Why so blue? - Methylene blue in Distributive Shock

Clinical Scenario:
You are working in Trauma Critical Care when a middle aged male with end-stage liver disease presents with altered mental status.  He is hypotensive  and tachycardic.  You resuscitate him with IV fluids, start broad spectrum antibiotics and initiate vasopressors.  You confirm a source of infection with a paracentesis. Despite multiple and escalating doses of pressors, the patient's blood pressure continues to fall.  You perform a RUSH exam, run through your differential diagnosis again, and confirm that all lines and tubes are connected appropriately.  As you prepare his family for the worst and sign him out to the ICU, your colleague suggests - what about methylene blue?  Is it worth a shot?

Clinical Question:
Is there a role of methylene blue in management of septic shock?

Image source: webmd.com

Literature Review:

Methylene blue was initially developed as a dye for the textile industry, then used as a stain for TB, treatment for malaria, treatment of cyanide toxicity, and more recently methemoglobinemia.  Typical dosing for methemoglobinemia is 1-2mg/kg of 1% solution IV.

In a recent review performed by the Toxicology Department at UCSD published in the Journal of Emergency Medicine in 2013, the authors presented the evidence behind the utility of methylene blue in the septic patient [1].  

Methylene blue (MB) is useful in septic shock due to its ability to increase peripheral vascular resistance and its reversal of myocardial depression.  Its mechanism of action is thought to be due to inhibition of inducible nitric oxide synthase (up regulated by endotoxin and cytokines producing vasodilatory nitric oxide and guanylate cyclase (makes vasodilatory cGMP) [2,3].  There have only been two randomized controlled trials that studied MB in septic shock (n=20; n=30).  In these studies MB was found to increased mean arterial pressure (MAP) and decrease vasopressor requirements, but there was no statistically significant difference in survival rates.

Other studies reviewed for this publication were case series and case reports.  In these, varying doses of MB were used ranging from 1-3mg/kg over 10-20 minutes, which all increased MAP, systemic vascular resistance (SVR), and mean pulmonary arterial pressure.  However MAP and SVR returned to baseline 2-4 hours after MB administrations.

With doses greater than 4mg/kg or rapid or prolonged (greater than 6-10 hrs) infusion, potential side effects of MB use includes serotonin syndrome reaction (if already taking serotoninergic agents, MB inhibits monoamine oxidase), methemoglobinemia (if G6PD deficiency, or at high doses MB acts as oxidizer instead of reducer), platelet aggregation/reduction, and vasoconstrictive effects with possible decreases in splanchnic perfusion and arterial oxygenation (do not use in ARDS or pulmonary hypertension) [1,3,4].  The clinical effects of MB persist for 2-3 hours (half-life=102 minutes) and should be preferably administered centrally as peripheral administration can cause cutaneous necrosis [3,4].

Take home points:

-Methylene blue may prove a useful adjunct to vasopressors in cardiovascular collapse.  

-Remember additional shock management strategies include adequate volume resuscitation and source control, inotropy, respiratory support, correction of electrolytes (K, Ca, Mg, Phos) and glucose, consideration of endocrine dysfunction (thyroid, adrenal, vasopressin), and ruling out obstructive etiologies.

References:

1. Lo JC, Darracq MA, Clark RF. A review of methylene blue treatment for cardiovascular collapse. J Emerg Med. 2014 May;46(5):670-9.
2. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001; 345(8): 588-595.

3. Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjørnsson B, Nedashkovsky EV, Bjertnaes LJ. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med 2001; 29(10): 1860-1867.
4. Juffermans NP, Vervloet MG, Daemen-Gubbels CR, Binnekade JM, de Jong M, Groeneveld AB.. A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide 2010; 22(4): 275-280.

Submitted by Lydia Luangruangrong, PGY-3.

Edited by  Steven Hung (@DocHungER), PGY-2

Faculty reviewed by Chris Holthaus

IV lidocaine for analgesia in the ED?

Clinical scenario:

You’re in the midst of a busy evening shift, when out of the corner of your eye you think you notice a patient you just took care of a few days ago. You check the board, and sure enough you’re right. She is an unfortunate female in her 20's with a history of SLE complicated by both  ESRD on dialysis and recurrent VTE. She also has chronic recurring chest pain of unclear etiology. She has had several full cardiac workups and CT imaging which have yet to reveal an etiology of her recurring pain. She tells you the pain is identical in character to her prior presentations. It is not associated with SOB, diaphoresis, lightheadedness, palpitations, or N/V. The patient is not interested in further diagnostics, and flat-out refuses admission, further CT imaging, or cardiac testing. She just wants some relief from her pain. In the past, hydromorphone at relatively high doses has been somewhat effective, but your attending is wary of continuing to provide high-dose hydromorphone at frequent intervals during your patient’s repeated ED visits. He suggests IV lidocaine may be effective for your patient.

Clinical question:

Is IV lidocaine a safe and effective parenteral analgesic alternative to narcotic pain control in the ED?

#FOAMed digest No. 9: For the Visually Oriented

As was discussed in conference by Jason Wagner last week, and brought up by EM Curious in this tweet,

humans are visual learners and there is little substitute for an image when it comes to retention of information.   Therefore, the focus of this installment of the #FOAMed digest is on visually-oriented FOAMed resources - from static visual aids, to procedural videos or talks.  Since I think the same applies to Case-based learning (I know that I personally learn best from cases that I have seen or heard of), I've thrown some of that in too.

Visual aids: EMCurious has created some wonderful visual aids that allow you to navigate patient management, evidence based medicine and #FOAMed content. I particularly like these infographics on management of Afib with RVR in the emergency department or this infographic on vasopressors in septic shock.   For a simple visual algorithm (and cognitive aid) on managing the difficult airway, check out the vortex approach (I recommend watching the video as it explains the image). 

Ultrasound : It would be impossible to properly teach ultrasound without case examples and visual demonstrations.  There are some excellent online resources to enhance your ultrasound learning.  Laura Wallace (@labellalaura) recommended the Ohio State ultrasound website for tutorials on common US exams.  If you like a little entertainment with your ultrasound, check out the emc to learn about ultrasound findings and pathophysiology of both cardiac tamponade and PE.  For the combination of case-based learning and excellent videos, be sure to add the ultrasound of the week to your weekly to do list.  I particular liked this case of a patient with lung cancer and shortness of breath because it gave me good reminder to look at everything in the ultrasound image (sorry for the sort-of-spoiler alert). 

Procedures:  Much like my husband did when he fixed the dishwasher,  I have used YouTube when refreshing on a procedure before doing it in the ER.  I have also watched procedural videos in anticipation of having to do the procedure (such as this set of emcrit central line videos the night before my first TCC shift as an intern).  As far as #FOAMed procedural videos, EM Curious has a "procedures club" of videos for those less frequent but high-stress ED procedures, including ED thoracotomy , lateral canthotomy, and crichothyrotomy.  Our own PD, Jason Wagner, has made this video of simulated perimortem C-section. 

EM Basics & Board Review: The possibilities for this category are endless.  Here are a couple resources that may be helpful.  For case-based and visual learning, Northwestern has an excellent site for Orthopedics review, complete with case scenarios and excellent X-ray images.  For board review in general, see the EM Board review blog - here is a link to a rapid fire review you may want to watch before the inservice.  If flashcards are your thing,  here is a link to a flashcard host site for board review flashcards based in Rosen's shared by Boring EM.

On being human - Sometimes we need to be reminded that we are human and our patients are too.  To me, when it comes to medical error and mistakes, individual cases motivate me for change more than any jumbo jet analogy.  I think we all have some cases where we sat down to think about (or lay in bed awake at night wondering) what we could have done differently.  Here are talks, by both doctors and patient families, on mistakes that happen and what we can do better:
              The story of Elaine Bromiley
              Doctor's make mistakes - Can we Talk About That? 
              Transparency and Truth in Medical Errors

 Enjoy the tour,
Maia Dorsett, PGY-3 (@maiadorsett)

Too many choices: Ankle sprain treatment - ace wrap, brace, or boot?

Clinical Scenario:
A 22 year old was running in the park when she accidentally rolls her ankle on the uneven ground.  There is significant swelling over the lateral malleolus that is tender to palpation.  She is unable to bear weight on her ankle so you obtain x-rays, which are normal.  As you are about to send her home, you debate what is the best treatment for her ankle.

Clinical Question:
In a severe ankle sprain, what is the preferred treatment – ace wrap, aircast brace, or air walker boot?

Literature Review:
Grade I injury is a mild stretching of the ligament without joint instability, Grade II injury is a partial rupture of the ligament with mild instability, Grade III is a complete rupture of the ligament with joint instability.   Generally grade II or III are considered severe sprains.

A study released in the Lancet in 2009 compared 584 participants with severe sprains who received a below-knee cast for 10 days, ace wrap, aircast brace, or an air walker boot.  The patients were followed up at 3 months and assessed for quality of ankle function, pain, symptoms, and activity.  The superior method of treatment was the 10 day below-knee cast (when compared to the ace wrap) for overall quality of ankle function (mean difference 9%; 95% CI 2.4-15.0).  The aircast brace was also found to improve quality of ankle function compared to ace wrap and air walker boot, but was not superior with regard to pain, symptom, or activity.  The air walker boot was not superior to the ace wrap.  Another study from 2005 compared ace wraps to the aircast brace for lateral ankle sprains and also found that the aircast ankle brace was superior to an ace wrap at 10 days and one month. In a systematic review published in Sports Med in 2011, they too concluded the superiority of an ankle brace over an ace wrap with regard to functional outcome.

The British Medical Bulletin in a systematic review concluded that for mild to moderate ankle sprains, functional treatment options (ace wrap, aircast brace) where found to be statistically better than immobilization.  For severe ankle sprains, a short period of immobilization in a below-knee cast resulted in a quicker recovery than other functional treatments

Take home points:

-The most practical approach is to offer an aircast brace, which has been shown to offer better functional outcome compared to ace wrap and air walker boot.
-In severe ankle sprains, short below-knee cast immobilization resulted in the best functional outcome

References:

1. Boyce SH, Quigley MA, Campbell S. Management of ankle sprains: a randomised controlled trial of the treatment of inversion injuries using an elastic support bandage or an Aircast ankle brace. Br J Sports Med. 2005 Feb;39(2):91-6.

2. Lamb SE, Marsh JL, Hutton JL, Nakash R, Cooke MW; Collaborative Ankle Support Trial (CAST Group). Mechanical supports for acute, severe ankle sprain: a pragmatic, multicentre, randomised controlled trial. Lancet. 2009 Feb 14;373(9663):575-81.

3. Kemler E, van de Port I, Backx F, van Dijk CN. A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types. Sports Med. 2011 Mar 1;41(3):185-97.

4. Seah R, Mani-Babu S. Managing ankle sprains in primary care: what is best practice? A systematic review of the last 10 years of evidence. Br Med Bull. 2011;97:105-35.

Images from: www.1staidsupplies.com, www.betterbraces.com, orthotape.com.

Submitted by Lydia Luangruangrong, PGY-3.

Edited by  Steven Hung (@DocHungER), PGY-2

Faculty reviewed by Chris Brooks

EKG Challenge #4 Case Conclusion: In Syncope, You Can't Miss These

You are riding along with EMS when you get a call for "difficulty breathing".  You enter the house to find fire department already on scene performing CPR on a high school age male.  The paramedics give 2mg of intra-nasal Narcan without response.  The patient is placed on the monitor and the following rhythm strip is obtained:

The patient is defibrillated x 2 with ROSC and his post-defibrillation strip:

After return of pulses, the patient is bagged on transport to the emergency department.  An additional 2mg of narcan is given IV without effect. A 12 lead EKG is obtained:

 On evaluating the EKG, you are struck by the short PR interval and up-sloping of the QRS.  You review the initial rhythm strip and identify an irregular and fast (~ 300 bpm) consistent with atrial fibrillation with a wide QRS. You call Cardiology, who agrees with your diagnosis of WPW.

To review, WPW is a pre-excitation syndrome in which there is a manifest accessory pathway for conduction between the atria and the ventricles.  This accessory pathway predisposes to a number of serious arrythmmias.  See a nice review from Life in the Fast Lane here.  Technically, WPW is a syndrome in which the congenital accessory pathway is present and patients are symptomatic secondary to episodes of tachyarrythmmia.

Source: Hamilton and Sanatani. http://www.rjmatthewsmd.com/Definitions/supraventricular_tachyarrhythmias.htm

Once you understand the electrophysiology, the triad of ECG findings in WPW makes sense:
 1) shorted PR interval because ventricular stimulation begins earlier than normal via the accessory pathway.
2) a slurred rather than sharp upstroke of the QRS (delta wave) due to ventricular stimulation through the accessory pathway.
3) a widened QRS complex which it represents fusion of two excitation wavefronts through the ventricles.

WPW is most likely to degenerate into Vtach or Vfib arrest when atrial fibrillation occurs.  Atrial fibrillation occurs in up to 20% of patients with WPW, and because the accessory pathway has no refractory period for conduction like the AV node, the ventricular rate can be very high - upwards of 300 bpm [1].  The hallmarks?  Look at the initial rhythm strip for this patient: irregular, bizarre-appearing, wide complexes at a rate of ~ 300 bpm.

Back to our patient...
 
Almost immediately after ED arrival, the patient is intubated for continued poor GCS, admitted to the ICU, where he gradually stablilizes, and is eventually discharged with normal neurologic status.  Prior to discharge, he undergoes an electrophysiology study which identifies and ablates an accessory pathway, and his post-procedure EKG is notable for the absence of a delta wave:

post-ablation

On further review of the  patient's EMR, you see that he was seen in an emergency department three years earlier after  being found confused/altered.   At the time, mental status was thought to be secondary to reported intake of OTC sleep meds and marijuana use.  An EKG was obtained during the visit:

Review of this EKG reveals a short PR interval and evidence of a delta wave in several leads (see II, aVF), and diffuse ST changes.  The patient was discharged home at that time with a diagnosis of drug abuse.   Despite the number of a "normal EKGs" we see on a daily basis for patients who present with syncope, it is important to maintain vigilance for the Can't miss EKGs findings in the young person with syncope: 

1. WPW:  As mentioned above, you can read about WPW at Life in the Fast Lane.  You can also watch Amal Mattu's episodes on WPW with atrial fibrillation and on orthodromic and antidromic SVT, or read about the emergent treatment of arrythmmias associated with WPM here.

2. Brugada syndrome:  Brugada is a genetic syndrome of sudden death associated with specific electrocardiographic findings: RBBB (possibly incomplete) and ST elevation in the right precordial leads (V1 - V3).  The ST elevation can have a coved or saddle-back morphology (see Figure below).  Brugada is associated with cardiac arrest secondary to ventricular fibrillation and most typically presents with syncope (if the rhythm self-terminates) or sudden cardiac death, usually in the 4th or 5th decade of life [4].  Patients with suspected Brugada should undergo EP testing, as treatment with an AICD can be lifesaving.  For further edification, watch Amal Mattu's ECG of the week on Brugada syndrome or read a written review published in Emergency Medicine News.

3. Long QT syndrome:  A prolonged QTc interval is considered > 440 ms in males and > 460 ms in females.  A basic rule of thumb is that the QT should measure < 1/2 of the RR interval.  While we normally think of prolonged QT as a risk factor for cardiac arrythmmia (Torsades de Pointes) in the context of QT-prolonging medications or electrolyte abnormalities, there are a number of genetic

mutations in sodium and potassium channels that also lead to prolonged QT syndrome which can present as sudden cardiac arrest early in life.  In a study of 647 patients who were carriers for one of these mutations, 87% experience cardiac arrest or death over a period of 28 years [2].  The first medical presentation for cardiac event (including syncope) is usually in the range of 10 - 35 years [2].  Because of the electrophysiologic effects of the mutations, patients are particularly susceptible to cardiac arrest during adrenergic stimulation.  Beware, the computer does not always measure the QTc correctly, here is a tutorial from Life in the Fast Lane on how to measure it correctly yourself and an example from Steve Smith's ECG blog.

4. Hypertrophic Cardiomyopathy (HCM):   HCM is the most common cause of sudden cardiac death in young athletes.  HCM is actually a heterogeneous group of cardiac conditions due to genetic

mutations in components of the cardiac sarcomere that have variable penetrance and severity of clinical presentation.  Patients can present initially with symptoms predominantly due to LVOT obstruction (exertional syncope, lightheadedness on exertion) or sudden cardiac death. The common phenotype is left ventricular hypertrophy, which is usually most pronounced in the anterior septum and can result in obstruction of the left ventricular outflow tract (LVOT).  The most common EKG findings are LVH with associated ST and T wave changes.  In addition, these patients can have narrow & deep Q waves in the lateral leads with a duration of < 40 ms.  These reflect septal hypertrophy and are often mistaken for changes of prior ischemic event.  The EKG findings of HCM can precede an abnormal echo.  For an excellent summary and several good ECG examples, read the HCM review from Life in the Fast Lane.

5. Arrythmogenic Right Ventricular Dysplasia (ARVD):  Arrythmogenic Right Ventricular Dysplasia is a genetic disease characterized by progressive replacement of the right ventricular myocardium by fatty fibrous tissue.   At the cellular level, it is a disease of desmosome dysfunction.  As a reminder, desmosomes are connections between cardiac myocytes that allow them to electrically communicate with each other.  ARVD has been proposed to explain 3-5% of sudden cardiac death under the age of 65 [5].  It is associated first with ventricular arrythmmias (with a LBBB pattern because they originate in the right ventricular outflow tract) leading to sudden death (80% of patients present with cardiac arrest).  Those who survive eventually develop right heart failure. The EKG findings of ARVD are related to extensive scarring of and slowed conduction through the right ventricle [6]:
           - Epsilon wave  - a small positive deflection at the very end of the QRS complex
           - T wave inversions in V1-3
           - localized QRS widening and prolonged S-wave upstroke in V1-V3.

Here is another great review and case scenario for ARVD from Life in the Fast Lane.  If you like to watch videos instead, see this case review from Amal Mattu.

Given the role of the ECG in diagnosing conditions that may later present as cardiac arrest, is there any role for screening ECGs in asymptomatic patients? Several other countries think so: Japan has mandatory ECG screening of all children and in Italy all children have a screening  ECG before sports-participation [7].  While the ECG has a very high negative predictive value for LQTS, WPW, and HCM (in the realm of 99 - 100% depending on the condition), the positive predictive value is very low because of the overall low prevalence of disease (45 per 100,000 for WPW; 7 per 100,000 for LQTS; 136 per 100,000 for WPW), leading to a number needed to screen to detect one abnormality in the realm of 500-2000 children [8].  Given the poor positive predictive value, the overall rate of false positives is high, leading to potential unnecessary testing and anxiety.   Thus, further studies will be necessary to determine whether ECG screening of asymptomatic children (and in what context)  is worthwhile public health policy [8].

Take Home Points: Know the Can't miss EKG findings young syncope patients [Brugada, WPW, long QT, hypertrophic cardiomyopathy, ARVD ] and refrain from attributing altered mental status or syncope to drugs of abuse when the EKG is abnormal.   While we will did not discuss them here, it goes without saying - keep vigilance for cardiac ischemia and PE in the syncope patient,  even a young one.

References:
[1] Dovgalyuk, J., Holstege, C., Mattu, A., & Brady, W. J. (2007). The electrocardiogram in the patient with syncope. The American journal of emergency medicine, 25(6), 688-701.
 [2]  Priori, S. G., Schwartz, P. J., Napolitano, C., Bloise, R., Ronchetti, E., Grillo, M., ... & Cappelletti, D. (2003). Risk stratification in the long-QT syndrome. New England Journal of Medicine, 348(19), 1866-1874.
[3]Kelly, B. S., Mattu, A., & Brady, W. J. (2007). Hypertrophic cardiomyopathy: electrocardiographic manifestations and other important considerations for the emergency physician. The American journal of emergency medicine, 25(1), 72-79.
[4] Mattu, A., Rogers, R. L., Kim, H., Perron, A. D., & Brady, W. J. (2003). The Brugada syndrome. The American journal of emergency medicine, 21(2), 146-151.
[5]Marcus, F. I., McKenna, W. J., Sherrill, D., Basso, C., Bauce, B., Bluemke, D. A., ... & Zareba, W. (2010). Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia Proposed Modification of the Task Force Criteria. European heart journal, ehq025.
[6] Marcus, F. I., & Zareba, W. (2009). The electrocardiogram in right ventricular cardiomyopathy/dysplasia. How can the electrocardiogram assist in understanding the pathologic and functional changes of the heart in this disease?. Journal of electrocardiology, 42(2), 136-e1.
[7] Vetter, V. L. (2009). The role of ECG screening in the evaluation of risk of sudden cardiac arrest in the young. Pacing and Clinical Electrophysiology, 32(s2), S6-S14.
[8] Rodday, A. M., Triedman, J. K., Alexander, M. E., Cohen, J. T., Ip, S., Newburger, J. W., ... & Leslie, L. K. (2012). Electrocardiogram screening for disorders that cause sudden cardiac death in asymptomatic children: a meta-analysis. Pediatrics, 129(4), e999-e1010.

Submitted by Maia Dorsett (@maiadorsett), PGY-3
Faculty Reviewed by Doug Char
Thanks again to Heather Webb (@webbmd) for another great case

Brought in by Ambulance, #4: Pour Some Sugar on Me

Case Scenario: 

Your unit is responding on the quiet to a 36 year-old F with chief complaint of “sick.”  You arrive to find a cachectic woman (BMI 16) who suffers from lifelong anorexia. She complains of shortness of breath, abdominal pain and general malaise. She walks herself to the ambulance and after her vitals are taken, a FSBS is 56.  According to your protocol, this should be treated in the following manner: the EMT-B administers 15 gm oral glucose solution and repeat as needed, while the EMT-P administers 25 gm D50W IV/IO or D10W IV/IO, or glucagon 1 mg IM if no IV/IO access available.  The medic asks your opinion and as the patient was symptomatic, you suggested starting with oral glucose solution. However, this made her feel nauseated. Once again, the medic asks you whether to give D10W or D50W. You elected for D10W, but you admittedly have no evidence for doing so. After an uneventful ride to the hospital, the patient’s repeat blood glucose was 254 mg/dL.

Clinical Question:
What is the best way to treat hypoglycemia in the prehospital environment?

Literature Review:  

Most common sources define hypoglycemia as less than 60-70 mg/dL. According to the Endocrine Society’s Clinical Practice Guidelines, hypoglycemia should only be treated and investigated in patients showing signs of "Whipple’s triad" -- signs and symptoms of hypoglycemia, a low plasma glucose reading, and resolution of symptoms with elevation of plasma glucose concentration [1]. The signs and symptoms of hypoglycemia are quite vague and nonspecific; they can include shakiness, anxiety, headaches, and weakness, progressing to seizures and unconsciousness [2]. Severe symptoms typically occur with serum glucose values less than 40 mg/dL [3]. It seems obvious that seizures and unconsciousness attributed to hypoglycemia should be treated, but any of the minor signs and symptoms could easily be appreciated on almost any primary scene response. Therefore the vast majority of hypoglycemic patients encountered by EMS providers are most likely going to be treated.

Once we have decided to treat prehospital hypoglycemia, we must determine the optimum modality for doing so. We could find no published work doing a heads-up comparison of oral versus intravenous carbohydrate administration, but there has been work related to D10W versus D50W. An EMS system in California published data from their experience replacing 50mL D50W with 100mL D10W as the standard treatment for hypoglycemia [7]. In 164 treated patients, the median pretreatment glucose was 38 mg/dL, and at 8 minutes after treatment was 98 mg/dL.Twenty-nine patients required an additional dose, and one patient required a third. There were no adverse events reported. The authors conclude these results demonstrate the feasibility, safety, and efficacy of D10 as an alternative to D50.

One unblinded randomized controlled trial compared D10W to D50W in prehospital hypoglycemic patients with GCS < 15 (approx. 25 pts in each group) with regards to the ability of the solutions to raise glucose to normal values and the time to reach a GCS of 15 [4]. The mean repeat glucose value in these groups was 112 and 169 in the D10W and D50W groups, respectively (p = 0.003). The authors note that the average D10 given was 10g (100 mL) and D50 given was 25g (50 mL) (p < 0.001). There were no significant differences between the groups in median time to recovery, median post-treatment GCS, or number of patients experiencing another hypoglycemic episode within 24 hours. The authors conclude that due to the efficacy of treatment with lower risk of hyperglycemia, D10 should be the preferred agent.

   

Not only is D50 more likely to cause hyperglycemia after administration, but it also carries with it the risk of hypertonicity and tissue necrosis. D50 has an osmolarity of 2,525 mOsm/L and a pH between 3.5 and 6.5. This is in contrast to D10 which has an osmolarity of 506 mOsm/L and is pH neutral. Usual IV therapy recommendations state that solutions with osmolarity greater than 900 mOsm/L should be administered through central access. There have also been several case reports of extremity amputation after dextrose extravasation [5,8].

To illustrate the difficulty in administering D50, one of our toxicology faculty compared the injection of D50 to injecting maple syrup. This is not a facetious analogy, as a simple look at the nutrition label of a bottle of syrup reveals:

Note that D50 = 50g of sugar per 100mL of soluion. Each "amp" of D50 contains 25g of sugar in 50mL. Compare that to Aunt Jemima's, which contains 32g of sugar in 60mL solution.

The primary EMS agency bringing patients to our facility recently updated their protocols to make D10 the preferred agent for treating hypoglycemia prehospital. The Medical Director of this agency reiterated the preferable safety profile of D10 compared with D50, and remarked on another important advantage of D10 -- it does not need to be diluted for use in pediatric patients.

In the absence of IV/IO access, evidence exists for the efficacy of IM glucagon in treating prehospital hypoglycemia [9]. The response to glucagon may take longer than when oral or IV glucose solutions are used [10, 11], though may cause a greater increase in blood glucose levels than 10g of glucose solution [12].
   

Take-home:

- If mental status allows, hypoglycemic patients should first be offered oral glucose -- preferably 15gm of a standard glucose formula, but syrup, juice, or honey can also be used. (Note that honey has a lower glycemic index than most juices or glucose solution and thus theoretically may not be as effective.) 
- The next line of therapy should probably be IV D10, as there is good evidence to suggest efficacy on par with that of D50 but with a more favorable safety profile.
- If no IV/IO access is available and oral glucose is unable to be administered, it is reasonable to administer 1mg IM glucagon.

References:
[1] Evaluation and management of adult hypoglycemic disorders.  J Clin Endocrinol Metab, 2009, 94(3), 709.
[2] American Diabetes Association.  Diabetes.org
[3] National Diabetes Information Clearinghouse.  Diabetes.niddk.nih.gov
[4] Moore and Woolard. Emerg Med J, 2005, 22, 512-515.
[5] Kumar et al. ANZ Journal of Surgery, 2001, 71, 285-289.
[6] Is D50 Too Much of a Good Thing?  Stephen Wood, 2007, m.jems.com/article/patient-care
[7] Kiefer et al. Prehosp Disaster Med, 2014, 29(2), 190-194.
[8] Lawson et al. Am J Emerg Med, 2013, 31(5), 886:e3-5.
[9] Vukmir et al. Ann Emerg Med, 1991, 20(4), 375-9.
[10] Howell et al. J Accid Emerg Med, 1997, 14(1), 30-2.
[11] Carstens and Sprehn. Prehosp Disaster Med, 1998, 13(2-4), 44-50.
[12] Vermeulen et al. Diabetes Care, 2003, 26(8), 2472-3.

Submitted by Chris Miller, PGY-2.
Edited by C. Sam Smith (@CSamSmithMD), PGY-3.
Faculty reviewed by Hawnwan P. Moy.

Expert Commentary: Troubleshooting Hypoxia on the Vent

In emergency medicine education, we tend to focus on establishing the airway but spend less time discussing the aftercare and managing the ventilator.  While we have spent more time on this recently, thanks to Brian Fuller and his research on the importance of low tidal volume ventilation in the ER (see EM Journal club summary and podcast from February 2014),  most of us are still more comfortable putting the ET tube in than managing the vent.

Luckily for us, here at WashU we have some EM-Critical Care wise guys who can teach us a thing or two, and today we share with you Brian Fuller's method for trouble-shooting hypoxia on the vent, forwarded to us by PGY-3 Brendan Fitzpatrick:

>>From: Fitzpatrick, Brendan
>>To: Fuller, Brian
>>Subject: vent desats

Dr. Fuller,

Good working with you last night. I was trying to recall how you broke down desats on the vent last night, but somewhere between little sleep and my kids' halloween parade, I've lost the finer points.

In all your free time, would you mind jotting down what you told me so I can review it?

thanks,

Brendan

 
>From: "Fuller, Brian"
>To: "Fitzpatrick, Brendan"
>Subject: RE: vent desats

For the purposes of acute deterioration (in the form of hypoxia) on the ventilator, we are gonna talk about two airway pressures: peak pressure and plateau pressure. As an aside, mean airway pressure is the average pressure over one cycle of inspiration and expiration. It is largely governed by PEEP and I:E ratio. It really governs oxygenation- higher it is, more you open up stiff alveoli in sick vented patients.

Peak pressure is the summation of pressure generated from: 1) tidal volume and compliance; 2) resistance and peak inspiratory flow; and 3) PEEP
 
Plateau pressure is a reflection of compliance. Think "how stiff the lungs are"; or "how much transalveolar stretch is occurring".
Compliance is ∆ volume/∆pressure. Specifically, tidal volume/(plateau pressure - PEEP)




So the first thing I do when somebody becomes acutely hypoxic on the ventilator is to look at their peak airway pressure:

1. If decreased: you have an air leak or the patient is hyperventilating/tugging hard and therefore pulling the airway pressures down. Air leak would be something like: bronchopleural fistula, the chest tube you just put in has a leak in the system, your ETT has migrated or cuff has a leak and air is escaping.

2. If increased: see above- this could either be primarily a compliance or resistance problem. So your next step is to look at the plateau pressure to figure out where the problem lies.

If no change in plateau, you therefore have a bigger difference between the peak pressure and the plateau pressure than existed before the hypoxic event. See above for what governs these pressures, so you can tell that this is therefore a resistance problem. Think: airway obstruction from bronchospasm, clogging of the ETT with secretions, kinking of the ETT.

If plateau pressure is also increased, you now have a situation where the peak and plateau pressures both increased. See above for what governs these pressures, so you can tell that this is therefore a compliance problem. Think: pulmonary edema, abdominal distention, pneumothorax, atelectasis, etc.

3. If no change: think "Something made my patient hypoxic but didn't change my airway pressures." Not a lot of stuff does that. Think: pulmonary embolism, PFO.

Sometimes it is difficult to figure out "Is the ventilator and my ventilator settings the problem, or is this a patient problem?" If you remove the patient from the ventilator, and therefore take that out of the equation, bag them and they get better, it is probably a ventilator problem. If you bag them and they stay bad, it is probably a patient problem.

Hope this helps. Hit me back with questions PRN.

Feel free to share with others.
Be good man.
B


For those of you who like pictures, here is a visual representation of the algorithm:

Want to do a little more reading or watching about this? Life in the Fast Lane had a nice review of Pulmonary Mechanics.  I recommend the second Eric Strong video on pulmonary pressures as a supplement to understanding the above material (and hell, it only takes 9 minutes to watch).

Expert Commentary by Brian Fuller
Visual aids by Maia Dorsett (@maiadorsett), PGY-3 
Expert inquiry, sharing skills and parenting by Brendan Fitzpatrick, PGY-3.

EKG Challenge #4: Sometimes electricity works better than narcan ...

You are riding along with EMS when you get a call for "difficulty breathing".  You enter the house to find fire department on scene already performing CPR on a high school age male.  The paramedics 2mg of intranasal Narcan is given without response.  The patient is placed on the monitor and the following rhythm strip is obtained:

The patient is defibrillated x 2 with ROSC and his post-defibrillation strip:

After return of pulses, the patient is bagged on transport to the emergency department.  An additional 2mg of narcan is given IV without effect. A 12 lead EKG is obtained on ED arrival:

 What is your diagnosis?

Read our case conclusion here

Pediatrics: There's blood in the stool!

Clinical Scenario:

A 2 week old child presented to the emergency department with blood in the stool.  The child was otherwise well, tolerating feeds, no apparent abdominal pain, no abdominal distension, no fever.  Other than the dark red blood, the stool appeared about the same.  Child was born via vaginal delivery following an uncomplicated 40 week pregnancy.  Had stool within minutes of birth and has had normal stooling since.

Clinical Question:

What should be considered in a neonate/infant presenting with bloody stool?

Differential Diagnosis (DDx) of bloody stool in neonate:

-Swallowed maternal blood

-Anorectal fissure

-Necrotizing enterocolitis (NEC)

-Malrotation with midgut volvulus

-Hirschsprung disease

-Food protein-induced proctitis/colitis (not to be confused with similar food protein-induced enterocolitis syndrome [FPIES] where child is usually sicker and involves vomiting)

Other Differentials in later infancy:

-Intussusception (more common between 6-36 months of age, 60% before 1 year, 80% before 2 years)

-Infectious colitis – rare during neonate period given reduced exposure

-Meckel’s direrticulum – rare cause of bleeding in neonatal period

Several of the DDxs listed above could be excluded after review of the history and physical exam. Physical exam in this patient excluded anorectal fissure.  The child was 2 weeks old, making persistent swallowed maternal blood highly improbable.  As the patient was a well appearing neonate NEC and malrotation were also unlikely.  Normal stooling made Hirschsprung less likely.  Her age made intussusception, infectious colitis, and Meckel’s less likely.  This left food protein allergy, most commonly due to cow’s milk.  But there was a problem: I remembered asking the mother about the child’s diet, and she had reported that the infant was exclusively breastfed.  How could cow’s milk be a causal factor in a breast fed infant?

Literature review: 

As it turns out, many of the proteins consumed by mothers are passed onto their infants and can cause food protein-induced proctitis/colitis in which the only symptom in infants under 2 months of age is blood in the stool.  A small study of 95 breastfed infants presenting with only bloody stool found that elimination of specific proteins in the maternal diet or through use of extensively hydrolyzed casein-based formula resolved the bleeding within 72 to 96 hours.  65% of the infants were found to be sensitive to cow’s milk, 19% to egg, 6% to corn, and 3% to soy.  This proctitis/colitis, as the name implies, only induces an inflammatory response in the rectum and distal sigmoid colon.  At least half of the infants manifesting this condition are breast fed.  The symptoms will usually resolve by one year of age with the elimination of the offending protein, and most of these children can go on an unrestricted diet with no further problems.  Interestingly, this reaction does not appear to be IgE-mediated, so routine food allergy testing is not recommended.

Take home points:

-With blood in stool, must have wide differential

-If child otherwise well, with other dangerous conditions ruled out, can send stool culture and discharge home with trial of elimination of most common offending agents

-Most common agent is cow's milk, even if the only source is through the mother's breast milk

References:

1. Lake AM. Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr 2000;30 Suppl:S58

2. Odze RD, Wershil BR, Leichtner AM, Antonioli DA. Allergic colitis in infants. Journal of Pediatrics 1995;126(2):163-170.

Submitted by Steven Hung (@DocHungER), PGY-2

Faculty reviewed by Joan Noelker

Salicylate Toxicity with Normal Anion Gap Acidosis?

Clinical Scenario:

A teenager with no significant past medical history presents to an outside hospital with tachypnea, nausea, vomiting, and altered mental status. There is no history of illness preceding today and the parents do not believe there was any ingestion.  The patient appears to be tiring from extreme tachypnea, so is intubated and transferred to your ED for further management, where new labs were drawn, including an ABG and BMP.  Sodium is 151, potassium 3.7, chloride 128, bicarbonate 8, which is an anion gap of 15. ABG shows pH 6.9, pCO2 44, pO2 268, bicarbonate 8. 

Clinical Questions:

In a patient with a normal or near normal anion gap metabolic acidosis, do you still have to worry about toxic ingestions?

Should a patient with suspected salicylate toxicity be intubated and placed on mechanical ventilation to prevent respiratory failure from fatigue?

Photo: Wiki Commons

#FOAMed Digest No. 8: Thank You Sir, May I Have Another?

In the spirit of demonstrating how FOAM resources can reinforce resident curriculum, I thought for this installment of #FOAMed digest we would do something a little different and highlight FOAM resources that build on the topics and discussions from conference last week.  For those of you who didn't make it, the conference run down from last week:

             GI core content: esophagus and stomach
             Trauma Case Conference: Traumatic cardiac arrest in the blunt trauma patient 
                                                           Traumatic cerebrovascular injury
             Key papers in critical care
             Navigating the politics of innovation
                .... and a little on cognitive overload

For those of you who want to solidify and expand your knowledge,  you need not wait for tommorrow's review.  Here are some FOAM resources to help you do just that:

Disorders of the esophagus and stomach: Medical school taught you to memorize buzzwords and basics of management for disorders of the esophagus and stomach, but the FOAM world can expand

on this background and sometimes teach you to think critically about management decisions.  Here are some good FOAM resources on the Upper GI bleed:
              Who can I send home?  An oldie but goodie - a review from our own journal club on risk stratification for patients presenting with a GI bleed.
               Here is a critical review by EM Lyceum of upper GI bleed management including PPIs, octreotide in variceal bleeds, and conclusions from the good old NG lavage.  Some of things we do are really not that evidence-based.

Dr. Wessman's review of key article in critical care touched on GI also, recommending that we all read  this article published in NEJM, and reset our transfusion goal to 7 in the absence of massive hemorrhage.

And here is a link to the Scott Weingart video on Blakemore placement shown in conference. 

Traumatic Arrest:  Let's see if we can learn about things being done a little differently ... and prehospital -  Listen to this emcrit podcast  on management of a patient in traumatic arrest with Irish Road Racing doctor and RAGE team member, John Hinds.  Be sure to read the commentary, because there is an excellent discussion/debate bringing up important considerations for management of traumatic arrest.

Traumatic arrest patients usually do not need meds to facilitate intubation, but as an aside last week one of our trauma colleagues brought up whether we should be using ketamine instead of etomidate

Photo credit: http://inkrose98.deviantart.com/art/Car-Crash-2-254652116

when intubating trauma patients (especially hypotensive ones) in our ED.   I highly recommend this critical review posted last week by the SGEM about ketamine's undeserved bad reputation.  You might just make it your go-to in your next trauma patient even if you suspect intracranial pathology.

What blood products should we be giving to our patients?  A recent body of research from the THOR consortium (Traumatic Hemostasis and Oxygenation Research which includes St. Louis Children's Hospital PICU attending Phil Spinella), suggests whole blood.  Here is a link to the THOR website and articles of interest published by the consortium.

Last week during conference we asked the FOAMed world via twitter for input on CPR in traumatic arrest.  The response was largely negative.  Steve Carroll of @embasic mentioned potential use of REBOA.  For those of you unfamiliar with this device here is a description of the procedure and current evidence regarding its use from the Hennepin County site HQMeded.  If you are still interested, here is  an amazing story recounted on emcrit of prehospital REBOA use for a pelvic fracture. 

And finally... if you still have not watched Cliff Reid's talk on Making Things Happen on leading a resuscitation, do it now.  You will not regret it.

Traumatic vertebral artery injury: If you need a basic review of the talk given by our surgery colleagues, you can read the East Guidelines on Blunt Cerebrovascular Injury.  If you are wondering about the data on the sensitivity of CTA for detection of blunt cerebrovascular injury, you can listen to a podcast by the SGEM here.  Finally, our own blog took on the subject of whether vascular imaging is mandated in the presence of a cervical seatbelt sign, read what we had to say here.   

Navigating the politics of innovation: When I think about what I like about FOAMed, it is that it is a a bottom --> up innovation.  As we learned from Dr. Andrew Knight's talk last week, one of the barriers to dissemination of innovation is top-down decision making with the expectation of bottom-up use.  This is important when thinking about how to effect culture change, but also useful when thinking about managing patient expectations.  I think two good reads on how to talk to patients regarding management decisions are this article in Wired about David Newman and the NNT as a method for data translation, and the "Ed in the ED" blog as a discussion forum on difficult patient conversations.

Wild Style, the epitome of quick-thinking-calm-under-pressure

... and a little on Cognitive Overload : I highly recommend this lecture from Air Force pararescuer Mike Lauria on enhancing cognition and critical decision making in acute care that was shared on the emcrit blog.   Take a Deep Breath.


Enjoy,
Maia Dorsett (@maiadorsett), PGY-3

EKG Challenge #3 Case Conclusion - Mind your p's and K's.

You are working on a busy night in TCC when an elderly lady is brought in by EMS with a complaint of dizziness. The paramedic looks a bit more stressed than you expect for the average old lady with a case of the dizzies and rightly so. As he reports her vital signs, you are shocked to hear that her HR has been steadily below 30 with a systolic blood pressure in the 80s and you’re even more shocked to hear that she’s awake! She reports feeling generally weak and thinks she has the “stomach flu”. As the nurses get down to business placing the patient on the monitor and obtaining IV access, the tech hands you this EKG.

You note the absence of P waves, widened QRS and prominent T wave. You place the patient on an external pacer and run through your differential. Did she overdose on her antihypertensives? Is she having an MI? Does she have heart block? Something else?

You ask your nurse to get a whole blood potassium and give the patient calcium gluconate as you set up for internal pacing. As you’re ready to pass the pacer, you hear that her whole blood potassium is nearly 7. You aggressively treat her hyperkalemia with insulin/dextrose, albuterol, IV fluids and give renal a call. To your relief, her pulse and BP improve dramatically.


Given the importance of recognizing the EKG changes of acute hyperkalemia (indeed, you will save a life by doing so), you decide to take a moment to review the breadth of EKG findings associated with hyperkalemia, the sensitivity/specificity of these findings, and a little about the electrophysiology of why these changes happen.

EKG findings of hyperkalemia: Remember, Hyper-K is the syphilis of EKGs.
Classic EKG findings of hyperkalemia are peaked Twaves, QRS widening and prolongation of the PR interval [Ref 1]. But beware, these classics are not the only EKG abnormalities observed in hyperkalemia! As serum potassium increases, p wave amplitude decreases until p waves disappear entirely and intraventricular, fascicular and bundle branch blocks can occur in severe hyperkalemia. At extremes, QRS widening becomes so pronounced and a “sine-wave” pattern develops and eventually deteriorates to VF and asystole. It is important to note that while common and widely recognized, T waves can appear reassuringly normal in a patient with LVH and chronically inverted lateral T waves to have “pseudonormalization” of their T waves during an acute hyperkalemic episode.

But what about sensitivity and specificity of EKG changes as a rapid assessment for hyperkalemia? Unfortunately, they are not great. A retrospective case study found a sensitivity of only 52% for ANY EKG change in hyperkalemia [Ref 2]. Additionally the presence of new or resolving peaked T waves was not significantly associated with serum potassium concentration. When evaluating an EKG with a prominent T wave it is important to remember than other important disease processes can induce tall T waves, including acute MI and benign early repolarization (BER) [Ref 3]. Eventhough the T waves are tall in all these conditions, there are some morphological differences that can help you distinguish between them:

Figure Modified from Reference 3 with additional tracings

 - Normal T waves are symmetric. The amplitudes are usually greatest in leads II and V4, are greater in men than women, and decrease with age. Generally accepted upper limits of normal T-wave amplitude are 0.50 mV in the limb leads and 1.0 mV in precordial leads.

- Hyperacute T waves of acute MI:The T waves are typically broad, prominent, and asymmetric (can sometimes be symmetric). The T waves are often associated with reciprocal ST segment depression in other leads. The R wave also increases in amplitude and the J point (end of QRS and beginning of ST segment) may be elevated.

- Peaked T waves of hyperkalemia: Often described as tall, peaked, symmetric T waves. With further progression of hyperkalemia, the T wave tends to become taller with eventual QRS complex widening. Sometimes in severe hyperkalemia with QRS complex widening, there may also be some ST elevation that simulate an infarction pattern. It has also been observed that a terminal slur in the QRS complex or an S wave in lead I or V6 without gross QRS widening is commonly associated with hyperkalemic T waves.

- Benign Early Repolarization (BER): This is a variant of the normal ECG, found in people of all ages, but more common in young men. In BER, there is "(1) ST-segment elevation; (2) upward concavity if the initial portion of the QRS complex; (4) widespread or diffuse distribution of ST-segment elevation on the ECG; and (6) relative temporal stability." (Ref 3). Click here for a  review by Amal Mattu on the differences between EKG findings of BER and endocarditis. 

Unfortunately, many of the discussed features above are not exclusive to certain conditions. These T wave changes can also been seen in LVH, pre-excitation syndromes, bundle branch block, and acute pericarditis. When evaluating an ECG, the physician must also consider age, comorbidities, and presenting complaint and overall clinical picture.


Throwback to Medical School: Why does hyperkalemia result in a peaked T on the EKG?

First, let’s think a little bit about potassium. The normal extracellular potassium concentration (what we ask the lab guys to measure) is around 4 – 4.5mEq/L, but this represents only a tiny fraction of total body potassium as 95% is intracellular. The kidneys take the lead in potassium regulation, with the gut getting rid of only about 10%.

If we shift our focus over to the cardiac myocyte in particular we’ll remember that potassium and sodium are the major role players. Potassium is concentrated intracellularly and sodium is hanging out extracellularly. The good old Sodium-Potassium pump is keeping the peace, the peace being a negative resting membrane potential. The concentration gradient across this membrane plays an important role in maintaining this action potential. As the extracellular potassium concentration increases, the resting membrane potential gets less negative. This is important because the resting membrane potential (the flat part before the action potential gets going) directly impacts the number of voltage-gated sodium channels available to generate the action potential. Fewer sodium channels means slower impulse conduction and prolonged membrane depolarization. How do we see this? QRS widening, P wave prolongation, PR widening.

What about the peaked T?! This is where it gets a little weird. Remember that the T wave represents repolarization, or phase 3 of the cardiac action potential when the calcium channels have closed and the potassium channels remain open. For some crazy reason “Not well understood” per the literature, increased extracellular potassium leads these channels to pump more potassium out of the cell, shortening repolarization, producing the much talked about peaked T. Check out the Figure below from Parham et al. (Ref 4).

Fig. 3 Illustration of a normal action potential (solid line) and the action potential as seen in the setting of hyperkalemia (interrupted line). The phases of the action potential are labeled on the normal action potential. Note the decrease in both the resting membrane potential and the rate of phase 0 of the action potential (Vmax) seen in hyperkalemia. Phase 2 and 3 of the action potential have a greater slope in the setting of hyperkalemia compared with the normal action potential.


Take home points:
- While EKG findings are common, they have poor sensitivity and specificity for hyperkalemia.
-Common findings include peaked T waves, PR prolongation, P wave flattening, QRS widening all eventually producing sine wave ECG, Vfib and asystole.
-Underlying conduction abnormalities and history of CKD can impact the EKG morphology at various K levels.
- The "tall T wave" has a differential diagnosis. T wave morphology can give you important clues to your diagnosis.

Submitted by Sara Manning, PGY-3 and Steven Hung, PGY-2.
Faculty Reviewed by Doug Char

References:
[1] Amal Mattu, William J Brady and David A Robinson. “Electrocardiographic Manifestations of Hyperkalemia,” American Journal of Emergency Medicine. 2000; 18: 721-729.

[2]Montague, B et al, “Retrospective review of the Frequency of ECG changes in Hyperkalemia,” Clinical Journal of the American Society of Nephrology. 2008. (3); 324-330.

[3]Somers MP, Brady WJ, Perron AD, Mattu A. “The prominent T wave: Electrocardiographic differential diagnosis.” American Journal of Emergency Medicine 2002;20(3):243-251

[4] Walter A Parham, Ali A Mehdirad, Kurt M Biermann and Carey S Fredman. “Hyperkalemia Revisited.” Texas Heart Institute Journal. 2006; 33(1): 40 – 47