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A Clinical Review of Common Medications Used in Emergency Dermatological Situations

Mo, Joshua H., BS*; Chapman, Lance W., MD, MBA*; Cohen, Joel L., MD*,†

doi: 10.1097/DSS.0000000000001789
Review Article
Free

BACKGROUND Medical emergencies can occur in any environment, including dermatologic and procedural surgical settings. There are many options available to dermatologic surgeons, which they should consider having easily accessible in the office in case an emergency arises.

OBJECTIVE To summarize the current understanding about major medications that should be on-hand during dermatological surgeries. To review their mechanism of action, examine their general use, and dermatological use during surgical emergencies.

METHODS AND MATERIALS A comprehensive review using PubMed was performed, searching for studies using these various medications in relation to cutaneous surgeries.

RESULTS Distinct items such as hyaluronidase, nitroglycerin paste, aspirin, injectable epinephrine, and defibrillators are potential options to address various emergencies and should be readily accessible to dermatologic surgeons.

CONCLUSION Dermatologic surgeons' knowledge of key medications and options to have in the office allow for a proper response in the event an emergency arises.

*Department of Dermatology, University of California—Irvine, Irvine, California;

AboutSkin Dermatology and DermSurgery, Greenwood Village, Colorado

Address correspondence and reprint requests to: Joshua H. Mo, BS, Department of Dermatology, University of California—Irvine, 118 Medical Surge I, Irvine, CA 92697, or e-mail: jhmo@uci.edu

The authors have indicated no significant interest with commercial supporters.

Medical emergencies occur in any environment, including dermatologic procedural and surgical settings. We sought to lay out the options dermatologic surgeons should consider having easily accessible in the office in case an emergency arises. This review will include distinct items such as hyaluronidase, nitroglycerin paste, aspirin, injectable epinephrine, and defibrillation. We outline each of these major medications and define their use—with an emphasis in dermatologic surgery.

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Hyaluronidase

Hyaluronidase is a naturally found enzyme that breaks down hyaluronic acid (HA) in the body. Commercially, the enzyme may be purified from animal sources or produced recombinantly.1 Different marketed brands include Amphadase, Vitrase, and Hylenex, which are all used interchangeably in clinical practice.2,3 Formulations are available as a dry powder that is prepared before administration or as a nonpreserved and sterile solution that is ready to use.4

Medically, hyaluronidase is delivered by injection and is indicated as an adjuvant for a few purposes: to supplement hydration alongside subcutaneous fluid delivery, to increase the spread and absorption of injected drugs and subcutaneous radiopaque dyes, and to help in diluting out infiltration injuries after IV administration of drugs such as chemotherapy.2 For these issues, injections are preferably delivered subcutaneously or intramuscularly because proteins in the blood swiftly inactivate hyaluronidase activity; the enzyme requires time to breakdown HA, and so, intra-arterial injections are not as effective as other delivery methods.5

In dermatology, injected hyaluronidase is used off-label to target complications with HA fillers.2 These include faulty injections that are too superficial causing nodular or Tyndall appearance, filler product precipitating granuloma formation, and vascular compromise associated with filler injections.6–8 Previous studies have shown that hyaluronidase injections have been a successful intervention in these various complications.9 Faulty HA filler injections can lead to occlusion of facial vessels and loss of retinal circulation, leading to sudden vision loss. Immediate retrobulbar injections of hyaluronidase can potentially rescue the occlusion and resume retinal circulation, thereby partially reversing the damage to sight.10,11 Infection associated with HA filler injection responded well to broad spectrum antibiotics with the addition of repeated hyaluronidase injections (up to 100 units) directly into each inflammatory nodule.12 Beyond use in treating HA filler complications, hyaluronidase has also been effective at treating skin problems associated with excessive glycosaminoglycan deposition including dermatological changes from hypothyroidism (myxedema), scleredema associated with diabetes mellitus, and localized scleroderma. Studies using ranges of below 100 units to a couple 100 units of hyaluronidase in various settings to treat these difficult dermatological complications were successful.13–15 But much higher doses (150–500 units of hyaluronidase enzyme every hour until improvement) have been advocated for the pressing office use for impending necrosis or the emergent situation of filler-induced amaurosis (sudden visual loss)—which are 2 reasons we recommend keeping it on-hand and available in the office setting.16,17 The shelf-life of this product is often short, on the order of 6 months, so a regular system to check expiration dates is recommend as an office standard operating procedure.17

Adverse effects associated with hyaluronidase treatment are extremely rare. Less than 0.1% of patients respond with hives or angioedema, and there have been no documented cases of anaphylaxis in response to subcutaneous injection.2 Patch tests for hypersensitivity are recommended for the animal-derived brands of hyaluronidase, and a positive reaction of wheal formation and itching within 30 minutes is a contraindication to its use.18 In addition, there is worry that extensive use of hyaluronidase may breakdown the body's own HA and lead to cosmetic defects. One group reported repeated facial injection of hundreds of units of hyaluronidase per mL of filler HA, and even over a 10-day use period, found no noticeable cosmetic changes or reduction in natural facial volume.13,19 They concluded that large quantity usage was both effective at targeting filler HA, with no appreciable damage to the body's natural HA. This is likely associated with the rapid turnover qualities of native HA, where one-third of the native compound is broken down and rebuilt daily.20 Damage to body's natural HA networks associated with hyaluronidase injections is likely restored by this continual cycling (Table 1).

TABLE 1

TABLE 1

New recommendations for hyaluronidase use in acute HA filler complications suggest that 500 units should be injected every hour for compromised regions until ischemia resolves and should follow a rough estimation of the nose, lip, and forehead as dosage regions. The use of this high-dose, repeated injection as a clinical guideline has been extremely successful when started within 72 hours of vascular compromise.16 As long as indications are properly followed, repetitive doses of hyaluronidase are safe and effective at treating both emergent and nonemergent HA complications, making it essential in any dermatological office.21

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Nitropaste

Nitroglycerin is an organic compound that is metabolized to nitric oxide in the body, leading to potent vasodilation. These effects are used to treat angina and congestive heart failure, with some additional use in decreasing blood pressure during surgical operations.22 Delivery of the drug can be intravenous, by oral tablets, lingual sprays, transdermal patches, or through a topical paste.23

There are many possible adverse effects that should be considered before use. The patient may experience hypotension and dizziness, as well as erythema, edema, and burning at the site of application. These local complications are rare.24

In dermatology, off-label topical nitroglycerin paste (nitropaste) is used as a therapeutic option to address ischemic complications with fillers.25 Dermal fillers are used to augment lips, volumize facial contours, decrease wrinkles, and lift pitted scars. During these procedures, the filler rarely may inadvertently be injected into a blood vessel, causing occlusion. Larger filler volumes can also compress the regional vasculature, preventing adequate blood flow to surrounding tissues. Although these complications are rare, they can lead to dermal ischemia. If left untreated, irreversible tissue necrosis can occur.25–27

Currently, dermatology practitioners often choose the administration of 2% nitroglycerin paste, based on previous recommendation. The topical paste is repeatedly applied at the first sign of dermal blanching until the ischemic event improves.28 We agree with these recommendations and suggest that topical nitroglycerin paste should be kept on-hand by dermatologic surgeons to manage filler-related vasculature compromise emergencies.

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Aspirin

Acetylsalicylic acid, commercially known as aspirin, is an antiplatelet drug that is taken orally for fever, pain, and inflammation.29 As a nonsteroidal anti-inflammatory drug (NSAID), its effects are mediated by the irreversible inactivation of the cyclooxygenase enzymes (COX1/2). This prevents the generation of the lipid thromboxane A2, which normally has prothrombotic effects such as vasoconstriction and platelet aggregation.30 Common side effects include upset stomach and heartburn. Rarely, serious internal bleeding can accompany use.31

Aspirin is also given for cardiovascular complications such as angina, myocardial infarction, and ischemic stroke. Prophylactically, aspirin is used to prevent heart attacks and strokes, as well as off-label prevention of complications such as thromboembolism and pericarditis.32

The drug is typically discontinued 1 to 2 weeks before any surgical procedure to try to minimize bleeding complications. However, there have since been several studies, which collectively concluded that there was no significant increase in bleeding risks with aspirin use during dermatologic surgeries. In fact, additional studies on sudden discontinuation of antiplatelet medication suggest that this course of action could endanger patients.33–35 Patients currently taking aspirin with a pre-established cardiovascular disease diagnosis can enter a hypercoagulative state upon cessation, putting them at risk for stroke or pulmonary embolism.36

These data have largely evolved the recommendation on aspirin's use with cutaneous procedures, particularly when taken for a specific therapeutic indication (such as a history of myocardial infarction, deep vein thrombosis, or atrial fibrillation). Dermatological surgeons have also evolved their practice, as evidenced by a 2005 survey of Mohs surgeons where only 3% of 271 surgeons surveyed always discontinued aspirin use perioperatively; this was a much smaller fraction compared with the reported 26% in the 2002 survey.37–39 If a patient is currently taking aspirin for therapeutic value, such as prevention of cardiovascular events, we recommend that they should not discontinue the drug before cutaneous surgery, as the benefits exceed the potential bleeding risk.

Although there is no definitive evidence that aspirin improves outcomes with filler-associated vascular occlusion, there have been reported cases of successful intervention to occlusive events using a combination of hyaluronidase, aspirin, and nitropaste.40,41 Some cosmetic surgeons include aspirin in their recommendations for treatment of filler injection complications.42

In the event of an acute cardiac episode in the office setting, proper training will allow dermatologic surgeons to better address the situation while waiting for help to arrive. The American Heart Association has developed 2 training certifications to prepare medical professionals for these emergencies: Basic Life Support (BLS) and Advanced Cardiovascular Life Support (ACLS).43 We strongly encourage dermatologic surgeons to obtain BLS certification because emergency situations can arise in any setting. The decision to pursue ACLS certification is also recommended, as this training prepares physicians to recognize and intervene cardiac arrest, stroke, or other emergencies. With this further training, dermatologic surgeons in the office will be prepared to assess for a myocardial infarction and effectively administer aspirin if necessary.

We recommend keeping aspirin available in the office, for use in the event of a filler-related vascular occlusion episode. Furthermore, if the dermatologic surgeon is ACLS certified and feels comfortable evaluating a cardiac arrest event, they should also have aspirin on-hand to provide as an early intervention.

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Epinephrine Autoinjector

Epinephrine autoinjectors are devices used to deliver immediate treatment for emergency anaphylaxis. The instantaneous delivery of epinephrine leads to bronchodilation, increased heart rate, and peripheral vasoconstriction. Each injector contains a dose of 0.3 mg of epinephrine, which is injected directly into the thigh musculature at the first sign of anaphylaxis.44 Recently, epinephrine autoinjectors have been in the news due to exponential price increases by the very small number of companies (namely Mylan) that produce these important products, which is exacerbated by the fact that they have a fairly short shelf-life.

During dermatologic surgery, there may be a rare allergic reaction to topical anesthetics (such as ester anesthetics such as tetracaine and benzocaine). In general, the vast supply of local anesthetics may lead to various allergic responses, either local or systemic. In these situations, we first strongly emphasize the importance of BLS training, so that physicians in the office setting are adequately trained to monitor and maintain a patent airway. In the case of a systemic reaction and anaphylaxis, dermatologic surgeons should always be prepared with epinephrine that can be quickly delivered to the patient. Epinephrine autoinjectors effectively fulfill this role and should be kept in the office to prevent fatal events associated with delayed anaphylaxis treatment.44,45

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Defibrillator

Defibrillation is the method of delivering a large dose of electric shock to the heart, which depolarizes the cardiac muscle to allow the pacemaker cells of the sinoatrial node to restore normal sinus rhythm. This intervention is indicated for patients with ventricular fibrillation or ventricular tachycardia.46

There are several types of devices that supply the defibrillation shock: advanced life support (ALS) units, automatic external defibrillators (AEDs), implantable cardiac defibrillators, and wearable defibrillators.47,48

In the case of emergencies, our dermatologic surgery clinics have either an ALS unit or an AED available in the office. Having at least an AED available in the office setting allows for a potentially life-saving intervention to be initiated in the case of a cardiac emergency such as a patient collapsing in the office during skin cancer surgery or laser resurfacing. In an actual hospital operating room, the surgeon should have an ALS unit nearby, should the patient develop a serious cardiac arrhythmia.49 In addition to having an AED or ALS unit on-hand, dermatologic surgeons need to know how to fundamentally use a defibrillator and be able to recognize emergencies where they are required. This can be fulfilled by either BLS or ACLS certification, which we again encourage dermatologic surgeons to acquire, so that they have the training to intervene whenever necessary.

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Sugar Source to Rub Into a Patient's Lip Sulcus for Presumed Diabetic Hypoglycemia

Diabetic hypoglycemia is 1 potential issue that dermatologic surgeons may encounter with an unresponsive patient in their office. In these situations, cake icing is kept in our emergency office supplies in the event a known-diabetic patient becomes unresponsive. This simple and innocuous sugar source can be topically rubbed into the lower or upper lip sulcus while waiting for emergency services to arrive to more thoroughly evaluate an unresponsive patient. A glucose meter is also important to have on-hand in these situations because a brief check of the unresponsive patient's blood sugars can verify that their symptoms are indeed related to a hypoglycemic state.

Dermatologic surgeons' knowledge of key medications and options to have in the office allow for a proper response, should an emergency arise. Here, we have laid out the items that dermatologic surgeons should consider having easily accessible in the office, in case such an event arises. For filler-related occlusive emergencies, hyaluronidase, nitropaste, and aspirin should be kept on-hand for quick intervention. Epinephrine autoinjectors should be kept as anaphylaxis treatment. Defibrillators, with BLS or ACLS training, should be on-hand for cardiac emergencies. Finally, a sugar source and glucose meter should be available in the event a patient enters a hypoglycemic state. With these options available, dermatologic surgeons will be able to properly respond to emergencies in the office setting.

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