Managing migraine headaches in complicated patients

migraineCase vignette: A 42-year-old female presents at 10 pm with a throbbing right frontal headache associated with nausea, vomiting, photophobia, and phonophobia. The headache is severe, rated as “10” on a 0 to 10 triage pain scale. The headache began gradually while the patient was at work at 2 pm. Since 2 pm, she has taken 2 tablets of naproxen 500 mg and 2 tablets of sumatriptan 100 mg without relief.

The patient has a diagnosis of migraine without aura. She reports 12 attacks per month. The headache is similar to her previous migraine headaches. She is forced to present to an Emergency Department (ED) on average 2 times per month for management of migraine refractory to oral therapy. She reports a history of dystonic reactions and akathisia after receiving IV dopamine antagonists during a previous ED visit. The physical exam is non-contributory including a normal neurological exam, normal visual fields and fundoscopic exam, and no signs of a head or face infection. When you are done evaluating her, the patient reports that she usually gets relief with 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM, and asks that you administer her usual treatment. What do you do?


Migraine is a neurological disorder characterized by recurrent painful headaches and abnormal processing of sensory input resulting in symptoms such as photophobia, phonophobia, and osmophobia [1]. Central to disease pathogenesis is abnormal activation of nociceptive pathways [2]. Disease severity ranges from mild to severe. Patients at one end of the spectrum have rare episodic headaches. On the other end are patients who have headaches on more days than not, patients who are functionally impaired by their headaches, and patients who frequently cannot participate fully in work or social activities. Chronic migraine, a sub-type of migraine defined by ≥15 days with headache for at least 3 consecutive months, is experienced by 1-3% of the general population [3].

ED use for treatment of migraine is common. 1.2 million patients present to U.S. ED’s annually for management of this primary headache disorder [4]. Parenteral opioids are used to treat the acute headache in slightly more than 50% of all ED visits [4]. Multiple authorities have cautioned against the use of opioids for migraine [5,6]. However, the frequent use of opioids has continued unabated, despite the publication in the EM, neurology, and headache literature of dozens of randomized controlled trials (RCTs) demonstrating safety and efficacy of parenteral alternatives, most notably dopamine antagonists and non-steroidal anti-inflammatory drugs [7].

Opioids have been associated with a variety of poor outcomes in migraine patients including:

  1. Progression of the underlying migraine disorder from episodic to chronic migraine [8]
  2. Increased frequency of return visits to ED [9]
  3. Less responsiveness to subsequent treatment with triptans [10]
  4. Less frequent headache relief than patients who received dihydroergotamine or dopamine antagonists [11]

In contrast, a high quality, ED-based RCT did not demonstrate more harm from 1 or 2 doses of meperidine than from dihydroergotamine [12]. Hydromorphone, the parenteral opioid currently used most commonly in U.S. EDs [4], has never been studied experimentally in migraine patients. However, given the wide range of parenteral alternatives, the possibility that opioids may worsen the underlying migraine disorder, and the fact that they are less efficacious than other treatments, opioids should not be offered as first- or second-line therapy for patients who present de novo to an ED with an acute migraine (assuming no contraindications to alternative medications).


1) Other than opioids, what parenteral therapies can be offered to this patient?

The 3 classes of parenteral therapeutics with the most evidence supporting safety and efficacy for use as first-line therapy for migraine are the following [13]:

  1. Dopamine antagonists
  2. NSAIDs
  3. Subcutaneous sumatriptan

However, this patient has relative contraindications to each of these. Other parenteral medications used for migraine are listed in the following table.

Table: Alternative parenteral migraine therapies

Agent Dose Adverse events Evidence supporting efficacy Notes
Acetaminophen (APAP) [17, 18] 1 gm IV Well tolerated In one trial, IV APAP did no better than placebo. In another, IV APAP was comparable to an IV NSAID.
Dihydroergotamine [19] 0.5 mg -1 mg IV infusion Nausea is common. Pre-treat with anti-emetics. In one trial, DHE was less effective than sumatriptan at 2 hours but more effective by 4 and 24 hours. Use cautiously in patients with cardiovascular risk factors.
Ketamine [20] 0.08 mg/kg SC Fatigue, delirium In one low quality cross-over RCT, ketamine outperformed placebo.
Magnesium [21-24] 1-2 gm IV Flushing In RCTs of varying quality, IV mg did not consistently outperform placebo Efficacy data is most compelling for migraine with aura.
Octreotide [25] 0.1 mg SC Diarrhea, injection site reactions In a high quality RCT, octreotide did not outperform placebo
Propofol [26,27]

10 mg IV every 10 minutes as needed up to 80 mg


30-40 mg IV with 10-20 mg bolus every 3-5 minutes up to 120 mg

Sedation, hypoxia In a low quality RCT, propofol outperformed dexamethasone. In another low quality trial, propofol outperformed sumatriptan. It is not clear whether the migraine returns after propofol administration has been completed. Previous ALiEM post on migraines and propofol.
Valproic acid [28,29] 1000 mg IV Well tolerated In a high quality RCT, valproate was outperformed by metoclopramide and ketorolac. In a lower quality RCT, valproate was comparable to IV aspirin.

APAP= acetaminophen; DHE= dihydroergotamine; Mg= magnesium


In some patients, greater occipital nerve blocks with a long-acting local anesthetic such as bupivaciane may play a role [14]. While the above alternative parenteral therapies may benefit this patient, available evidence regarding risks and benefits does not dictate that these other therapies must be offered prior to use of opioids.

2) Does the fact that this patient makes frequent use of the ED indicate an unmet medical need?

As with congestive heart failure and asthma, frequent use of an ED for migraine is associated with worse underlying disease [15]. These frequent users are more likely to have chronic migraines (> 15 headache days per month) and psychiatric co-morbidities [15]. Concomitant medication overuse headache, a disorder defined by an upward spiral of increasing headache frequency in the setting of increased usage of analgesic or migraine medication, is also common [16]. Management of complicated patients with migraines is exceedingly difficult, particularly during a busy ED shift, and may lead to frustration for both the healthcare practitioner and the patient. Ideally, outpatient healthcare practitioners with appropriate expertise should direct management of complicated patients with migraines.

3) Should the patient be administered 3 doses of hydromorphone 2 mg + diphenhydramine 50 mg IM as she wishes?

Management of chronic pain patients can be trying and demoralizing for emergency physicians because the underlying problem cannot be solved, and all avenues of treatment are flawed.  Allowing the patient to suffer without appropriate justification is cruel. Delaying opioid administration during good faith efforts to identify alternative effective therapeutic agents is reasonable. Withholding opioids on principle is problematic because for most patients in most circumstances, published data do not establish that the benefit of pain relief is outweighed by the potential for opioid induced harm. On the other hand, thoughtlessly acquiescing to repeated requests for opioids during multiple ED visits is a violation of good medical practice, because of the concern of exacerbating the underlying migraine disorder, which could result in more ED visits, increased number of headache days, and the potential to cause refractoriness to standard migraine medication. One might compare it to administering antibiotics for bronchitis.

Case Resolution

The best solution for the patient in the case vignette is to administer parenteral opioids only as rescue therapy for patients who adhere to an established outpatient plan of care. Acutely, the patient should not be allowed to suffer. However distasteful it may be, the harm arising from 3 isolated doses of parenteral opioids during one ED visit is unlikely to be either long-lasting or severe. But a prerequisite to treatment with opioids during a subsequent visit should be adherence to appropriate outpatient treatment: specifically, patients who require parenteral opioids for migraines should regularly attend outpatient appointments with an appropriate healthcare provider within the ED’s healthcare system.

Department-wide opioid policies are essential, as physician to physician variability in care may undermine a strict approach to opioids. Ideally, a committee with relevant expertise can monitor frequently presenting pain patients and develop patient-specific interventions that will be enforced by all practitioners during subsequent visits. If need be, the terms of treatment can be reinforced with a written document (example in the Appendix). This written document is not meant to be legally binding, but should be used to establish expectations. The last thing a busy emergency physician needs is a battle over opioids with a frequently presenting migraine patient. But before discharge, there should be a conversation about expectations during future ED visits. This will contribute to increased satisfaction for both the provider and the patient.


Top image: (c) Can Stock Photo

APPENDIX: Sample document to establish expectations for ED patients who require opioids


Author information

Cindy Prettypaul

Cindy Prettypaul

Medical Student
Lake Erie College of Osteopathic Medicine
Seton Hill

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Congratulations to the winners of 2016 ALiEM Awards!

imgresCongratulations to the winners of the first ever 2016 ALiEM Awards! We had great submissions and the decision making process was tough, but ultimately we felt that these winners below represent the true spirit of medical education and online innovations!

Most of all, congratulations to all the submissions, we are proud of all you do for the medical education community!


Most Innovative Blog or Podcast


Winner – a tie! We could not decide between and and chose them both.

About: Both blogs push the boundary of dynamic content – emDocs especially with their series EM Mindset and Feminem’s with their emphasis of highlighting issue related to women practitioners in the emergency department. Both blogs provide content that is valuable for the medical education and emergency medicine online community.



Best New Blog or Podcast


Winner – GEMCAST Podcast

About: GEMCAST, a newly launched podcast in 2015 is dedicated towards furthering the knowledge base for practitioners who regularly care for the elderly in acute care settings. They even have grant funding with the John A. Hartford foundation and the Atlantic Philanthropies.


Most Innovative Educator


Winner – Dr. David Snow (@davidcsnow)

About: Dr. Snow is Assistant Residency Director at University of Illinois Chicago. Among his many accomplishments, he has helped to launch and supports the UIC’s EM Residency blog Brown Coat Nation as the Editor in Chief. As a testament to his impact, he has also won the UIC Attending Physician of the Year award 2 years in a row!

Author information

Nikita Joshi, MD

Nikita Joshi, MD

ALiEM Associate Editor
Editorial Board Member
ALiEM Social Media and Digital Fellowship Director
Clinical Instructor
Stanford University, Department of Emergency Medicine

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Trick of the Trade: Pre-Charge the Defibrillator

Pre-Charge the Defibrillator CPRIn cardiac arrest care it is well accepted that time to defibrillation is closely correlated with survival and outcome [1]. There has also been a lot of focus over the years on limiting interruptions in chest compressions during CPR. In fact, this concept has become a major focus of the current AHA Guidelines. Why? Because we know interruptions are bad [2,3]. One particular aspect of CPR that has gotten a lot of attention in this regard is the peri-shock period. It has been well established that longer pre- and peri-shock pauses are independently associated with decreased chance of survival [4,5]. Can we do better to shock sooner and minimize these pauses?

Current ACLS standards

Traditionally during manual CPR when a shockable rhythm is encountered at the rhythm check, providers will charge the uncharged defibrillator at that time. In the meantime, chest compressions are typically resumed while waiting for the defibrillator to charge. Once the defibrillator has finished charging, providers are forced to pause yet again in order to “clear” for shock delivery.

“When a rhythm check by a manual defibrillator reveals VF/VT, the first provider should resume CPR while the second provider charges the defibrillator. Once the defibrillator is charged, CPR is paused to ‘clear’ the patient for shock delivery. After the patient is ‘clear,’ the second provider gives a single shock as quickly as possible to minimize the interruption in chest compressions (‘hands-off interval’).” – 2010 AHA/ACC guidelines


Pre-Charge the Defibrillator figure 1

Figure 1: Perfusion pressure changes during CPR without pre-charging the defibrillator. Once a shockable rhythm is identified, there is a delay in shock delivery while awaiting defibrillator charging. There is not just 1 but 2 interruptions in chest compressions. The exact decrease in perfusion pressure during these pauses is variable. Modified from [2].


Trick of the Trade:

Pre-charge the defibrillator during the active chest compression phase of CPR in anticipation of a shockable rhythm

Why should we wait until a shockable rhythm is encountered at the rhythm check point to charge the defibrillator? This makes little sense. Charging the defibrillator prior to the rhythm check is far more logical. With the defibrillator already charged and ready to go, if a shockable rhythm is encountered at the rhythm check point, the shock can be delivered immediately; and importantly, the second interruption is averted entirely.


Pre-Charge the Defibrillator CPR Perfusion Pressure 2

Figure 2: Perfusion pressure changes during CPR with pre-charging the defibrillator. Not only is the shock delivered earlier but the second interruption seen in Figure 1 is avoided completely. Modified from [2].


Logistical tips: How to do this

The most important key to ensuring this process runs smoothly lies in preparation and team briefing prior to patient arrival. There must be clear understanding and communication. The timekeeper is tasked with announcing prior to all rhythm checks (15-30 seconds prior is reasonable) that the rhythm check is approaching. Example:

”In 20 seconds we are due for a rhythm check.”

At this point the team member running the defibrillator charges the defibrillator as chest compressions continue uninterrupted until the rhythm check.

With the defibrillator pre-charged, the team is armed and ready to combat a shockable rhythm immediately as it is encountered at the rhythm check.

What if the rhythm check reveals a non-shockable rhythm? 

If the rhythm check happens to reveal a non-shockable rhythm, CPR can continue as per usual without any alteration. The charge can be manually disarmed, but note that current defibrillators will “hold” the shock for some time (~60 seconds), and if the shock is not delivered in this time frame, the charge will automatically dissipate and require re-charging. (This is why pre-charging should take place within this set time period prior to a rhythm check.) Simply test your particular defibrillator to figure out exactly how long it holds the charge.

Why is pre-charging the defibrillator not in the AHA/ACLS guidelines?

The only arguments I have ever heard against the implementation of this strategy is that it may increase the incidence of inappropriate or inadvertent shocks. Presumably, these theoretical concerns have prevented this technique from being recommended as standard practice.

Are there any studies on pre-charging the defibrillator? 

A multicenter retrospective study was published in 2010 by Edelson et al [6]. Data were gathered from CPR-sensing defibrillator transcripts over a 3-year period. They looked at 680 charge-cycles from 244 cardiac arrests. Charging during compressions correlated with a decrease in median pre-shock pause and total hands-off time in the 30 seconds preceding defibrillation. Interestingly, there was no difference in inappropriate shocks, and there was only one instance of inadvertent shock administration during compressions (which went unnoticed by the compressor).


There will likely never be robust data looking at this particular aspect of CPR. Pre-charging the defibrillator is a small thing, but with potentially huge impact. It can be easily taught, easily learned, and is free. I have personally been practicing CPR this way for years now. It has been my experience that it is an incredibly smooth process. All it takes is a little practice and team briefing to ensure all providers are on the same page.

Even with the implementation of other recent techniques that may similarly minimize pauses in chest compressions, such as mechanical CPR and “hands-on defibrillation” (which is of questionable safety), pre-charging the defibrillator still decreases time to defibrillation.

Does it improve outcomes? We may never definitively know. Will it ever make the guidelines? I suspect that eventually it will, perhaps with verbiage similar to something like this:

“It is reasonable to consider pre-charging the defibrillator during chest compressions…”

Until then, it is my opinion that based on early literature, logic, and reasoning, pre-charging the defibrillator in anticipation of a shockable rhythm at the rhythm check is how we should be running our codes.


Pre-charging the defibrillator during chest compressions in anticipation of a shockable rhythm at the rhythm check shortens time to defibrillation and minimizes the number of pauses in chest compressions during CPR.



  1. Chan PS, Krumholz HM, Nichol G, Nallamothu BK, American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators. Delayed time to defibrillation after in-hospital cardiac arrest. N Engl J Med. 2008; 358(1):9-17. PMID: 18172170
  2. Berg RA, Sanders AB, Kern KB, et al. Adverse hemodynamic effects of interrupting chest compressions for rescue breathing during cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest. Circulation. 2001; 104(20):2465-70. PMID: 11705826
  3. Cunningham LM et al. Cardiopulmonary resuscitation for cardiac arrest: the importance of uninterrupted chest compressions in cardiac arrest resuscitation. Am J Emerg Med 2012; 30 (8): 1630 – 8. PMID: 2263371.Clement RA. An extension of Helmholtz’s explanation of Listing’s law. Ophthalmic Physiol Opt. 1990; 10(4):373-80. PMID: 2263371
  4. Brouwer TF, Walker RG, Chapman FW, Koster RW. Association Between Chest Compression Interruptions and Clinical Outcomes of Ventricular Fibrillation Out-of-Hospital Cardiac Arrest. Circulation. 2015; 132(11):1030-7. PMID: 26253757
  5. Cheskes S, Schmicker RH, Christenson J, et al. Perishock pause: an independent predictor of survival from out-of-hospital shockable cardiac arrest. Circulation. 2011; 124(1):58-66. PMID: 21690495
  6. Edelson DP, Robertson-Dick BJ, Yuen TC, et al. Safety and efficacy of defibrillator charging during ongoing chest compressions: a multi-center study. Resuscitation. 2010; 81(11):1521-6. PMID: 20807672


Author information

Sam Ghali, MD

Sam Ghali, MD

Clinical Assistant Professor of Emergency Medicine
University of Kentucky

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ALiEM BookClub | Lean In: Women, Work, and The Will to Lead

Lean In“We still have a problem” Sheryl Sandberg alarms us in her influential 2010 TED Talk, Why we have too few women leaders. “Women are not making it to the top of any profession anywhere in the world.” While women are getting more college degrees and graduate degrees, and more women are entering the workforce than ever before, when it comes to leadership positions, women do not come close to matching their male counterparts. “The blunt truth is that men still run the world.”

Sandberg believes that the key to fixing this problem is to keep women in the workforce. In her book, Lean In: Women, Work, and The Will to Lead, she points out that the way to prevent women from dropping out of the workforce is by focusing on change at the individual level. She asks that we all do our part to change the messages we tell ourselves, the women we work with, and what we share with our daughters.

Lean In offers 3 valuable pieces of advice for all women who want to stay in the workforce and pursue leadership:

  1. Sit at the table.
  2. Don’t leave before you leave.
  3. Make your partner a real partner.


While Lean In is a book about advice for women and the workplace, it also serves as a pseudo-memoir where Sandberg outlines her pathway to a successful professional life starting with her childhood, descriptions of her mentors, highlights of critical moments in her college and post college years, and the variety of jobs she held before COO of Facebook. Each chapter focuses upon an important lesson illustrated with personal examples, critical references, and hard numbers. Through the book’s dialogue the reader learns that Sandberg’s decisions along her career path were not merely intuitive, but based upon considerable deliberation and weighing of priorities. Sandberg skillfully balances her own experience with  numerous examples from other colleagues, mentors and friends – both men and women – in attempt to provide a more widespread discussion of her conclusions about the United States current work culture. The book, of course is published before the widely known tragic death of her husband Dave Goldberg in May of 2015. However, because the book is written as a means to start a conversation, the reader is encouraged to Lean In and go further. The reader walks away from the book, not necessarily an expert, or with the tools to exactly obtain success, but rather with considerable evidence to ponder upon as they determine what “Lean In” means to them, their life partner, and their personal and professional goals.

Message #1: Sit at the table

No one gets to the corner office by sitting at the side, not at the table, and no one gets the promotion if they don’t think they deserve the success or understand their success.

Sandberg observes that men are reaching for opportunities and putting themselves forward far more often than women. She admits that even she has failed to correct for this gap on many occasions. Sandberg asks that “If we want a world with greater equality, we need to acknowledge that women are less likely to keep their hands up. We need institutions and individuals to notice and correct for this behavior by encouraging, promoting and championing more women. And women have to learn to keep their hands up, because when they lower them, even managers with the best intentions might not notice.”

Women very often underestimate their own abilities and attribute their success to external forces such as luck and help from others, whereas males contribute their success to their own doing. Sandberg points out “it’s cliché but opportunities are rarely offered; they’re seized.”  Given how fast the world is moving today, It’s more important than ever for women to reach for these opportunities.  Sandberg shares that women often don’t believe they are deserving of their success, and often think they do not have the skills for a reach job. Sandberg discusses how taking initiative pays off. She gives several examples from her own experience in business of women not reaching, not leaning in, and how this has hurt their individual progress. She compares this to stories of both men and women who have taken initiative. “It is hard to visualize someone as a leader if she is always waiting to be told what to do.”

In the chapter Success and Likability, Sandberg highlights that while success and likability are positively correlated for men, they are negatively correlated for women. In terms of negotiation men are expected to ask for advances, however women must justify their requests. For women to negotiate effectively requires a strategic process of smiling, emphasizing common goals, and appreciation. It often is not a single discussion, but a drawn out process. “No wonder women don’t negotiate as much as men. It’s like trying to cross a minefield backward with high heels.”  However, the only way to make progress Sandberg argues it to believe in yourself, negotiate for yourself, and own your own success.

Message # 2: Don’t leave before you leave

Of all the ways women hold themselves back, perhaps the most pervasive is that they leave before they leave.

Sandberg acknowledges that women often face harder choices between professional success and personal fulfillment than their male colleagues. Yet, too often women are leaving the workforce prematurely. She warns women that planning too far in advance to accommodate for a family will often close doors rather than open them. “What often happens is that women will make small decisions along the way, making accommodations and sacrifices that they believe will be required to have a family.” Sandberg advises that the time before having a family is the critical time to lean in, pursue opportunities, and prepare for the career that she most desires. By scaling back too early, women inevitably end up in less fulfilling and less engaging jobs which ultimately makes it even harder for them to stay in the work force. “When they finally have a child, the choice- for those who have one- is between becoming a stay-at-home mother or returning to a less-than-appealing professional situation.

Message #3: Make your partner a real partner

I believe that the single most important career decision that a woman makes is whether she will have a life partner and who that partner is. I don’t know of one woman in a leadership position whose life partner is not fully-and I mean fully- supportive of her career. No exceptions.

Sandberg points out that women have made more progress in the work setting than we have in our homes. If a man and woman both work full time jobs, it is likely that that the women will do twice as much house work and three times the amount of child care than the man does.

Sandberg believes societal pressures have a lot to do with this. Common stereotypes of a working mom and a crying baby, and expectations that a man should be the bread winner, make it difficult for women not to feel guilt-ridden about working, and similarly challenging for men to take more of a role at home. In an attempt for a fifty-fifty partnership with her own husband, Sandberg reveals that it was not easy, but is essential if a woman desires to be a leader. “It takes continual communication, honesty, and a lot of forgiveness to maintain a rickety balance. We are never at fifty-fifty at any given moment- perfect equality is hard to define or sustain- but we allow the pendulum to swing back and forth between us.” If we are to see women in leadership, we need more women to lean in, negotiate for higher positions, acknowledge their success, and “we need more men to sit at the the table – the kitchen table.” As it turns out – couples who share in domestic responsibility have more sex. Not a bad trade-off for doing a few dishes!

In the chapter, The Myth of Doing It All, Sandberg reminds women that “trying to do it all and expecting that it all can be done exactly right is a recipe for disappointment.” Sandberg recommends setting obtainable goals, embrace that done may be better than perfect, and decide what matters and what doesn’t matter. “If I had to embrace a definition of success, it would be that success is making the best choices we can, and accepting them.”

Gender Disparity in Medicine

The medical profession is no exception to the gender gap highlighted by Sandberg. Within academic medicine female faculty are less likely to be advanced to higher leaderships positions in their institution. We see less females as associate and full professors. In addition, accounting for other variables, females earn less as attending physicians in their private practices. Emergency Medicine may provide addition unique biases. These are some of the issues that drove the founding of the blog in 2015 by Dr. Dara Kass.

 Book Club Questions:

  1. Sandberg begins the book with an eye opening experience she had during her first pregnancy while in a leadership position at Google. She tells of a difficult pregnancy, of morning sickness that lasted into the third trimester, significant weight gain, and discomfort. During this period, she was running to meet a client and the only parking spot was extremely far away. She later discussed the situation with her husband who pointed out that in his company there are designated parking spots for expecting women. “to this day, I’m embarrassed that I didn’t realize that pregnant women needed reserved parking until I experienced my own aching feet. As one of Google’s most senior women, didn’t I have a special responsibility to think of this?” Is there inadvertent discrimination against pregnant women in the workplace?  How can work places better accommodate pregnant women, and make allowances for family in general?
  2. In the chapter, Success and Likeability, Sandberg points out that women succeed by showing a commitment to the group. This is a strength which ultimately benefits any team, because a well-functioning group is always stronger than its members. Do we value and reward equally traits that are classically considered female to those that are male, especially in a group setting?
  3. Lean In is a call to action. Sandberg’s message for women in leadership has continued to evolve since her publication of Lean In. In a recent Facebook post Sandberg acknowledges the many struggles faced by single mothers, and admits she did not recognize how hard it is until the passing of her husband, Dave. In what ways does Lean In fall short of advocating for women in the work force? In what ways can we work towards a more effective work place?

Google Hangout Discussion (Scheduled May 19, 2016)

The discussion will feature writers and editors from

Go Further

For more information on Sheryl Sandberg’s Lean In, we recommend visiting her website:

Author information

Jordana Haber, MD

Jordana Haber, MD

Attending Physician
Department of Emergency Medicine
Maimonides Medical Center

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PEM Pearls: The nonvisualized appendix quandary on ultrasound

Screen Shot 2016-05-04 at 3.15.39 PM

A 10-year old girl presents with progressively worsening right lower quadrant pain for the last 2 days. She reports having chills and feeling warm. Her review of systems is negative for nausea, vomiting, diarrhea, or urinary symptoms. Her abdominal exam is unremarkable except for some diffuse, mild tenderness with deep palpation in bilateral lower quadrants. Labs: WBC 9 x 10^9/L. Because of radiation exposure concerns, you order an abdominal ultrasound as the initial imaging modality to evaluate for appendicitis. The radiologist’s reading was: “Unable to visualize the appendix.” Now, what do you do?

Appendicitis background

Appendicitis is one of the most common surgical emergencies and accounts for 5-10% of all abdominal pain among pediatric patients. Diagnosis can be deceptively difficult given that the complaints can be vague and nonspecific among children. Furthermore, this disease can mimic and be mimicked by many other pathologies making the clinical exam challenging. Laboratory tests, as well as clinical decision-making tools can help guide a clinician, but are limited, especially since early in disease progression, there may not be any demonstrated abnormalities [1].

Imaging modalities for appendicitis

The use of some type of imaging modality is now more frequently incorporated to help assess for appendicitis. The sensitivity and specificity for computer tomography (CT) has been quoted as 94 and 95%, respectively, while for ultrasound (US), it  is around 88% and 94%, respectively [1]. In one particular 2012 study by Trout et al., the sensitivity for US for the diagnosis of acute appendicitis was as low as 66.4%, although the specificity was 95.9%, with a false negative rate of 33.5% [2].

While CT/MRI improves diagnostic accuracy, many institutions use US as the initial imaging modality in order to minimize radiation exposure, and need for IV access and sedation [1] [9]. However, US results can vary for many reasons [2]:

  • Operator ability: Dedicated pediatric sonographers were able to identify the appendix at a significantly higher rate than non-pediatric sonographers
  • Patient characteristics (e.g. obesity) and cooperation
  • Location of the appendix: A retrocecal appendix or an appendix in the deep pelvis, can be difficult to visualize.

The ultrasound reading is neither positive or negative. Now what?

Often clinicians are left in a quandary when the interpretation for the appendix is “equivocal,”  “non-visualized,” “limited,” or “inconclusive.” This occurs 25-73% of the time [3][4]So now what? Many times, we progress to CT/MRI imaging as if the US study was never performed. Some clinicians incorporate other strategies including serial abdominal exams or repeated US studies. These alternative strategies, however, require a much longer ED stay.

Is there any value to a single “non-visualized appendix” US study result?

New data suggests that an adequately performed US examination has some negative predictive value (NPV) for appendicitis despite the appendix not being seen (“non-visualized”), assuming that there are no other abnormalities present [4][5]

A recent Journal of Pediatric Surgery 2015 study reports that an indeterminant abdominal US has some negative predictive power in risk stratifying the patient for appendicitis. From 2004-2013 at a single tertiary academic center, Cohen et al. did a retrospective chart review study of 1,260 patients who underwent abdominal US where appendicitis was suspected. 63% of the initial US findings were deemed non-diagnostic, with 56% of these due to non-visualization of the appendix. The authors then calculated NPV for non-diagnostic and non-visualized US results, as a function US alone, a serum WBC cutoff of 7.5 x 10^9/L, and a serum WBC cutoff of 11.0 x 10^9/L. The results are summarized in the table [5].

Screen Shot 2016-05-11 at 1.14.28 PM

This study, examined the relationship between a non-diagnostic US and a primary outcome measure of appendicitis. With a non-diagnostic US and a serum WBC count of <7.5 x 10^9/L, one might be able to have a shared decision discussion with the family about observing the patient at home or as an inpatient without further immediate imaging. The NPV is 97.1% (or 98.9% if the appendix was not visualized). A limitation of this study is that it is a single-site retrospective study [5].

But is it that simple?

For many clinicians, when we get a “non-visualized appendix” US reading, we still feel pressed to get further imaging, even if our suspicion is low. For those low-risk patients, regardless of the next imaging modality, they will already have a high NPV (86.4% in one study) [6].

Radiologists will also look for secondary findings suggestive of appendicitis, including the presence of an appendicolith, free fluid or fluid collection, echogenic inflammatory changes or hyperemia. A study by Ross et al. found that those with at least one of these secondary signs had an odds ratio of 6.52 of having appendicitis [3].

A major part of the problem is how US findings are reported, because they can wildly vary by institution and by US technician. Providing a standardized and comprehensive report can help minimize confusion and clarify what descriptives mean. Fallon et al, created an “Appy-Score” which helped categorize various findings, though their “equivocal” definition was a catch-all for those that did not fit into the other groups (e.g. periappendiceal inflammatory changes or borderline enlargement with an otherwise normal appendix). They demonstrated that by using their US scoring system, they were able to reduce overall CT use by 38% [7].

Screen Shot 2016-05-04 at 3.12.24 PM

Larson et al. used 5 specific interpretative categories to provide more description about their US findings. In patients with a non-visualized appendix but with positive secondary findings, the appendicitis rate was 39.3%, while those without any secondary findings, had a rate of 3.8% [4].

How can we also use clinical decision tools to help risk stratify the need for additional imaging?

Given a 50/50 chance of having an equivocal US exam, having a pre-test risk probability based on clinical exam and/or scores (e.g. Alvarado score) may help risk stratify your patients when combined with imaging.

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In a study by Blitman et al., they found a NPV of 99.6% for those patients who had an inconclusive US test, but a low Alvarado score (<5) and 89.7% for those with a score of 5-8 [8].

Bottom line

Many institutions have created a staged approach where they will use ultrasound first, followed by a CT or MRI, if they are unable to visualize the appendix. Given new evidence, we now might consider avoiding additional imaging in certain low-risk populations. These low risk patients have ALL of the following:

  1. Low Alvarado Score (<5)
  2. Non-elevated serum WBC value
  3. Nonvisualized appendix with no secondary findings on US

In the hands of a proficient US operator, a nonvisualized appendix without secondary findings on US no longer means an automatic CT or MRI scan.



  1. Estey A, Poonai N, Lim R. Appendix not seen: the predictive value of secondary inflammatory sonographic signs. Pediatr Emerg Care. 2013;29(4):435-439. PMID: 23528502
  2. Trout A, Sanchez R, Ladino-Torres M, Pai D, Strouse P. A critical evaluation of US for the diagnosis of pediatric acute appendicitis in a real-life setting: how can we improve the diagnostic value of sonography? Pediatr Radiol. 2012;42(7):813-823. PMID: 22402833
  3. Ross M, Liu H, Netherton S, et al. Outcomes of children with suspected appendicitis and incompletely visualized appendix on ultrasound. Acad Emerg Med. 2014;21(5):538-542. PMID: 24842505
  4. Larson D, Trout A, Fierke S, Towbin A. Improvement in diagnostic accuracy of ultrasound of the pediatric appendix through the use of equivocal interpretive categories. AJR Am J Roentgenol. 2015;204(4):849-856. PMID: 25794076
  5. Cohen B, Bowling J, Midulla P, et al. The non-diagnostic ultrasound in appendicitis: is a non-visualized appendix the same as a negative study? J Pediatr Surg. 2015;50(6):923-927. PMID: 25841283
  6. Ly D, Khalili K, Gray S, Atri M, Hanbidge A, Thipphavong S. When the Appendix Is Not Seen on Ultrasound for Right Lower Quadrant Pain: Does the Interpretation of Emergency Department Physicians Correlate With Diagnostic Performance? Ultrasound Q. April 2016. PMID: 27082937
  7. Fallon S, Orth R, Guillerman R, et al. Development and validation of an ultrasound scoring system for children with suspected acute appendicitis. Pediatr Radiol. 2015;45(13):1945-1952. PMID: 26280638
  8. Blitman N, Anwar M, Brady K, Taragin B, Freeman K. Value of Focused Appendicitis Ultrasound and Alvarado Score in Predicting Appendicitis in Children: Can We Reduce the Use of CT? AJR Am J Roentgenol. 2015;204(6):W707-12. PMID: 26001260
  9. Dillman J, Gadepalli S, Sroufe N, et al. Equivocal Pediatric Appendicitis: Unenhanced MR Imaging Protocol for Nonsedated Children-A Clinical Effectiveness Study. Radiology. 2016;279(1):216-225. PMID: 26458209

Author information

Delphine Huang, MD

Delphine Huang, MD

Emergency Medicine resident

UCSF-San Francisco General Hospital Residency Program

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