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Show Notes Jeff: Welcome back to EMplify the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum and I’m back with Nachi Gupta for the 30th episode of EMplify and the first Post-Ponte Vedra Episode of 2019. I hope everybody enjoyed a fantastic conference. This month, we are sticking in the abdomen for another round of evidence-based medicine, focusing on Emergency Department Management of Patients With Complications of Bariatric Surgery. Nachi: As the obesity epidemic continues to worsen in America, bariatric procedures are becoming more and more common, and this population is one that you will need to be comfortable seeing. Jeff: Thankfully, this month’s author, Dr. Ogunniyi, associate residency director at Harbor-UCLA, is here to help with this month’s evidence-based article. Nachi: And don’t forget Dr. Li of NYU and Dr. Luber of McGovern Medical School, who both played a roll by peer reviewing this article. So let’s dive in, starting with some background. Starting off with some real basics, obesity is defined as a BMI of greater than 30. Jeff: Oh man, already starting with the personal assaults, I see how this is gonna go… Show More v Nachi: Nah! Just some definitions, nothing personal! Jeff: Whatever, back to the article… Obesity is associated with an increased risk of hypertension, hyperlipidemia, and diabetes. Rising levels of obesity and associated co-morbidities also lead to an increase in bariatric procedures, and thereby ED visits! Nachi: One study found a 30-day ED utilization rate of 11% for those undergoing bariatric surgery with an admission rate of 5%. Another study found a 1-year post Roux-en-y ED visit rate of 31% and yet another found that 25% of these patients will require admission within 2 years of surgery. Jeff: Well that’s kind worrisome. Nachi: It sure is, but maybe even more worrisome is the rising prevalence of obesity. While it was < 15% in 1990, by 2016 it reached 40%. That’s almost half of the population. Additionally, back in 2010, it was estimated that 6.6% of the US population had a BMI> 40 – approximately 15.5 million adults!! Jeff: Admittedly, the US numbers look awful, and honestly are awful, but this is a global problem. From the 80’s to 2008, the worldwide prevalence of obesity nearly doubled! Nachi: Luckily, bariatric surgical procedures were invented and honed to the point that they have really shown measurable achievements in sustained weight loss. Along with treating obesity, these procedures have also resulted in an improvement in associated comorbidities like hypertension, diabetes, NAFLD, and dyslipidemia. Jeff: A 2014 study even showed an up to 80% reduction in the likelihood of developing DM2 postoperatively at the 7-year mark. Nachi: Taken all together, the rising rates of obesity and the rising success and availability of bariatric procedures has led to an increased number of bariatric procedures, with 228,000 performed in the US in 2017. Jeff: And while it’s not exactly core EM, we’re going to briefly discuss indications for bariatric surgery, as this is something we don’t often review even in academic training programs. Nachi: According to joint guidelines from the American Society for Metabolic and Bariatric Surgery, the American Association of Clinical Endocrinologists, and The Obesity Society, there are three groups that meet indications for bariatric surgery. The first is patients with a BMI greater than or equal to 40 without coexisting medical problems. The second is patients with a BMI greater than or equal to 35 with at least one obesity related comorbidity such as hypertension, hyperlipidemia, or obstructive sleep apnea. And finally, the third is patient with a BMI of 30-35 with DM or metabolic syndrome though current evidence is limited for this group. Jeff: Based on the obesity numbers, we just cited – it seems like a TON of people should be eligible for these procedures. Which again reiterates why this is such an important topic for us as EM clinicians to be well-versed in. Nachi: As far as types of procedures go – while there are many, there are 3 major ones being done in the US and these are the lap sleeve gastrectomy, Roux-en-Y gastric bypass, and lap adjustable gastric banding. In 2017, these were performed 60%, 18%, and 3% of the time. Jeff: And sadly, no two procedures were created alike and you must familiarize yourself with not only the procedure but also its associated complications. Nachi: So we have a lot to cover! overall, these surgeries are relatively safe with one 2014 review publishing a 10-17% overall complication rate and a perioperative 30 day mortality of less than 1%. Jeff: Before we get into the ED specific treatment guidelines, I think it’s worth discussing the procedures in more detail first. Understanding the surgeries will make understanding the workup, treatment, and disposition in the ED much easier. Nachi: Bariatric procedures can be classified as either restrictive or malabsorptive, with restrictive procedures essentially limiting intake and malabsorptive procedures limiting nutrient absorption. Not surprisingly, combined restrictive and malabsorptive procedures like the Roux-en-y gastric bypass tend to be the most effective. Jeff: Do note, however that 2013 guidelines do not recommend one procedure over another and leave that decision up to local surgical expertise, patient specific risk factors, and treatment goals. Nachi: That’s certainly an important point for the candidate patient. Let’s start by discussing the lap gastric sleeve. In this restrictive procedure, 80% of the greater curvature of the stomach is excised producing early satiety and weight loss from decreased caloric intake. This has been shown to have both low mortality and a low overall rate of complications. Jeff: Next we have the lap adjustable gastric band. This is also a restrictive procedure in which a plastic band is placed laparoscopically around the fundus leaving behind a small pouch that can change in size as the reservoir is inflated and deflated percutaneously. Nachi: Unfortunately this procedure is associated with a relatively high re-operation rate – one study found 20% of patients required removal or revision. Jeff: Even more shockingly, some series showed a 52% repeat operation rate. Nachi: 20-50% chance of removal, revision, or other cause for return to ER - those are some high numbers. Finally, there is the roux-en-y gastric bypass. As we mentioned previously this is both a restrictive and a malabsorptive procedure. In this procedure, the duodenum is separated from the proximal jejunum, and the jejunum is connected to a small gastric pouch. Food therefore transits from a small stomach to the small bowel. This leads to decreased caloric intake and decreased digestion and absorption. Jeff: Those are the main 3 procedures to know about. For the sake of completeness, just be aware that there is also the biliopancreatic diversion with or without a duodenal switch, as well as a vertical banded gastroplasty. The biliopancreatic diversion is used infrequently but is one of the most effective procedure in treating diabetes, though it does have an increased risk of complications. Expect to see this mostly in those with BMIs over 50. Nachi: Now that you have a sense of the procedures, let’s talk complications, both general and specific. Jeff: Of course, it should go without saying that this population is susceptive to all the typical post-operative complications such as venous thromboembolic disease, atelectasis, pneumonia, UTIs, and wound complications. Nachi: Because of their typical comorbidities, CAD and PE are still the leading causes of mortality, especially within the perioperative period. Jeff: Also, be on the lookout for self-harm emergencies as patients with known psychiatric disorders are at increased risk following bariatric surgery. Nachi: Surgical complications are wide ranging and can be grouped into early and late complications. More on this later… Jeff: Nutritional deficiencies are common enough to warrant pre and postoperative screening. Thiamine deficiency is one of the most common deficiencies. This can manifest within 1-3 months of surgery as beriberi or later as Wernicke encephalopathy. Symptoms of beriberi include peripheral neuropathy, ataxia, muscle weakness, high-output heart failure, LE edema, and respiratory distress. Nachi: All of that being said, each specific procedure has it’s own unique set of complications that we should discuss. Let’s start with the sleeve gastrectomy. Jeff: Early complications of sleeve gastrectomy include staple-line leaks, strictures, and hemorrhage. Leakage from the staple line typically presents within the first week, but can present up to 35 days, usually with fevers, tachycardia, abdominal pain, nausea, vomiting sepsis, or peritonitis. This is one of the most serious and dreaded early complications and represents an important cause of morbidity with an incidence of 3-7%. Nachi: Strictures commonly occur at the incisura angularis of the remnant stomach and are usually due to ischemia, leaks, or twisting of the gastric pouch. Patients with strictures usually have n/v, reflux, and intolerance to oral intake. Jeff: Hemorrhage occurs due to erosions at the staple line, resulting in peritonitis, hematemesis, or melena. Nachi: Late complications of sleeve gastrectomies include reflux, which occurs in up to 25% of patients, and strictures, which lead to epigastric discomfort, nausea, and dysphagia. Jeff: I’m getting reflux and massive heartburn just thinking about all of these complications, or the tacos i just ate…. Next we have the Roux-en-Y bypass. Nachi: Early complications of the Roux-en-Y Gastric Bypass include anastomotic or staple line leaks, hemorrhage, early postoperative obstruction, and dumping syndrome. Jeff: Leak incidence ranges from 1-6%, usually occurring at the gastro-jejunostomy site. Patients typically present within the first 10 days with abdominal pain, nausea, vomiting, and the feeling of impending doom. Some may present with isolated tachycardia while others may present with profound sepsis – tachycardia, hypotension, and fever. Nachi: Similar to the sleeve, hemorrhage can occur both intraperitoneally or intraluminally. This may lead to hematemesis or melena depending on the location of bleeding. Jeff: Early obstructions usually occur at either the gastro-jejunal or jejuno-jejunal junction. Depending on the location, patients typically present either within 2 days or in the first few weeks in the case of the gastro-jejunal site. Nachi: If the obstruction occurs in the jejuno-jejunostomy site, this can cause subsequent dilatation of the excluded stomach and lead to perforation, which portends a very poor prognosis. Jeff: Next, we have dumping syndrome. This has been seen in up to 50% of Roux-en-Y patients. Nachi: Early dumping occurs within 10-30 minutes after ingestion. As food rapidly empties from the stomach, this leads to distention and increased contractility, leading to nausea, abdominal pain, bloating, and diarrhea. This usually resolves within 7-12 weeks. Jeff: Moving on to late complications of the roux-en y - first we have marginal ulcers. Peptic ulcer disease and diabetes are risk factors and tobacco use and NSAIDs appear to increase your risk. In the worse case, they present with hematemesis or melena. Nachi: Internal hernias, intussusception, and SBOs are also seen after Roux-en-y gastric bypass. Patients with internal hernias usually present late in the postoperative period following significant weight loss. Jeff: Most studies cite a rate of 1-3% for internal hernias, with mortality up to 50% if there is strangulation. Nachi: And unfortunately for us on the front lines, diagnosis can be challenging. Presenting symptoms may be vague and CT imaging may be negative when patients are pain free, thus laparoscopy may be needed to definitively exclude an internal hernia. Jeff: Strictures may occur both during the early and late period. Most are minor, but significant strictures may result in obstruction. Nachi: Trocar site hernias and ventral hernias are also late complications, usually found after significant weight loss. Jeff: Cholelithiasis is another very common complication of bypass surgery, occurring in up to one third of patients, usually occurring during a peak incidence period between 6-18 months. Nachi: For this reason, the current recommendation is that patients undergoing bypass be placed on ursodeoxycholic acid for 6 months preventatively. Jeff: Some even go as far as to recommend prophylactic cholecystectomy to prevent complications, but as of 2013, the recommendation was only ‘to consider’ it. Nachi: Nutritional deficiencies are also common complications. Vitamin D, B12, Calcium, foate, iron, and thiamine deficiencies are all well documented complications. Patients typically take vitamins postoperatively to prevent such complications. Jeff: And next we have late dumping syndrome, which is far more rare than the last two complications. In late dumping syndrome, 1-3 hours after a meal, patients suffer hypoglycemia from excessive insulin release following the food bolus entering the GI tract. Symptoms are those typical of hypoglycemia. Nachi: Lastly, let’s talk about complications of lap adjustable gastric band surgery. In the early post op period, you can have esophageal and gastric perforations, which typically occur during balloon placement. Patients present with abd pain, n/v, and peritonitis. These patients often require emergent operative intervention. Jeff: The band can also be overtightened resulting in distention of the proximal gastric pouch. Presenting symptoms include abd pain with food and liquid intolerance and vomiting. Symptoms resolves once the balloon is deflated. The band can also slip, allowing the stomach to move upward and within the band. This occurs in up to 22% of patients and can cause strangulation. Presentation is similar to bowel ischemia. Nachi: Later complications include port site infections due to repeated port access. The infection can spread into connector tubing and the peritoneal cavity causing systemic symptoms. Definitely start antibiotics and touch base with the bariatric surgeon. Jeff: The connector can also dislodge or rupture with time. This can present as an arrest in weight loss. It’s diagnosed by contrast injection into the port. Of note, this complication is less common due to changes in the technique used. Nachi: Much like early band slippage and prolapse, patients can also experience late band slippage and prolapse after weeks or months. In extreme cases, the patients can again have strangulation and symptoms of bowel ischemia. More mild cases will present with arrest in weight loss, reflux, and n/v. Jeff: The band can also erode and migrate into the stomach cavity. If this occurs, it usually happens within 2 years of the initial procedure with an incidence of 4-11%. Presenting symptoms here include epigastric pain, bleeding, and infections. You’ll want to obtain emergent imaging if you are concerned. Nachi: And lastly there are two rare complications worth mentioning from any gastric bypass surgery. These are nephrolithiasis, possibly due to increased urinary oxalate excretion or hypocitraturia, and rhabdomyloysis. Jeff: That was a ton of information but certainly valuable as most EM clinicians, even ones in practice for decades, are unlikely to have that depth of knowledge on bariatric surgery. Nachi: And truthfully these patients are complicated. Aside from the pathologies we just discussed, you also have to still bear in mind other abdominal conditions unrelated to their surgery like appendicitis, diverticulitis, pyelo, colitis, hepatitis, pancreatitis, mesenteric ischemia, and GI bleeds. Jeff: Moving on to my favorite - prehospital care - as always, ABCs first. Consider IV access and early IV fluids in those at risk for dehydration and intra-abdominal infections. In terms of destination, if it’s feasible and the patient is stable consider transport directly to the nearest bariatric center - early efforts up front will really expedite patient care. Nachi: Once in the ED, you will want to continue initial stabilization. Special considerations for the airway include a concern for a difficult airway due to body habitus. Make sure to position appropriately and preoxygenate the patients if time allows. Keep the patient upright for as long as possible as they may desaturate quickly when flat. Jeff: We both routinely raise the head of the bed for all of our intubations. This is ever more important for your obese patients to help maximize your chance of first pass success without significant desaturation. Nachi: And though I’m sure we all remember this from residency, it’s worth repeating: tidal volume settings on the ventilator should be based on ideal body weight, not actual body weight. At 6 to 8 mL/kg. Jeff: Tachycardic patients should make you concerned for hypovolemia 2/2 dehydration, sepsis, leaks, and blood loss. Consider performing a RUSH exam (that is rapid ultrasound for shock and hypotension) to identify the cause. A HR > 120 with abdominal pain should make you concerned enough to discuss urgent ex-lap with the surgeon to evaluate for the post op complications we discussed earlier. Nachi: If possible, obtain a view of the IVC also while doing your ultrasound to assess for volume status. But bear in mind that ultrasound will undoubtedly be more difficult if the patient has a large body habitus, so don’t be disappointed if you’re not getting the best views. Jeff: Resuscitation should be aimed at early fluid replacement with IV crystalloids for hypovolemic patients and packed RBC transfusions for patients presumed to be unstable from hemorrhage. No real surprises there for our listeners. Nachi: Once stabilized, gather a thorough history. In addition to the usual questions, ask about po intolerance, early satiety, hematemesis, and hematochezia. Definitely also gather a thorough surgical history including name of procedure, date, known complications post op, and name of the surgeon. Jeff: You might also run into “medical tourism” or global bariatric care. Patients are traveling overseas to get their bariatric care more and more frequently. Accreditation and oversight is variable in different countries and there isn’t a worldwide standard of care. Just an important phenomenon to be aware of in this population. Nachi: On physical exam, be sure to look directly at the belly, making note of any infections especially near a port-site. Given the reorganized anatomy and extent of soft tissue in obese patients, don’t be reassured by a benign exam. Something awful may be happening deeper. Jeff: This naturally brings us into diagnostic testing. Not surprisingly, labs will be helpful in these patients. Make sure to check abdominal labs and a lipase. Abnormal LFTs or lipase may indicate obstruction of the biliopancreatic limb in bypass patients. Nachi: A lactic acid level will help in suspected cases of hypoperfusion from sepsis or bowel ischemia. Jeff: And as we mentioned earlier, these patients are often at risk for ACS given their comorbidities. Be sure to check a troponin if you suspect cardiac ischemia. Nachi: If concerned for sepsis, draw blood cultures, and if concerned for hemorrhage, be sure to send a type and screen. Urinalysis and urine culture should be considered especially for early post op patients, symptomatic patients, or those with GU complaints. Jeff: And don’t forget the urine pregnancy test for women of childbearing age, especially prior to imaging. Nachi: Check an EKG immediately after arrival for any patient that may be concerning for ACS. A normal ekg of course does not rule out a cardiac cause of their presentation. Jeff: As for imaging, plain radiographs certainly play a role here. For patients with respiratory complaints, check a CXR. In the early postoperative period, there is increased risk for pneumonia. Nachi: Unstable patients with abdominal pain will benefit from an emergent abdominal series, which may show free air under the diaphragm, pneumatosis, air-fluid levels, or even dilated loops of bowel. Jeff: Of course don’t forget that intra abd air may be seen after laparoscopic procedures depending on how recently the operation was performed. Nachi: Plain x-ray can also help diagnose malpositioned or slipped gastric bands. But a negative study doesn’t rule out any of these pathologies definitively, given the generally limited sensitivity and specificity of x-ray. Jeff: You might also consider an upper GI series. Emergent uses include diagnosis of slipped or prolapsed gastric bands as well as gastric or esophageal perforations. Urgent indications include diagnosis of strictures. These can also diagnose gastric band erosions and help identify staple-line or anastomotic leaks in stable patients. Nachi: However, upper GI series might not be easy to obtain in the ED, so it’s often not the first test performed. Jeff: This brings us to the workhorse for diagnostic evaluation. The CT. Depending on suspected pathology, oral and/or IV contrast will be helpful. Oral contrast can help identify gastric band erosions, staple-line leaks, and anastomotic leaks. Leaks can be identified in up 86% of cases with oral contrast. Nachi: CT will also help diagnose internal hernias. You might see the swirl sign on CT, which represents swirling of the mesenteric vessels. This is highly predictive of an internal hernia, with a sensitivity of 78-100% and specificity of 80-90% according to at least two studies. Jeff: While CT is extremely helpful in making this diagnosis, note that it may be falsely negative for internal hernias. A retrospective review showed a sensitivity of 76% and a specificity of 60%. It also showed that 22% of patients with an internal hernia on surgical exploration had a negative CT in the ED. Another study found a false negative rate of 32%. What does all this mean? It likely means that a negative study may still necessitate diagnostic laparoscopy to rule out an internal hernia. Nachi: While talking about CT, we should definitely mention CTA for concern of pulmonary embolism. In order to limit contrast exposure, you might consider doing a CTA chest and CT of the abdomen simultaneously. Jeff: Next up is ultrasound. Ultrasound is still the first-line imaging modality for assessing the gallbladder and for biliary tract disease. And as we mentioned previously, ultrasound should be considered for your RUSH exam and for assessing the IVC. Nachi: We also should discuss endoscopy, which is the test of choice for diagnosing gastric band erosions. Endoscopy is also useful for evaluating marginal ulcers, strictures, leaks, and GI bleeds. Endoscopy additionally can be therapeutic for patients. Jeff: When treating these patients, attempt to contact the bariatric surgeon for guidance as needed. This shouldn’t delay imaging however. Nachi: For septic patients, make sure your choice of antibiotics covers intra-abdominal gram-negative and anaerobic organisms. Port-site infections require gram-positive coverage to cover skin flora. Additionally, give IV fluids, blood products, and antiemetics as appropriate. Jeff: Alright, so this month, we also have 2 special populations to discuss. First up, the kids. Nachi: Recent estimates from 2015-2016 put the prevalence of obesity of those 2 years old to 19 years old at about 19%. As obese children are at higher risk for comorbidities later in life and bariatric surgery remains one of the best modalities for sustained weight loss, these surgical procedures are also being done in children. Jeff: Criteria for bariatric surgery in the adolescent population is similar to that of adults and includes a BMI of 35 and major comorbidities (like diabetes or moderate to severe sleep apnea) or patients with a BMI 40 with other comorbidities associated with long term risks like hypertension, dyslipidemia, insulin resistance and impaired quality of life. Nachi: Despite many adolescents meeting criteria, they should be referred with caution as the long term effects are unclear and the adolescent experience is still in its infancy with few pediatric specific programs. Jeff: Still, the complication rate is low - about 2.3% with generally good clinical outcomes including improved quality of life and reducing or staving off comorbidities. Nachi: Women of childbearing age are the next special population. They are at particular risk because of the unique caloric and nutrient needs of a pregnant mother. Jeff: Pregnant women who have had bariatric surgery have an increased risk of perinatal complications including prematurity, small for gestational age status, NICU admission and low Apgar scores. However, these risks come with benefits as other studies have shown reduced incidence of pre-eclampsia, large for gestational age neonates, and gestational diabetes. Nachi: 2013 guidelines from various organizations recommend avoiding becoming pregnant for at least 12-18 months postoperatively, with ACOG recommending a minimum of 2 years. Bariatric surgery patients who do become pregnant require serial monitoring for fetal growth and higher doses of supplemental folate. Jeff: We also have 2 pretty cool cutting edge techniques to mention this month before getting to disposition. Nachi: Though these are certainly not going to be done in the ED, you should be aware of two new techniques. Recently, the FDA approved 3 new endoscopic gastric balloon procedures in which a balloon is inflated in the stomach as a means of simulating a restrictive procedure. Complications include perforation, ulceration, GI bleeding, and migration with obstruction. As of now, they are only approved as a temporary modality for up to 6 months. Jeff: And we also have the AspireAssist siphon, which was approved in 2016. With the siphon, a g tube is placed in the stomach, and then ⅓ of the stomach contents is drained 20 minutes after meals, thus limiting overall digested intake. Nachi: Pretty cool stuff... Jeff: Yup - In terms of disposition, decisions should often be made in conjunction with the bariatric surgical team. Urgent and occasionally emergent surgery is required for those with hemodynamic instability, anastomotic or staple line leaks, SBO, acute band slippage with dilatation of the gastric pouch, tight gastric bands, and infected port sites with concurrent intra abdominal infections. Nachi: And while general surgeons should be well-versed in these complications should the patient require an emergent surgery, it is often best to stabilize and consider transfer to your local bariatric specialty facility. Jeff: In addition to the need for admission for surgical procedures, admission should also be considered in those with dehydration and electrolyte disturbances, those with persistent vomiting, those with GI bleeding requiring transfusions, those with acute cholecystitis or choledococholithiasis, and those with malnutrition. Nachi: Finally, patients with chronic strictures, marginal ulcers, asymptomatic trocar or ventral hernias, and stable gastric band erosions can usually be safely discharged after an appropriate conversation with the patient’s bariatric surgeon. Jeff: Definitely a great time to do some joint decision making with the patient and their surgeon. Nachi: Exactly. Let’s close out with some Key points and clinical pearls. Jeff: Bariatric surgeries are being performed more frequently due to both their success in sustained weight loss and improvements in associated comorbidities. Nachi: There is an increased risk of postoperative myocardial infarction and pulmonary embolism after bariatric surgery. There is also an increased risk of self-harm emergencies after bariatric surgery, mostly in patients with known psychiatric co-morbidities. Jeff: Nutritional deficiencies can occur following bariatric surgery, with thiamine deficiency being one of the most common. Look for signs of beriberi or even Wernicke encephalopathy. Nachi: Staple-line leaks are an important cause of postoperative morbidity. Patients often present with abdominal pain, vomiting, sepsis, and peritonitis. Jeff: Strictures can also present postoperatively and cause reflux, epigastric discomfort, and vomiting. Nachi: Intraperitoneal or intraluminal hemorrhage is a known complication of bariatric surgery and may present as peritonitis or with hematemesis and melena. Jeff: After significant weight loss, internal hernias with our without features of strangulation are a late complication. Nachi: Late dumping syndrome is a rare complication following Roux-en-Y bypass occurring months to years postoperatively. It presents with hypoglycemia due to excessive insulin release. Jeff: Esophageal or gastric perforation are early complications of adjustable gastric band surgery. These patients require emergent surgical intervention. Nachi: Overtightening of the gastric band results in food and liquid intolerance. This resolves once the balloon is deflated. Jeff: Late complications of gastric band surgery include port-site infections, connector tubing dislodgement or rupture, band slippage or prolapse, and band erosion with intragastric migration. Nachi: Given the myriad of possible bariatric surgeries, emergency clinicians should be cognizant of procedure-specific complications. Jeff: Consider obtaining a lactic acid level for cases of suspected bowel ischemia or sepsis. Nachi: Endoscopy is the best method for diagnosing and treating gastric band erosions. Jeff: Septic patients should be treated with antibiotics that cover gram-negative and anaerobic organisms. Suspected port site or wound infections require gram positive coverage. Nachi: Pregnant patients who previously had bariatric surgery are at risk for complications from their prior surgery as well as pregnancy-related pathology. Jeff: A plain radiograph may be useful in unstable patients to evaluate for free air under the diaphragm, pneumatosis, air-fluid levels, or dilated loops of bowel. Nachi: CT of the abdomen and pelvis is the mainstay for evaluation. Oral and/or IV contrast should be considered depending on the suspected pathology. Jeff: Have a low threshold for emergent surgical consultation for ill-appearing, unstable, or peritonitic patients. Nachi: So that wraps up Episode 30! Jeff: As always, additional materials are available on our website for Emergency Medicine Practice subscribers. If you’re not a subscriber, consider joining today. You can find out more at ebmedicine.net/subscribe. Subscribers get in-depth articles on hundreds of emergency medicine topics, concise summaries of the articles, calculators and risk scores, and CME credit. You’ll also get enhanced access to the podcast, including any images and tables mentioned. PA’s and NP’s - make sure to use the code APP4 at checkout to save 50%. Nachi: And the address for this month’s cme credit is ebmedicine.net/E0719, so head over there to get your CME credit. As always, the [DING SOUND] you heard throughout the episode corresponds to the answers to the CME questions. Lastly, be sure to find us on iTunes and rate us or leave comments there. You can also email us directly at EMplify@ebmedicine.net with any comments or suggestions. Talk to you next month! Most Important References Altieri MS, Wright B, Peredo A, et al. Common weight loss procedures and their complications. Am J Emerg Med. 2018;36(3):475-479. (Review article) Colquitt JL, Pickett K, Loveman E, et al. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014(8):CD003641. (Cochrane review; 22 trials) Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient—2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery. Obesity (Silver Spring). 2013;21 Suppl 1:S1-S27. (Society practice guidelines) Phillips BT, Shikora SA. The history of metabolic and bariatric surgery: development of standards for patient safety and efficacy. Metabolism. 2018;79:97-107. (Review article) Contival N, Menahem B, Gautier T, et al. Guiding the nonbariatric surgeon through complications of bariatric surgery. J Visc Surg. 2018;155(1):27-40. (Review article) Parrott J, Frank L, Rabena R, et al. American Society for Metabolic and Bariatric Surgery integrated health nutritional guidelines for the surgical weight loss patient, 2016 update: micronutrients. Surg Obes Relat Dis. 2017;13(5):727-741. (Society practice guidelines) Chousleb E, Chousleb A. Management of post-bariatric surgery emergencies. J Gastrointest Surg. 2017;21(11):1946-1953. (Review article) Goudsmedt F, Deylgat B, Coenegrachts K, et al. Internal hernia after laparoscopic Roux-en-Y gastric bypass: a correlation between radiological and operative findings. Obes Surg. 2015;25(4):622-627. (Retrospective review; 7328 patients) Michalsky M, Reichard K, Inge T, et al. ASMBS pediatric committee best practice guidelines. Surg Obes Relat Dis. 2012;8(1):1-7. (Society practice guidelines)

Show Notes Jeff: Welcome back to EMplify the podcast corollary to EB Medicine’s Emergency medicine Practice. I’m Jeff Nusbaum and I’m back with Nachi Gupta for your regularly scheduled monthly dose of evidence based medicine. This month, we are tackling an incredibly important topic – Assessing abdominal pain in adults, a rational, cost effective, and evidence-based strategy. Nachi: This incredibly important topic was chosen to mark the 20th anniversary of Emergency Medicine Practice. It is actually a revision of the first issue of Emergency Medicine Practice in 1999, now with updated evidence and recommendations. Thanks Robert Williford and Dr. Colucciello for getting this all started 2 decades ago! Jeff: Wow – 20 years – that’s amazing considering Emergency Medicine as a specialty hadn’t even been around all that long at the time and as Dr. Jagoda writes in his intro “evidence based education was still finding its footing.” Nachi: As a tribute to the man who started it all, EB Medicine again turned to Dr. Colucciello, who is no longer wearing his editor in chief hat, but instead is a professor at the University of North Carolina School of Medicine, to update his original article with the latest evidence. Jeff: Before we dive into the meat and potatoes of this month’s issue, let me also recognize Drs. Taylor and Shaukat of Emory and Coney Island Hospital respectively for their efforts in peer reviewing this huge topic. Show More v Nachi: For a number of reasons, this month is going to be a little different. You will notice that we will focus more on safe disposition instead of on diagnosis. Which is reasonable, as that is the crux of our job as emergency physicians. Jeff: Indeed. So for those of you who can’t wait, here’s a quick spoiler, The CBC isn’t all that useful. CT is good but you really should learn ultrasound, and lastly, sick patients need prompt consultation and resuscitation, not rapid trips to radiology. Nachi: All valid points, but let’s dive in too some actual detail. Jeff: Abdominal pain is the one of most frequent complaint in US emergency departments, representing 8% of all adult ED visits, with admission rates for all patients with abdominal pain ranging between 18-42% and reaching as high as 60% for the elderly. Nachi: With respect to the elderly, statistically speaking, 20% presenting with abdominal pain will undergo surgery, and 5% will die. Jeff: Often the etiology of the abdominal pain is never determined. This happens up to 40% of the time by the end of the ED visit. Nachi: I feel like that needs to be restated for emphasis – nearly half of patients who present to the ED with abdominal pain will have no determined etiology for their pain. Clearly, that doesn’t mean you are a bad ED physician – it’s just the way it goes. Jeff: Definitely still a win to be told you aren’t having an intra-abdominal catastrophe at the end of your visit! Nachi: Moving on to pathophysiology. Visceral pain results from distention or inflammation of the hollow organs or from ischemia from any internal organ, while the more localized, somatic pain is typically from irritation of the adjacent peritoneum. Jeff: And don’t forget about referred pain. Due to the movement of organs and stretching of nerve pathways during fetal development, pain may be referred to distant sites, like diaphragmatic irritation presenting as shoulder pain. Nachi: Let’s talk differential diagnosis. The differential for abdominal pain is tremendously broad and includes both intra-abdominal and extra abdominal pathologies. Check out table 2 for a very thorough list. Jeff: Table 1 is also worth reviewing while you’re on page 3 as it lists a few of the common dangerous mimics that often lead to misdiagnosis on initial presentation. To highlight a few – a AAA can masquerade as renal colic, diverticulitis, or a lumbar strain; an ectopic may present similar to PID, a UTI, or a corpus luteum cyst, and mesenteric ischemia may present shockingly similar to gastroenteritis, constipation, ileus, or an SBO. Nachi: Though misdiagnosis is certainly possible at any age, one must be particularly cautious with the elderly. Abdominal pain in the elderly is complicated by a number of factors, they often have no fever, no leukocytosis, or no localized tenderness despite surgical disease, surgical problems progress more rapidly, and lastly, they are at risk for vascular catastrophes, which don’t typically afflict the younger population Jeff: Dr. Colucciello closes the section on the elderly with a really thought-provoking point – we routinely admit 75 year old with chest pain and benign exams, yet we readily discharge a 75 year old with abdominal pain and a benign exam even though the morbidity and mortality of abdominal pain in this group exceeds that of the chest pain group. Nachi: That’s an interesting perspective, but we still have to think about this in the context of what an admission would offer in either of these cases. Most of the testing for abdominal pain can be done in the ED, CT being the workhorse. This point certainly merits more thought though. Jeff: Most clinicians have a low threshold to scan their elderly patients with abdominal pain, and the data behind this practice is quite compelling. In one study, CT altered the admission decision in 26%, need for surgery in 12%, the need for antibiotics in 21%, and changed the suspected diagnosis in 45%. Nachi: That latter figure, 45% change in suspected diagnosis, that was also confirmed in another study in which CT revealed a clinically unsuspected diagnosis in 43% of the elderly. Jeff: And it’s worth mentioning, that even though CT may be the go-to-tool - biliary tract disease, which we know is best visualized on ultrasound, is actually the most common cause of abdominal pain, especially sudden onset abdominal pain in the elderly. Nachi: The next higher risk group to discuss are patients with HIV. While anti retroviral therapy has certainly decreased the burden of opportunistic infections, don’t forget to keep a broader differential in this group including bacterial enterocolitis, drug-induced pancreatitis, or AIDS related cholangiopathy Jeff: Definitely make sure to check to see if the patient has a recent CD4 count to give you a sense of their disease and what they may be at risk for. At less than 200, cryptosporidium, isospora, cyclospora, and microsporidium all make their way onto the differential in addition to the standard players. Nachi: For more information on HIV and its management, check out the February 2016 issue of Emergency Medicine Practice, which covered this and more in depth. Jeff: The next high risk population we are going to discuss are women of childbearing age. Step one is always the same - diagnose pregnancy! Always get a pregnancy test for women between menarche and menopause. Nachi: The pregnancy test is important not only for diagnosing an intrauterine pregnancy, but it’s also a reminder, that we need to consider and rule out an ectopic. Jeff: Along similar lines, you also need to consider torsion, especially in your pregnant population, as 20% of cases of ovarian torsion occur during pregnancy. Nachi: Unfortunately, you cannot rely on the physical exam alone in this age group, as the pelvic exam may be misleading. Up to a quarter of women with appendicitis can exhibit cervical motion tenderness -- a finding typically associated with PID. Sadly, errors are common and ⅓ of women of childbearing age who ultimately were found to have appendicitis were initially misdiagnosed. Jeff: To help reduce your risk in the pregnant population, consider imaging, particularly with radiation reduction strategies, including using ultrasound and MRI, which is gaining favor in the diagnosis of appendicitis in pregnancy. Nachi: Diagnosis of appendicitis, in a pregnant patient, ultrasound vs. mri. Sounds familiar. Didn’t we just talk about this in Episode 24 back in January? Jeff: We sure did! Take another listen if that doesn’t ring a bell. Nachi: That was focused on first trimester only, but while we’re talking about appendicitis in pregnancy - keep in mind that during the second half of pregnancy, the appendix has moved out of the RLQ and is more likely to be found in the RUQ. Jeff: As yes, the classic RUQ appendix. As if our jobs weren’t hard enough, now anatomy is changing… Anyway, the last high risk group we are going to discuss here are those patients with prior abdominal surgery. Make sure to ALWAYS examine the patient's exposed skin to look for scars. Adhesions are the leading cause of SBOs in the industrialized world, followed by malignancy, IBS, and internal or external hernias. Nachi: Also keep a high index of suspicion for patients who have undergone bariatric surgery. They are especially prone to surgical causes of abdominal pain including skin infections and surgical leaks. Jeff: For this reason, CT imaging should be done with IV and oral contrast, with those having undergone a Roux-en-Y receiving oral contrast on the CT table. Nachi: Perfect. Let’s move on to evaluation once in the ED! Jeff: As we mentioned a few times already - diagnosis is difficult, a comparison of initial and final diagnosis only has about 50-65% accuracy. For this reason, Dr. C suggests taking a ‘worst first’ approach to forming your differential and guiding your workup. Nachi: And as a brief aside, before we continue… Missed appendicitis is one of the three most common causes of emergency medicine malpractice lawsuits - with MI and fractures being the other two. That being said, you, as a clinician, have either missed appendicitis or likely will in the future. In a study of cases of misdiagnosed appendicitis brought to litigation, several themes recurred. For example, patients with misdiagnosed disease has less RLQ pain and tenderness as well as diminished anorexia, nausea, and vomiting. Jeff: Well that’s scary - I know I’ve already missed a case, but luckily, he returned thanks to good return precautions, which we’ll get to in a few minutes. Also, note that in addition to imaging and the physical exam, history is often the key to uncovering the cause of abdominal pain. Nachi: Not to harp on litigation, but in malpractice cases brought up for failure to diagnose abdominal conditions, deficiencies in data gathering and charting were often to blame rather than misinterpretation of data. Jeff: As no shocker here, getting a complete history remains tremendously important in your practice as an emergency clinician. A recurring theme of EMplify for sure. Nachi: In order to really nail this down, consider using a standardized history form -- or memorizing one. An example is shown in Table 1. Standardized forms have been shown to improve patient satisfaction and diagnostic accuracy. Jeff: An interesting question for your abdominal pain patient is to ask about the ride to the hospital. Experiencing pain going over a speed bump has been shown to be about 97% sensitive and 30% specific for appendicitis. So fairly sensitive, but not too specific. Nachi: That’s interesting and may help guide you, but it’s certainly no replacement for CT. And remember that you can have stump appendicitis. This can occur in the appendiceal remnant after an appendectomy and is found in about 0.15% of all appendectomies. Jeff: Alright, so on to the physical exam. Like always, let’s start with vital signs. An elevated temp can be associated with intra abdominal infection, but sensitivity and specificity vary greatly here. Always consider a rectal temp, as these are generally more reliable. Nachi: And remember that hypothermic patients who are septic have worse outcomes than those who are hyperthermic and septic. Jeff: Elevated respiratory rate can be due to pain or subdiaphragmatic irritation. However, it can also be due to hypoxia, sepsis, anemia, PE, or metabolic acidosis, so consider all of those also in your differential. Nachi: Moving on to blood pressure: frank hypotension should make you immediately think of a ruptured AAA or septic shock 2/2 an intra abd infection. You can also use the shock index, which as a reminder is simply the HR/SBP. In one study, a SI > 0.7 was sensitive for 28-day mortality in sepsis. Jeff: Speaking of HR, tachycardia can be a response to pain, anxiety, fever, blood loss, or sepsis. An irregularly irregular rhythm -- or a fib -- is an important risk factor for mesenteric ischemia in elderly patients. This is important to consider in your differential early as it may guide your imaging modality. Nachi: With vitals done, we can move on to the abdominal exam - it is rare that a serious abdominal condition will present without tenderness in a young adult patient, but remember that the elderly patient may not present with much tenderness at all due decreased peritoneal sensitivity. Abdominal tenderness that is greatest when the abdominal muscles are contracted is likely due to abdominal wall pain. This can be elicited by having the patient lift their head or let their legs off the bed. This finding is known as Carnett sign and is about 95% accurate for distinguishing abdominal wall pain from visceral abdominal pain. Jeff: Though tenderness itself is helpful, the location of tenderness can be misleading. Note that while 80% of patients with appendicitis have RLQ tenderness, 20% don’t. The old 80-20 rule! So definitely don’t let RLQ tenderness be your sole guide! Nachi: Voluntary guarding is due to fear, anxiety, or even a reaction to a clinician’s cold hands. Involuntary guarding (also called rigidity) is more likely to occur with surgical disease. Remember that rigidity may be a less common finding in the elderly despite surgical disease. Jeff: Peritoneal signs are the true hallmark of surgical disease. These include rebound pain, pain with coughing, pain with shaking the stretcher or pain with striking the patient’s heel. Rebound historically has been thought to be pathognomonic for surgical disease, but recent literature hasn’t found it to be all that useful, with one study claiming it has no predictive value. Nachi: As an alternative, consider the “cough test”. Look for evidence of posttussive abd pain (like grimacing, flinching, or grabbing the belly). Studies have found the cough sign to be 80-95% sensitive for peritonitis. Jeff: In terms of other sings elicited during the abdominal exam: The murphy sign, ruq palpation that causes the patient to stop a deep inspiration -- in one study had a sensitivity of 97%, but a specificity of just under 50%. The psoas sign, pain elicited by extending the RLE towards the back while the patient lies on their left side -- in one study had a specificity of 95%, but only had a sensitivity of 16%. Nachi: Neither the obturator sign (pain with internal rotation of the flexed hip) nor the rosving sign (pain in the RLQ by palpating the LLQ) have been rigorously studied. Jeff: Moving a bit further south, from the abdomen to the pelvis - let’s talk about the pelvic exam. Most EM training programs certainly emphasize the importance of the the pelvic exam for women with lower abdominal pain, but some recent papers have questioned its role. A 2018 study involving 288 women 14-20 years old found that the pelvic didn’t increase sensitivity or specificity of diagnosis of chlamydia, gonorrhea, or trichomoniasis when compared with history alone. Another study questioned whether the pelvic exam can be omitted in these patients with an early intrauterine pregnancy confirmed on ultrasound, but it was unable to reach a conclusion, possibly due to insufficient power. Nachi: While Jeff and I do find it valuable to elicit as much as information from the history as possible and take value in the possibility of omitting the pelvic in certain cases in the future, given the current evidence based medicine, we both agree with the author here. Don’t abandon the pelvic for these patients just yet! Jeff: While on this topic, we should also briefly mention a reminder about fitz-hugh-curtis syndrome, perihepatic inflammation associated with PID. Nachi: As for the digital rectal exam, this can certainly be of use when considering and diagnosing prostatitis, perirectal disease, stool impactions, rectal foreign bodies, and gi bleeds. Jeff: And let’s not forget the often overlooked scrotal and testicular exam. In men with abdominal or flank pain, this should always be considered. Testicular torsion often presents with isolated abdominal or flank pain. The scrotal exam will help diagnose inguinal and scrotal hernias. Nachi: Getting back to malpractice case reviews for a minute --- in a 2018 review involving testicular torsion, almost ⅓ of the patients with missed torsion had presented with abdominal pain --- not scrotal pain! In ⅕ of the cases, no testicular exam was performed at all. Also, most cases of missed torsion occured in patients under 25 years old. Jeff: Speaking of torsion, about 6% occur over the age of 31, so have an increased concern for this in the young. Of course, if concerned for torsion, consult urology immediately and consider manual detorsion. Nachi: And if you, like me, were taught to manually detorse by rotating in the lateral or open book direction, keep in mind that in a study of 200 males with torsion, ⅓ had rotated laterally, not medially. Jeff: Great point. And one last quick point here. Especially if you are unsure about the diagnosis, make sure to perform serial exams both in the ED and also in the next few days at their PCP’s office. In one study, a 30 hour later repeat exam for patients discharged with nonspecific abdominal pain resulted in a clinically relevant change in diagnosis and therapy in almost 25% of patients. Nachi: So that wraps up the physical. Let’s get into diagnostic studies, starting with lab work and everybody’s favorite topic... the cbc. Jeff: Yup, just the other day I was asked by a consultant “what’s the white count.” in a patient with CT proven appendicitis. Man, a small part of my soul dies every time this happens. Nachi: It appears you must have an evidenced based soul then. According to a few studies, anywhere from 10-60% of patients with surgically proven appendicitis have an initially normal WBC. So in some studies, it’s even worse than a coin flip. Jeff: Even worse, in children the CBC is less helpful. In children, an elevated WBC detects a mere 53% of severe abdominal pathology - so again not all that helpful. Nachi: That being said, at the other end of the spectrum, in the elderly, an elevated WBC may imply serious disease. Jeff: So let’s make this perfectly clear. A normal WBC should not be reassuring, but an elevated WBC, especially in the elderly, should be very concerning. Nachi: The CRP is up next. Though not used frequently, it’s still worth mentioning, as there is a host of data on it in the setting of abdominal pain. In one meta analysis, CRP was approximately 62% sensitive and 66% specific for appendicitis. Jeff: And while lower levels of CRP do not rule out positive findings, increasing levels of CRP do predict, with increasing likelihood, the chances of positive findings. Nachi: Next we have lipase and amylase. The serum lipase is the best test for suspected pancreatitis. The amylase adds limited value and should not be routinely ordered. Jeff: As for the lactate. The greatest value of a lactate level is to detect occult shock and sepsis. It is also useful to screen for visceral ischemia. Nachi: And the last lab test we’ll discuss is the UA. The urinalysis is a potentially misleading test. In two studies, 20-30% of patients with appendicitis also had hematuria with leukocytes and bacteria on their UA. In a separate study of those with a AAA, there was an 87% incidence of hematuria. Jeff: That’s pretty troubling. Definitely not great to diagnosis someone with hematuria and a primary GU problem, when their aorta is actually exploding. Nachi: And that’s a great reminder to always avoid premature diagnostic closure. Jeff: Also worth mentioning is that not all ureteral stones present with hematuria. At least 6% have no hematuria on microscopy. Nachi: Alright, so that brings us to imaging. First up: plain films. I’m going to quote this directly from the article since I think it's so important, ‘never rely on plain films to exclude surgical disease.” Jeff: This statement is certainly evidence based as in one study 40% of x-ray findings were inconsistent with the final diagnosis. In another study, 43% of patients with major surgical disorders had either normal or misleading plain film results. So again, the take home here is that XR cannot rule out surgical disease, and should not be routinely ordered except for in specific settings. Nachi: And perhaps the most important of all those settings is in the setting of possible free air under the diaphragm. In this case, an upright chest visualizing the area under the diaphragm would be the test of choice. But again, even this doesn’t rule out surgical disease as free air may be absent on plain films in ⅓ to ½ of patients who have already perfed. Jeff: Next we have everybody’s favorite, the ultrasound. Because of it’s low cost and ease of use, bedside ultrasound is gaining traction. And we’ve cited this and other similar studies in other issues, this is a skill emergency medicine physicians must have in this day and age and it’s a skill they can learn quickly. Nachi: Ultrasound can visualize most solid organs, but it is best suited for the Right upper quadrant and pelvis. In the RUQ, we are looking for wall thickening, pericholecystic fluid, ductal dilatation, and sonographic murphys sign. Jeff: In the pelvis, there is a role for both transabdominal and transvaginal to rule out ectopic and potentially rule in intrauterine pregnancy. I know the thought of performing your own transvaginal ultrasound may sound crazy to some, but we both trained in places where ED TVUS was the norm and certainly wasn’t that hard to learn. Nachi: Ah, the good old days of residency. I’m certainly grateful for the US tech where I am now though! Next up we have CT. CT scans are ordered in just under 30% of patients with abdominal pain. Jeff: It’s worth noting, that while many used to scan with triple contrast - oral, rectal and IV, recent literature has shown that IV contrast alone is adequate for the diagnosis of most surgical conditions, including appendicitis. Nachi: If you’re still working in a shop that scans for RLQ pain with oral or rectal contrast, definitely check out the 2018 american college of radiology appropriateness criteria that states that IV contrast is generally appropriate for assessing the RL. Jeff: And while we are on the topic of contrast, let’s dive a bit deeper into the, perhaps myth, that contrast leads to contrast induced nephropathy. Nachi: This is another really important point. Current data show that being ill enough to be admitted to the hospital is a risk factor for acute kidney injury and that IV contrast for CT does not add to that risk. In 2015, the american college of radiology noted in their manual on contrast media that the concern for the development of contrast induced nephropathy is not an absolute contraindication for using IV contrast. IV contrast may be necessary regardless of the risk of nephrotoxicity in certain clinical situations. Jeff: Ok, so contrast induced nephropathy may be real, but more studies and a definitive statement are still needed. Regardless, if the patient is sick and they need the scan with contrast, don’t hold back. Nachi: I think that’s a fair take home. As another note about the elderly, CT should be almost routine in the elderly patient with acute abdominal pain as it improves accuracy, optimizes appropriate hospitalization, and boosts ED management decision making confidence for this patient group. Jeff: If they are over 65, make sure you chart very carefully why they don’t need a scan. Nachi: Speaking of not needing a scan, two quick caveats on CT before moving to MRI. Unstable patients do not belong in a radiology suite - they belong in the ED resus bay to be resuscitated first. Prompt surgical consultation and bedside ultrasound if indicated are both a must in unstable patients. Jeff: The second caveat is on the other end of the spectrum - not all CT scanning is created equally - the interpretation depends on the scanner, the quality of the scan, and the experience and training of the reading radiologist. In one study, nearly 13% of abdominal CT scans may initially be misread. Nachi: So if you’re concerned, consider consultation or an extended ED observation to monitor for any changes in the patient’s status. Jeff: Next up is MRI - MRI has an ever expanding role in the ED. The accuracy of MRI to diagnose appendicitis is very similar to CT, so consider it in all pregnant patients, though ultrasound is still considered first line. Nachi: And finally let’s touch upon the ekg and ACS. In patients over 40 with upper abdominal pain, an EKG and troponin should always be considered. Jeff: Don’t be reassured by a response to a GI cocktail either - this does not exclude myocardial ischemia. Nachi: Next, let’s talk the role of analgesia in treating the undifferentiated abdominal pain patient. Jeff: While there was formerly a concern of ‘masking the pain’ with opiates, the evidence says otherwise. Pain medicine may even aid in the diagnosis, so definitely don’t withhold it in the setting of acute abdominal pain. Nachi: Wait I get that masking the pain is no longer considered a concern, but how would it aid in the diagnosis? Jeff: Good question. Analgesics might facilitate the gathering of history and allow a more complete physical exam by relaxing the abdominal musculature. Nachi: Ahh that makes sense. So certainly treat pain! Both morphine at 0.1 mg/kg and fentanyl at 1 mic/kg are appropriate analgesics for acute abdominal pain. In those that are a difficult stick, a recent study showed that 2 micrograms/kg of fentanyl via a nebulizer was a safe alternative. Remember, fentanyl is quick on, quick off, which may make it desirable in certain situations. It actually has the shortest time of onset of any opioid. It’s also safer in patients with a “marginal” blood pressure. Jeff: And just like the GI cocktail - response to opiate analgesics does not exclude serious pathology. These patients need serial exams and likely labs and imaging if their pain is so severe. Nachi: Few things are more important prior to discharge of an abdominal pain patient than documenting repeat exams and a PO trial. Jeff: True. You should also consider haloperidol for patients with gastroparesis and cannabinoid hyperemesis as a growing body of literature supports its use in such settings. Check out the August 2018 EMP or EMplify for more details if you’re curious. Nachi: The last analgesic to discuss is our good friend ketamine. Low dose ketamine at 0.3 mg/kg over 15 minutes is gaining traction as the analgesic of choice in many ED’s. Jeff: The key there, is that it must be given over 15 minutes. Ketamine has a great safety profile, but you make it so much safer and a much better experience if you give it slowly. Nachi: Before we get to disposition, let’s talk controversies and cutting edge - and there is just one this month - and that’s the use of the Alvarado score. Jeff: In the Alvarado score, you get two points for RLQ tenderness and 2 points for a leukocytosis over 10,000. You get an additional point for all of the following; rebound, temp over 99.1, migration of pain to the RLQ, anorexia, n/v, and a left shift. The max score is therefore 10. A score of 3 or less make appendicitis unlikely, 4-6 warrants CT imaging, and 7 or more a surgical consultation. Nachi: A 2007 study suggests that using the Alvarado score along with bedside ultrasound might allow for rapid and inexpensive diagnosis of appendicitis. Jeff: I don’t think we should change practice based on this just yet, but more ultrasound diagnosis may be on the horizon. If you want to start using the Alvarado score in your practice, MDcalc has a great easy to use calculator. Nachi: Let’s get to the final section. Disposition! Jeff: As we mentioned at the beginning of this episode, the diagnosis is less important than proper disposition. For patients with suspected ruptured AAA, torsion, or mesenteric ischemia - the disposition is easy - they need immediate surgical consultation and likely operative intervention. Nachi: For others, use the tools we outlined above - ct, us, labs, etc, to help support your decision. Keep in mind, that serial exams are a great tool and of little expense - so make sure to lay your hands on the patient's abdomen frequently, especially when the diagnosis is unclear. Jeff: For those that look well after a work up, with no clear diagnosis, it may be reasonable to discharge them home with prompt follow up, assuming prompt follow up is plausible. The key here is that these patients need good discharge instructions. Check out figure 2 on page 20 for a sample discharge template. Nachi: But if the patient is still uncomfortable, even after a thorough workup, there may be a role for ED observation units. In one study of 220 patients admitted for to ED obs units for serial exams, 39% eventually underwent surgery with only 5% having negative laparotomies. Jeff: This month’s issue wraps up with some super important time and cost effective strategies, so let’s see if we can quickly breeze through some of the most important points before closing out this episode. Nachi: First - limit your abdominal x-rays as they offer limited value and are rarely helpful except in the setting of perforation, when an early upright chest film should be used liberally. Jeff: Next - limit electrolyte testing especially in young adults with nausea, vomiting and diarrhea. In those 18 to 60, clinically significant electrolyte abnormalities occur in only 1% of those with gastro. Nachi: With respect to urine testing, urine cultures are rarely indicated for uncomplicated cystitis in young women. Along similar lines, don’t anchor on the diagnosis of UTI as other lower abdominal conditions often lead to abnomal urine studies. Jeff: In your alcoholic patients, although all should be approached with an abundance of caution, limit testing to repeat abdominal exams in your non-toxic appearing patient who is already tolerating PO. Nachi: For those with suspected renal colic, especially those with a history of renal colic, limit CT use and instead consider ultrasound to look for hydro. This approach is endorsed by ACEPs choosing wisely campaign. Jeff: But as a reminder, this is for low risk patients only. Anyone with signs of infection should also undergo CT imaging. Nachi: And lastly - consider incorporating bedside US into your routine. The US is fast and accurate and compares similarly to radiology, especially in the context of detecting acute cholecystitis. Jeff: Alright, so that wraps up the new material for this episode, let’s close out with some key points and clinical pearls. The peritoneum becomes less sensitive with aging, and peritonitis can be a late or absent finding. Be wary of early diagnostic closure and misdiagnosis with a mimic of a more severe and dangerous pathology. The elderly, immunocompromised, women of childbearing age, and patients with prior abdominal surgeries are all at a higher risk for misdiagnosis. Elderly patients can present without fever, leukocytosis, or abdominal tenderness, but still have surgical abdominal pathology. Consider diagnostic imaging in all geriatric patients presenting with abdominal pain. Consider plain film if you suspect a viscus perforation or for certain foreign body ingestions. Do not forget the pelvic exam, testicular exam, and rectal exam as part of your physical, when appropriate. Testicular torsion can present with abdominal pain only. If suspected, consult urology and consider manual detorsion. A normal white blood cell count does not rule out appendicitis or other intra-abdominal pathology. Serum amylase should not be used in your assessment of the abdominal pain patient. Lack of microscopic hematuria does not rule out renal colic. CT of the abdomen with IV contrast alone is enough for most surgical conditions including appendicitis. Oral and rectal contrast does not need to be routinely administered. The 2018 American College of Radiology (ACR) Appropriateness Criteria discuss concern for delay in diagnosis associated with oral contrast use and an increased rate of perforation. There is recent literature to support that IV contrast does not cause nephropathy. The ACR 2015 Manual on Contrast Media states that concern for contrast induced nephropathy is not an absolute contraindication, and IV contrast may be necessary in many situations. Ultrasound can be used to evaluate the aorta, gallbladder, kidneys, appendix, bowel, spleen, pancreas, uterus, and ovaries. Consider bedside ultrasound and emergency surgical consult for all unstable patients with abdominal pain. For stable pregnant patients with concern for appendicitis, start with an ultrasound. If inconclusive, order an MRI. Epigastric pain in an elderly patient should raise concern for ACS. An EKG and troponin should be considered. For analgesia in patients with gastroparesis or cannabinoid hyperemesis syndrome, haloperidol is considered first-line. Low-dose ketamine (0.3mg/kg over 15 minutes) may be a better choice than opiate analgesia for abdominal pain. Nachi: So that wraps up Episode 29! Jeff: As always, additional materials are available on our website for Emergency Medicine Practice subscribers. If you’re not a subscriber, consider joining today. You can find out more at ebmedicine.net/subscribe. Subscribers get in-depth articles on hundreds of emergency medicine topics, concise summaries of the articles, calculators and risk scores, and CME credit. You’ll also get enhanced access to the podcast, including any images and tables mentioned. PA’s and NP’s - make sure to use the code APP4 at checkout to save 50%. Nachi: And last reminder here -The clinical Decision Making in Emergency Medicine Conference is just around the corner and spots are quickly filling up. Don’t miss out on this great opportunity and register today. Jeff: And the address for this month’s cme credit is ebmedicine.net/E0619, so head over there to get your CME credit. As always, the [DING SOUND] you heard throughout the episode corresponds to the answers to the CME questions. Lastly, be sure to find us on iTunes and rate us or leave comments there. You can also email us directly at emplify@ebmedicine.net with any comments or suggestions. Talk to you next month!   Most Important References 18. Gardner CS, Jaffe TA, Nelson RC. Impact of CT in elderly patients presenting to the emergency department with acute abdominal pain. Abdom Imaging. 2015;40(7):2877-2882. (Retrospective study; 464 patients aged ≥ 80 years) 38. Kereshi B, Lee KS, Siewert B, et al. Clinical utility of magnetic resonance imaging in the evaluation of pregnant females with suspected acute appendicitis. Abdom Radiol (NY). 2018;43(6):1446-1455. (Retrospective study; 212 MRI examinations) 41. Lewis KD, Takenaka KY, Luber SD. Acute abdominal pain in the bariatric surgery patient. Emerg Med Clin North Am. 2016;34(2):387-407. (Review) 57. Wagner JM, McKinney WP, Carpenter JL. Does this patient have appendicitis? JAMA. 1996;276(19):1589-1594. (Review) 67. Magidson PD, Martinez JP. Abdominal pain in the geriatric patient. Emerg Med Clin North Am. 2016;34(3):559-574. (Review) 83. Macaluso CR, McNamara RM. Evaluation and management of acute abdominal pain in the emergency department. Int J Gen Med. 2012;5:789-797. (Review) 94. Bass JB, Couperus KS, Pfaff JL, et al. A pair of testicular torsion medicolegal cases with caveats: the ball’s in your court. Clin Pract Cases Emerg Med. 2018;2(4):283-285. (Case studies; 2 patients) 106. Kestler A, Kendall J. Emergency ultrasound in first-trimester pregnancy. In: Connolly J, Dean A, Hoffman B, et al, eds. Emergency Point-of-Care Ultrasound. 2nd edition. Oxford UK: John Wiley and Sons; 2017. (Textbook)

  Jeff: Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta. This month, we’re talking about a topic… Nachi: … woah wait, slow down for a minute, before we begin this month’s episode – we should take a quick pause to wish all of our listeners a happy new year! Thanks for your regular listenership and feedback. Jeff: And we’re actually hitting the two year mark since we started this podcast. At 25 episodes now, this is sort of our silver anniversary. Nachi: We have covered a ton of topics in emergency medicine so far, and we are looking forward to reviewing a lot more evidence based medicine with you all going forward. Jeff: With that, let’s get into the first episode of 2019 – the topic this month is first trimester pregnancy emergencies: recognition and management. Nachi: This month’s issue was authored by Dr. Ryan Pedigo, you may remember him from the June 2017 episode on dental emergencies, though he is perhaps better known as the director of undergraduate medical education at Harbor-UCLA Medical center. In addition, this issue was peer reviewed by Dr. Jennifer Beck-Esmay, assistant residency director at Mount Sinai St. Luke’s, and Dr. Taku Taira, the associate director of undergraduate medical education and associate clerkship director at LA County and USC department of Emergency Medicine. Jeff: For this review, Dr. Pedigo had to review a large body of literature, including thousands of articles, guidelines from the American college of obstetricians and gynecologists or ACOG, evidence based Practice bulletins, ACOG committee opinions, guidelines from the American college of radiology, the infectious diseases society of America, clinical policies from the American college of emergency physicians, and finally a series of reviews in the Cochrane database. Nachi: There is a wealth of literature on this topic and Dr. Pedigo comments that the relevant literature is overall “very good.” This may be the first article in many months for which there is an overall very good quality of literature. Jeff: It’s great to know that there is good literature on this topic. It’s incredibly important as we are not dealing with a single life here, as we usually do... we are quite literally dealing with potentially two lives as the fetus moves towards viability. With opportunities to improve outcomes for both the fetus and the mother, I’m confident that this episode will be worth your time. Nachi: Oh, and speaking of being worth your time…. Don’t forget that if you’re listening to this episode, you can claim your CME credit. Remember, the indicates an answer to one of the CME questions so make sure to keep the issue handy. Jeff: Let’s get started with some background. First trimester emergencies are not terribly uncommon in pregnancy. One study reported 85% experience nausea and vomiting. Luckily only 3% of these progressed to hyperemesis gravidarum. In addition, somewhere between 7-27% experience vaginal bleeding or miscarriage. Only 2% of these will be afflicted with an ectopic pregnancy. Overall, the maternal death rate is about 17 per 100,000 with huge racial-ethnic disparities. Nachi: And vaginal bleeding in pregnancy occurs in nearly 25% of patients. Weeks 4-8 represent the peak time for this. The heavier the bleeding, the higher the risk of miscarriage. Jeff: Miscarriage rates vary widely based on age, with an overall rate of 7-27%. This rises to nearly 40% risk in those over 40. And nearly half of miscarriages are due to fetal chromosomal abnormalities. Nachi: For patient who have a threatened miscarriage in the first trimester, there is a 2-fold increased risk of subsequent maternal and fetal adverse outcomes. Jeff: So key points here, since I think the wording and information you choose to share with often scared and worried women is important – nearly 25% of women experience bleeding in their first trimester. Not all of these will go on to miscarriages, though the risk does increase with maternal age. And of those that miscarry, nearly 50% were due to fetal chromosomal abnormalities. Nachi: So can we prevent a miscarriage, once the patient is bleeding…? Jeff: Short answer, no, longer answer, we’ll get to treatment in a few minutes. For now, let’s continue outlining the various first trimester emergencies. Next up, ectopic pregnancy… Nachi: An ectopic pregnancy is implantation of a fertilized ovum outside of the endometrial cavity. This occurs in up to 2% of pregnancies. About 98% occur in the fallopian tube. Risk factors for an ectopic pregnancy include salpingitis, history of STDs, history of PID, a prior ectopic, and smoking. Jeff: Interestingly, with respect to smoking, there is a dose-relationship between smoking and ectopic pregnancies. Simple advice here: don’t smoke if you are pregnant or trying to get pregnant. Nachi: Pretty sound advice. In addition, though an IUD is not a risk factor for an ectopic pregnancy, if you do become pregnant while you have in IUD in place, over half of these may end up being ectopic. Jeff: It’s also worth mentioning a more obscure related disease pathology here – the heterotopic pregnancy -- one in which there is an IUP and an ectopic pregnancy simultaneously. Nachi: Nausea and vomiting, though not as scary as miscarriages or an ectopic pregnancy, represent a fairly common pathophysiologic response in the first trimester -- with the vast majority of women experiencing nausea and vomiting. And as we mentioned earlier, only 3% of these progress to hyperemesis gravidarum. Jeff: And while nausea and vomiting clearly sucks, they seem to actually be protective of pregnancy loss, with a hazard ratio of 0.2. Nachi: Although this may be protective of pregnancy loss, nausea and vomiting can really decrease the quality of life in pregnancy -- with one study showing that about 25% of women with severe nausea and vomiting had actually considered pregnancy termination. 75% of those women also stated they would not want to get pregnant again because of these symptoms. Jeff: So certainly a big issue.. Two other common first trimester emergency are asymptomatic bacteriuria and UTIs. In pregnant patients, due to anatomical and physiologic changes in the GU tract – such as hydroureteronephrosis that occurs by the 7th week and urinary stasis due to bladder displacement – asymptomatic bacteriuria is a risk factor for developing pyelonephritis. Nachi: And pregnant women are, of course, still susceptible to the normal ailments of young adult women like acute appendicitis, which is the most common surgical problem in pregnancy. Jeff: Interestingly, based on epidemiologic data, pregnant women are less likely to have appendicitis than age-matched non-pregnant woman. I’d like to think that there is a good pathophysiologic explanation there, but I don’t have a clue as to why that might be. Nachi: Additionally, the RLQ is the the most common location of pain from appendicitis in pregnancies of all gestational ages. Peritonitis is actually slightly more common in pregnant patients, with an odds ratio of 1.3. Jeff: Alright, so I think we can put that intro behind us and move on to the differential. Nachi: When considering the differential for abdominal pain or vaginal bleeding in the first trimester, you have to think broadly. Among gynecologic causes, you should consider miscarriage, septic abortion, ectopic pregnancy, corpus luteum cyst, ovarian torsion, vaginal or cervical lacerations, and PID. For non-gynecologic causes, you should also consider appendicitis, cholecystitis, hepatitis, and pyelonephritis. Jeff: In the middle of that laundry list you mentioned there is one pathology which I think merits special attention - ovarian torsion. Don’t forget that patients undergoing ovarian stimulation as part of assisted reproductive technology are at a particularly increased risk due to the larger size of the ovaries. Nachi: Great point. Up next we have prehospital care... Jeff: Always a great section. First, prehospital providers should attempt to elicit an ob history. Including the number of weeks’ gestation, LMP, whether an IUP has already been confirmed, prior hx of ectopic, and amount of vaginal bleeding. In addition, providers should consider an early destination consult both to select the correct destination and to begin the process of mobilizing resources early in those patients who really need them, such as those with hemodynamic instability. Nachi: As with most pathologies, the more time you give the receiving facility to prepare, the better the care will be, especially the early care, which is critical. Jeff: Now that the patient has arrived in the ED we can begin our H&P. Nachi: When eliciting the patient’s obstetrical history, it’s common to use the G’s and Ps. This can be further annotated using the 4-digit TPAL method, that’s term-preterm-abortus-living. Jeff: With respect to vaginal bleeding, make sure to ask about the number of pads and how this relates to the woman’s normal number of pads. In addition, make sure to ask about vaginal discharge or even about the passage of tissue. Nachi: You will also need to elicit whether or not the patient has a history of a prior ectopic pregnancies as this is a major risk for future ectopics. And ask about previous sexually transmitted infections also. Jeff: And, of course, make sure to elicit a history of assisted reproductive technology, as this increases the risk of a heterotopic pregnancy. Nachi: Let’s move on to the physical. While you are certainly going to perform your standard focused physical exam, just as you would for any non-pregnant woman - what does the evidence say about the pelvic exam? I know this is a HOTLY debated topic among EM Docs. Jeff: Oh it certainly is. Dr. Pedigo takes a safe, but fair approach, noting, “A pelvic exam should always be performed if the emergency clinician suspects that it would change management, such as identifying the source of bleeding, or identifying an STD or PID.” However, it is noteworthy that the only real study he cites on this topic, an RCT of pelvic vs no pelvic in those with a confirmed IUP and first trimester bleeding, found no difference between the two groups. Obviously, the pelvic group reported more discomfort. Nachi: You did leave out one important fact about the study enrollment - they only enrolled about 200 of 700 intended patients. Jeff: Oh true, so a possibly underpowered study, but it’s all we’ve got on the topic. I think I’m still going to do pelvic exams, but it’s something to think about. Nachi: Moving on, all unstable patients with vaginal bleeding and no IUP should be assumed to have an ectopic until proven otherwise. Ruptured ectopics can manifest with a number of physical exam findings including abdominal tenderness, with peritoneal signs, or even with bradycardia due to vagal stimulation in the peritoneum. Jeff: Perhaps most importantly, no history or physical alone can rule in or out an ectopic pregnancy, for that you’ll need testing and imaging or operative findings. Nachi: And that’s a perfect segue into our next section - diagnostic studies. Jeff: Up first is the urine pregnancy test. A UPT should be obtained in all women of reproductive age with abdominal pain or vaginal bleeding, and likely other complaints too, though we’re not focusing on them now. Nachi: The UPT is a great test, with nearly 100% sensitivity, even in the setting of very dilute urine. False positives are certainly plausible, with likely culprits being recent pregnancy loss, exogenous HCG, or malignancy. Jeff: And not only is the sensitivity great, but it’s usually positive just 6-8 days after fertilization. Nachi: While the UPT is fairly straight forward, let’s talk about the next few tests in the context of specific disease entities, as I think that may make things a bit simpler -- starting with bHCG in the context of miscarriage and ectopic pregnancy. Jeff: Great starting point since there is certainly a lot of debate about the discriminatory zone. So to get us all on the same page, the discriminatory zone is the b-HCG at which an IUP is expected to be seen on ultrasound. Generally 1500 is used as the cutoff. This corresponds nicely to a 2013 retrospective study demonstrating a bHCG threshold for the fetal pole to be just below 1400. Nachi: However, to actually catch 99% of gestational sacs, yolk sacs, and fetal poles, one would need cutoffs of around 3500, 18000, and 48,000 respectively -- much higher. Jeff: For this reason, if you want to use a discriminatory zone, ACOG recommends a conservatively high 3,500, as a cutoff. Nachi: I think that’s an understated point in this article, the classic teaching of a 1500 discriminatory zone cutoff is likely too low. Jeff: Right, which is why I think many ED physicians practice under the mantra that it’s an ectopic until proven otherwise. Nachi: Certainly a safe approach. Jeff: Along those lines, lack of an IUP with a bHCG above whatever discriminatory zone you are using does not diagnose an ectopic, it merely suggests a non-viable pregnancy of undetermined location. Nachi: And if you don’t identify an IUP, serial bHCGs can be really helpful. As a rule of thumb -- in cases of a viable IUP -- b-HCG typically doubles within 48 hours and at a minimum should rise 53%. Jeff: In perhaps one of the most concerning things I’ve read in awhile, one study showed that ⅓ of patients with an ectopic had a bCHG rise of 53% in 48h and 20% of patients with ectopics had a rate of decline typical to that of a miscarriage. Nachi: Definitely concerning, but this is all the more reason you need to employ our favorite imaging modality… the ultrasound. Jeff: All patients with a positive pregnancy test and vaginal bleeding should receive an ultrasound performed by either an emergency physician or by radiology. Combined with a pelvic exam, this can give you almost all the data necessary to make the diagnosis, even if you don’t find an IUP. Nachi: And yes, there is good data to support ED ultrasound for this indication, both transabdominal and transvaginal, assuming the emergency physician is credentialed to do so. A 2010 Meta-Analysis found a NPV of 99.96% when an er doc identified an IUP on bedside ultrasound. So keep doing your bedside scans with confidence. Jeff: Before we move on to other diagnostic tests, let’s discuss table 2 on page 7 to refresh on key findings of each of the different types of miscarriage. For a threatened abortion, the os would be closed with an IUP seen on ultrasound. For a completed abortion, you would expect a closed OS with no IUP on ultrasound with a previously documented IUP. Patients may or may not note the passage of products of conception. Nachi: A missed abortion presents with a closed os and a nonviable fetus on ultrasound. Findings such as a crown-rump length of 7 mm or greater without cardiac motion is one of several criteria to support this diagnosis. Jeff: An inevitable abortion presents with an open OS and an IUP on ultrasound. Along similar lines, an incomplete abortion presents with an open OS and partially expelled products on ultrasound. Nachi: And lastly, we have the septic abortion, which is sort of in a category of its own. A septic abortion presents with either an open or closed OS with essentially any finding on ultrasound in the setting of an intrauterine infection and a fever. Jeff: I’ve only seen this two times, and both women were incredibly sick upon presentation. Such a sad situation. Nachi: For sure. Before we move on to other tests, one quick note on the topic of heterotopic pregnancies: because the risk in the general population is so incredibly low, the finding of an IUP essentially rules out an ectopic pregnancy assuming the patient hasn’t been using assisted reproductive technology. In those that are using assisted reproductive technology, the risk rises to 1 in 100, so finding an IUP, in this case, doesn’t necessarily rule out a heterotopic pregnancy. Jeff: Let’s move on to diagnostic studies for patients with nausea and vomiting. Typically, no studies are indicated beyond whatever you would order to rule out other serious pathology. Checking electrolytes and repleting them should be considered in those with severe symptoms. Nachi: For those with symptoms suggestive of a UTI, a urinalysis and culture should be sent. Even if the urinalysis is negative, the culture may still have growth. Treat asymptomatic bacteriuria and allow the culture growth to guide changes in antibiotic selection. Jeff: It’s worth noting, however, that a 2016 systematic review found no reliable evidence supporting routine screening for asymptomatic bacteriuria, so send a urinalysis and culture only if there is suspicion for a UTI. Nachi: For those with concern for appendicitis, while ultrasound is a viable imaging modality, MRI is gaining favor. Both are specific tests, however one study found US to visualize the appendix only 7% of the time in pregnant patients. Jeff: Even more convincingly, one 2016 meta analysis found MRI to have a sensitivity and specificity of 94 and 97% respectively suggesting that a noncontrast MRI should be the first line imaging modality for potential appendicitis. Nachi: You kind of snuck it in there, but this is specifically a non-contrast MRI. Whereas a review of over a million pregnancies found no associated fetal risk with routine non-contrast MRI, gadolinium-enhanced MRI has been associated with increased rates of stillbirth, neonatal death, and rheumatologic and inflammatory skin conditions. Jeff: CT is also worth mentioning since MRI and even ultrasound may not be available to all of our listeners. If you do find yourself in such a predicament, or you have an inconclusive US without MRI available, a CT scan may be warranted as the delay in diagnosis and subsequent peritonitis has been found to increase the risk of preterm birth 4-fold. Nachi: Right, and a single dose of ionizing radiation actually does not exceed the threshold dose for fetal harm. Jeff: Let’s talk about the Rh status and prevention of alloimmunization. While there are no well-designed studies demonstrating benefit to administering anti-D immune globulin to Rh negative patients, ACOG guidelines state “ whether to administer anti-D immune globulin to a patient with threatened pregnancy loss and a live embryo or fetus at or before 12 weeks of gestation is controversial, and no evidence-based recommendation can be made.” Nachi: Unfortunately, that’s not particularly helpful for us. But if you are going to treat an unsensitized Rh negative female with vaginal bleeding while pregnant with Rh-immune globulin, they should receive 50 mcg IM of Rh-immune globulin within 72 hours, or the 300 mcg dose if that is all that is available. It’s also reasonable to administer Rh(d)-immune globulin to any pregnant female with significant abdominal trauma. Jeff: Moving on to the treatment for miscarriages - sadly there isn’t much to offer here. For those with threatened abortions, the vast majority will go on to a normal pregnancy. Bedrest had been recommended in the past, but there is little data to support this practice. Nachi: For incomplete miscarriages, if visible, products should be removed and you should consider sending those products to pathology for analysis, especially if the patient has had recurrent miscarriages. Jeff: For those with a missed abortion or incomplete miscarriages, options include expectant management, medical management or surgical management, all in consultation with an obstetrician. It’s noteworthy that a 2012 Cochrane review failed to find clear superiority for one strategy over another. This result was for the most part re-confirmed in a 2017 cochrane review. The latter study did find, however, that surgical management in the stable patient resulted in lower rates of incomplete miscarriage, bleeding, and need for transfusion. Nachi: For expectant management, 50-80% will complete their miscarriage within 7-10 days. Jeff: For those choosing medical management, typically with 800 mcg of intravaginal misoprostol, one study found this to be 91% effective in 7 days. This approach is preferred in low-resource settings. Nachi: And lastly, remember that all of these options are only options for stable patients. Surgical management is mandatory for patients with significant hemorrhage or hemodynamic instability. Jeff: Since the best evidence we have doesn’t suggest a crystal clear answer, you should rely on the patient’s own preferences and a discussion with their obstetrician. For this reason and due to the inherent difficulty of losing a pregnancy, having good communication is paramount. Nachi: Expert consensus recommends 6 key aspects of appropriate communication in such a setting: 1 assess the meaning of the pregnancy loss, give the news in a culturally competent and supportive manner, inform the family that grief is to be expected and give them permission to grieve in their own way, learn to be comfortable sharing the products of conception should the woman wish to see them, 5. provide support for whatever path she chooses, 6. and provide resources for grief counselors and support groups. Jeff: All great advice. The next treatment to discuss is that for pregnancy of an unknown location and ectopic pregnancies. Nachi: All unstable patients or those with suspected or proven ectopic or heterotopic pregnancies should be immediately resuscitated and taken for surgical intervention. Jeff: For those that are stable, with normal vitals, and no ultrasound evidence of a ruptured ectopic, with no IUP on ultrasound, -- that is, those with a pregnancy of unknown location, they should be discharged with follow up in 48 hours for repeat betaHCG and ultrasound. Nachi: And while many patients only need a single additional beta check, some may need repeat 48 hour exams until a diagnosis is established. Jeff: For those that are stable with a confirmed tubal ectopic, you again have a variety of treatment options, none being clearly superior. Nachi: Treatment options here include IM methotrexate, or a salpingostomy or salpingectomy. Jeff: Do note, however, that a bHCG over 5000, cardiac activity on US, and inability to follow up are all relative contraindications to methotrexate treatment. Absolute contraindications to methotrexate include cytopenia, active pulmonary disease, active peptic ulcer disease, hepatic or renal dysfunction, and breastfeeding. Nachi: Such decisions, should, of course, be made in conjunction with the obstetrician. Jeff: Always good to make a plan with the ob. Moving on to the treatment of nausea and vomiting in pregnancy, ACOG recommends pyridoxine, 10-25 mg orally q8-q6 with or without doxylamine 12.5 mg PO BID or TID. This is a level A recommendation as first-line treatment! Nachi: In addition, ACOG also recommends nonpharmacologic options such as acupressure at the P6 point on the wrist with a wrist band. Ginger is another nonpharmacologic intervention that has been shown to be efficacious - 250 mg by mouth 4 times a day. Jeff: So building an algorithm, step one would be to consider ginger and pressure at the P6 point. Step two would be pyridoxine and doxylamine. If all of these measures fail, step three would be IV medication - with 10 mg IV of metoclopramide being the agent of choice. Nachi: By the way, ondansetron carries a very small risk of fetal cardiac abnormalities, so the other options are of course preferred. Jeff: In terms of fluid choice for the actively vomiting first trimester woman, both D5NS and NS are appropriate choices, with slightly decreased nausea in the group receiving D5NS in one randomized trial of pregnant patients admitted for vomiting to an overnight observation unit. Nachi: Up next for treatment we have asymptomatic bacteriuria. As we stated previously, asymptomatic bacteriuria should be treated. This is due to anatomical and physiologic changes which put these women at higher risk than non-pregnant women. Jeff: And this recommendation comes from the 2005 IDSA guidelines. In one trial, treatment of those with asymptomatic bacteriuria with nitrofurantoin reduced the incidence of developing pyelonephritis from 2.4% to 0.6%. Nachi: And this trial specifically examined the utility of nitrofurantoin. Per a 2010 and 2011 Cochrane review, there is not evidence to recommend one antibiotic over another, so let your local antibiograms guide your treatment. Jeff: In general, amoxicillin or cephalexin for a full 7 day course could also be perfectly appropriate. Nachi: A 2017 ACOG Committee Opinion analyzed nitrofurantoin and sulfonamide antibiotics for association with birth defects. Although safe in the second and third trimester, they recommend use in the first trimester -- only when no other suitable alternatives are available. Jeff: For those, who unfortunately do go on to develop pyelo, 1g IV ceftriaxone should be your drug of choice. Interestingly, groups have examined outpatient care with 2 days of daily IM ceftriaxone vs inpatient IV antibiotic therapy and they found that there may be a higher than acceptable risk in the outpatient setting as several required eventual admission and one developed septic shock in their relatively small trial. Nachi: And the last treatment to discuss is for pregnant patient with acute appendicitis. Despite a potential shift in the standard of care for non pregnant patients towards antibiotics-only as the initial treatment, due to the increased risk of serious complications for pregnant women with an acute appy, the best current evidence supports a surgical pathway. Jeff: Perfect, so that wraps up treatment. We have a few special considerations this month, the first of which revolves around ionizing radiation. Ideally, one should limit the amount of ionizing radiation exposure during pregnancy, however avoiding it all together may lead to missed or delayed diagnoses and subsequently worse outcomes. Nachi: It’s worth noting that the American College of Radiology actually lists several radiographs that are such low exposure that checking a urine pregnancy test isn’t even necessary. These include any imaging of the head and neck, extremity CT, and chest x-ray. Jeff: Of course, an abdomen and pelvis CT carries the greatest potential risk. However, if necessary, it’s certainly appropriate as long as there is a documented discussion of the risk and benefits with the patient. Nachi: And regarding iodinated contrast for CT -- it appears to present no known harm to the fetus, but this is based on limited data. ACOG recommends using contrast only if “absolutely required”. Jeff: Right and that’s for iodinated contrasts. Gadolinium should always be avoided. Let me repeat that Gadolinium should always be avoided Nachi: Let’s also briefly touch on a controversial topic -- that of using qualitative urine point of care tests with blood instead of urine. In short, some devices are fda-approved for serum, but not whole blood. Clinicians really just need to know the equipment and characteristics at their own site. It is worth noting that there have been studies on determining whether time can be saved by using point of care blood testing instead of urine for the patient who is unable to provide a prompt sample. Initial study conclusions are promising. But again, you need to know the characteristics of the test at your ER. Jeff: One more controversy in this issue is that of expectant management for ectopic pregnancy. A 2015 randomized trial found similar outcomes for IM methotrexate compared to placebo for tubal ectopics. Inclusion criteria included hemodynamic stability, initial b hcg < 2000, declining b hcg titers 48 hours prior to treatment, and visible tubal pregnancy on trans vaginal ultrasound. Another 2017 multicenter randomized trial found similar results. Nachi: But of course all of these decisions should be made in conjunction with your obstetrician colleagues. Jeff: Let’s move on to disposition. HDS patients who are well-appearing with a pregnancy of undetermined location should be discharged with a 48h beta hcg recheck and ultrasound. All hemodynamically unstable patients, should of course be admitted and likely taken directly to the OR. Nachi: Also, all pregnant patients with acute pyelonephritis require admission. Outpatient tx could be considered in consultation with ob. Jeff: Patient with hyperemesis gravidarum who do not improve despite treatment in the ED should also be admitted. Nachi: Before we close out the episode, let’s go over some key points and clinical pearls... J Overall, roughly 25% of pregnant women will experience vaginal bleeding and 7-27% of pregnant women will experience a miscarriage 2. Becoming pregnant with an IUD significantly raises the risk of ectopic pregnancy. 3. Ovarian stimulation as part of assisted reproductive technology places pregnant women at increased risk of ovarian torsion. 4. Due to anatomical and physiologic changes in the genitourinary tract, asymptomatic bacteriuria places pregnant women at higher risk for pyelonephritis. As such, treat asymptomatic bacteriuria according to local antibiograms. 5. A pelvic exam in the setting of first trimester bleeding is only warranted if you suspect it might change management. 6. Unstable patients with vaginal bleeding and no IUP should be assumed to have an ectopic pregnancy until proven otherwise. 7. If you are to use a discriminatory zone, ACOG recommends a beta-hCG cutoff of 3500. 8. The beta-hCG typically doubles within 48 hours during the first trimester. It should definitely rise by a minimum of 53%. 9. For patients using assisted reproductive technology, the risk of heterotopic pregnancy becomes much higher. Finding an IUP does not necessarily rule out a heterotopic pregnancy. N. Send a urine culture for patients complaining of UTI symptoms even if the urinalysis is negative. J. The most common surgical problem in pregnancy is appendicitis. N, If MRI is not available and ultrasound was inconclusive, CT may be warranted for assessing appendicitis. The risk of missing or delaying the diagnosis may outweigh the risk of radiation. J. ACOG recommends using iodinated contrast only if absolutely required. N. For stable patients with a pregnancy of unknown location, plan for discharge with follow up in 48 hours for a repeat beta-hCG and ultrasound. J For nausea and vomiting in pregnancy, try nonpharmacologic treatments like acupressure at the P6 point on the wrist or ginger supplementation. First line pharmacologic treatment is pyridoxine. Doxylamine can be added. Ondansetron may increase risk of fetal cardiac abnormalities N So that wraps up episode 24 - First Trimester Pregnancy Emergencies: Recognition and Management. J: Additional materials are available on our website for Emergency Medicine Practice subscribers. If you’re not a subscriber, consider joining today. You can find out more at www.ebmedicine.net/subscribe. Subscribers get in-depth articles on hundreds of emergency medicine topics, concise summaries of the articles, calculators and risk scores, and CME credit. You’ll also get enhanced access to the podcast, including the images and tables mentioned. You can find everything you need to know at ebmedicine.net/subscribe. N: And the address for this month’s credit is ebmedicine.net/E0119, so head over there to get your CME credit. As always, the you heard throughout the episode corresponds to the answers to the CME questions. Lastly, be sure to find us on iTunes and rate us or leave comments there. You can also email us directly at emplify@ebmedicine.net with any comments or suggestions. Talk to you next month!  

Jeff:  Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta and we’ll be taking you through the September 2018 issue of Emergency Medicine Practice - Emergency Department Management of North American Snake envenomations. Nachi: Although this isn’t something we encountered too frequently – it does seem like I’ve been hearing more about snake bites in the recent months. Jeff: I actually flew someone just the other day because the local ED ran out of CroFab after an envenomation in Western PA. Nachi: Yeah, this is definitely more than “just a boards topic,” and it’s really important to know about in those rare circumstances. In terms of incidence, there are actually about 10,000 ED visits in the US for snake bites each year, and 1/3 of these involve venomous species. Jeff:  That’s a good teaser, so let’s start by recognizing this month’s team – the two authors, Dr. Sheikh, a medical toxicologist, and Patrick Leffers, a pharmD, and emergency medicine and clinical toxicology fellow. Both are at the University of Florida Jacksonville, and they reviewed a total of 120 articles from 2006-2017, in addition to reviews from both Cochrane and Dare. Nachi: And don’t forget our peer reviewers this month, Dr. Daniel Sessions, a medical toxicologist working at the South Texas Poison Center, and our very own editor-in-chief, Dr. Andy Jagoda, who is also Chair of the Department of Emergency Medicine at Mount Sinai in New York City. Jeff: What a team! But, let’s get back to the snakes. As some background, from 2006-2015 there were almost 66,000 reported snake exposures and 31 deaths from snake envenomation in the US.  Of course, this number likely underestimates the true total. Nachi: And there are two key subfamilies of venomous snakes to be aware of – the Crotalinae – or pit vipers – which includes rattlesnakes, copperheads, and water moccasins; and the Elapidae – of which you really only need to know about the coral snake. Jeff:  And while those are the only two NATIVE snake subfamilies to be acutely aware of, don’t forget that exotic snakes, which are shockingly popular pets -- they can also cause significant morbidity and mortality. Nachi:  Oh, and one other quick note before we get into the epidemiology – most of the recommendations this month come from expert opinion, as high quality RCTs are obviously difficult.  In addition, many of the studies were based in other countries, where the snakes, the anti-venoms and their availability, and the general healthcare systems are different from those that most of us work in. Jeff:  Unless we have listeners abroad? Do we have listeners in other countries? Nachi: Oh we definitely do... but we are going to be a bit biased towards US envenomation today. In any case, venomous snake bites occur most frequently in men aged 18 to 49 during warmer months with provoked bites occurring more frequently in the upper extremities and unprovoked bites in the lower extremities. Jeff:  In one study of poison center data from the last decade, nearly half of all victims of snake bites were victims of unknown type snakes.  However, of those that were known, copperheads were the most common, while rattlesnakes caused the most fatalities – 19 of 31 in this dataset. Nachi:  In a separate study of snake bites in the early 2000s, 32% of exposures were from venomous snakes and 59% of those resulted in admission. That’s remarkably high. Jeff:  Snake bite severity depends on several key factors: the amount of venom, the composition of the venom, the body size of the bite victim, the victim's clothing, the size of the bite, comorbid conditions, and the timing and quality of medical care the victim receives. Nachi:  To be a bit more specific - First, the amount of venom will depend on the species of snake, with variations even occurring within the same species.  Secondly, while there is a correlation between rattlesnake size and bite severity, there is much more at play.  Some snakes can even vary the amount of venom based on threat risk – with defensive bites having different profiles than bites to strike prey. Jeff: I found it pretty interesting that  an estimated 10-25% of pit viper bites are considered dry bites, that is, ones in which no venom is released. Nachi:  Right, this is just one reason why all victims shouldn’t immediately get anti-venom, but we’ll get there. Jeff:  We definitely will.  As we already stated – venom composition varies greatly.  Pit vipers produce a predominantly hemotoxic venom.  Systemic effects include tachycardia, tachypnea, hypotension, nausea, vomiting, weakness, and diaphoresis.  Neurotoxicity is rare and is usually due to inter-breeding between species. Nachi:  While rattlesnake bites are associated with higher morbidity and mortality, the more common copperhead bites typically only cause local tissue effects.  More serious systemic findings such as coagulopathy and respiratory failure have been reported though. Jeff:  So that’s a solid background to get us started.  Let’s talk about the individual snakes.  Why don’t you start with the crotalinae family – aka the pit vipers. Nachi:  Sure – the crotalinae includes rattlesnakes, cottonmouths (also known as water moccasins), and copperheads.  These make up the vast majority of reports to the poison centers.  They can be identified by their heat sensing pits located behind their nostrils (hence pit vipers).  As a general rule, you can also identify the venomous snakes by their triangular or spade-like head, elliptical pupils, and hollow retractable fangs. Jeff:  wait, so you want me to walk up to the snake and ask to see if their fangs retract… yea, no thanks. Nachi: Haha, of course not, I’m just giving you some of the general principles here. In contrast, non-venomous pit vipers have rounded heads, round pupils, a double row of vertical scales, and they lack fangs. Jeff: In terms of location, rattlesnakes are found in all states but Hawaii, and cottonmouths and copperheads are distributed mostly throughout the southern and southeastern states, with copperheads also extending further north, even into Massachusetts. Nachi: Moving on to the Elapidae –  there are 3 species of coral snakes, only two of which you need to know about, Micrurus fulvius fulvius or the eastern coral snake and Micrurus tener or the Texas coral snake.  Of the two, the eastern or Micrurus fulvius fulvius produces more potent venom. Jeff:  As you may have guessed by their names, the eastern coral snake is found in the southeastern united states, specifically, east of the Mississippi -- whereas the Texas coral snake lives west of the Mississippi. Nachi:  Venomous North American coral snakes can be recognized by the red and yellow bands around their bodies whereas their nonvenomous counterparts can be recognized by their characteristic black band between the red and yellow bands. I’m sure you’ve heard the popular mnemonic for this… Red touch yellow kill a fellow, red touch black, venom lack. Jeff:  I have heard that one, and it’s not a bad mnemonic. Just remember that this is more of a guideline than a rule, as it doesn’t always hold true. Nachi: Coral snakes also tend to chew rather than bite thanks to their short, fixed, hollow fangs.  Locally, bites can lead to muscle destruction thanks to a certain myotoxin.  Systemic signs of infection include nausea, vomiting, abdominal pain, and dizziness.  Jeff: The venom also contains a neurotoxin which can lead to diplopia, difficulty swallowing and speaking and generalized weakness. Nachi: Complicating matters even further, the onset of these symptoms may be delayed for many hours. Jeff:  Alright, so I think that about wraps up the background.  Let’s move on to the meat and potatoes of this article, starting with the differential. Nachi:  For differential this month, we are really focusing on differentiating a venomous snake from a non-venomous one. Jeff: Oh yeah, this is where you want us to ask the snake if it can retract its fangs, right? Nachi: Ha very funny – Although the type of snake may be obvious if the patient owns the snake, for most cases you see in the ED, the type of snake won’t be clear. Try to get a description of the snake and consider your local geography. Some patients may even bring the snake in with them. Jeff: yea, no thanks. As for prehospital care, it’s actually pretty interesting stuff as recommendations have changed many times.  You may have heard of the recommendations for incision / excision, use of venom extraction devices, tourniquets, chill methods and even electroshock therapy – well these methods are all OUT. Nachi:  Not only are they out, they actually worsen outcomes, so definitely don’t pursue any of them.  Instead,  since no treatment has been shown to improve outcome, you should prioritize prompt transport. Jeff: And while we definitely don’t want to encourage ill-advised attempts at capturing the snake, taking pictures at a distance may be helpful in identifying it.  Oh and the authors do note- pretty terrifying stuff coming up here so brace yourself - even if the snake is dead the bite reflex is still intact… Nachi: And that’s why I work in city hospitals… Jeff:  There’s also a bit of controversy here with regards to pressure immobilization, which is definitely something I thought we were supposed to do in the prehospital setting. Apparently in other countries, like Australia, prehospital providers frequently employ pressure immobilization – that is, wrapping bandages proximally up a splinted limb to impede lymphatic toxin spread. Nachi:  Right, but in Australia, not only are the snakes more venomous but the hospital transport distances are much longer, so, basically they sacrifice the limb to potentially save a life.  In the US, with our current indigenous snake population and the relatively short transport distances, this isn’t justified at all! Jeff:  Take home: based on the current literature, the American College of Medical Toxicology, other experts, and Drs. Sheikh and Leffers recommend against pressure immobilization in lieu of prompt patient transport to definitive treatment. Nachi:  Good to know – alright so now we have the patient in the emergency department, let’s begin ED care.  As always – IV, O2, Monitor including end tidal CO2 if you suspect a neurotoxic or exotic snake bite.  Of course, avoid using the affected limbs for vitals… Jeff: If not done already, remove any constrictive clothing or jewelry and mark the leading edge of pain, edema, and erythema both above and below the bite.  If EMS has placed bandages, leave them in place until antivenom and resuscitative equipment is ready. Nachi:  And definitely involve the poison control center or a medical toxicology service early as they are an amazing resource. It’s an easy number to remember.. 1-800-222-1222. If you just type “poison control center” into google, that number will come up immediately. Jeff: Hypotension should be treated with isotonic fluids and, as usual, anaphylaxis should be treated with the usual cocktail of antihistamines and epinephrine at first IM and then via infusion if refractory. Note that antivenom will NOT reverse anaphylaxis on its own. Nachi:  When eliciting a history, there are a number of important factors to look out for, including – time and location of the bite, description of the snake, tetanus status, comorbid conditions, medications and allergies, any systemic or neurologic symptoms, muscle cramps, perioral tingling or numbness, metallic taste, history of previous snakebites and any reactions to previous envenomation or antivenom treatment. Jeff: Moving on to the physical exam, when examining the wound, look specifically for local tissue effects which occur in over 90% of patients after pit viper envenomations.  In such cases, you would expect pain, erythema, swelling, tenderness, and myonecrosis beginning at the wound site and then spreading via the lymphatic system. Nachi:  In addition, specifically with pit viper envenomations, monitor the patient for possible compartment syndrome as the venom can lead to local tissue destruction, increased cell permeability, third spacing of fluids, and bleeding.  And remember that while the local compartment may be hypertensive, the patient may also have systemic hypotension. Jeff: Just to reiterate what I said before – hypotension may indicate severe anaphylaxis and its not necessarily just due to third spacing.  Regardless, the treatment is the same – epinephrine. Nachi:  Good point, but let’s focus on compartment syndrome for a minute.  True compartment syndrome is actually quite rare --- its really subcutaneous hypertension with preservation of otherwise normal compartment pressures that you’re most likely to see.  Compartment syndrome should therefore only be diagnosed by actual compartment measurements and not just the exam.  However, if you are dealing with compartments that can’t be measured, like in the fingers, you’re only choice is to be guided by the exam… Jeff:  Risk factors for compartment syndrome in the setting of a snake bite include envenomations in small children, involvement of digits, application of ice or cold packs, and delayed or inadequate antivenom administration. Nachi: In terms of respiratory effects of envenomations – they aren’t common.  Both bites to the head or neck and neurotoxin containing venom are potential causes. In the setting of respiratory failure, be prepared with advanced airway maneuvers like nasotracheal intubation or cricothyroidotomy. Antivenom will not reverse respiratory failure. Jeff: Neurologic effects may be present upon arrival but may also be delayed up to 12 hours in the case of eastern coral snake bites. Nachi: It’s noteworthy that in one study of almost 400 eastern coral snake exposures, the onset of systemic symptoms occurred on average 5.6 hours after the bite.  So definitely remember that repeat exams and observation will be tremendously important. Jeff:  The actual neurologic symptoms to look for depend on the snake.  Coral snake venom can produce a descending flaccid paralysis characterized by motor weakness, especially of the cranial nerves.  Similarly pit vipers, especially the Mojave rattlesnake, have also been associated with muscular weakness of the cranial nerves and even respiratory insufficiency. Nachi:  Pit viper envenomation can also lead to myokymia which is repetitive small muscle fasciculations.  Unfortunately, this myokymia may not respond to antivenom administration and myokymia of the chest well and torso can necessitate intubation in extreme cases.  Both myokymia and myonecrosis may lead to rhabdo in the case of significant envenomations. Jeff:  Pit viper envenomation can also cause hematologic effects.  Fibrinolysis and platelet consumption at the bit site can lead to decreased fibrinogen and thrombocytopenia.  In severe cases this can lead to systemic bleeding and even hemorrhagic shock.  Those on anticoagulants and anti-platelet agents are at increased risk. Nachi:  Dermal effects such as edema, ecchymosis, bullae, and bleeding are not uncommon, but up to 50% of coral snake bite victims may have none of these. Jeff:  And to round out this section – just be aware that rare effects such as osteonecrosis, ischemic stroke, massive PE, and septic shock have all been reported. Nachi: Let’s move on to diagnostic studies.  Most patients require a CBC, coags, and a fibrinogen concentration.  Those with systemic toxicity should also have their electroyltes, CPK, creatinine, glucose, and urine tested. Jeff:  And while the data is somewhat mixed, one study suggests that all patients with pit viper envenomations need their coags checked, not just those with severe symptoms as in one series nearly 90% of patients had missed coagulation abnormalities.  The clinical consequences of this aren’t clearly explained, so the authors don’t make a specific recommendation. Nachi:  In terms of imaging, a chest x-ray should be obtained in those with respiratory symptoms and ultrasound may even have an expanding role here for tracking edema, looking for fluid collections, and assessing deep muscle compartments and vascular flow. Jeff: I feel like we should get some entry music for every ultrasound reference because it seems to make its way into just about every episode. Nachi: What would it sound like? You bring this up every month. I’ll look into something for a future episode. If any of our listeners have a suggestion, shoot us an e-mail at emplify@ebmedicine.net. In terms of monitoring and observation, this is important, ALL patients with suspected pit viper envenomations should be observed for 8-12 hours with the leading edge marked every 15-30 minutes. Jeff:  In addition, serial diagnostic testing may also be needed as such changes will be used to guide treatment.  In those with systemic symptoms, lab testing will be required every 4-6 hours prior to discharge. Nachi:  Before we move onto treatment – let me quickly mention grading.  There is no universal grading system.  The snakebite severity score, the minimum-moderate-severe score, and grade 1-4 score which consider symptoms, exam findings, and lab abnormalities have all been studied.  None have been validated and none track changes, so the authors recommend relying on severity of symptoms and progression of symptoms to guide treatment. Jeff:  The crux of treatment for pit viper envenomations is with supportive care and anti-venom. Nachi:  FabAV or CroFab is the antivenom of choice for pit viper envenomations.  This antivenom is made from extracting the Fab portion of anti-venom antibodies from envenomated sheep and processing them with papain. Jeff:  Since the sheep are injected with venom from the western diamondback, eastern diamondback and Mojave rattlesnake as well as the cottonmouth, the FabAV is most effective against venom from these snakes, however it does have cross reactivity to other immunologically similar venoms. Nachi:  Indications for FabAV include a more than minimal local swelling, rapid progression of swelling, swelling crossing a major joint, evidence of hemotoxicity, signs of systemic toxicity including hemodynamic compromise, neuromuscular toxicity, and late or recurrent new-onset coagulopathy. Jeff:  Initially, dose FabAV as a bolus of 4-6 vials, IV.  With life threatening envenomations or those with cardiovascular collapse, double the starting dose to 8-12 vials.  The goal is arresting progression, improvement in coagulation abnormalities, and resolution of systemic symptoms. Nachi: Although FabAV will reduce the duration and severity of symptoms and lab abnormalities, it will not reverse tissue necrosis and may not reverse neurologic effects. Jeff:  Once the symptoms have been controlled after the bolus dose or a second bolus dose, maintenance dosing of 2 vials every 6 hours for 3 doses is recommended to prevent recurrence. Nachi:  So to reiterate.  4-6 vial bolus to start, doubled in severe cases and then 2 vials every 6 hours for 18 hours after that. Jeff:  You got it. Nachi:  And like most, maybe all medicines, there are side effects and contraindications to be aware of.  Hypersensitivity reactions and serum sickness to FabAV have been reported as 8% and 13% respectively.   Most are mild and can be treated with your standard bundle of steroids, antihistamines, fluids and epi. Jeff:  Risk factors for developing allergic reactions to FabAV include  a known allergy to papaya, papain, chymopapin, pineapple enzyme bromelain, and previous allergic reaction to FabAV. Nachi:  Although FabAV isn’t produced using copperhead venom, it may be effective in severe envenomations and in one study, FabAV reduced limb disability compared to placebo. Jeff:  Therefore, the authors very reasonably advise that you should use the patient’s clinical picture and individual factors rather than the snake species to guide your treatment. Nachi:  Interestingly, compartment syndrome should be treated with the initial 4-6 vial dose of antivenom and not necessarily a fasciotomy.  Fasciotomies have not been shown to improve outcomes and are reserved only for those failing anti-venom treatment. Jeff:  The reason for this is that antivenom may reduce tissue pressures obviating the need for fasciotomy.  In addition, fasciotomy wouldn’t affect muscle necrosis that is occurring so fascia removal really doesn’t solve anything. Nachi:  And just as anti-venom can be used to treat elevated compartment pressures, it can also be used to treat coagulopathy. Jeff:  Blood products should be used for those who are actively bleeding or severely anemic as venom does not discriminate and will destroy whatever blood it comes across. Nachi:  Recurrent and late onset coagulopathy after FabAV treatment has also been well described.   Although not exactly clear why, some speculate that it occurs for one of 4 reasons. 1) because the half life of FabAV is shorter than that of the venom, or 2) because the venom is initially stored in the soft tissues and then slowly released over time or 3) because the venom has a late onset component, or lastly, 4) there is delayed dissociation of the venom-antivenom complexes.  Regardless of the mechanism, late onset coagulopathy can be treated with FabAV. Jeff:  Luckily, bleeding associated with coagulopathy and bleeding associated with late onset coagulopathy are both extremely rare.   Nachi:  Moving on to coral snakes.  Coral snake bites should be treated with NACSA or North American Coral Snake anti-venom.  This antivenom halts or at least limits the progression of muscle paralysis and shortens the clinical course. Jeff:  Most experts recommend NACSA treatment with the first signs of systemic toxicity and not for all comers.  This recommendation is backed by the literature as in one observational study those treated with prophylactic NACSA did less favorably as compared to those who got it only after symptoms onset.  This is probably because NACSA doesn’t reverse neuromuscular weakness and only limits progression. Nachi:  And it’s not like you are just sitting by and watching while doing nothing – focus your initial treatment on wound care, pain control, and then observation for the development of systemic symptoms.  The exact length of observation will depend on the snake, but should be somewhere between 8 and 24h. Jeff:  As for dosing – the initial NACSA dose is 3-5 vials IV for both peds and adults with a repeat dose if the initial symptoms don’t improve. Nachi: Side effects and adverse reactions occur somewhere between 8-11% of the time with dermal reactions being most common and anaphylaxis being the most severe. Jeff: There is also one last anti-venom to be aware of – Coralmyn, for coral snake envenomations.  Coralmyn is a polyclonal antivenom F(ab’)2 coral snake antivenom, developed because the current lot of NACSA has technically expired although the date has been extended numerous times.  It’s currently in a phase 3 trial, so keep your eyes out. Nachi:  Other non-antivenom treatments that have been tested include acetylcholinesterase inhibitors and trypsin at the bite site – both should be considered experimental at this point. Jeff:  To wrap up the treatment section, let’s talk exotic snakes.  You may recall from the intro that these have a higher morbidity and mortality compared to native species. Nachi:  You will have to rely on your local poison control center or toxicologist for advice and you may even need to turn to the zoo or aquarium for antivenom, if it exists at all.  Patients with bites from exotic snakes should be monitored, likely in the ICU, for up to 24 hours as toxicity from some venom may have a delayed onset of up to 20 hours. Jeff:  Scary stuff, hopefully the patient knows which type of exotic snake they own and you don’t have to sort through a million google images to try to get to the bottom of this.  Anyway, there are 3 special populations to discuss.  First are pregnant patients. Nachi:  The authors cite a 1.4% incidence of snake bites in pregnant patients.  They note that this is low, but from my perspective, this seems shockingly high – why would a pregnant person ever get anywhere near a snake, seems just ill advised… Jeff:  haha, true.   But regardless, treatment is the same with antivenom as needed for all the same indications.  With fetal demise rates as high as 30%, in addition to maternal monitoring, the fetus should also be monitored. Nachi:  That number may seem high, but keep in mind that that’s from studies in other countries with more venomous snakes, so it’s likely to be lower in the US.  But the point remains, that antivenom is generally recommended to be given if the mother has indications for treatment, as poor fetal outcome is tied directly to the severity of envenomation in the mother. Jeff: Continuing right along, the next special population to discuss are pediatric patients.  Because dosing is based on the amount of venom delivered and not on patient specific factors, dosing is the same for peds and adults. Nachi:  How rare – so few meds seem to be the same for peds and adults.  The last population to discuss are anticoagulated patients.  Patients on antiplatelet or anti-coagulants are at increased risk of bleeding after pit viper envenomations and therefore should have their coags checked every 2 days following the last dose of FabAV. Jeff:  I think we’ve at least mentioned most of this months controversies, but it’s probably worth quickly reviewing them since they mostly dispel common myths. Nachi:  Good idea.  Incision and suction of snake bites is nearly universally not recommended. Jeff:  In the absence of ischemia, fasciotomy for snake bites is not recommended, even with elevated compartment pressures.  Instead treat compartment syndrome with anti-venom and save the fasciotomy for true cases of ischemia refractory to antivenom. Nachi:  With a known or suspected coral snake envenomation, due to shortages of NACSA, wait until the patient develops symptoms instead of empirically treating all bite victims. Jeff:  Maintenance dosing of FabAV continues to be debated.  The manufacturer recommends 2 doses every 6 hours for 3 doses while some experts recommend only maintenance dosing as needed.  It’s therefore probably safest to punt this to whatever poison control center or toxicologist you speak with. Nachi:  I feel like we are plugging the poison center a lot, but it’s such a good free, and usually very nice consult to have on your team. Jeff: Nice consultant – what a win!  Moving on to the cutting edge.  There is a new Crotalidae antivenom called Crotalidae Immune F(ab’)2 or, more simply, Anavip.  It should be available in the next few months.  The dosing will be 10 vials up front over 60 minutes followed by an additional 10 vials if the symptoms having been controlled.  4 more vials may be given for symptom recurrence.  Patients must be observed for a minimum of 18 hours after initial control of symptoms. Nachi: This would be a really nice development as Anavip has a longer half life and therefore should reduce the rates of late coagulopathy and decrease the need for maintenance dosing, follow up, and repeating coags. Jeff:  And finally, like we mentioned before, injection of the trypsin has been tried as a bridge to antivenom, as has carbon monoxide, which may mediate degradation of fibrinogen dependent coagulation. Nachi:  Alright, so let’s talk about the disposition next. Victims of pit viper envenomations should be monitored for 8-12 hours from the time of the bite.  They will need baseline labs and repeat testing ever 4-6 hours.  IF there is no progression of the symptoms and repeat testing is normal, the patient can be discharged. Jeff: Victims of coral snake bites should be admitted and observed for 12-24 hours regardless of symptoms. Nachi: Victims of rattle snake envenomations who initially develop hematologic abnormalities and are treated with FabAV should have repeat testing done in 2-4 days and 5-7 days. Jeff:  Wounds should also be closely followed to avoid complications and long term disfigurement and disability.  PT/OT may be necessary as well. Nachi:  Perfect, let’s round this episodes out with a review of the key points and clinical pearls from this month’s issue. There are about 10,000 ED visits in the US for snake bites each year, and 1/3 of these involve venomous species. Pit vipers produce a predominantly hemotoxic venom. Both local and systemic effects can occur. Systemic effects include tachycardia, tachypnea, hypotension, nausea, vomiting, weakness, and diaphoresis. In general, venomous snakes have a triangular or spade-like head, elliptical pupils, and hollow retractable fangs. In contrast, non-venomous snakes have a rounded head, round pupils, lack fangs, and can have a double row of vertical scales on the tail. Venomous North American coral snakes often have adjacent red and yellow bands, whereas their nonvenomous counterparts usually have a characteristic black band between the red and yellow bands. For prehospital care in the US, the following strategies are not recommended: incision or excision, use of venom extraction devices, tourniquets, chill methods, and electroshock therapy -- and they can all actually worsen outcomes.  Prehospital providers should focus on rapid transport. Be cognizant of compartment syndrome, but measure compartments when possible, as some envenomations present similarly but have only subcutaneous hypertension. Neurologic effects can be delayed up to 12 hours after coral snake envenomations. Symptoms can include a descending paralysis. For diagnostic testing, consider a CBC, coags, fibrinogen level, electrolytes, cpk, creatine, glucose, and urine studies.  All patients with envenomation should be observed for at least 8 hours. Mark the site of envenomation circumferentially to monitor for changes. Management of patients with snake bites should be treated with supportive care, pain control, and specific antivenom when indicated. FabAV or CroFab is the antivenom of choice for pit viper envenomations. Although FabAV will reduce the duration and severity of symptoms and lab abnormalities, it will not reverse tissue necrosis and may not reverse neurologic effects. Be aware of the possibility for a hypersensitivity reaction or serum sickness to FabAV. Treat with steroids, antihistamine, IV fluids, and epinephrine as appropriate. Coral snake envenomations can be treated with NACSA, which halts or at least limits the progression of muscle paralysis and shortens the clinical course.  Side effects to NACSA include dermal reaction as the most common -- and anaphylaxis as the most severe. Patients with bites from exotic snakes should be monitored, likely in the ICU, for up to 24 hours as toxicity from some venom may have a delayed onset of up to 20 hours. You may have to turn to your local zoo for help with anti-venoms here. Management of pregnant patient\s is the same as nonpregnant patients with regards to snake envenomations. Dosing of antivenom is based on the amount of venom. Dosing is the same regardless of the age of the patient. All patients requiring antivenom or with suspected envenomation should be admitted.  Seek consultation with your regional poison center and local toxicologist Jeff: So that wraps up the September 2018 episode of Emplify. Nachi: As always - the address for this month’s credit is ebmedicine.net/E0918, so head over there right away to get your credit.  Remember that the  you heard throughout the episode corresponds to the answers to the CME questions. Jeff: And don’t forget to grab your free issue of Synthetic Drug Intoxication in Children at ebmedicine.net/drugs specifically for emplify listeners. Feel free to share the link with your colleagues or through social media too. Next month we are talking sepsis and the ever frequently changing guidelines so it’s not something you want to miss.  Talk to you soon   Most Important References 4. *Lavonas EJ, Ruha AM, Banner W, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;11:2-227X-11-2. (Consensus panel) 6. *Bush SP, Ruha AM, Seifert SA, et al. Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: a prospec­tive, blinded, multicenter, randomized clinical trial. Clin Toxicol (Phila). 2015;53(1):37-45. (Randomized controlled trial; 121 patients) 7. *Gerardo CJ, Vissoci JR, Brown MW, et al. Coagulation parameters in copperhead compared to other Crotalinae envenomation: secondary analysis of the F(ab’)2 versus Fab antivenom trial. Clin Toxicol (Phila). 2017;55(2):109-114. (Ran­domized controlled trial; 121 patients) 8. *American College of Medical Toxicology, American Acad­emy of Clinical Toxicology, American Association of Poison Control Centers, European Association of Poison Control Centres and Clinical Toxicologists, International Society on Toxinology, Asia Pacific Association of Medical Toxicology. Pressure immobilization after North American Crotalinae snake envenomation. Clin Toxicol (Phila). 2011;49(10):881-882. (Position statement) 10. *Wood A, Schauben J, Thundiyil J, et al. Review of eastern coral snake (Micrurus fulvius fulvius) exposures managed by the Florida Poison Information Center Network: 1998-2010. Clin Toxicol (Phila). 2013;51(8):783-788. (Retrospective; 387 patients) 48. *Cumpston KL. Is there a role for fasciotomy in Crotalinae envenomations in North America? Clin Toxicol (Phila). 2011;49(5):351-365. (Review) 75. *Walker JP, Morrison RL. Current management of copper­head snakebite. J Am Coll Surg. 2011;212(4):470-474. (Retro­spective; 142 patients) 81. *Kitchens C, Eskin T. Fatality in a case of envenomation by Crotalus adamanteus initially successfully treated with polyvalent ovine antivenom followed by recurrence of defibrinogenation syndrome. J Med Toxicol. 2008;4(3):180-183. (Case report) 118. *Hwang CW, Flach FE. Recurrent coagulopathy after rattle­snake bite requiring continuous intravenous dosing of anti­venom. Case Rep Emerg Med. 2015;2015:719302. (Case report)