92/2406/0340$1.25
ance, progression and resolution of symptoms. In the first stage of PGS, a pale blue or dark purple discoloration appears around the IV insertion site 2-12 hours after administration of the drug. In mild cases or in cases where there is no extravasation, the pale blue discolored area is slightly raised, but not indurated, and may be accompanied by petecchiae on the finger pads and palm of the affected hand. The discoloration without induration or infiltration distinguishes PGS from common IV infiltration. Also, PGS spreads to the hand and forearm during the first 24 hours, unlike common IV infiltration which does not spread after IV discontinuation. When IV phenytoin extravasates during administration, discoloration during the first stage of PGS will be dark purple, slightly depressed and clearly demarcated (Fig 1).
The second stage, progression, occurs during the next 12-16 hours as edema develops and discoloration continues to spread around all sides of the fingers, hand and forearm (Fig 2, 3). During this
340
Fig 1. Left hand with purple discoloration 90 minutes after phenytoin extravasation.
Fig 2. Right hand 19 hours after IV phenytoin administration, but 8 hours after PGS was evident, edema and discoloration continue to develop.
stage, the severity becomes more apparent. The degree of discoloration, edema and tissue damage may be dose-related. In the author’s experience, signs and symptoms were more pronounced when several doses or one large, loading dose were given through the same site, than after one, nonextravasated maintenance dose. Typically, in mild cases arterial blood flow is present, skin discoloration is reddish-purple, capillary refill is brisk and the arm feels warm. This is usually a partialthickness soft tissue injury. 9,13 In severe cases, edema progresses rapidly and arterial vessels may become occluded. Skin develops a dusky, greyishblue or dark purple-blue discoloration without capillary refill and will feel cool. This represents either a full-thickness soft tissue injury,9,13 or more likely, the beginning of a compartment syndrome.
The intensity and extent of discoloration may indicate the potential for skin to blister or slough. Extensive deep reddish-purple discoloration that evenly covers a large Portion of the hand and forearm is likely to blister. The more extensive and dark this discoloration is, the more likely it is to blister and slough. Smaller deep purple or blackened purple areas of discoloration surrounded by lighter areas of discoloration may be the only areas that will blister, but they may not slough. Those
Fig 3. 40 hours after phenytoin extravasation the entire forearm is discolored. Edema is beginning to subside.
Fig 4. 6 days after phenytoin extravasation. Edema is resolved, discoloration is receding.
areas that appear almost blackened may eventually feel hard and insensitive like an area of eschar after a burn.
Finally, purple glove syndrome is exquisitely painful during all three stages, much more painful than a common IV infiltration. The combination of exquisite pain, distribution of discoloration and generalized edema are the clinical clues that distinguish PGS from IV infiltration.
Systemic complications such as hemodynamic instability or sepsis that reduce peripheral blood flow may further compromise tissue perfusion of the hand and forearm when purple glove syndrome has already developed. Thus, an identified case of mild PGS may evolve to a severe case in the presence of hemodynamic instability or sepsis.
Healing occurs in the last stage of PGS. During this stage, discoloration recedes from the outer edges toward the original site of injury. In general, edema resolves before discoloration recedes (Fig 4, 5). Mild edema resolves with elevation. Severe
Fig 5. Even after PGS is resolved, there is a difference in the appearance of both hands. The hand on the left is still slightly discolored and edematous.
342 JOURNAL OF NEUROSCIENCE NURSING, DECEMBER, 1992, VOL 24, NO 6
edema may progress rapidly during stage 2 to occlude radial or ulnar arteries, necessitating emergency surgical intervention such as fasciotomy.2,12 If ischemia progresses after fasciotomy, amputation may be necessary. Both .the Food and Drug Administration and Parke-Davis, the manufacturer of phenytoin, are aware of amputations due to purple glove syndrome.
Proposed Etiologies of Purple Glove Syndrome
Several etiologies of purple glove syndrome havé been proposed. The most probable theory proposes that phenytoin’s highly basic solution, with a pH of 12, induces a reactive vasocontriction in veins as it is administered. This vasoconstriction then leads to a breakdown of vascular integrity so IV phenytoin, which is 90% protein bound, freely weeps into the soft tissue. Once in the interstitial space, osmotic pressure changes causing shifts of proteins and fluids from the extracellular to the interstitial spaces. These changes are manifest as edema and possibly, discoloration.
Another theory is that IV cannulation of the vein causes a “microtear” of the vessel, too small to cause observable infiltration, but large enough to allow IV phenytoin to weep into the soft tissue. This is a variation of the theory that PGS occurs only after extravasation. Although extravasation puts an individual at risk of developing the full syndrome, many cases of PGS have been reported where there was no reason to suspect IV infiltration prior to or during administration. Thus, purple glove syndrome can develop under the best of circumstances.
Another theory proposes that IV phenytoin precipitates as it mixes with blood within the IV cannula. This forces some phenytoin to back up and enter the soft tissue through the IV insertion site. Still another theory attributes the damage of PGS to the propylene glycol solvent used to stablilize phenytoin in solution for IV administration.
One of the most compatible rationales for the delayed and localized development of edema and discoloration is the notion that once in the soft tissue, phenytoin pulls proteins and fluids into this compartment thus forcing a shift in osmotic pressure and changing the gradient of flow through the capillary bed. Perhaps with mild PGS, mild edema permits adequate blood flow, evident as skin warmth and a brisk capillary refill. Yet, with severe PGS, edema occludes arterial blood flow leading to compartment syndrome accompanied by pulseless, cool skin without capillary refill.
Risk Factors and Preventive Interventions
Several factors are believed to increase risk for developing PGS. Factors include presence of vascular disease, age 60 years or older or 7 years or younger, or a history of other disease that weakens vascular and skin integrity.
Pain may be a clinical indicator related to preventing PGS. Yet, many individuals receiving IV phenytoin are unable to indicate pain. Those most likely to receive IV phenytoin are individuals at high risk for seizures with a depressed level of consciousness, where time to achieve a steady-state, therapeutic level is of the essence or enteral administration of phenytoin is contraindicated. This population includes trauma, postictal or comatose patients or those under general anesthesia for cranial surgery. Having a depressed level of consciousness in common, they are unable to indicate pain at the injection site when IV phenytoin is administered, and may be at risk for developing PGS.
At present, the 50 mg/min maximum rate of IV phenytoin administration is aimed at preventing life-threatening systemic effects such as hypotension and arrhythmias. Nevertheless, in patients at high risk for PGS, this rate may be too rapid and may contribute to vasocontriction that leads to weeping of IV phenytoin into the soft tissue. Current recommendations from clinicians who have observed PGS are to administer IV phenytoin to adults no faster than 40 mg/min and to reduce the rate of administration to 20-25 m [min for any adult within a known risk group.3,1 In patients who have previously developed PGS, the recommendation has been made to reduce the rate of administration of subsequent doses to an extremely
14
cautious rate of 5-10 mg/min. If it is necessary to use a very slow rate of administration such as 5-10 mg/min, an IV pump is contraindicated for administration since these vary in the amount of pressure generated within the vein. Administration of IV phenytoin to infants and neonates poses special risle due to the delicacy of their vascular systems. Neonates who receive IV phenytoin must be treated with utmost caution with the administered
11
phenytoin at 1-3 mg/kg/min. Enteral administration of subsequent doses of phenytoin as soon as possible is the most desirable approach to preventing PGS.
The type, amount and method of administration of flush solution may be factors contributing to the development of PGS. The preferred flush solution is IV normal saline (NS) packaged in an IV bag and delivered through a piggy-backed IV line, rather than NS from a vial delivered by syringe. Bacteriostatic NS from a vial is not advised since the benzyl alcohol preservative is believed to cause precipitation of IV phenytoin. 10 When the rate of administration is equal, use of IV NS as a flush solution through a piggy-backed IV tubing is preferred because this method allows the flush solution to drip into the vein with less turbulence and force than a syringe-administered injection of flush solution.
The recommended IV angiocath size is 20 gauge or larger. Spengler reported that patients had a higher rate of PGS when small IV angiocaths were used. 13 Yet, PGS has occurred even when IV angiocaths as large as 16g and 18g were used. The size of the IV angiocath alone is not enough to prevent PGS if other precautions are not taken and if individual risk factors are ignored.
The issue of whether a loading dose is to be given at one time or divided into several doses a few hours apart has frequently come under scrutiny within the medical and pharmaceutical communities. Individuals at high risk for developing PGS may achieve a steady-state therapeutic level and avoid PGS when the loading dose is broken into several smaller doses a few hours apart. Yet, for individuals over 60 years of age with vascular disease and a decreased level of consciousness, PGS may begin with the first small dose, only to intensify with subsequent doses given at the same site during that initial 12 hour period. Therefore, since prevention is not certain, detection and early intervention may be a clinician’s only recourse.
As discussed earlier, a vessel microtear may not be clinically detectable when IV phenytoin is administered. If there is a microtear, blood return will be brisk and there will be no immediate evidence of edema or infiltration. Also, phenytoin will be administered without any resistance. Of all the interventions that can be taken to prevent PGS, the most important would be to immediately discontinue any IV that appears infiltrated. If a patient with poor veins hieeds IV phenytoin and no other access is available, an infiltrated IV does not allow phenytoin into the patient’s bloodstream, and contributes to the development of PGS as well as erratic absorption of phenytoin which precludes development of a steady state of antiepileptic drug coverage.
To test for infiltration prior to administration, the tourniquet test may be used. Based on the fact that IV fluid will not flow after an IV is inserted until the tourniquet is removed, a tourniquet can be applied proximal to the IV site. If IV flow stops when the tourniquet is applied, the vein is patent and not damaged. If the IV continues to flow when the tourniquet is in place, especially if it continues to flow slowly, it is infiltrating the soft tissue.
Site location has also come under scrutiny as different individuals have tried to prevent PGS. Some clinicians recommend using large veins in the forearm, rather than small, dorsal hand veins. Yet, early detection may be facilitated when dorsal hand rather than forearm veins are used. Since cases of PGS have developed at different sites in the same individual, including forearm veins and hand veins, it is difficult to support a recommendation to use only forearm veins. A prudent approach would be to use a vein that appears to be large and sturdy and is not damaged. Again, in individuals with vascular disease or chronic illness, finding such a vein may be difficult.
Fishel et al recommend administering IV phenytoin through a central rather than peripheral line if one is available. Although central administration of IV phenytoin may occur in practice without obvious adverse effect, some question the effect that propylene glycol, phenytoin’s main solvent, may have on the myocardium and recommend that central administration be avoided. Cardiac ectopy, a well documented adverse effect of IV phenytoin is attributed to the rate of administration, independent of location of administration. However, Collins and Lutz reported that the type of central line used may increase precipitate development during administration, which may make central administration undesirable in some cases. This recommendation, derived from nursing research, emphasizes the need for further investigation through collaborative research.
Therapeutic Nursing Interventions
Early identification and prompt intervention are key aspects of limiting damage when PGS occurs. The most important nursing intervention is to immediately remove the IV and avoid any use of the extremity until it is healed. Additionally, nurses may want to caution others to avoid venipuncture or cuff blood pressures on the affected extremity until it is healed. The extremity should be elevated to decrease edema which develops during the second stage of PGS.9 Dry, gentle heat should be applied. The application of heat is believed to facilitate, along with elevation, the redistribution and reabsorption of phenytoin throughout the forearm. At the Mayo Medical Center, nurses use a light heating pad pre-set at 980 F. In contrast, moist or extreme heat may cause maceration and skin breakdown. Although pain medications may reduce the pain associated with PGS, heat and elevation will promote comfort by relieving or minimizing symptoms. Nevertheless, due to the severity of pain, patients will not be able to easily participate in passive range of motion or use the affected hand for self-care activities.
Frequent, continual nursing assessments of capillary refill, skin temperature, discoloration, edema and the presence and quality of peripheral pulses to light touch are important. Assessment information may be used by physicians in determining whether emergency surgical intervention is required. If pulses are no longer palpable, but are only audible by Doppler, a surgeon must evaluate the need for fasciotomy. Nurses should not wait until the pulse is completely absent before informing the physician.
Case Study #1
Mr. A. , a 79 year-old, white male with a 10 year history of AlzheimeEs disease and hypertension was in his usual health at a nursing home when he had a generalized tonic-clonic seizure. Mr. A. was taken to the emergency/trauma unit (ETU) where seizure activity continued. In the ETV, he was unable to moye
his left hand and leg to deep pain stimuli. After his IV solution was changed from D5W to NS, and his IV was well flushed with NS, he received 900 mg IV phenytoin through a 20g angiocath in the dorsum of his left hand. During administration the drug clearly extravasated. The IV was immediately removed and loading was continued in the the right hand without adverse reaction. The rate of administration never exceeded 50 mg/min.
Except for the initial area of extravasation, Mr. A’s hand remained essentially unchanged for 16 hours. However, once his level of consciousness returned to baseline, he indicated severe discomfort and pain as evidenced by crying and moaning whenever his hand was touched. Due to pre-existing Alzheimes disease he was unable to localize pain or withdraw his hand, even though he was able to move it spontaneously and purposefully. It was elevated in a Richard’s sling and gentle, dry heat was applied at 980. Hourly nursing assessments were made. Mr. A.’s hand became swollen and edematous 16 hours after extravasation. He continued to develop edema and discoloration for 72 hours before it began to resolve. It took one week for the edema, discoloration and pain to resolve. Mr. A’s hand and forearm healed uneventfully.
Discussion
This case was identified during phenytoin administration which led to early intervention to limit the potential damage of PGS. Subsequent doses could have been given and other events could have occurred resulting in a serious outcome. Instead, interventions such as removal of the IV, elevation, no further venipuncture or blood pressure assessment of the affected extremity, and dry, gentle heat.application may have contributed to uncomplicated and rapid healing.
Mr. A. was at high risk for developing PGS because he is elderly, has a history of hypertension and was unable to indicate pain at the site and time of injection. Once seizure activity ceased and he was no longer post-ictal, he was able to grimace and cry when he had pain, but was unable to localize pain due to pre-existing Alzheimer’s disease. His pain diminished as the edema resolved. The average time for complete resolution of PGS noted in the literature is 15-21 days-2’4’5’6’8 Mr. A’s hand and forearm were completely healed within 7 days of the original injection and first sign of PGS. The relatively rapid resolution of PGS supports the notion that nursing interventions either minimized tissue damage, or actively maximized healing and comfort once the syndrome began.
Case Study #2
Ms. B., a 63 year-old, white female who had a stroke one year prior to admission, was admitted through the ETU for decreased level of consciousness and onset of seizure activity. She received an 800 mg loading dose of IV phenytoin through a 20g angiocath located in her right hand. The IV was well situated and well flushed with IV NS solution before and after drug administration. The drug was administered IV push at a rate less than 20 mg/min.
Eight hours after the administration of IV phenytoin, Ms. B.’s hand was noted to be edematous and discolored. Her IV was discontinued at that site. Her hand and forearm were elevated in a Richard’s sling and dry, gentle heat was applied. Ms. B., not fully aware of her own behavior, indicated exquisite pain in the hand and forearm through facial grimace, frequent repositioning of her hand and moaning.
The second stage of PGS began within the next 12 hours when discoloration and pain increased. At that time, her hand felt warm to touch and had brisk capillary refill (Fig 2). Twentyfour hours later as the discoloration and edema began to diminish in intensity, Ms. B. became hemodynamically unstable with maximum systolic blood pressure of 70 mm Hg.
During the period of hemodynamic instability, this area of localized soft-tissue injury sustained secondary damage due to peripheral vasoconstriction resulting from hemodynamic changes. Ms. B.’s course of healing was prolonged to 2 full weeks. When the hand appeared to be mostly healed, it still differed in appearance from her other hand (Fig 5).
Discussion
This case highlights the typical time course of PGS as a delayed, localized syndrome, but also points to the effect systemic complications may have on this local adverse reaction to IV phenytoin. Due to peripheral vasoconstriction, Ms. B.’s hand appeared to be re-injured when the systemic complications occurred and she required a longer time to heal. Ms. B.’s hand was mostly healed 14 days after the initial administration of the loading dose of IV phenytoin, yet, 2 areas on her fingers that had turned a blackened purple during the period of hemodynamic instability continued to be insensitive and hard. She did not lose movement of her fingers, but the compromised sensitivity affected how well she was able to use her hand afterwards. Like Mr. A. , Ms. B. had predisposing risk factors, such as a history of vascular disease and age over 60 years. Each also required loading doses of IV phenytoin due to new onset of seizure activity and decreased level of consciousness.
Summary
Nurses can prevent some cases of PGS by identifying individuals at high risk, advocating use of oral phenytoin whenever possible and administering IV phenytoin at half the currently accepted rate. To ease the pain of PGS nurses can elevate the extremity in anticipation of edema that is likely to develop, apply gentle, dry warmth to the extremity to facilitate reabsorption of the drug and prevent secondary trauma by limiting venipuncture and blood pressure measurements on the affected extremity until it heals. The measures nurses take to ease the pain of PGS are believed to be the measures that maximize healing.
Two measures not recommended are use of antidotes or cold compresses. At present there is no known antidote for phenytoin and when one was attempted, a poor outcome was reported. 16 In view of how Ms. B.’s hand was reinjured when she sustained peripheral vasoconstriction due to decreased blood pressure, application of cold compresses with the intent of localizing the phenytoin would not seem to facilitate healing.
Since 1956, IV phenytoin has been a drug of choice to treat seizure activity in patients unable to
receive enteral antiepileptic drugs. The population of patients most likely to develop PGS includes those with vascular disease, individuals over age 60 or under age 7, and individuals who are unable to indicate pain at the site of injection at the time IV phenytoin is administered. Measures to prevent and treat purple glove syndrome are currently based on observation, anecdotal accounts in the literature and prudent caution. Many measures to prevent or treat PGS and its pain are worthy of future nursing research efforts to add to the scientific basis of neuroscience nursing practice.
Acknowledgment
The author thanks Judeann Sharp, RN, MSN and Peter Post, PharmD for their support of this project, and expresses deep appreciation to the many colleagues at the Mayo Medical Center who collaborated on prevention and care related to PGS.
References
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Comer JB: Extravasation from intravenous phenytoin. American Journal of IV Therapy and Clinical Nutrition 29.
Earnest MP, Marx JA, Drury LR: Complications of intravenous phenytoin for acute treatment of seizures. JAMA
Fishel M, Sauer S, Allen J: When you give phenytoin IV. RN 1990;
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Il. Package Information: Pages 1-6 in: Parenteral Dilantin (Phenytoin Sodium Injection, USP). Parke-Davis, 1987.
Rao VK, Feldman PD, Dibbell DG: Extravasation injury to the hand by intravenous phenytoin. J Neurosurg 1988; 68: 967-969.
Spengler RF, Arrowsmith JB, Kilarski DJ et al: Severe softtissue injury following intravenous infusion of phenytoin: Patient and drug administration risk factors. Arch Intern Med 1988; 148: 1329-1333.
Tuttle CB: Guidelines for phenytoin infusions. Canadian Journal Hospital Pharmacy 1984; 34 (4):137-139.
Upton J, Mulliken JB, Murray JE: Major intravenous extravasation in juries. Am J Surgery 1979; 137: 497-5()6.
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