Volume 32 Number 8 August 2018

Tourist Trap The ease and speed of travel facilitate exposure to conditions not endemic to the area where patients seek treatment. With international travel on the rise, particularly during summer months, emergency physicians must be prepared to evaluate and manage patients who become ill abroad. It is critically important to build a framework for assessing returned travelers who present with fever, as such cases can pose serious threats to patients and public health.

Feeling No Pain Emergency physicians manage a spectrum of acute medical and traumatic conditions that often require painful treatments. In such cases, aptly administered procedural sedation and analgesia can improve the experience for both the provider and the patient. Because the appropriate regimen varies based on the particulars of each case, clinicians should thoroughly understand the advantages and potential risks of sedatives, dissociative agents, and analgesics.

THE OFFICIAL CME PUBLICATION OF THE AMERICAN COLLEGE OF EMERGENCY PHYSICIANS IN THIS ISSUE Lesson 15 n Fever in the Returned Traveler ...... 3 Critical Procedure ...... 13 Critical Decisions in Emergency Medicine is the official CME publication of the American College of Emergency LLSA Literature Review ...... 14 Physicians. Additional volumes are available. Critical Image ...... 16 EDITOR-IN-CHIEF Critical ECG ...... 18 Michael S. Beeson, MD, MBA, FACEP Northeastern Ohio Universities, Lesson 16 n Procedural Sedation ...... 19 Rootstown, OH CME Questions ...... 30 SECTION EDITORS Drug Box/Tox Box ...... 32 Joshua S. Broder, MD, FACEP Duke University, Durham, NC Andrew J. Eyre, MD, MHPEd Brigham & Women’s Hospital/Harvard Medical School, Contributor Disclosures. In accordance with the ACCME Standards for Commercial Boston, MA Support and policy of the American College of Emergency Physicians, all individuals with control over CME content (including but not limited to staff, planners, reviewers, and Frank LoVecchio, DO, MPH, FACEP authors) must disclose whether or not they have any relevant financial relationship(s) to Maricopa Medical Center/Banner Phoenix Poison learners prior to the start of the activity. These individuals have indicated that they have and Drug Information Center, Phoenix, AZ a relationship which, in the context of their involvement in the CME activity, could be Amal Mattu, MD, FACEP perceived by some as a real or apparent conflict of interest (eg, ownership of stock, grants, University of Maryland, Baltimore, MD honoraria, or consulting fees), but these individuals do not consider that it will influence the CME activity. Joshua S. Broder, MD, FACEP; GlaxoSmithKline; his wife is employed by Lynn P. Roppolo, MD, FACEP GlaxoSmithKline as a research organic chemist. All remaining individuals with control over UT Southwestern Medical Center, CME content have no significant financial interests or relationships to disclose. Dallas, TX

This educational activity consists of two lessons, a post-test, and evaluation questions; Christian A. Tomaszewski, MD, MS, MBA, FACEP as designed, the activity should take approximately 5 hours to complete. The participant University of California Health Sciences, should, in order, review the learning objectives, read the lessons as published in the print San Diego, CA or online version, and complete the online post-test (a minimum score of 75% is required) Steven J. Warrington, MD, MEd and evaluation questions. Release date August 1, 2018. Expiration July 31, 2021. Orange Park Medical Center, Orange Park, FL

Accreditation Statement. The American College of Emergency Physicians is accredited ASSOCIATE EDITORS by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Wan-Tsu W. Chang, MD University of Maryland, Baltimore, MD The American College of Emergency Physicians designates this enduring material for a Walter L. Green, MD, FACEP maximum of 5 AMA PRA Category 1 Credits™. Physicians should claim only the credit UT Southwestern Medical Center, commensurate with the extent of their participation in the activity. Dallas, TX Each issue of Critical Decisions in Emergency Medicine is approved by ACEP for 5 ACEP John C. Greenwood, MD Category I credits. Approved by the AOA for 5 Category 2-B credits. University of Pennsylvania, Philadelphia, PA Commercial Support. There was no commercial support for this CME activity. Danya Khoujah, MD University of Maryland, Baltimore, MD Target Audience. This educational activity has been developed for emergency physicians. Sharon E. Mace, MD, FACEP Cleveland Clinic Lerner College of Medicine/ Critical Decisions in Emergency Medicine is a trademark owned and published monthly by the American Case Western Reserve University, Cleveland, OH College of Emergency Physicians, PO Box 619911, Dallas, TX 75261-9911. Send address changes and Nathaniel Mann, MD comments to Critical Decisions in Emergency Medicine, PO Box 619911, Dallas, TX 75261-9911, or to Massachusetts General Hospital, Boston, MA [email protected]; call toll-free 800-798-1822, or 972-550-0911. Jennifer L. Martindale, MD, MSc Copyright 2018 © by the American College of Emergency Physicians. All rights reserved. No part of this Mount Sinai St. Luke’s/Mount Sinai West, publication may be reproduced, stored, or transmitted in any form or by any means, electronic or mechanical, New York, NY including storage and retrieval systems, without permission in writing from the Publisher. Printed in the USA. David J. Pillow, Jr., MD, FACEP The American College of Emergency Physicians (ACEP) makes every effort to ensure that contributors to its UT Southwestern Medical Center, Dallas, TX publications are knowledgeable subject matter experts. Readers are nevertheless advised that the statements and opinions expressed in this publication are provided as the contributors’ recommendations at the time George Sternbach, MD, FACEP of publication and should not be construed as official College policy. ACEP recognizes the complexity of Stanford University Medical Center, Stanford, CA emergency medicine and makes no representation that this publication serves as an authoritative resource Joseph F. Waeckerle, MD, FACEP for the prevention, diagnosis, treatment, or intervention for any medical condition, nor should it be the basis for the definition of or standard of care that should be practiced by all health care providers at any particular University of Missouri-Kansas City School of Medicine, time or place. Drugs are generally referred to by generic names. In some instances, brand names are added Kansas City, MO for easier recognition. Device manufacturer information is provided according to style conventions of the American Medical Association. ACEP received no commercial support for this publication. EDITORIAL STAFF To the fullest extent permitted by law, and without Rachel Donihoo, Managing Editor limitation, ACEP expressly disclaims all liability for [email protected] errors or omissions contained within this publication, Suzannah Alexander, Publishing Assistant and for damages of any kind or nature, arising out of use, reference to, reliance on, or performance of such Lexi Schwartz, Subscriptions Coordinator information. Marta Foster, Director, Educational Products ISSN2325-0186(Print) ISSN2325-8365(Online) Tourist Trap Fever in the Returned Traveler

LESSON 15

By Lauren Page Black, MD, MPH; Andrew Martin, MD; and Elizabeth DeVos, MD, MPH Dr. Black is an emergency medicine fellow at the University of Florida, College of Medicine — Jacksonville. Dr. Martin is an attending physician in the Department of Emergency Medicine at Emergency Resources Group in Jacksonville, Florida. Dr. DeVos is an associate professor of emergency medicine and the medical director of International Emergency Medicine Education at the University of Florida, College of Medicine — Jacksonville. Reviewed by David J. Pillow, Jr, MD, FACEP

OBJECTIVES On completion of this lesson, you should be able to: CRITICAL DECISIONS 1. List the elements of a complete travel history. n What specific details should be obtained when 2. Identify and manage cases of suspected malaria and inquiring about a patient’s travel history? viral hemorrhagic fever. 3. Synthesize an assessment based on involved organ n How should suspected malaria be approached, systems and travel history to identify high-risk and what other diseases should be considered? conditions in febrile returned travelers. n What are the potential causes of hemorrhagic 4. Recognize reportable causes of fever in the returned fever, and how should they be managed? traveler. n What diseases should be considered in a febrile FROM THE EM MODEL returned traveler with abdominal pain, respiratory 1.0 Signs, Symptoms, and Presentations complaints, or neurological symptoms? 1.1 Abnormal Vital Signs n Which diseases must be reported to the CDC? 1.1.2 Fever

The ease and speed of travel facilitate exposure to conditions not endemic to the area where patients seek treatment. With international travel on the rise, especially during summer months, emergency physicians must be prepared to evaluate and manage those who become ill abroad. An estimated 64% of travelers become ill abroad.1 Fortunately, most of these diseases are mild and self-limiting, evidenced by upper- respiratory and gastrointestinal symptoms.2

August 2018 n Volume 32 Number 8 3 CASE PRESENTATIONS ■ CASE ONE ■ CASE TWO ■ CASE THREE A 35-year-old woman presents A 40-year-old man presents with A 50-year-old man presents with generalized malaise, fever, chills, the sudden onset of fever, fatigue, with a cough, shortness of breath, headache, and abdominal pain over the and myalgia, starting 2 days ago, and an associated fever. His past week. Initial laboratory tests show followed by vomiting, diarrhea, temperature is 39°C (102.2°F), mild anemia and thrombocytopenia and abdominal pain 1 day later. and he is tachycardic and with a normal WBC count. The patient Today, he has had bloody stools. The tachypneic with increased work of reveals that she returned from Uganda patient explains that he returned breathing. His family reports that in East Africa 14 days ago, where she from Guinea in West Africa 10 days he returned 7 days ago from a trip was visiting her grandparents. She did ago, where he was volunteering in a not take any prophylactic medications to Saudi Arabia. rural hospital. during her trip.

However, more serious pathogens, of exposure, and timing of illness in animals, or reported insect bites.5 Details including malaria, dengue fever, rickettsial relation to travel. Some studies suggest about a traveler’s accommodations and infections, and typhoid fever, are diagnosed that longer trips are correlated with an activities can provide critical information, with varying frequencies in returned increased risk and incidence of illness.1 as business travelers can experience travelers with systemic febrile illness. Furthermore, due to the variation far different exposures than adventure Travel-related diseases can pose of incubation periods, the timing of travelers or front-line humanitarian significant diagnostic challenges for symptoms related to travel can help workers. Possible risk factors should be physicians who do not encounter these measure a patient’s risk for certain investigated: Did the patient have bed nets conditions regularly, but preparation and conditions. or screens? Was the patient in a more rural an organized clinical approach can help Pre-Travel History or urban environment? Was the patient mitigate the risks associated with these staying in a hotel, camping, or visiting The emergency physician should common disorders. farms? These factors can suggest differing also evaluate a patient’s pre-travel susceptibilities to various infections. preparation. Travelers who visit a clinic CRITICAL DECISION Travelers who were visiting friends or prior to departure are less likely to family are at increased risk for certain What specific details should be present with fever, acquire malaria, or illnesses due to increased exposure to local obtained when inquiring about a experience severe disease than those who populations. patient’s travel history? depart without a pre-trip assessment. In addition, the clinician should inquire A careful travel history should identify, When managing a case of suspected malaria, for example, the clinician as to whether a patient sought medical at minimum, the geographic region visited, care overseas. Whether a patient went reason for travel, timeline of travel, possible should ask if the patient received to a clinic, local hospital, or purchased exposures, pre-travel immunizations, and chemoprophylaxis at a travel clinic and medications from a local pharmacy can be chemoprophylaxis. assess compliance with the prescribed regimen. valuable information. In many countries, Travel Destination In one case series of US civilians, antibiotics and other medications can be Disease risk varies significantly by 6% of patients with malaria purchased over-the-counter without a region. For example, a febrile patient who reported adherence to appropriate prescription. This information can help returns from Sub-Saharan Africa may be chemoprophylaxis.4 It is important to to explain a delayed or atypical clinical more likely to have malaria than someone remember that a traveler who has taken presentation. who returns from another region, where chemoprophylactic medications can still CRITICAL DECISION dengue fever or other diseases are more acquire malaria, although the incidence prominent.3 Similarly, rickettsial infections, is less likely. How should suspected malaria yellow fever, enteric fever, and many other be approached, and what other Other Historical Details diseases are endemic to certain areas, so diseases should be considered? the risk of exposure varies greatly based on To further narrow the differential Several epidemiological studies of the region visited (Table 1). diagnosis and risk stratify a case, the emergency physician should seek to fever in returned travelers indicate that, Timeline identify possible exposures, such as when a specific etiological diagnosis It is essential to establish a travel a history of freshwater swimming, is made, malaria (Figure 1) is the most and exposure timeline, including details known ingestions of contaminated frequently identified illness.3,6,7 However, related to the duration of the trip, timing food or water, interactions with farm differentiating malaria from other travel-

4 Critical Decisions in Emergency Medicine related systemic febrile illnesses can be challenging due to the nonspecific FIGURE 1. Life Cycle of the Malaria Parasite findings that are associated with this condition. Malaria, particularly in uncomplicated infections, is characterized by symptoms similar to those of other minor viral illnesses.8 Early symptoms of uncompli­ cated cases include fever, malaise, myalgia, headache, and chills. The classic paroxysms of chills and fever followed by diaphoresis are infrequently observed with falciparum malaria infection.2 The nonspecific early findings of malaria overlap significantly with other causes of acute febrile illness in returned travelers, such as dengue, chikungunya, and Zika (Figure 2). Although myalgia is common with malarial infections, it is usually less severe than when associated with dengue, and muscle tenderness is less prominent with malaria than with leptospirosis or typhus.8 Malaria is also less likely to present with a rash than dengue, chikungunya, Zika, typhus, enteric fever, or meningo­ coccal septicemia.8 Petechiae are often associated with viral hemorrhagic disseminated intravascular coagulation Malaria is caused by Plasmodium fevers (VHFs) but are rarely seen with (DIC).8 High fevers, splenomegaly, parasites spread via an Anopheles malaria. Petechiae are only found in thrombocytopenia, mild jaundice, and mosquito vector. Five Plasmodium severe falciparum malaria infections abdominal tenderness are commonly species cause the disease in humans: associated with complications such as found. P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Other TABLE 1. Selected Infectious Diseases by Region confounding causes of acute febrile illness in the returned traveler are also Incubation Period Incubation Period Incubation Period Incubation Period of <10 Days of <21 Days of >21 Days of Months vector-borne; for example, dengue, Caribbean Chikungunya Leptospirosis Zika, yellow fever, and chikungunya Dengue are all arboviruses whose primary Zika vector is the Aedes aegypti mosquito. Central Dengue Enteric fever Leishmaniasis Chagas disease Details about the travel timeline America Zika Leptospirosis Leishmaniasis South Dengue Enteric fever Leishmaniasis Chagas disease and geographic area visited can America Yellow fever Leptospirosis Leishmaniasis be particularly valuable. Although Zika significant overlap exists in South Central Chikungunya Enteric fever endemic areas of malaria, dengue, Asia Dengue chikungunya, Zika, African trypano­ SARS somiasis, and leptospirosis, a travel Southeast Chikungunya Japanese Leishmaniasis Leishmaniasis timeline can help differentiate them. Asia Dengue encephalitis Chikungunya, dengue, and Zika SARS Enteric fever Leptospirosis have incubation periods of less than Sub-Saharan Hemorrhagic Hemorrhagic Filariasis Filariasis 2 weeks, while the incubation period Africa fevers fevers Leishmaniasis Leishmaniasis for malaria varies by species. The Yellow fever Schistosomiasis incubation period for P. falciparum Widespread Malaria HIV Hepatitis A, E Malaria is approximately 12 to 14 days, Malaria HIV Tuberculosis with a range from 7 to 30 days. The Malaria overwhelming majority of cases of

August 2018 n Volume 32 Number 8 5 FIGURE 2. Global Distribution of Arboviruses

P. falciparum malaria occur within parasite cannot be visualized, blood cases, health care providers can call the 1 month of return, but P. vivax and smears should be repeated every 12 to CDC Emergency Operations Center at P. ovale infections can present months 24 hours for 2 days.8 In cases of altered 770-488-7100.12 or even years after the initial infection.9 mental status and fever after travel to While no emergency treatment is Complications of malaria can develop endemic areas, cerebrospinal fluid (CSF) required, the clinical presentation of Zika rapidly and include encephalopathy, should be evaluated to rule out other can overlap greatly with malaria and is hypoglycemia, acidosis, acute renal causes of encephalopathies; CSF in another important consideration in the failure, pulmonary edema, hepatic patients with malaria is usually normal febrile returned traveler, particularly for dysfunction, intravascular hemolysis, or demonstrates nonspecific, mildly females of childbearing age. In cases of DIC, and shock. Because of the rapid elevated protein and mild pleocytosis.10 suspected Zika, the emergency provider onset of complications, patients with Treatment varies based on the should follow state guidelines for testing. signs of severe disease or a parasite load severity of the illness, drug susceptibility, Although dengue, chikungunya, and Zika of greater than 5% should be treated and species of parasite. Due to have been specifically mentioned, other immediately with intravenous (IV) increasing drug resistance in endemic diseases can present similarly. Therefore, antimalarial agents. Pregnant patients and areas, the World Health Organization a broad differential diagnosis should children are more susceptible to morbidity (WHO) recommends artemisinin-based be considered in returned travelers who and mortality related to malarial compounds as the first-line therapy present with acute febrile illness, including infections; clinicians should be vigilant for falciparum malaria infections.8,11 acute HIV, enteric fever, leptospirosis, when managing these patients, even those In addition to initial therapy to treat African trypanosomiasis, yellow fever, with seemingly mild symptoms. erythrocytic forms, patients with visceral leishmaniasis, hepatitis, influenza, Malaria is diagnosed based on P. vivax or P. ovale infections require tick-borne rickettsioses, and many other demonstration of the parasite, which primaquine to eradicate the dormant illnesses. is accomplished via thick and thin liver hypnozoites and prevent relapse.8 blood smears or more advanced The Centers for Disease Control CRITICAL DECISION methods, including rapid antigen tests and Prevention (CDC) maintains a What are the potential causes of and polymerase chain reaction (PCR) 24-hour malaria hotline, which provides hemorrhagic fever, and how should techniques.8 A febrile traveler who has clinicians with diagnostic and treatment returned from an endemic area should advice from a Malaria Branch expert at they be managed? promptly have thick and thin blood all times. The CDC Malaria Hotline can The WHO defines acute hemorrhagic smears examined for the parasite, after be reached Monday through Friday from fever syndrome as an acute onset of fever notifying the lab personnel about the 9 AM to 5 PM EST at 855-856-4713; of less than 3 weeks duration in a severely concern for the infrequently seen disease. for after-hours assistance with diagnosis ill patient, plus any two of the following: When suspicion is high and the or management of suspected malaria • Hemorrhagic or purpuric rash

6 Critical Decisions in Emergency Medicine • Epistaxis The combination of virulence and Dengue Virus • Hematemesis mortality of both Ebola and other Dengue virus infection is the most • Hemoptysis causes of VHF makes transmission common mosquito-borne illness • Blood in stools prevention a critically important focus. worldwide.21,22 Transmission is • Other hemorrhagic symptoms and no Early symptoms of VHF can be similar ubiquitous throughout the subtropics known predisposing host factors for to, and therefore difficult to distinguish and tropics, with more than half the 13 hemorrhagic manifestations. from, other febrile illnesses. During world’s population at risk of infection.23 Hemorrhagic fevers can be caused by an outbreak, febrile patients should be Manifestations of the infection can viral, bacterial, or rickettsial diseases. routinely screened for travel to endemic range from acute febrile illness, Viral causes can be classified into the areas and symptoms concerning for VHF. commonly referred to as dengue fever, following families: filoviruses (Ebola Clinicians must maintain a high degree of to dengue hemorrhagic fever and dengue and Marburg), arenaviruses (Lassa suspicion in any patient who has recently shock syndrome. fever, Junin, Machupo, Lujo, Sabia, returned from an endemic area or has The Aedes aegypti mosquito and Chapare), flaviviruses (yellow had contact with someone with VHF who is the primary vector for dengue fever, dengue, Omsk hemorrhagic presents with fever, muscle aches, severe virus transmission. The incubation fever, Kyasanur Forest disease), and headache, diarrhea, vomiting, abdominal period ranges from 3 to 14 days, bunyaviruses (Crimean-Congo hemorr­ pain, or any unexplained hemorrhage. but symptoms usually begin 4 to 7 hagic fever, Rift Valley fever, and If VHF is suspected, extreme caution days after being bitten by an infected Hantaan hemorrhagic fever). Each must be taken to prevent transmission mosquito. Dengue fever can present as virus is associated with a specific within the health care facility. The an acute febrile illness; it is colloquially host species, and human infection is patient should immediately be placed referred to as “breakbone fever” due to incidental. These host-virus associations in an isolated room with a designated the associated arthralgia. The WHO generally limit the distribution of each bathroom or bedside commode. Health recommends considering this diagnosis disease to specific geographical areas, care workers should act in designated when fever is accompanied by two although travelers can carry disease to roles to minimize the number of workers or more of the following symptoms: nonendemic areas. Human-to-human who manage the patient. All personnel severe headache, retro-orbital pain, spread can cause significant outbreaks, who come into contact with the patient joint pain, myalgia, nausea, vomiting, as exemplified by the recent Ebola should wear appropriate personal swollen glands, or rash.24 Hemorrhagic outbreak in West Africa. protective equipment, and interactions manifestations, such as epistaxis and should be recorded in a log. scattered petechiae, are seen in cases Ebola Virus For a comprehensive review of of uncomplicated dengue infection; Ebola virus disease sets itself apart appropriate personal protective however, they can also indicate more from other causes of hemorrhagic fever equipment, see the CDC guidelines severe disease. Patients with dengue by its virulence and mortality. Mortality at http://www.cdc.gov/vhf/ebola/ fever can also present with abdominal rates have reached as high as 70% to healthcare-us/ppe/guidance.html. The pain, lethargy, restlessness, or elevated 15,16 90% in prior epidemics. Ebola viruses facility’s infection control program and liver transaminases, but these should are found in several African countries. the local health department should be alert the provider to possible severe The infamous West African Ebola notified, and a workup should continue, dengue infection. epidemic of 2014 to 2015 turned the using only dedicated equipment in Symptoms of severe illness usually virus into a household name. compliance with local protocols. For manifest 2 to 5 days after the onset of The Ebola and Marburg viruses, further details on the approach to triage, typical dengue fever.25 In addition to of the filovirus family, are among the see the algorithm published by the CDC.20 fever, patients with hemorrhagic forms most virulent diseases in humans.16 If clinical suspicion remains high of the disease exhibit the following Unlike other causes of VHF, the primary after the initial evaluation, testing should triad of features: reservoir for Ebola is uncertain, although proceed in conjunction with the local • Evidence of increased vascular many believe that fruit bats serve this health department. Various forms of permeability role.17 Humans can contract the virus testing are available, including PCR, • Marked thrombocytopenia through contact with infected bats, enzyme-linked immunosorbent assay (100,000 cells/mm3 or less) primates, or other humans. Once humans (ELISA), virus isolation, and IgM and IgG • Spontaneous bleeding or signs of are infected, the disease can spread for patients later in the disease course. For hemorrhagic tendency26 rapidly. Human-to-human transmission most causes of VHF, no specific treatment When dengue is accompanied occurs through direct contact with bodily exists. Management should therefore by signs of circulatory failure (eg, fluids from an infected person, by objects be supportive with IV fluids, electrolyte hypotension, narrow pulse pressure, that have been contaminated with such replacements, supplemental oxygen, or weak pulses) in addition to features bodily fluids, and even through the semen vasopressors, and mechanical ventilation, of dengue hemorrhagic fever, the term of males who previously recovered from and combined with the treatment of other dengue shock syndrome is often used. the disease.18,19 infections, as needed. Historically, the virus has been classified

August 2018 n Volume 32 Number 8 7 Abdominal Pain and Fever FIGURE 3. Tourniquet Test Concerning features such as jaundice, The tourniquet test is part of the new WHO case definition for dengue. The test, which organomegaly, or hematochezia should is a marker of capillary fragility, can be used as a triage tool to differentiate patients prompt the clinician to pursue an with acute gastroenteritis, for example, from those with dengue. Note: Even if a expanded workup. Lab studies and tourniquet test was previously done, it should be repeated if it was previously imaging stool microscopy, stool negative or there is no bleeding manifestation. — culture and sensitivity, stool ova and How to perform the test: parasites, stool serology, hemoccult 1. Measure and record the patient’s blood pressure (eg, 100/70). testing, blood cultures, or other 2. Inflate the cuff to a point midway between SBP advanced diagnostic tools — should be and DBP; maintain for 5 minutes. (100 + 70) ÷ 2 = ordered as clinically indicated. Empiric 85 mm Hg treatment can be indicated based on the 3. Reduce and wait 2 minutes. suspected diagnoses. 4. Count petechiae below the antecubital fossa Aspects of a patient’s presentation (see image). can guide the emergency provider to A positive test is indicated by 10 or more narrow the differential diagnosis for petechiae per 1 square inch. fever and abdominal pain. For example, a chief complaint of watery diarrhea can into dengue fever, dengue hemorrhagic cuff is examined for petechiae, and the suggest enterotoxigenic Escherichia coli, fever, and dengue shock syndrome. number of petechiae is recorded. The test cryptosporidiosis, giardiasis, cholera, Although these terms are still frequently is considered positive if there are 10 or or a rotavirus. A history of bloody used in clinical practice, nomenclature more petechiae per 1 square inch of skin. diarrhea can suggest an invasive or has more recently been simplified to A positive test indicates microvascular inflammatory etiology, including both dengue with or without warning signs fragility and a hemorrhagic tendency. bacterial and parasitic causes, such as and severe dengue.26 In the updated Although dengue is generally a enterohemorrhagic E. coli, enteroinvasive classification system, severe dengue fever clinical diagnosis, more advanced E. coli, Salmonella, shigellosis, is defined by severe plasma leakage, confirmatory testing exists. Management Campylobacter enteritis, Yersinia severe hemorrhage, and/or severe organ is supportive, consisting primarily of enterocolitica, or Entamoeba histolytica. impairment. Understanding both systems volume resuscitation and analgesia. Pain However, these patients often present can help the provider recognize signs of management should be achieved with with watery diarrhea as well. more serious illness and communicate medications other than nonsteroidal Jaundice can imply etiologies such as effectively with consulting services. anti-inflammatory agents, as these are hepatitis, severe malaria, leptospirosis, yellow fever, dengue, or other VHFs. Signs of increased vascular contraindicated in cases of dengue fever.2 Organomegaly can suggest malaria, permeability include pleural effusion, leishmaniasis, amoebic liver abscesses, ascites, or hemoconcentration, which can CRITICAL DECISION enteric fever, brucellosis, schistosomiasis, be diagnosed with bedside ultrasound, What diseases should be or hepatitis. Petechiae can be due to chest radiographs, or chest or abdomen considered in a febrile returned leptospirosis, yellow fever, dengue, CT. These complications usually begin traveler with abdominal pain, or other VHFs. Abdominal pain and 3 to 7 days after the onset of typical respiratory complaints, or fever accompanied by a rash should dengue fever, usually coinciding with the alert the emergency physician to VHFs, time of defervescence. The sequelae of neurological symptoms? brucellosis, or enteric fever, among profound vascular leakage can include For undifferentiated fevers in returned other illnesses. Shigellosis should be respiratory distress and overt shock.26 travelers, the involved organ systems can considered in patients with diarrhea, Hemorrhagic manifestations of dengue provide additional clues for diagnosis. febrile seizures, and a history of travel. In virus include spontaneous bleeding, As with other travel-related illnesses, patients with fever, abdominal pain, and generally petechiae or ecchymoses, it is essential to elicit a detailed travel eosinophilia associated with pulmonary or evidence of hemorrhagic tendency. history to identify potentially important symptoms, the clinician should consider Hemorrhagic tendency is demonstrated exposures. Organ-specific signs and helminthic sources, such as hookworms by a positive “tourniquet test.” The test symptoms can assist the clinician. or roundworms. (Figure 3) is performed by taking the The approach to fever in the returned patient’s blood pressure and then inflating traveler with abdominal pain, respiratory Traveler’s Diarrhea the blood pressure cuff on the arm to symptoms, or neurological symptoms Diarrhea and gastroenteritis are midway between the systolic and diastolic should begin with the consideration of among the most common travel-related blood pressures, keeping it inflated for nontravel causes, and then be expanded complaints. Although it is important 5 minutes. The pressure is then released to a differential diagnosis that includes to consider more concerning etiologies, for 2 minutes. The skin beneath the travel-related etiologies. most patients with fever, abdominal

8 Critical Decisions in Emergency Medicine pain, and diarrhea are suffering from nonspecific. When suspicion exists, water, raw fruits and vegetables traveler’s diarrhea, a mild and self- malaria should be ruled out, and grown in fields fertilized with sewage, limited disorder that generally resolves other diagnoses should be considered, food and drinks from street vendors; within 3 to 7 days.27 Primary treatment is including hepatitis, VHFs, bacterial flooding; and suboptimal hand-washing targeted at fluid resuscitation, as needed. enteritis, dengue, brucellosis, rickettsial practices.30 Patients should be asked Antibiotic and antimotility agents can be infections, leptospirosis, amoebic liver about their immunization history, as used to limit the severity and duration of abscesses, acute HIV, cholera, amoebic many travelers who acquire typhoid symptoms. When there is suspicion for dysentery, and parasitic etiologies, such fever have not been appropriately enterohemorrhagic E. coli (eg, a history as Giardia and Cryptosporidium. immunized, and the vaccine can be less of bloody stools), caution should be used, The incidence of enteric fever is than 75% effective.31 as antibiotic treatment is associated with highest in South and Southeast Asia, The initial presentation of enteric but it should also be considered for an increased risk of hemolytic uremic fever is variable, but fever is generally travelers returning from Africa, East syndrome. present in the early stages. Vital Asia, West Asia, Central America, and Bacterial and viral pathogens signs can show relative bradycardia South America.28,29 The incubation associated with traveler’s diarrhea compared to what is expected for period for the disease ranges from generally have an incubation period of fever, sometimes referred to as pulse- 5 to 21 days.30 Humans are the 6 to 72 hours; the incubation period temperature dissociation or the Faget for protozoal pathogens is considerably only hosts of Salmonella Typhi and sign. The classically described “rose longer (typically 1-2 weeks).27 Markedly Salmonella Paratyphi, and both ill and asymptomatic chronic carriers can spots” of typhoid fever are groups elevated fever and blood or pus in the of faint, salmon-colored, blanching stool are uncommon and should raise shed bacteria in stool. Most cases are maculopapules, primarily found on suspicion for another etiology. transmitted via contaminated food or water. However, transmission has the trunk; when present, they are Enteric Fever been described in health care workers usually evident during the latter part Enteric fever, caused by Salmonella (exposed via both patient and specimen of the first week or during the second Typhi or Salmonella Paratyphi, can contact) and also between male sexual week of infection.30 Abdominal produce fever and abdominal pain partners.30 pain, nausea, vomiting, anorexia, in the returned traveler, particularly Risk factors for transmission include hepatosplenomegaly, myalgia, and undifferentiated prolonged fever. The the consumption of contaminated water headache can also be present. Patients presentation of the disease is somewhat or ice, food washed in contaminated with severe infection can present with gastrointestinal bleeding, intestinal FIGURE 4. Lung X-Ray of a Patient with Q Fever perforation with resulting peritonitis, septic shock, or altered mental status.30 A definitive diagnosis of Salmonella Typhi or Salmonella Paratyphi is made by isolation of the organism. The physician should consider ordering stool and blood cultures during the initial evaluation. Stool cultures are often negative during the first week of the disease course, while blood cultures are commonly positive. An important treatment consideration is the increasing rate of multidrug-resistant strains of Salmonella Typhi and strains with decreased ciprofloxacin susceptibility.30 For severe or complicated disease courses, ceftriaxone is considered the first-line empiric therapy. Antibiotic therapy for uncomplicated disease courses depends on the risk of antibiotic resistance; azithromycin is typically recommended for the empiric treatment of enteric fever acquired in areas with high fluoroquinolone resistance.

August 2018 n Volume 32 Number 8 9 Respiratory Complaints Adventure travelers, who participate Similarly, the CDC currently In one study, respiratory complaints in boating and swimming activities in recommends that patients with fever associated with fever occurred in Sub-Saharan Africa or Southeast Asia, and pneumonia be assessed for Middle about one in seven cases of fever in the are at risk for Katayama fever due to East respiratory syndrome coronavirus returned traveler.3 Although the vast acute schistosomiasis. In these patients, (MERS-CoV) if they have returned majority of cases are attributable to an immunological response to the from travel in the Arabian peninsula common bacterial and viral pathogens, schistosomal worms can cause fever, within the last 14 days, if they: it is important to note that travelers in nonproductive cough, bronchospasm, • have had close contact with such a close contact with the local population, urticaria, fatigue, and organomegaly. traveler, such as those visiting family or staying Pulmonary infiltrates on x-ray and • are febrile with respiratory in relatives’ homes, are at an increased eosinophilia typically present 4 to 6 complaints after spending time in risk for pneumonia and influenza, weeks after travel; the diagnosis is a health care facility (as a visitor, as compared to tourists and business primarily clinical.33,34 employee, or patient) in a territory travelers.3 Some other considerations Recent years have seen outbreaks of where health care-associated cases of include legionellosis, acute rapidly progressive respiratory distress MERS have recently been identified, schistosomiasis, Q fever, leptospirosis, syndromes. Ongoing public health • or have had close contact with a severe acute respiratory syndrome syndromic surveillance and the use of MERS patient. (SARS), and Middle East respiratory appropriate personal protection and Emergency physicians should follow syndrome (MERS). patient isolation can aid in the timely established guidelines for testing and Patients with a history of travel that diagnosis and prevention of further reporting in such cases.37 includes farm work, particularly with disease spread. For the SARS outbreak Neurological Complaints cattle, goats, or sheep, should be eval­ of 2002 to 2003, risk factors included uated for acute Q fever caused by health care workers, work caring for Altered Mental Status Coxiella burnetii, which is typically or slaughtering wildlife for human Altered mental status and fever transmitted in aerosolized animal consumption, male gender, advanced in travelers returning from malaria- excrement or contaminated soil (Figure 4). age, and air travel. The coronavirus, endemic regions requires emergent Unpasteurized milk is another source. transmitted by aerosolized droplets, had evaluation for cerebral malaria, bacterial meningitis, and encephalitis. Incubation is approximately 3 weeks, an incubation period of approximately Venezuelan equine encephalitis, and patients can present with pulmonary 4 to 6 days; patients typically presented Japanese encephalitis, and tick-borne symptoms, headaches, and other non­ with fever greater than 38°C (100.4°F) encephalitis should also be considered, specific signs. Emergency physicians should and pneumonia or acute respiratory depending on the area of travel. also be aware that Q fever can progress to distress syndrome (ARDS) on chest 2 Tick-borne encephalopathies are most endocarditis or vascular infections.3 radiograph.35,36 common in Eastern European outdoor adventurers. Neisseria meningitidis TABLE 2. National Notifiable Travel-Related Diseases (2018) should be considered for those patients who have visited Sub-Saharan Africa’s Arboviral diseases Giardiasis Typhoid fever meningitis belt, which encompasses • California serogroup virus Hantavirus Vibriosis 26 countries from Senegal to Ethiopia; • Chikungunya virus Hepatitis A Viral hemorrhagic fevers however, outbreaks are sometimes seen • Eastern equine encephalitis Hepatitis E • Crimean-Congo in other parts of the world. Although a vaccine is now required • Powassan virus HIV • Ebola virus for Muslim pilgrims who travel to • St. Louis encephalitis Malaria • Lassa virus Mecca, the vaccination does not cover • West Nile virus Meningococcal disease • Lujo virus all strains; physicians should remain • Western equine encephalitis Measles • Marburg virus alert for meningococcal meningitis. Cryptococcal meningitis and tuberculous Babeseosis Plague • Guanarito virus meningitis are further considerations Brucellosis Q fever • Junin virus when assessing immunocompromised Campylobacteriosis Salmonellosis • Machupo virus patients with prolonged travel and those Cholera Shigellosis • Sabia virus who have lived among local populations in Sub-Saharan Africa. Cryptosporidiosis Tuberculosis Yellow fever Dengue virus Tularemia Zika virus Seizure The two most common causes of Note: This list is not comprehensive; follow local reporting protocols. seizures worldwide, neurocysticercosis Data modified from the Centers for Disease Control and Prevention. https://www.cdc. and schistosomiasis, can present gov/nndss/conditions/notifiable/2018 with fever, but they are uncommon

10 Critical Decisions in Emergency Medicine in casual travelers.38 Seizures with febrile diarrheal illness should raise concern for shigellosis. Patients who present with febrile seizures after travel to endemic areas should also be evaluated for Japanese encephalitis, n Review assessments for international travel screening or other CDC and dengue hemorrhagic fever, and cerebral WHO information to help identify high-risk patients. malaria.38 Japanese encephalitis is a n Infections with seasonal fluctuations can present at atypical times due to mosquito-borne flavivirus that is vaccine varying times of transmission in other geographic areas. preventable. Travelers to rural and n If initial testing is negative, patients with suspected malaria should undergo periurban areas in Southeast Asia and repeat blood smears within 12 to 24 hours of presentation, as sensitivity the Western Pacific are at the highest improves with repeated tests. risk of exposure. Although only 1 in n When malaria has been excluded, consider enteric fever for cases of 250 infections causes serious clinical prolonged fever. disease, such cases can be heralded by fever, headaches, seizures, parkinsonian diseases, as compiled by the CDC, features, and even coma. In severe designation; reporting a notifiable that are unique to the returned disease courses, the case fatality rate disease is voluntary. Each state traveler. reaches 30%; up to another 30% determines what diseases fall under of patients experience permanent each category, so reportable diseases Summary neuropsychological problems.39,40 are unique to each state. Providers, While travel-related diseases are Diagnosis is based on serologic hospitals, and laboratories should report uncommonly seen in US emergency and CSF confirmatory studies, and cases to the local health department, departments, prompt recognition treatment is symptomatic. Refer to which then shares the information and appropriate management are the previous discussions on dengue with the CDC. Some laboratories essential for the safety of patients shock syndrome and malaria for automatically report positive results, but and the public. Emergency physicians further information. Remember that providers should familiarize themselves must be adept at taking a complete pregnant women, children, nonimmune with the procedures in their individual travel history, including prophylaxis populations, and those taking inadequate practice settings. and immunizations, and should be chemoprophylaxis are at increased risk Reporting cases of certain infectious comfortable forming an appropriate for cerebral malaria. diseases serves many purposes, most differential diagnosis. importantly helping to slow the Travel history, incubation period, CRITICAL DECISION spread of communicable diseases. and organ-system involvement should This information also facilitates Which diseases must be reported lead physicians toward specific surveillance, which can help to identify to the CDC? diagnoses. An increased index of sources of outbreaks; allows public suspicion should be maintained for In the interest of public health, the health organizations to plan preventive patients with higher-risk exposures, CDC must be informed of the diagnosis measures and control strategies; and such as adventure travelers, of several infectious diseases. It is the expedites the initiation of appropriate humanitarian workers, those visiting responsibility of the provider, not the treatment options. Specific diseases friends and relatives, and those with patient, to notify the CDC. Such diseases receive reportable designations based fevers lasting longer than 1 week. In are designated as either reportable or on virulence, communicability, and the addition, physicians must ensure that notifiable. It is mandatory to report potential for morbidity and mortality. patients are appropriately isolated, cases of any disease with a reportable Table 2 lists notifiable infectious personal protection protocols are followed, and specific diseases of concern are reported to the CDC. REFERENCES 1. Hill DR. Health problems in a large cohort of Americans traveling to developing countries. J Travel Med. 2000 Sep-Oct;7(5):259-266. 2. Venugopal R, D’Andrea S. Global travelers. In: n Neglecting to ask about recent travel or collect a thorough travel history. Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM, eds. Tintinalli’s Emergency n Ignoring personal safety precautions and appropriate isolation procedures. Medicine: A Comprehensive Study Guide. 8th ed. New York, NY: McGraw-Hill Education; 2016: n Failing to follow appropriate reporting protocols. 1094-1108. 3. Wilson ME, Weld LH, Boggild A, et al. Fever in n Failing to recognize patients at increased risk for more severe disease, returned travelers: results from the GeoSentinel including children, pregnant women, elderly patients, and immuno­- Surveillance Network. Clin Infect Dis. 2007 Jun 15; com­promised individuals. 44(12):1560-1568. 4. Cullen KA, Arguin PM; Centers for Disease Control and Prevention. Malaria surveillance – United States,

August 2018 n Volume 32 Number 8 11 CASE RESOLUTIONS ■ CASE ONE full-transmission precautions were and Streptococcus pneumoniae undertaken. Laboratory tests revealed The emergency physician were both negative; viral panels for elevated BUN and creatinine levels, suspected malaria in the woman influenza, respiratory syncytial virus, elevated liver enzymes, leukopenia, and with generalized malaise, fever, parainfluenza virus, and adenovirus thrombocytopenia. PCR confirmed the chills, headache, and abdominal were all negative; and sputum diagnosis of Ebola virus disease. The pain. Thick and thin blood smears cultures for acid-fast bacilli showed patient was treated supportively with revealed falciparum malaria with a IV fluids, electrolyte replacement, blood no growth. parasite density of 3%. At the time product transfusions, and eventually The clinician sent a lower of diagnosis, the patient exhibited mechanical ventilation. Despite these respiratory specimen for reverse- no manifestations of severe malaria. efforts, he died 7 days later. transcriptase polymerase chain She was treated with artemether- reaction (rRT-PCR) testing for lumefantrine twice a day for 3 days ■ CASE THREE MERS-CoV, which returned positive. and made a complete recovery. The 50-year-old man’s respiratory status worsened; he required intubation The patient received aggressive ■ CASE TWO for mechanical ventilation. His CT scan supportive care in the ICU, and after The 40-year-old man with bloody showed ground-glass opacities. Urine a 30-day hospitalization, eventually stools was isolated, and mandatory, antigens for Legionella pneumophila stabilized for extubation.

2011. MMWR. 2013 Nov 1;62(ss05):1-17. http://www. 17. Hayman DT, Yu M, Crameri G, et al. Ebola virus 29. Mogasale V, Maskery B, Ochiai RL, et al. Burden of cdc.gov/mmwr/preview/mmwrhtml/ss6205a1.htm. antibodies in fruit bats, Ghana, West Africa. Emerg typhoid fever in low-income and middle-income Accessed October 26, 2016. Infect Dis. 2012 Jul;18(7):1207-1209. countries: a systematic, literature-based update with risk-factor adjustment. Lancet Glob Health. 2014 5. Fairley JK. General approach to the returned traveler. 18. Crozier I. Ebola virus RNA in the semen of male Oct;2(10):e570-e580. In: Centers for Disease Control and Prevention. CDC survivors of Ebola virus disease: the uncertain gravitas Health Information for International Travel 2016. of a privileged persistence. J Infect Dis. 2016 Nov 15; 30. Pegues DA, Miller SI. Salmonellosis. In: Kasper DL, New York, NY: Oxford University Press; 2016. http:// Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo 214(10):1467-1469. wwwnc.cdc.gov/travel/yellowbook/2016/post-travel- J, eds. Harrison’s Principles of Internal Medicine. evaluation/general-approach-to-the-returned- 19. Uyeki TM, Erickson BR, Brown S, et al. Ebola virus 19th ed. New York, NY: McGraw-Hill Education; 2015: traveler. Accessed August 27, 2016. persistence in semen of male survivors. Clin Infect Dis. 1049-1055. 6. Schlagenhauf P, Weld L, Goorhuis A, et al. Travel- 2016 Jun 15;62(12):1552-1555. 31. Jackson BR, Iqbal S, Mahon B; Centers for Disease associated infection presenting in Europe (2008-12): 20. US Department of Health and Human Services; Control and Prevention. Updated recommendations an analysis of EuroTravNet longitudinal, surveillance Centers for Disease Control and Prevention. Ebola for the use of typhoid vaccine — Advisory Committee data, and evaluation of the effect of the pre-travel virus disease (Ebola): algorithm for evaluation of the on Immunization Practices, United States, 2015. consultation. Lancet Infect Dis. 2015 Jan;15(1):55-64. returned traveler. Centers for Disease Control and MMWR. 2015 Mar 27;64(11):305-308. https://www. 7. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum Prevention website. https://www.cdc.gov/vhf/ebola/ cdc.gov/mmwr/preview/mmwrhtml/mm6411a4.htm. of disease and relation to place of exposure among pdf/ed-algorithm-management-patients-possible- Accessed September 20, 2016. ill returned travelers. N Engl J Med. 2006 Jan 12; ebola.pdf. Accessed September 1, 2016. 32. Delord M, Socolovschi C, Parola P. Rickettsioses and Q fever in travelers (2004-2013). Travel Med Infect Dis. 354(2):119-130. 21. Barlam TF, Kasper DL. Approach to the acutely ill 2014 Sep-Oct;12(5):443-458. 8. White NJ, Breman JG. Malaria. In: Kasper DL, Fauci infected febrile patient. In: Kasper DL, Fauci AS, AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds. 33. Puylaert CA, van Thiel PP. Images in clinical medicine. Katayama fever. N Engl J Med. 2016 Feb 4;374(5):469. eds. Harrison’s Principles of Internal Medicine. 19th ed. Harrison’s Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill Education; 2015:1368-1384. New York, NY: McGraw-Hill Education; 2015:779-784. 34. Doherty JF, Moody AH, Wright SG. Katayama fever: an 9. Wilson ME. Fever in returned travelers. In: Centers acute manifestation of schistosomiasis. BMJ. 1996 Oct 22. Bhatt S, Gething PW, Brady OJ, et al. The global for Disease Control and Prevention. CDC Health 26;313(7064):1071-1072. distribution and burden of dengue. Nature. 2013 Apr Information for International Travel 2016. New York, 35. World Health Organization, Department of 25;496(7446):504-507. NY: Oxford University Press; 2016. http://wwwnc.cdc. Communicable Disease Surveillance and Response. gov/travel/yellowbook/2016/post-travel-evaluation/ 23. Brady OJ, Gething PW, Bhatt S, et al. Refining the Consensus Document on the Epidemiology of fever-in-returned-travelers. Accessed August 27, 2016. global spatial limits of dengue virus transmission Severe Acute Respiratory Syndrome (SARS). Geneva, 10. Misra UK, Kalita J, Prabhakar S, Chakravarty A, Kochar by evidence-based consensus. PLoS Negl Trop Dis. Switzerland: World Health Organization; 2003. http:// D, Nair PP. Cerebral malaria and bacterial meningitis. 2012;6(8):e1760. www.who.int/csr/sars/en/WHOconsensus.pdf. Ann Indian Acad Neurol. 2011 Jul;14(Suppl 1):S35-S39. 24. World Health Organization. Dengue and severe Accessed September 29, 2016. 11. World Health Organization. Guidelines for the dengue. World Health Organization website. http:// 36. Case definitions for surveillance of severe acute Treatment of Malaria. 3rd ed. Geneva, Switzerland: www.who.int/mediacentre/factsheets/fs117/en. respiratory syndrome (SARS). World Health World Health Organization; 2015. http://apps.who.int/ Accessed October 25, 2016. Organization website. http://www.who.int/csr/sars/ casedefinition/en/. Updated May 1, 2003. Accessed iris/bitstream/10665/162441/1/9789241549127_eng. 25. Kuhn JH, Peters CJ. Arthropod-borne and rodent- pdf?ua=1&ua=1. Accessed October 1, 2016. October 15, 2016. borne virus infections. In: Kasper DL, Fauci AS, Hauser 37. People who may be at increased risk for MERS. 12. Steele S. CDC Malaria Hotline — When the Caller is Ill SL, Longo DL, Jameson JL, Loscalzo J, eds. Harrison’s Abroad. Centers for Disease Control and Prevention Centers for Disease Control and Prevention website. Principles of Internal Medicine. 19th ed. New York, NY: https://www.cdc.gov/coronavirus/mers/risk.html. website. https://blogs.cdc.gov/global/2013/08/12/ McGraw-Hill Education; 2015:1304-1323. cdc-malaria-hotline—when-the-caller-is-ill-abroad/. Accessed November 1, 2016. Published August 12, 2013. Accessed October 28, 26. World Health Organization. Dengue: Guidelines 38. Han MH, Zunt JR. Neurologic aspects of infections in 2016. for Diagnosis, Treatment, Prevention and Control: international travelers. Neurologist. 2005 Jan;11(1): New Edition 2009. Geneva, Switzerland: World 13. World Health Organization. WHO Recommended 30-44. Health Organization; 2009. http://www.who.int/tdr/ Surveillance Standards. http://www.who. 39. Japanese encephalitis. World Health Organization int/csr/resources/publications/surveillance/ publications/documents/dengue-diagnosis.pdf?ua=1. website. http://www.who.int/mediacentre/factsheets/ whocdscsrisr992syn.pdf. Accessed October 25, 2016. Accessed September 10, 2016. fs386/en. Published December 31, 2015. Accessed 14. WHO Ebola Response Team, Aylward B, Barboza P, 27. Connor BA. Travelers’ diarrhea. In: Centers for Disease November 1, 2016. et al. Ebola virus disease in West Africa — the first 9 Control and Prevention. CDC Health Information 40. Thakur KT, Zunt JR. Approach to the international months of the epidemic and forward projections. for International Travel 2016. New York, NY: Oxford traveler with neurological symptoms. Future N Engl J Med. 2014 Oct 16;371(16):1481-1495. University Press; 2016. http://wwwnc.cdc.gov/travel/ Neurology. 2015;10(2):101-113. https://www.medscape. com/viewarticle/842226. Accessed November 1, 2016. 15. Bray M, Murphy FA. Filovirus research: knowledge yellowbook/2016/the-pre-travel-consultation/ expands to meet a growing threat. J Infect Dis. 2007 travelers-diarrhea. Accessed August 27, 2016. Nov 15;196(Suppl 2):S438-S443. 28. Crump JA, Luby SP, Mintz ED. The global burden 16. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. of typhoid fever. Bull World Health Organ. 2004 Lancet. 2011 Mar 5;377(9768):849-862. May;82(5):346-353.

12 Critical Decisions in Emergency Medicine The Critical Procedure Temporomandibular Joint Reduction

Temporal bone

By Michael Gibbons, MD, MBA Dr. Gibbons is an attending physician in the Department of Emergency Medicine at Articular Putnam Community Medical Center eminence Glenoid in Palatka, Florida, and North Florida fossa Regional Medical Center in Gainesville. Reviewed by Steven Warrington, MD, MEd Mandibular condyle

DISLOCATION REDUCTION NORMAL

Dislocation at the temporomandibular joint (TMJ) is caused by dislocation of the mandibular condyle(s). The disorder is commonly precipitated by trauma or excessive opening of the mouth. Spasms of the mastication muscles of the jaw, including the masseter, temporalis, and internal pterygoid, result in trismus and must be overcome for reduction to occur. Anatomically, the mandibular condyle generally becomes fixed in the anterior-superior aspect of the articular eminence.

Benefits and Risks ridge can be used as a resting point, instead of the teeth. TMJ reduction in the emergency department is a quick Proper positioning and preparation can also improve the odds procedure that can alleviate a patient’s discomfort and anxiety. of success and decrease the risks that can arise from sedation Its primary risks include injury to the person performing the or intraoral manipulation. procedure or further injury to the patient. Other risks include Special Considerations adverse effects caused by medications or sedation administered Cases that involve extensive facial trauma, mandibular prior to or during the procedure. fractures, or extensive dental hardware should be discussed with Since the clinician’s fingers or hands are often positioned intraorally and the muscles of the jaw are quite strong, a a consultant regarding the optimal treatment plan. However, the patient’s tooth can puncture the glove or skin. Loose dentition patient’s pain and anxiety should be considered while defining or dental hardware can be damaged during the process. that plan. After closed reduction, it is important to advise patients Finally, the possibility of iatrogenic damage to the bone and to implement a soft diet and avoid extreme opening (eg, yawning) surrounding tissues during reduction should be considered. while the jaw heals (approximately 1 week). Additionally, some patients may benefit from a nonsteroidal anti-inflammatory agent Alternatives and/or a wrap that helps keep the jaw closed. In addition to the intraoral technique previously described, an extraoral method can facilitate TMJ reduction. For the extraoral technique, the clinician massages over the dislocated TECHNIQUE condyle and muscles to relax the spasm and direct the 1. Position the patient in the supine/recumbent or sitting dislocation back to the joint space. A local anesthetic can be position, with the back resting against the bed. used as an adjunct and injected toward the lateral pterygoid 2. Provide sedation and/or an anxiolytic agent; consider and into the joint space. Surgical repair may be considered if adjunctive local anesthesia. external reduction cannot be achieved. 3. Apply gauze (over your glove) to digits that will be positioned intraorally, generally thumb(s). Prior to Reducing Side Effects applying the gauze, consider applying half of a tongue Contraindications to the procedure include severe facial depressor along the palmar surface of the thumb that will trauma and fracture of the mandible. To reduce the risk of be in contact with the patient’s teeth. clinician injury, some providers wrap their fingers with gauze 4. Apply consistent, downward traction with slight flexion and/or place a tongue depressor (cut in half) or finger splints and posterior displacement. between digits and dentition. Alternatively, the mandibular

August 2018 n Volume 32 Number 8 13 The LLSA Literature Review Venous Thrombosis in Pregnancy

By Eric Vaught, MD, MC, LT; and Daphne Morrison Ponce, MD, LCDR Naval Medical Center, Portsmouth, Virginia Reviewed by Andrew J. Eyre, MD, MHPEd

Greer IA. Pregnancy complicated by venous thrombosis. N Engl J Med. 2015 Aug 6;373(6):540-547.

Venous thromboembolism days with no interim anticoagulation for suspected DVT, as these two (VTE), which includes deep vein treatment. Iliocaval venous thrombosis conditions often arise concurrently. If thrombosis (DVT) and pulmonary is usually extensive and is often a patient with PE symptoms has a DVT embolism (PE), is the leading cause identified with compression ultra­ identified with ultrasound, no further of morbidity and mortality in sonography; however, MRI or x-ray imaging is needed and the diagnosis pregnant women in the developed venography can be considered for of PE can be made empirically. As in world. Although the absolute incidence evaluation if suspicion is high. nonpregnant patients, clinical suspicion of VTE in pregnancy is 1 to 2 per The majority of pregnant patients for PE should be heightened for those 1,000, this risk is 5 times higher than with PE also have DVT. A PE whose ECG shows sinus tachycardia or in nonpregnant patients. Most VTEs imaging workup can begin with the right heart strain. during pregnancy occur within the first same compression ultrasound used Oxygen saturation is an unreliable 20 weeks of gestation, but the overall incidence is greatest during the first 6 weeks postpartum. DVTs in pregnant KEY POINTS n women are more likely to be in the DVTs in pregnancy are more likely to be proximal and in the left leg. The left leg (85% in the left leg versus diagnostic test of choice is serial compression duplex ultrasonography. n 55% in the right leg) and proximal in If a DVT is identified in a patient with PE symptoms, no further imaging is the iliofemoral region (72% proximal needed, and empiric treatment should begin. n versus 9% distal). The strongest VQ scans and CTPA have similar negative predictive values (100% and 99%, predictive risk factor is previous VTE respectively). VQ scans emit a fetal radiation dose of 0.5 mGy, and CTPA emits a fetal radiation dose of 0.1 mGy. Both tests fall below the estimated in pregnancy. Other risk factors include level for teratogenesis and childhood cancer. venous stasis, immobilization, elevated n CTPA can be used in patients with an abnormal chest x-ray or indeterminate BMI, and dehydration from emesis. VQ scan, or if there is concern for other etiologies. Suspected DVT is best assessed n LMWH is the first-line treatment for VTE in pregnancy. There is no evidence with serial compression duplex to support an optimal dosing regimen for pregnant patients. ultrasonography; one prospective study n Warfarin can be used in the postpartum period but should not be used in demonstrated a negative predictive pregnant patients. Direct thrombin inhibitors and antifactor Xa inhibitors value of 99.5%. If the initial ultrasound are contraindicated. examination is negative but clinical n Thrombolysis is indicated for the management of hemodynamically suspicion remains high, it is safe to unstable PEs or for DVTs that threaten leg viability. repeat the examination in 3 to 7

Critical Decisions in Emergency Medicine’s series of LLSA reviews features articles from ABEM’s 2018 Lifelong Learning and Self-Assessment Reading List. Available online at acep.org/llsa and on the ABEM website.

14 Critical Decisions in Emergency Medicine diagnostic tool in pregnant or 100 IU/kg twice daily) or tinzaparin hemodynamic compromise or for DVTs postpartum women. Similarly, D-dimer (175 units/kg daily). There is no data that are threatening leg viability. Caval levels are not sensitive or specific to support tracking antifactor Xa levels filters can be used for recurrent PEs, enough to aid in the diagnosis. There while a patient is taking LMWH. despite adequate anticoagulation or is limited clinical data to support the LMWH should be stopped 24 hours if anticoagulation is contraindicated. validity of the Modified Wells’ Criteria before delivery or neuraxial anesthesia, Elastic compression stockings provide for Pulmonary Embolism and LEFt and when labor starts or is suspected. symptomatic relief only in patients clinical prediction tools (left leg >2-cm Anticoagulation can be restarted with DVT. difference, edema, and first trimester) 4 hours after delivery or after the The views expressed in this article are those of the authors and do not necessarily reflect the for diagnosing pregnant patients epidural catheter has been removed. with VTE. official policy or position of the Department of Anticoagulation is continued for the Navy, Department of Defense or the United If further imaging is required to at least 6 weeks postpartum (for a States Government. assess for PE, radiation exposure to the *** minimum total of 3 months). Warfarin fetus must be minimized. It is estimated We are military service members. This work was may be used in the postpartum period. prepared as part of our official duties. Title 17 that 1 mGy of radiation exposure Oral direct thrombin inhibitors and U.S.C. 105 provides that “Copyright protection in utero increases the risk of fatal under this title is not available for any work of antifactor Xa inhibitors should be childhood cancer by 0.006%. Chest the US Government.” Title 17 U.S.C. 101 defines avoided, as they cross the placenta and a US Government work as a work prepared by radiography emits more than 0.1 mGy a military service member or employee of the have adverse effects. Thrombolysis is of radiation; however, x-ray findings US Government as part of that person’s official reserved for life-threatening PEs with duties. can have limited clinical utility in assessing for PE. Ventilation-perfusion (VQ) scans have a high negative Factors That Increase VTE Risk in Pregnant Patients predictive value and are commonly performed after a normal chest x-ray. Computed tomographic pulmonary angiography (CTPA) is useful if the VQ scan is indeterminate, or if other diagnoses are suspected. Both tests minimize radiation to the fetus (CTPA = 0.1 mGy versus VQ scan = 0.5 mGy) and are well below the radiation threshold for teratogenesis. To further decrease radiation exposure, the ventilation portion of the VQ scan can be omitted without decreasing the negative predictive value. CTPA scans STASIS emit a maternal dose of 20 mGy to • Compression of iliac breast tissue, which is 20 to 100 times veins higher than VQ scan radiation; this risk • Right iliac artery over can be mitigated with breast shields. left iliac vein • Gravid uterus The treatment for VTE in pregnancy • Hormonally mediated is low molecular-weight heparin vein dilation (LMWH), which is more effective • Immobilization and has a better safety profile than unfractionated heparin in this patient VASCULAR DAMAGE HYPERCOAGULABLE BLOOD population. Warfarin is contraindicated • Vascular • á Procoagulant factors due to teratogenicity. The ideal dosing compression at á Fibrogen, factor V, IX, X, and VIII concentrations regimen for LMWH is unknown, delivery • â Anticoagulant activity and data is insufficient to support • Assisted or â Protein 5 concentration specific regimens in pregnant patients. operative delivery á Activated protein C resistance Therefore, enoxaparin (either 1 mg/kg • â Fibrinolytic activity twice daily or 1.5 mg/kg once daily, á PAI-1 and PAI-2 activity based on either prepregnancy or â tPA activity • More thrombin generation current weight) is acceptable. Other • Less clot dissolution appropriate dosing regimens include dalteparin (200 IU/kg once daily or

August 2018 n Volume 32 Number 8 15 The Critical Image A 30-year-old woman (G2 P2) with a history of ovarian cysts presents By Joshua S. Broder, MD, FACEP with 2 days of left lower-quadrant abdominal pain. The pain was Dr. Broder is an associate professor and the residency program director in the Division initially sharp, crampy, and intermittent but has now become constant. It of Emergency Medicine at Duke University is unaffected by eating. The patient reports nausea and vomiting; her last Medical Center in Durham, North Carolina. normal bowel movement was 24 hours before her emergency department Case contributor: Brandon Ruderman, MD visit. She denies fever, urinary symptoms, or vaginal bleeding or discharge. The patient’s vital signs are blood pressure 126/70, heart rate 97, respiratory rate 16, temperature 35.8°C (96.4°F), and oxygen saturation 100% on room air. She appears uncomfortable, and her left abdomen is tender to palpation, without rebound or guarding. Her pelvic examination is normal. Her laboratory tests, including urinalysis, liver function, lipase, and WBC count, are normal. A urine hCG test is negative. The emergency physician suspects ovarian torsion or a cyst. A pelvic ultrasound is performed, which shows bilaterally normal ovaries with normal blood flow. The patient continues to complain of severe pain, and a CT scan of the abdomen and pelvis with intravenous contrast is performed.

A Normal A-C. Axial, coronal, and sagittal CT images, small bowel Target sign, soft-tissue window. Enlarged panels are provided indicating for each to highlight the abnormal findings. In the bowel left abdomen, a segment of small bowel is seen within bowel telescoped within the surrounding small bowel. The proximal small bowel is not dilated, and therefore does not suggest accompanying obstruction.

B

Normal small bowel

Intussuscepted segment, with bowel within bowel

16 Critical Decisions in Emergency Medicine KEY POINTS typically can be reduced nonsurgically postoperative adhesions, and using an air-contrast enema. Although even devices such as feeding n Adult intussusception is rare; the enterocolic intussusception can occur tubes.4 One retrospective study incidence in one study was 37 (0.05%) in adults, more proximal enteroenteric suggests that intussusceptions per 69,040 abdominopelvic CTs intussusceptions frequently make shorter than 3.5 cm are likely to perform­ed over 4 years.1 In another this reduction technique difficult or be self-limited and more likely study, 45 cases of adult intussuscep­ impossible. Moreover, underlying to be benign.1 Other studies tion (0.08%) were identified in 58,000 malignancy reportedly accounts suggest that short segment surgeries over 12 years.2 for 16% to 65% of adult cases; as a intussusceptions with a narrow n Pediatric intussusception is often consequence, surgical reduction diameter and without obstruction clinically suspected based on some with or without resection of the are less likely to harbor combination of the classic triad affected bowel segment is frequently underlying pathology. However, of intermittent pain, bloody stool, performed.1-4 the rarity of the condition limits and palpable mass; ultrasound n Other causes of adult intussuscep­ study and requires clinical is commonly used as a targeted tion include inflammatory bowel judgment for each case to imaging technique. In contrast, adult disease, Meckel’s diverticulum, determine the need for surgery.5,6 intussusception is usually identified incidentally during CT performed to C evaluate for other potential causes of abdominal pain. Some patients present multiple times and undergo multiple imaging studies before the diagnosis is made, suggesting that adult intussusception is often intermittent. n Imaging findings in adults are similar to those seen in children with intussusception; in adults, CT Intussuscepted images through the short axis of the segment, bowel show a target sign with the with bowel invaginated intussusceptum visible within the within bowel concentric surrounding small or large bowel (intussuscipiens). Evidence of proximal obstruction may be present, in which case the diameter of the proximal small bowel will exceed 2.5 to 3 cm. The diagnosis of intussusception does not require the administration of enteric contrast. n The treatment of adult intussusception differs from that of pediatric cases. In children, ileocolic intussception is common and

CASE RESOLUTION The patient underwent laparoscopy, which confirmed an intussuscepted segment of jejenum in the left hemiabdomen. The bowel was reduced and appeared viable, but given the high risk of underlying pathology, a 15-cm segment of bowel, including the previously intussuscepted region, was resected. Pathology tests did not reveal any abnormalities, and the patient recovered uneventfully.

1. Lvoff N, Breiman RS, Coakley FV, Lu Y, Warren RS. Distinguishing features of self-limiting adult small-bowel intussusception identified at CT. Radiology. 2003 Apr;227(1):68-72. 2. Huang WS, Changchien CS, Lu SN. Adult intussusception: a 12-year experience, with emphasis on etiology and analysis of risk factors. Chang Gung Med J. 2000 May;23(5):284-290. 3. Yalamarthi S, Smith RC. Adult intussusception: case reports and review of literature. Postgrad Med J. 2005 Mar;81(953):174-177. 4. Marinis A, Yiallourou A, Samanides L, et al. Intussusception of the bowel in adults: a review. World J Gastroenterol. 2009 Jan 28;15(4):407-411. 5. Tresoldi S, Kim YH, Blake MA, et al. Adult intestinal intussusception: can abdominal MDCT distinguish an intussusception caused by a lead point? Abdom Imaging. 2008 Sep-Oct;33(5):582-588. 6. Kim YH, Blake MA, Harisinghani MG, et al. Adult intestinal intussusception: CT appearances and identification of a causative lead point. Radiographics. 2006 May-Jun;26(3):733-744.

August 2018 n Volume 32 Number 8 17 A 32-year-old woman with dyspnea. The Critical ECG Sinus rhythm, rate 84, acute pericarditis. Diffuse ST-segment elevation (STE) By Amal Mattu, MD, FACEP is present on this ECG. Although there are many conditions that can induce Dr. Mattu is a professor, vice chair, and STE on the ECG, the major diagnostic considerations in patients with diffuse director of the Emergency Cardiology Fellowship in the Department of STE are large acute myocardial infarction, acute pericarditis, benign early Emergency Medicine at the University repolarization, and left ventricular hypertrophy (LVH). LVH can be excluded of Maryland School of Medicine in by lack of voltage criteria. Of the remaining three considerations, acute Baltimore. pericarditis is the only one that causes PR-segment depression/downsloping, which is found in lead I and in the anterior and lateral precordial leads.

From Mattu A, Brady W. ECGs for the Emergency Physician 2. London: BMJ Publishing; 2008. Reprinted with permission.

18 Critical Decisions in Emergency Medicine Feeling No Pain Procedural Sedation

LESSON 16

By Sana Shahbaz, MD; and Sean Kivlehan, MD, MPH Dr. Shahbaz is an emergency medicine fellow at the South Asia Institute at Harvard University in Cambridge, Massachusetts. Dr. Kivlehan is the director of the International Emergency Medicine Fellowship in the Department of Emergency Medicine at Brigham and Women’s Hospital in Boston, Massachusetts. Reviewed by David J. Pillow, Jr, MD, FACEP

OBJECTIVES On completion of this lesson, you should be able to: CRITICAL DECISIONS 1. Describe procedural sedation, including its indications and n What levels of sedation can be achieved with contraindications. procedural sedation? 2. Discuss the different levels of sedation achieved through procedural sedation. n What are the indications and contraindications 3. Evaluate the various drug options available for procedural for procedural sedation? sedation. n What prerequisites, precautions, and preparations 4. Explain whether fasting is necessary prior to procedural are required for procedural sedation? sedation. n 5. Anticipate, identify, manage, and minimize the Is fasting a prerequisite for procedural sedation? complications of procedural sedation. n Which procedural sedation medications are safe 6. Perform safe procedural sedation in pregnant women. to use with pregnant patients? FROM THE EM MODEL n How can the complications of procedural sedation 19.0 Procedures and Skills Integral to the Practice be managed? of Emergency Medicine n What are the indications, contraindications, and 19.3 Anesthesia and Acute Pain Management doses of drugs used for procedural sedation? 19.3.3 Procedural sedation Because emergency physicians manage a spectrum of acute medical and traumatic conditions, they often perform painful procedures that require sedation. Procedural sedation and analgesia (previously known as conscious sedation) involves the use of several medications, including sedatives, dissociative agents, and/or analgesics.1 When aptly performed, the process reduces the pain and anxiety caused by invasive and noninvasive procedures, thus improving the experience for both the patient and clinician.2

August 2018 n Volume 32 Number 8 19 CASE PRESENTATIONS ■ CASE ONE an internally rotated hip and foot. initiates small boluses of IV normal His neurovascular status is intact. His saline and high-flow oxygen via face A 26-year-old man presents after blood pressure (BP) is 140/100; his mask. slipping and falling onto his shoulder. vital signs are otherwise normal. His X-rays confirm a dislocated right medical history includes hypertension, ■ CASE THREE shoulder without any fractures. He is coronary artery disease, and congestive A 22-year-old woman, who is given analgesia for pain management, heart failure. X-rays of the hip show 20 weeks pregnant, presents after while the emergency physician a posterior hip dislocation but no twisting her left ankle while walking prepares for a shoulder reduction. fracture. down the stairs. Her trauma survey On examination, the patient’s Acetaminophen and oxycodone are is normal, except for the deformed neurovascular status is intact in the administered for pain, while informed joint that needs reduction. She has no affected extremity, his vital signs are consent is obtained. The patient is medical history and is hemodynamically normal, and his pain score improves then taken to the resuscitation room stable. No neurovascular compromise from an initial 7 out of 10 to a 5 out to undergo hip reduction; he receives a is found. After obtaining informed of 10. pretreatment of fentanyl as an analgesic consent, the patient is transferred to and propofol as a sedative. The hip is the resuscitation room to undergo ■ CASE TWO successfully reduced, but soon after ankle reduction. Anxious to minimize A 70-year-old man is brought the procedure, the patient desaturates the side effects in both the mother and in by paramedics after falling at and becomes hypotensive. His oxygen fetus, the emergency physician reviews home. His trauma survey is normal; saturation level falls to 88%, and his the options for procedural sedation in examination of his right leg shows BP plummets to 80/60. The physician pregnant patients.

Because the appropriate regimen varies Patients respond to medications Dissociative Sedation based on the specifics of each case, differently, so levels of sedation vary Dissociative sedation creates a emergency physicians must thoroughly based on the circumstances. A clear line unique, trance-like state in which understand the advantages and between these states often does not exist, a patient experiences profound disadvantages of these medications and so clinicians must be prepared to manage analgesia and amnesia but be prepared to choose the most effective patients as they transition between retains airway protective reflexes, agent, administer it safely, and anticipate different sedation depths. potential complications. spontaneous respiration, and Minimal Sedation cardiopulmonary stability. Ketamine CRITICAL DECISION Minimal sedation describes a patient is the pharmaco­logical agent used to What levels of sedation can with a near-baseline level of alertness, produce dissociative sedation. be achieved with procedural who retains the ability to respond Deep Sedation normally to verbal commands. Although sedation? With deep sedation, a patient cognitive function and coordination Procedural sedation and analgesia cannot be easily aroused but responds may be impaired, ventilatory and — as defined by the American College purposefully to noxious stimulation. cardiovascular functions are unaffected. of Emergency Physicians (ACEP), Assistance may be needed to ensure In the emergency department, minimal American Society of Anesthesiologists that the airway is protected and sedation is commonly administered to (ASA), and Centers for Medicare and adequate ventilation is maintained. Medicaid Services (CMS) — is the facilitate minor procedures. Cardiovascular function is usually technique of administering sedatives Moderate Sedation stable; however, the patient must be or dissociative agents, with or without With moderate sedation, a patient closely monitored for any changes analgesics, to induce an altered state responds purposefully to verbal of consciousness, while preserving in ventilatory or cardiovascular commands alone or when accompanied cardiorespiratory function.2-4 During the function. by light touch. Droopy eyelids or slurred process, patients reach different levels General Anesthesia of sedation, depending on the dose, type speech with delayed verbal responses With general anesthesia, a patient of medication, and response to the drug also can be noted. Protective airway (Figure 1). Sedation depths are part of reflexes and adequate ventilation are is completely unresponsive to painful a continuum, ranging from minimal maintained without intervention, and stimuli and often requires assistance sedation to general anesthesia. However, cardiovascular function remains stable. to protect the airway and maintain ketamine is unique in that it is the only Patients frequently experience amnesia ventilation. Cardiovascular function agent that produces dissociative sedation. about the experience. may be impaired.

20 Critical Decisions in Emergency Medicine CRITICAL DECISION Contraindications vary according to predictive value (Table 1). For example, the type of procedure and the age and ASA class I and II patients have a low What are the indications and comorbidities of the patient. Pulmonary risk of complications, but keep in mind contraindications for procedural diseases such as chronic obstructive that risks rise with deeper levels of sedation? pulmonary disease (COPD), ischemic sedation. Procedural sedation can be used cardiac disease, heart failure, anemia, and Anticipating Difficult Airways in the emergency department for any neuromuscular diseases all increase the Before procedural sedation, all procedure that causes pain or anxiety associated risks of procedural sedation. patients should undergo a difficult- in the patient. Common procedures Emergency physicians should be aware airway assessment, and information not only of a patient’s chronic conditions, requiring procedural sedation include should be gathered about any previous but also of acute presentations that can fracture reduction and dislocation, experience with sedation and analgesia. foreign body removal, laceration affect the safety of the sedated patient, A history of a difficult or failed airway, repair (particularly in young children), including hypovolemia, renal failure, and or difficult bag-valve-mask ventilation, abscess drainage, lumbar puncture, acute respiratory infections. is a strong risk factor for complications; endoscopy, bronchoscopy, and electrical Drug allergies can typically be averted however, this information is frequently cardioversion. Procedural sedation can by using different medications, but the unavailable. One study identified the also facilitate diagnostic evaluations with physician should anticipate and prepare following five factors as independent CT or MRI, as well as burn dressing to address a difficult airway. The ASA’s predictors of difficult bag-valve-mask changes and the placement of chest tubes physical status classification system ventilation: age greater than 55 years, and central catheters.5 quantifies the risks into a meaningful body mass index (BMI) greater than 26 kg/m2, presence of a beard, absence of teeth, and a history of snoring.6 TABLE 1. ASA’s Physical Status Classification System Additional difficult-airway risk factors Definition Examples (Including But Not Limited To) include a short neck, micrognathia, a Class I A normal healthy Healthy, nonsmoking, and no or minimal alcohol use large tongue, trismus, morbid obesity, patient and anatomical abnormalities of the 7 Class II A patient with mild Mild diseases only, without substantive functional airway and neck. systemic disease limitations. Current smoker, social alcohol drinker, The Mallampati classification pregnant, obese (BMI 30-39.9), well-controlled diabetes system is a simple assessment tool that mellitus or hypertension, or mild lung disease correlates visualization of anatomical Class III A patient with severe Substantive functional limitations, with one or more oropharyngeal structures to intubation systemic disease moderate to severe diseases. Poorly controlled difficulty (Figure 2). The Mallampati diabetes mellitus or hypertension, COPD, morbid score is one component of a commonly obesity (BMI ≥40), active hepatitis, alcohol depen­ used mnemonic device — LEMON dence or abuse, implanted pacemaker, moderate — to predict potential complications reduction of ejection fraction, end-stage renal disease (Table 2).8,9 If a difficult airway or undergoing regularly scheduled dialysis, premature difficult mask ventilation is anticipated, infant with post-conceptional age <60 weeks, history anesthesia should be consulted; in such (>3 months) of myocardial infarction, cerebrovascular accident, transient ischemic attack, or coronary artery cases, it may be optimal to perform the disease/stents. procedure in the operating room. Class IV A patient with severe Recent (<3 months) myocardial infarction, Age Considerations systemic disease that cerebrovascular accident, transient ischemic attack, In children, active upper-respiratory is a constant threat or coronary artery disease/stents, ongoing cardiac infections and asthma significantly to life ischemia or severe valve dysfunction, severe reduction increase the risk of laryngospasm, which of ejection fraction, sepsis, disseminated intravascular should factor into the decision to sedate.5 coagulation, acute respiratory distress syndrome, or end-stage renal disease not undergoing regularly No upper age limit for procedural scheduled dialysis sedation exists, but the elderly have a higher risk of complications due to Class V A moribund patient Ruptured abdominal/thoracic aneurysm, massive who is not expected trauma, intracranial bleed with mass effect, ischemic several factors, including increased to survive without the bowel in the face of significant cardiac pathology, or drug sensitivity and interactions with operation multiple organ/system dysfunction chronic medications. Additionally, the Class VI A declared brain-dead higher prevalence of cardiovascular and patient whose organs pulmonary diseases in geriatric patients are being removed for increases the likelihood of hemodynamic donor purposes instability and respiratory difficulty.10 Reducing both the dose and frequency

August 2018 n Volume 32 Number 8 21 FIGURE 1. Safely Sedated — States of Consciousness Vary When Patients Get Anesthesia

General Deep sedation Moderate Minimal Regional Local anesthesia anesthesia Patients sleep sedation sedation anesthesia An anesthetic Patient is through surgery Patients feel Patients feel Injection near a drug is usually unconscious. with little drowsy and may relaxed and cluster of nerves injected into the Gases or vapors memory of the sleep through may be awake. numbs the area tissue to numb the are inhaled procedure upon the procedure. They can answer that requires specific location through a waking. Breathing Patients awaken questions and surgery. Patients requiring minor breathing mask can slow, and when spoken to or follow a physician’s stay awake or are surgery. or tube, and other supplemental touched. Memory instructions. given a sedative. drugs are given oxygen is often of the procedure through a vein. given. is minimal. Derived from The American Society of Anesthesiologists

of medications can help mitigate side emergency airway management, as Procedural sedation should be effects and avoid oversedation in this needed.2 While additional institutional administered in a spacious room vulnerable population.11-14 and departmental requirements may adequately stocked with equipment for apply, ACEP states that “short courses” airway management and resuscitation. CRITICAL DECISION such as Advanced Cardiac Life Support Continuous heart rate and pulse What prerequisites, precautions, (ACLS) serve only as focused review and oximetry monitoring should be available, 15 and preparations are required are superseded by board certification. along with interval blood pressure The minimum number of providers for procedural sedation? measurements. In addition, oxygen, required to perform procedural sedation suction, and airway adjuncts should be Only properly credentialed emergency is two: the physician who performs the immediately accessible. Reversal agents physicians with privileges at their procedure and another trained clinician, relevant to the agents being used, such institution should perform procedural such as a nurse, who continuously as naloxone or flumazenil, should be sedation. ACEP recommends that all monitors the patient and vital signs.2 obtainable. Intravenous (IV) access graduates of an emergency medicine The patient should be informed in detail should be available, as it is needed residency program accredited by the about the procedure and its potential for most agents; however, the need Accreditation Council for Graduate risks, benefits, and complications. Medical Education (ACGME) or the Verbal or written informed consent for access when using agents such as 15,16 American Osteopathic Association is acceptable, as long as institutional ketamine is controversial. (AOA) be credentialed on the basis of guidelines are followed.5,15 A history The ASA has provided detailed their training.15 and physical should be completed, guidelines about recommended The performing clinician is expected including an evaluation of comorbid equipment for nonanesthesiologist- to be familiar with the medications conditions and allergies to medications.15 performed sedation and anesthesia.4 used, relevant reversal agents, side Specifically, the patient should be asked All equipment should be checked, and effects, and complications. It is also about any previous exposure and a time-out should be called, with all imperative for providers to have the response to analgesia or anesthesia. involved staff present, immediately prior capacity to rescue a patient from a Finally, an airway assessment should be to performing the sedation. deeper level of sedation and provide performed, as previously discussed. By monitoring end-tidal carbon

dioxide (ETCO2) continuously TABLE 2. LEMON Mnemonic Device throughout the procedure, clinicians can reduce the risk of hypoxia and other L Look externally Look for facial trauma, a beard, tongue size, and so on. adverse respiratory events. It remains E Evaluate 3-3-2 rule 3-cm mouth opening; 3 finger breadths (chin to unclear, however, whether continuous hyoid bone); 2 finger breadths (hyoid bone to thyroid capnography monitoring reduces more cartilage). serious complications.2 The need for M Mallampati Calculate the patient’s Mallampati score. automatic supplementary oxygen O Obstruction Look for swelling, vomit, and so on. is debatable; a 2011 ACEP policy N Neck mobility Evaluate the range of neck motion. statement recommends that its use be left to the physician’s discretion.15

22 Critical Decisions in Emergency Medicine Ketamine, in particular, has been applies to emergency situations nor have been shown in animal models shown to be safe without the use of emergency department procedural to be deleterious to the fetus, so the supplemental oxygen.16 While some sedation. general recommendation is to provide physicians argue that supplemental Physicians also debate the need routine supplemental oxygen during oxygen can prevent hypoxia secondary for prophylactic antiemetics with the sedation of a pregnant patient.23 to hypoventilation, others counterargue procedural sedation. The ASA does Placing the patient in the left that it can delay the recognition of not recommend the routine use of lateral recumbent position during hypoxia and needed interventions.4,5,11,17 prophylactic antiemetics; however, its sedation is another simple precaution guidelines indicate that patients should that can reduce medication-related CRITICAL DECISION be fasting.19 While some agents used for hypotension by shifting the uterus off Is fasting a prerequisite for procedural sedation (eg, propofol) have the vena cava. Another precaution 11 procedural sedation? antiemetic properties, ketamine stands is the administration of IV fluids. out as being emetogenic. Ketamine- In addition, pregnant patients have Aspiration is a commonly cited associated vomiting has been well higher rates of reflux esophagitis risk of procedural sedation, although studied in pediatrics, with reported and heartburn, so prophylactic evidence of this complication in the rates as high as 28%. In one large metoclopramide or an H2 antagonist emergency department is sparse and study, the use of prophylactic atropine is recommended to reduce the risk of documented occurrences are rare. A and metoclopramide did not decrease vomiting and aspiration.11,23 2016 meta-analysis found 1 case of this rate.20 Studies show conflicting Limited data are available on the aspiration out of 2,370 sedations, data on the ability of ondansetron to safety of procedural medications in an incidence rate of 1.2 per 1,000 reduce vomiting.21,22 Thus, the use of pregnancy, so most recommendations 18 sedations. ACEP’s Clinical Policy: prophylactic antiemetics with procedural are based on animal data. Ketamine is Procedural Sedation and Analgesia in sedation in the emergency department is generally safe and has not been found the Emergency Department states that best left to the clinician’s discretion. to be teratogenic; however, it increases “Preprocedural fasting for any duration maternal heart rate and blood pressure has not demonstrated a reduction in CRITICAL DECISION and should be avoided when managing the risk of emesis or aspiration when Which procedural sedation a pregnant patient with hypertension.23 administering procedural sedation Propofol is considered safe, but 2 medications are safe to use and analgesia.” However, guidelines hypotension should be aggressively with pregnant patients? for preprocedural fasting vary by prevented and corrected. Furthermore, organization and institution. Clinicians must be aware that neonatal depression is a concern when Based on the current ASA guidelines, physiological changes during using these agents near the time of many institutions continue to pregnancy increase certain risk factors delivery.23 Midazolam has a conflicting recommend preprocedural fasting states during sedation. Decreased functional profile with possible teratogenicity and of 2 hours for clear liquids and 6 hours residual capacity, increased oxygen should be avoided. Short-acting agents, 19 for a meal. As noted in ACEP’s policy, demand, increased respiratory rate, such as remifentanil and nitrous oxide, the widely used ASA recommendations and relative hypotension are normal also can be considered.23 apply to elective general anesthesia in pregnancy and can be exacerbated cases in which airway manipulation by procedural sedation agents. Both CRITICAL DECISION is expected; neither recommendation maternal hypoxemia and hypercapnia How can the complications of procedural sedation be TABLE 3. Common Complications and First-Step Interventions managed? Complication Interventions The major complications of Agitation Calm patient; benzodiazepine procedural sedation are related to the Apnea Oxygen and bag-valve-mask ventilation; evaluate the need for airway and apnea, although hypotension intubation is common as well. A systematic review Aspiration Suction; treat hypoxia with oxygen; evaluate for the need for and meta-analysis of 9,652 cases found intubation and antibiotics that the most common adverse events are hypoxia (40.2 per 1,000), vomiting Bradycardia Usually self-resolving; atropine if persistent (16.4 per 1,000), hypotension (15.2 per Hypoxia Open airway; stimulate; oxygen 1,000), and apnea (12.4 per 1,000).18 Hypotension Usually self-resolving; fluid bolus or push-dose pressor if persistent Early recognition of a complication is Laryngospasm High-flow oxygen; bag-valve-mask ventilation; consider paralytics crucial, which is why close monitoring is and intubation a key component of the procedure. Once Vomiting Suction; left lateral position; airway management identified, simple and rapid action can correct most adverse effects (Table 3).

August 2018 n Volume 32 Number 8 23 FIGURE 2. Mallampati Classification System

Class I Class II Class III Class IV

When performed properly, procedural the medications used for sedation.18 based on the patient’s previous reaction sedation in the emergency department is Some providers opt to pretreat nausea history, comorbidities, and current safe: In the above cohort, no deaths, one with antiemetics such as ondansetron; hemodynamics. case of aspiration, and two unplanned however, studies conflict on the Apnea intubations were reported. effectiveness of this approach. Suction Midazolam, alone or in combination should be immediately accessible Hypoxia during sedation so that the airway can with an opiate, is the most likely sedative Continuous pulse oximetry should be cleared without delay if vomiting to cause apnea; however, apnea can be performed on all patients to occurs. Vomiting patients should occur with any sedative at sufficient immediately detect hypoxia. Many receive an antiemetic agent, and airway doses. Early recognition of apnea providers also place all patients on management should be escalated, can be achieved with capnography continuous oxygen during procedural as needed. Sedation may need to be monitoring and pulse oximetry. While sedation; however, continuous oxygen aborted, depending on the severity of mild symptoms can usually be corrected can mask early hypoxia and should be vomiting; remember that vomiting can by stimulating the patient, apnea should performed judiciously. Capnography continue even after reversal. always be taken seriously; intermittent monitoring can be used with pulse apnea can be a warning sign of severe, oximetry to provide earlier detection Hypotension impending complications. Reversal of hypoventilation and apnea, but it The clinical definition of hypotension agents, such as naloxone or flumazenil, has not been shown to reduce serious varies, and the significance of mild can be used, as needed. Newer data show events.2 hypotension during sedation is that apnea is frequently preceded by Propofol and the combined use of unclear. Propofol and the combination predictable alterations in ventilation of midazolam with an opiate most midazolam with an opiate result in (eg, an ETCO2 that rises from <30 mm Hg the highest rates of hypoxia.18 Once commonly precipitate a decrease in to >50 mm Hg).26 Apnea appears to 18 recognized, this complication should blood pressure. Hypotension caused be a common yet easily correctible be immediately corrected with oxygen by propofol is usually self-limiting due complication: All apneic events in the 24 and airway management techniques, to the short duration of action. Mild study were corrected with stimulation, as required. A basic maneuver (eg, elevations can be treated with an IV oxygen, or airway repositioning.26 head-tilt/chin-lift or jaw-thrust) is often fluid bolus (20 mL/kg) and by putting Laryngospasm sufficient to correct hypoxia. However, the patient in the supine position. More Laryngospasm is a major concern with the physician should be prepared to severe or persistent hypotension can the use of ketamine. Large meta-analyses escalate interventions, as needed, with often be corrected with a push-dose 25 have shown a 0.3% incidence rate in positive pressure ventilation or advanced pressor such as phenylephrine. In rare cases, sedation may need to be pediatric patients and a 0.4% incidence airway management. aborted if the patient’s hemodynamics rate in adults.18,27 High doses and pre- Vomiting cannot tolerate the medication effects. existing upper respiratory infections in While the highest incidence of Avoiding hypotension should be a children are thought to be risk factors, vomiting occurs with ketamine, this consideration when deciding which but laryngospasm can occur at any side effect can be triggered by any of drug to use; the decision should be time. Providers must always be prepared

24 Critical Decisions in Emergency Medicine for the possibility.16 If identified, bag- 4 mg/kg to 5 mg/kg for both action, and rapid recovery of cognitive valve-mask ventilation is generally populations. The typical duration of functions.5,31 Its other benefits include sufficient, although the provider should action for the drug is 15 to 30 minutes antiemetic and euphoric effects. Since be prepared to paralyze and intubate, for IV delivery and 30 to 60 minutes propofol does not have analgesic if needed. Applying inward pressure for IM delivery.16 Notably, IM delivery properties, appropriate analgesia should behind the lobule of the pinna of each produces higher rates of vomiting be provided when using it for painful ear, while anteriorly dislocating the jaw, and a longer recovery time, while IV procedures .32 at a location known as “Larson’s point” administration allows for repeat dosing, Propofol in adults and children is or the “laryngospasm notch” may as needed, to sustain the drug’s action. slowly injected, with an initial loading terminate laryngospasm.28 Ketamine transiently increases heart dose of 1 mg/kg IV, followed by doses Clinicians must be vigilant, both rate and blood pressure but does not of 0.5 mg/kg IV every 3 minutes, as during and after every sedation affect respiration unless rapidly injected. necessary until the appropriate level procedure, to watch for warning signs Since rapid injection can cause transient of sedation is achieved.24 The agent is of adverse events that require rapid respiratory depression, ketamine should contraindicated for patients allergic intervention. The sedated patient should be pushed slowly over 30 to 60 seconds to egg lecithin and soybeans.24 Major be given special attention directly after when given by IV.16,29 The agent also side effects include hypotension and the procedure; when the procedure is has nondissociative analgesic properties respiratory depression, which usually complete and the painful stimulus is at lower doses (<0.3 mg/kg) and can be resolve quickly due to the short duration removed, medication-induced apnea used for both general pain management of action. A short-acting, push-dose or hypotension previously masked and sedation.30 pressor can be used if hypotension is by sympathetic stimulation can The most commonly reported side severe. Elderly patients often exhibit become more pronounced. To prevent effect of ketamine is an emergence hypotension, so initial dosing should complications, emergency physicians reaction (seen in 10%-20% of patients), be reduced by 50%. A small amount of must choose the appropriate medications which can be managed with reassurance lidocaine can be administered to prevent for each patient in accordance with in most cases or with benzodiazepines pain at the injection site.24 in severe cases.29 Other adverse effects the procedure, age, comorbidities, Ketofol and expected difficulty in airway include laryngospasm, vomiting, and Ketofol is a combination of ketamine management. hypersalivation.29 Ketamine should not be and propofol, coadministered in a used for patients younger than 3 months 1:1 mixture, which has increased in CRITICAL DECISION due to an increased risk of adverse airway popularity in recent years. Theoretically, What are the indications, events, or for any patient with known or this approach balances the negative suspected schizophrenia.16 contraindications, and doses inotropic and respiratory effects of of drugs used for procedural Propofol propofol with the stimulant effects sedation? Propofol is a sedative-hypnotic agent of ketamine. Furthermore, propofol’s without analgesic properties. It has a antiemetic properties can balance No single recommended drug or drug rapid onset of action (within 30-60 ketamine’s proemetic effects; propofol’s regimen exists for procedural sedation. seconds) and a duration of action of sedative effects also can negate an The process can require a sedative, an 5 to 6 minutes.31 The benefits of the drug emergence reaction.2 Starting doses for analgesic, and/or a dissociative agent, include a rapid onset, short duration of this regimen are 0.5 mg/kg of each agent. depending on the situation (Table 4). Among the desirable drug qualities are a rapid onset, a short duration, and TABLE 4. Adult Procedural Sedation Agents maintenance of hemodynamic stability — Medication Initial Dose Route Peak Effect Duration all without causing major side effects.2 Ketamine 1 mg/kg IV 1-3 minutes 15-30 minutes Ketamine 2-5 mg/kg IM 5-20 minutes 30-60 minutes Ketamine is a dissociative agent Propofol 0.5-1 mg/kg IV 30-60 seconds 5-6 minutes that provides analgesia and sedation, Ketofol 1:1 mixture of 0.5 mg/kg ketamine IV 30-60 seconds 15 minutes while preserving the airway, breathing, and 0.5 mg/kg propofol and blood pressure.16,29 It can be given Etomidate 0.15 mg/kg IV 15-30 seconds 3-8 minutes intravenously or intramuscularly (IM), Midazolam 0.05-0.1 mg/kg IV 2-3 minutes 20-30 minutes the latter being used commonly for pediatric patients. The recommended 0.1 mg/kg IM 15-30 minutes 60-120 minutes dose for ketamine is 1 mg/kg to 2 mg/kg 0.2-0.5 mg/kg IN 10-15 minutes 45-60 minutes IV over 1 to 2 minutes for adults and 0.5-0.75 mg/kg PO 15-30 minutes 60-90 minutes 1.5 mg/kg to 2 mg/kg IV for pediatric Data from Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th ed. patients. Recommended IM dosing is

August 2018 n Volume 32 Number 8 25 Alternative Agents Ultrashort-acting opiates, such as alfentanil and remifentanil, have been used for procedural sedation in the emergency department. Early reports n Prepare all monitoring and airway management equipment prior to sedation, describe them as safe and effective, but keeping it readily available during the procedure. added benefits remain unclear, when n Consider the pros and cons of each medication and then tailor the sedation plan compared to established options.2 to the specific patient and context, accounting for the patient’s hemodynamic Nitrous oxide is an inhaled gas typically status and the type of procedure. composed of 30% oxygen and 30% to n Simple maneuvers like stimulation, opening the airway, and providing oxygen can 70% nitrous oxide that provides rapid correct most adverse apneic or hypoxic events. anesthesia and recovery due to the low n Ketamine and propofol are safe to use during pregnancy; however, midazolam solubility of nitrous oxide in the blood. should be avoided. The agent has a rapid onset of less The administration of ketofol for midazolam is 0.05 mg/kg IV or IM. than 1 minute and a recovery time does not appear to provide a clinical When given by IV, onset occurs within 2 of 5 minutes. Self-administration benefit over using either agent alone.33 to 3 minutes, with a duration of action is recommended for safe titration; Specifically, the drug does not reduce of 20 to 30 minutes.31,38 While repeat cardiovascular side effects are minimal. adverse respiratory events. Propofol, doses can be given in 3- to 5-minute However, sedation is often not complete on the other hand, causes slightly more increments, as needed, physicians should for more painful procedures, and overall hypotension when used alone, which is be cautious to avoid “dose stacking” use has been limited in emergency of unclear clinical significance.34 from the residual effects of previous departments due to the need to use gas doses. Midazolam is frequently used in scavenger systems.5,38 Etomidate pediatrics and can be given intranasally Etomidate is a short-acting, sedative- (IN) at 0.2 mg/kg or orally (PO) at Summary hypnotic agent that has minimal effects 0.5 mg/kg. While useful for children Procedural sedation is a safe on respiratory and cardiovascular status. who fear needles, the IN route can cause practice in the emergency department It can rapidly produce deep sedation irritation, and the PO route produces a that can reduce a patient’s anxiety but has no analgesic properties; thus, an 5 variable dosing response. or apprehension when undergoing a analgesic should be provided for painful Midazolam can cause respiratory potentially painful procedure. Since procedures. Adult dosing of etomidate for depression, bradycardia, and hypo­ the process is a core competency in sedation is 0.1 mg/kg; onset occurs in less tension, particularly when combined emergency medicine, providers must than 1 minute, with a duration of action with an opiate.5,18 Paradoxical reactions, understand the various medication of 3 to 8 minutes. Repeat doses can be in which the patient becomes agitated, options and how to balance the risks and administered every 3 to 5 minutes, as occur in 1% to 15% of pediatric benefits of each drug to determine the needed.35,36 Myoclonus occurs in 20% to patients.5 Obese patients, the elderly, 40% of patients; while myoclonus is not and those with hepatic dysfunction safest and most effective sedation plan dangerous to the patient, it can interfere can experience prolonged sedation.38 for each patient. Clinicians must also with the procedure.2 Adrenal suppression Flumazenil can reverse the effects, but be prepared to manage patients as they due to an etomidate-induced depression caution should be used for chronic transition between different sedation of cortisol levels, particularly in septic benzodiazepine users, as flumazenil can depths and be skilled at anticipating, or trauma patients, can occur; however, cause seizures in this population.31 detecting, and correcting complications. several studies have shown no clinical significance.2,37 Additional side effects include respiratory suppression, nausea, and vomiting.5,31,35 Midazolam Midazolam is a benzodiazepine with amnestic, hypnotic, and anxiolytic n Failing to prepare for hemodynamic and airway complications. properties, but no analgesic effect.38 It n Disregarding the increased risk of hypotension and apnea when using is frequently used in conjunction with a combinations like propofol and an opiate, or a benzodiazepine and an opiate. short-acting opiate like fentanyl. Of all n Overlooking the major risk factors and contraindications of various medications. the benzodiazepines, midazolam has the n Neglecting the patient immediately following the procedure, while the patient is most rapid onset and strongest amnestic still sedated. effects.38 The traditional starting dose

26 Critical Decisions in Emergency Medicine CASE RESOLUTIONS

24,39 ■ CASE ONE prior to discharge. The patient reduced hip. In retrospect, the provider was given written instructions that should have considered a reduced dose The young man with a dislocated explained the potential medication- of propofol or the use of alternative shoulder required procedural sedation specific side effects and solutions, as agents, such as ketamine or etomidate, to facilitate reduction. A detailed well as clear directions on when to that are more hemodynamically neutral. history was gathered, with a special return to the emergency department.16 focus on his medical history and details ■ CASE THREE about medication use, allergies, and ■ CASE TWO The young, pregnant woman with a fasting status. The patient’s airway Propofol had several benefits for dislocated ankle required sedation and was assessed for any signs of difficulty, the elderly man with a dislocated hip analgesia for reduction. The emergency using the LEMON mnemonic device. and an extensive medical history, physician considered the physiological The patient consented to the procedure including a rapid onset of action changes that occur during pregnancy, after the risks, benefits, and possible and short duration. Fentanyl was especially the added compression of complications were explained. appropriately coadministered for the inferior vena cava, higher risk of The sedation plan was coordinated its analgesic effects. The downside aspiration, and hypoxia secondary to with the nurse; monitoring equipment, of using propofol in this situation reduced functional residual capacity. including pulse oximetry and was its negative inotropic effect. Midazolam was not used because capnography, were available. An Although hypotension and respiratory it is categorized as a pregnancy airway and code cart were nearby, and depression frequently occur with class D drug due to its potential oxygen and suction were checked. A propofol alone, they are exacerbated teratogenicity. Instead, the physician time-out was called immediately prior when propofol is combined with an used propofol because it is generally to administering the medications. opioid analgesic. considered safe, and then monitored After the procedure, the nurse closely The patient’s blood pressure the patient for hypotension. Routine observed the patient until he fully improved with the 500-mL normal supplemental oxygen was provided, the regained consciousness and could saline bolus, and the hypoxia was patient was placed in the left lateral follow verbal commands. corrected with supplemental oxygen recumbent position, and IV fluids were Since most adverse events occur and a brief jaw thrust. The patient administered during the procedure. within 30 minutes after sedation, he recovered within 5 minutes and Prophylactic metoclopramide was also was observed for at least 30 minutes returned to baseline with a newly given.

REFERENCES 11. Frank RL. Procedural sedation in adults outside the 19. American Society of Anesthesiologists Committee. operating room. UpToDate website. http://www. Practice guidelines for preoperative fasting and the 1. Green SM, Krauss B. Procedural sedation uptodate.com/contents/procedural-sedation-in- use of pharmacologic agents to reduce the risk of terminology: moving beyond “conscious sedation”. adults-outside-the-operating-room. Published 2016. pulmonary aspiration: application to healthy patients Ann Emerg Med. 2002 Apr;39(4):433-435. Accessed January 4, 2017. undergoing elective procedures: an updated report 2. Godwin SA, Burton JH, Gerardo CJ, et al. Clinical 12. Weaver C. Procedural sedation. In: Tintinalli JE, by the American Society of Anesthesiologists policy: procedural sedation and analgesia in the Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Committee on Standards and Practice Parameters. emergency department. Ann Emerg Med. 2014 Cline DM, eds. Tintinalli’s Emergency Medicine: A Anesthesiology. 2011 Mar;114(3):495-511. Feb;63(2):247-258. Comprehensive Study Guide. 8th ed. New York, NY: 20. Lee JS, Jeon WC, Park EJ, et al. Adjunctive 3. Department of Health and Human Services (DHHS); McGraw-Hill Education; 2016:249-255. atropine versus metoclopramide: can we reduce Centers for Medicare and Medicaid Services (CMS). 13. Weaver CS, Terrell KM, Bassett R, et al. ED ketamine-associated vomiting in young children? CMS Manual System: Revised Appendix A, Interpretive procedural sedation of elderly patients: is it safe? Am A prospective, randomized, open, controlled study. Guidelines for Hospitals, §482.52 Condition of J Emerg Med. 2011 Jun;29(5):541-544. Acad Emerg Med. 2012 Oct;19(10):1128-1133. Participation: Anesthesia Services. Published 14. Shenvi C. Putting an older patient under: tips for 21. Lee JS, Jeon WC, Park EJ, et al. Does ondansetron December 2, 2011. geriatric procedural sedation. Academic Life in have an effect on intramuscular ketamine-associated 4. American Society of Anesthesiologists, Task Force Emergency Medicine website. https://www.aliem. vomiting in children? A prospective, randomized, on Sedation and Analgesia by Non-Anesthesiologists. com/2013/putting-an-older-patient-under-tips-for- open, controlled study. J Paediatr Child Health. 2014 Practice guidelines for sedation and analgesia by geriatric-procedural-sedation. Published October 31, Jul;50(7):557-561. non-anesthesiologists. Anesthesiology. 2002; 2013. Accessed January 4, 2017. 22. Langston WT, Wathen JE, Roback MG, Bajaj L. 96(4):1004-1017. 15. O’Conner RE, Sama A, Burton JH, et al. Procedural Effect of ondansetron on the incidence of vomiting 5. Krauss B, Green SM. Procedural sedation and sedation and analgesia in the emergency department: associated with ketamine sedation in children: a analgesia in children. Lancet. 2006 Mar 4; recommendations for physician credentialing, double-blind, randomized, placebo-controlled trial. 367(9512):766-780. privileging, and practice. Annals of Emergency Ann Emerg Med. 2008 Jul;52(1):30-34. 6. Langeron O, Masso E, Huraux C, et al. Prediction Medicine website. https://www.annemergmed.com/ 23. Neuman G, Koren G. Safety of procedural sedation in of difficult mask ventilation. Anesthesiology. 2000 article/S0196-0644(11)00720-7/fulltext. Published pregnancy. J Obstet Gynaecol Can. 2013 Feb; May;92(5):1229-1236. October 2011. Accessed January 4, 2017. 35(2):168-173. 7. Rosenberg MB, Phero JC. Airway assessment for 16. Green SM, Roback MG, Kennedy RM, Krauss 24. Miner JR, Burton JH. Clinical practice advisory: office sedation/anesthesia. Anesth Prog. 2015 B. Clinical practice guideline for emergency emergency department procedural sedation with Summer;62(2):74-80. department ketamine dissociative sedation: 2011 propofol. Ann Emerg Med. 2007 Aug;50(2):182-187. 8. Walls RM, Murphy MF, Luten RC, Schneider RE, eds. update. Ann Emerg Med. 2011 May;57(5):449-461. 25. Weingart S. Push-dose pressors for immediate blood Manual of Emergency Airway Management. 2nd ed. 17. Thomson D, Cowan T, Loten C, Botfield C, Holliday pressure control. Clin Exp Emerg Med. 2015 June 30; Philadelphia, PA: Lippincott Williams and Wilkins; E, Attia J. High-flow oxygen in patients undergoing 2(2):131-132. 2005. procedural sedation in the emergency department: 26. Krauss BS, Andolfatto G, Krauss BA, Mieloszyk 9. Boschert S. Think L-E-M-O-N when assessing a a retrospective chart review. Emerg Med Australas. RJ, Monuteaux MC. Characteristics of and difficult airway. ACEP News. ACEP website. Published 2017 Feb;29(1):33-39. predictors for apnea and clinical interventions November 2007. Accessed January 4, 2017. 18. Bellolio MF, Gilani WI, Barrionuevo P, et al. Incidence during procedural sedation. Ann Emerg Med. 2016 10. Miller MA, Levy P, Patel MM. Procedural sedation of adverse events in adults undergoing procedural Nov;68(5):564-573. and analgesia in the emergency department: what sedation in the emergency department: a systematic 27. Green SM, Roback MG, Krauss B, et al. Predictors are the risks? Emerg Med Clin North Am. 2005 May; review and meta-analysis. Acad Emerg Med. 2016 of airway and respiratory adverse events with 23(2):551-572. Feb;23(2):119-134. ketamine sedation in the emergency department:

August 2018 n Volume 32 Number 8 27 an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med. 2009 Aug;54(2):158-168. 28. Larson CP Jr. Laryngospasm—the best treatment. Anesthesiology. 1998 Nov;89(5):1293-1294. 29. Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008 Nov;26(9):985-1028. 30. Lee EN, Lee JH. The effects of low-dose ketamine on acute pain in an emergency setting: a systematic review and meta-analysis. PLoS One. 2016 Oct 27; 11(10):e0165461. 31. Hansen TG. Sedative medication outside the operating room and the pharmacology of sedatives. Curr Opin Anesthesiol. 2015 Aug;28(4):446-452. 32. Burbulys DB. Procedural sedation and analgesia. In: Marx JA, Hockberger RS, Walls RM, et al, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice, vol. 1. 8th ed. Philadelphia, PA: Saunders; 2014:50-60. 33. David H, Shipp J. A randomized controlled trial of ketamine/propofol versus propofol alone for emergency department procedural sedation. Ann Emerg Med. 2011 May;57(5):435-441. 34. Ferguson I, Bell A, Treston G, New L, Ding M, Holdgate A. Propofol or ketofol for procedural sedation and analgesia in emergency medicine—the POKER study: a randomized double-blind clinical trial. Ann Emerg Med. 2016 Nov;68(5):574-582. 35. Miner JR, Danahy M, Moch A, Biros M. Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department. Ann Emerg Med. 2007 Jan;49(1):15-22. 36. Brown TB, Lovato LM, Parker D. Procedural sedation in the acute care setting. Am Fam Physician. 2005 Jan 1;71(1):85-90. 37. Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database Syst Rev. 2015 Jan 8;1: CD010225. 38. Bahn EL, Holt KR. Procedural sedation and analgesia: a review and new concepts. Emerg Med Clin North Am. 2005 May;23(2):503-517. 39. Newman DH, Azer MM, Pitetti RD, Singh S. When is a patient safe for discharge after procedural sedation? The timing of adverse effect events in 1,367 pediatric procedural sedations. Ann Emerg Med. 2003 Nov; 42(5):627-635.

28 Critical Decisions in Emergency Medicine ALL-NEW PODCAST!

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August 2018 n Volume 32 Number 8 29 Reviewed by Lynn Roppolo, MD, FACEP

Qualified, paid subscribers toCritical Decisions in Emergency Medicine may receive CME certificates for up to 5 ACEP Category I credits, 5AMA PRA Category 1 CME Credits™, and 5 AOA Category 2-B credits for completing this activity in its entirety. Submit your answers online at acep.org/cdem; a score of 75% or better QUESTIONS is required. You may receive credit for completing the CME activity any time within 3 years of its publication date. Answers to this month’s questions will be published in next month’s issue.

An individual who visited a clinic prior to travel is likely A 45-year-old health care worker who returns from 1 to experience which of the following? 6 working in Sierra Leone in West Africa presents A. Fever with a fever of 38.6°C (101.5°F), abdominal pain, B. Malaria and diarrhea. His physical examination is significant C. Self-limited illness for a purpuric rash. What is the most appropriate D. Severe disease next step? A. Administer IV fluid bolus therapy Acute hemorrhagic fever syndrome includes a fever B. Contact the local health department 2 of what duration? C. Place him in isolation A. >1 month D. Place him on a cardiac monitor B. <1 month C. <1 week A 50-year-old man presents with fever and D. <3 weeks 7 pneumonia after a recent trip to the Arabian peninsula, where he volunteered at a local health By what route is Ebola transmitted? clinic. Which of the following pathologies should 3 A. An insect bite be suspected? B. Contaminated food A. Cryptococcal meningitis C. Contaminated water B. Japanese encephalitis D. Direct contact with infected bodily fluids C. MERS-CoV D. Q fever A 35-year-old man who recently returned from a trip 4 to East Africa presents with fever and generalized Which condition is correctly paired with its usual malaise. Other than a temperature of 38.3°C (100.9°F), 8 incubation period? his vital signs are normal. His physical examination is A. Chikungunya — 3 weeks unremarkable, CBC shows leukocytosis of 14,000 B. Hepatitis E — 1 week 3 cells/mm , a basic metabolic panel is unremarkable, and C. Malaria — <10 days to months no Plasmodium is visualized on peripheral blood smears. D. SARS — 2 weeks What is the most appropriate next step? A. Continue symptomatic care and repeat blood smears When a specific etiological diagnosis can be made, for 12 to 24 hours 9 what is the most frequently identified cause of B. Inform the patient that he does not have malaria and fever in the returned traveler? discharge home A. Dengue fever C. Start intravenous treatment with an artemisinin-based B. Ebola virus disease compound therapy C. Enteric fever D. Start outpatient chloroquine D. Malaria

Travelers from which geographic area are at the Which disease is correctly paired with its typical 5 highest risk of acquiring enteric fever? 10 mode of transmission? A. South America A. Chikungunya — contaminated food or water B. South Asia B. Ebola virus disease — deer tick C. Sub-Saharan Africa C. Enteric fever — Anopheles mosquito D. Western Europe D. Zika — Aedes aegypti mosquito

30 Critical Decisions in Emergency Medicine A 5-year-old boy presents after falling off his bike. A 20-year-old woman is under procedural sedation 11 He is alert and oriented and has a 5-cm laceration 16 for a dental procedure. A few minutes into the on his chin that requires stitches. He is anxious and procedure she starts shouting that there are bugs crying inconsolably. What medication(s) can be given all over the ceiling. Which medication can cause IM for stitching under procedural sedation? this phenomenon? A. Etomidate A. Etomidate B. Fentanyl B. Ketamine C. Ketamine C. Midazolam and morphine D. Midazolam D. Propofol What is the most common side effect of Under what thyroid cartilage–to-mandible distance etomidate? would you anticipate a difficult intubation? 17 12 A. Hypotension A. 2 finger breadths B. Myoclonus B. 3 finger breadths C. Nausea and vomiting C. 4 finger breadths D. Tachycardia D. 5 finger breadths Which of the following medications can be A young woman presents with a dislocated ankle 18 administered alone, without an analgesic agent, 13 that requires reduction. She has no medical for procedural sedation? history and takes no medications except for oral A. Etomidate contraceptives. She is allergic to peanuts and eggs. B. Ketamine Acetaminophen and ibuprofen have partially reduced C. Midazolam the pain. Which medication is contraindicated for D. Propofol procedural sedation? According to ACEP’s clinical policy, how long A. Etomidate 19 should a patient fast before undergoing B. Midazolam procedural sedation? C. Morphine A. 2 hours for liquids only D. Propofol B. 2 hours for liquids and 6 hours for solids C. 6 hours for solids only A 65-year-old man requires procedural sedation for D. No fasting is required 14 a shoulder relocation. He is diabetic and has COPD. Which medication would be most likely to induce Which medication should be avoided during hypotension? 20 procedural sedation to relocate the shoulder of a 25-year-old woman who is 34 weeks pregnant? A. Etomidate B. Ketamine A. Flumazenil B. Ketamine C. Morphine C. Midazolam D. Propofol D. Propofol Which side effect is more common with IM 15 ketamine? A. Agitation B. Apnea C. Hypotension D. Vomiting

ANSWER KEY FOR JULY 2018, VOLUME 32, NUMBER 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 D D D B A A D D A B A D A D C D D D B A

August 2018 n Volume 32 Number 8 31 Drug Box Tox Box

ANDEXANET ALFA QUETIAPINE OVERDOSE By Paris Cook, PharmD; and Aimee Mishler, PharmD, BCPS, By Jenna Otter, MD; and Christian A. Tomaszewski, MD, MS, Maricopa Medical Center, Phoenix, AZ MBA, FACEP, University of California, San Diego Andexanet alfa was recently approved by the FDA for the treatment of Quetiapine is a second-generation antipsychotic available life-threatening or uncontrolled bleeding caused by the anticoagulants in immediate- and extended-release formulations. It is FDA rivaroxaban and apixaban. It is the first agent approved for the reversal approved for schizophrenia, bipolar disorder, and as adjunct of these two factor Xa inhibitors. Andexanet alfa is available at limited treatment for major depressive disorder. sites throughout the US; wider distribution is expected in early 2019. Pharmacokinetics Mechanism of Action • Lipophilic with a large volume of distribution (not dialyzable) The antidote binds to and sequesters the factor Xa inhibitors. In • Levels peak after 2-3 hours, with a half-life of 6 hours. addition, it inhibits the activity of tissue factor pathway inhibitor • In overdose, antimuscarinic effects can delay absorption. (TFPI), increasing tissue factor-initiated thrombin generation. • Metabolized by CYP3A4 Dosing Mechanism of Action

If the last dose of medication was taken >8 hours ago, use low dose. • Weak antagonism at D2, M1, 5HT1A receptors = sedation

If the last dose of medication was taken <8 hours ago or unknown, • Potent antagonism at a1 adrenergic receptors = the dose should be based on the amount of factor Xa taken. hypotension Apixaban: Last dose ≤5 mg, use low dose; last dose >5 mg • Some blockade at fast sodium channels = QRS widening or unknown, use high dose. • Can affect delayed rectifier current = QT prolongation Rivaroxaban: Last dose ≤10 mg, use low dose; last dose Clinical Presentation >10 mg or unknown, use high dose. • Tachycardia from antimuscarinic effects a Low Dose: 400-mg IV bolus administered at a rate of • Hypotension from peripheral 1 blockade • Miosis with depressed mental status (opioid mimic) ~30 mg/minute, followed 2 minutes later by 4 mg/minute IV • Rarely associated with neuroleptic malignant syndrome infusion for up to 120 minutes (NMS) High Dose: 800-mg IV bolus administered at a rate of Diagnostic Evaluation ~30 mg/minute, followed 2 minutes later by 8 mg/minute IV • ECG nonspecific: tachycardia with prolonged QTc infusion for up to 120 minutes • Lab testing: nonspecific (may be false positive for TCA) Adverse Reactions • Evaluate for coingestants (eg, acetaminophen) The most common side effect is a local infusion site reaction Management and Disposition (≥10%), followed by deep vein thrombosis (6%), ischemic stroke • Consider activated charcoal in alert patients who present (5%), urinary tract infections, and pneumonia (both occurring <1-2 hours after a large overdose, especially with extended in ≥5% of patients). release formulations. FDA Black Box Warning: Treatment with andexanet alfa has been • Intubate, if necessary (rare with quetiapine). associated with life-threatening complications, including arterial • Treat hypotension with IV fluids; if persistent, add and venous thromboembolic events, ischemic events (including norepinephrine or phenylephrine. myocardial infarction and ischemic stroke), cardiac arrest, and • In cases of refractory shock, consider intralipid, given its sudden deaths. Monitor for thromboembolic events and initiate lipophilicity. anticoagulation when medically appropriate. Monitor for signs • Treat NMS with benzodiazepines and cooling. and symptoms that precede cardiac arrest and provide treatment • An asymptomatic patient with a normal ECG 6 hours after as needed. an overdose requires no further cardiac monitoring.