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

Brought in by Ambulance, #3: My leg hurts! Well, here's your C-collar...

Case Scenario:
You are doing your second supervisor ride along and hoping that your white cloud of peace will disperse so you can see some St. Louis action. You are called emergently to MVC vs. two pedestrians. On arrival to the scene, you find one patient on the ground with an open fracture of his leg.  ABC’s are fine. The patient notes the car came around the corner and hit his leg. He remembers everything, and complains only of his leg hurting. A quick examination of his neck reveals no midline tenderness and no pain with range of motion. However, secondary to his distracting injury a C-collar was placed. As the ambulance drives away with the patient, you wonder what the evidence behind C-collar use is, and if it was really necessary to place a collar in this gentleman without any neck pain.

Current EBM evidence:
Most of the recommendations on c-collar use are based on opinion and tradition. The American Association of Neurological Surgeons and the Congress of Neurological Surgeons Joint Commission have made recommendations; however, most of these recommendations are based on Level III evidence. Unfortunately, there is a paucity of evidence for the implementation and continued use of C-spine collars. In fact, a Cochrane review in 2007 noted there wasn’t a single prospective RCT on c-collar use.

Currently, most of the validated evidence we have for spinal cord protection is in terms of imaging. Both the NEXUS criteria and the Canadian C-spine rules have been validated, and are used by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons Joint Commission on their official recommendations on the management of acute spinal cord injury. The NEXUS criteria and the Canadian C-spine rules have been applied in the pre-hospital setting; those who will require imaging should therefore be placed in a cervical collar for C-spine stabilization.

Nexus Criteria:
No imaging if all of the following are true:
●No posterior midline cervical tenderness
●Normal level of alertness
●No evidence of intoxication
●No abnormal neurologic findings
●No painful distracting injuries

There has never been any control trial on patients examining if C-collars actually stabilize the spine. There have been a multitude of trials on volunteers and models, many of which have contradicting results. While some studies show that C-collars do stabilize the neck, others show that collars may actually increase neck movement. In a controversial study done by Hauswald et.al, un-immobilized patients in Malaysia had better neurological outcome than similar patients who were immobilized in New Mexico. While this study compared no immobilization to full spinal immobilization (and therefore flawed in the analysis), the overall philosophy that second injury due to transport is rare as the forces are weak compared to the force required to injure the spinal cord may still hold true.

While the evidence to support the use of C-collars is weak, there is an increasing amount of evidence noting potential risks and morbidity associated with C-collar use. While the goal of C- collars is to reduce movement of the cervical spine and protect the spinal cord, a few case studies have shown that forcing a neck into “anatomical position” can actually cause spinal cord injury, particularly in patients with ankylosing spondylitis. A study on cadavers noted that extrication collars caused an increased degree of separation between vertebrae when there is a dissociative injury.

In a systematic review done by Sparke et. al, there have been a few studies noting an increase of ICP pressure with the placement of C-collar. It is estimated that risk of increased ICP is 35.8%. It is thought that the increased ICP is secondary to pressure placed on the jugular veins (causing venous congestion); however there is no real knowledge of the etiology of the increased ICP. Sparke et. al also did a review of the risk of tissue ulcerations secondary to C-collar placement. A review of 14 studies showed the incidence of hospital acquired pressure ulcers from a C-collar range from 23.9-44%. While the review noted that the measurement of pressure from the C-collars was highly variable between studies, pressures from C-collars can be quite elevated (up to 150mmgHg). The review also notes that none of the studies examined in the review were randomized control trials.

The immobilization of the neck can cause increased difficulty in airway management and protection. It is often much more difficult to intubate a patient that has been placed in a C-collar. Patients who do not require intubation are at an increased risk of aspiration with vomiting.

Additionally, once a C-collar has been placed, the patient may be more likely to undergo imaging to have his C-spine cleared. In a study done by Kim et. al., children who were placed in a C-collar were much more likely to undergo imaging to clear the c-spine (56.6 vs 13.4%) and were much more likely to be admitted to the hospital 41.6 vs 14.3%). This can have serious implications on the length of stay on the patient, as well as overall cost to the patient and the hospital.

While the evidence supporting C-collars is minimal, the potential consequence of movement causing additional spinal cord injury is so severe that much better evidence will be required before a change can occur. However, there is the potential to try and reduce the number of C-collars placed, especially on low-risk individuals. In a prospective study done by Rose et. al, it was found that physical exam (no neuro deficit and no midline tenderness or pain with range of motion) was over 99% sensitive with a 99% negative predictive value. In this study, all patients with GCS greater than or equal to 14 were attempted to be clinically cleared regardless of ethanol level or presence of distracting injuries. All patients received CT imaging of their spine, even if they were clinically cleared. Of the 464 patients with distracting injuries that were clinically cleared, only one was found to have C-spine fracture (C2 lateral mass). It should be noted that of the 544 patients without distracting injury that were cleared clinically, one was also found to have a C-spine injury (C6 lamina and C7 superior facet).

Take Home:
-No prospective randomized study on use of c-collars
-There are possible adverse outcomes with use of c-collars (eg increased ICP, pressure ulcers)
-There is evidence supporting clearing c-collar clinically, even with distracting injuries

References:
1. Walters BC, Hadley MN, Hurlbert RJ, Aarabi B, Dhall SS, Gelb DE, Harrigan MR, Rozelle CJ, Ryken TC, Theodore N; American Association of Neurological Surgeons; Congress of Neurological Surgeons. Guidelines for the management of acute cervical spine and spinal cord injuries: 2013 update. Neurosurgery. 2013 Aug;60 Suppl 1:82-91.
2. Sundstrøm T, Asbjørnsen H, Habiba S, Sunde GA, Wester K.. Prehospital Use of Cervical Collars in Trauma Patients: A Critical Review. J Neurotrauma. 2014 Mar 15;31(6):531-40.
3. Hauswald M, Ong G, Tandberg D, Omar Z. Out-of-hospital spinal immobilization: its effect on neurologic injury. Acad Emerg Med. 1998 Mar;5(3):214-9.
4. Ben-Galim P, Dreiangel N, Mattox KL, Reitman CA, Kalantar SB, Hipp JA. Extrication collars can result in abnormal separation between vertebrae in the presence of a dissociative injury. J Trauma. 2010 Aug;69(2):447-50.
5. Papadopoulos MC, Chakraborty A, Waldron G, Bell BA. Lesson of the week: exacerbating cervical spine injury by applying a hard collar. BMJ. 1999 Jul 17;319(7203):171-2.
6. Sparke A, Voss S, Benger J. The measurement of tissue interface pressures and changes in jugular venous parameters associated with cervical immobilisation devices: a systematic review. Scand J Trauma Resusc Emerg Med. 2013 Dec 3;21:81.
7. Leonard J, Mao J, Jaffe DM. Potential adverse effects of spinal immobilization in children. Prehosp. Emerg. Care 16, 513-518.
8. Rose MK, Rosal LM, Gonzalez RP, Rostas JW, Baker JA, Simmons JD, Frotan MA, Brevard SB. Clinical clearance of the cervical spine in patients with distracting injuries: It is time to dispel the myth. J Trauma Acute Care Surg. 2012 Aug;73(2):498-502.

Submitted by Melissa Kroll, PGY-2.
Faculty Reviewed by Phil Moy.

Oh Shacka - Dantrolene for Neuroleptic Malignant Syndrome?

You are in a community emergency department when a middle-aged woman is brought in by her husband for worsening confusion over the last two days.  The charge nurse comes and asks if it should be a stroke page because the patient has “slurred speech”.   You rush into the room, NIHSS card in hand ready to wheel the patient off to CT and are confronted by a worrisome picture.  The patient is burning man re-incarnate - She is laid out on the stretcher with all 4 limbs stiff and outstretched, is febrile to 39.4 and tachycardic to the 140’s.  Her blood pressure is normal. She can answer some of your questions (says she has trouble “saying” words) but is definitely confused.  You think that this might be good old sepsis, but something about her sets your tox-sense tingling …. and you ask her husband immediately for a medication list which contains a number of pro-serotonergic anti-depressants and a single anti-psychotic. 

Could this be serotonin syndrome?  Could this be NMS?  You  send off a CK level (which comes back at > 1000), initiate a sepsis work-up, get a head CT and phone a friend.  Your tox expert by phone helps you with this by asking a single question:  Well, does she have myoclonus  (SS) or is she rigid (NMS)?  Rigid has it, and you create a mnemonic for future reference:

Oh SHACKA this patient might have NMS:

Now that you think that this is like NMS, how is it best treated?  You have memorized for your board exams that bromocriptine is the treatment for NMS, but your toxicology friend reminds you that bromocriptine can worsen the symptoms of serotonin syndrome [1], and given this patient’s med list and possible mixed-picture, may not be the best idea. What about dantrolene?  Well, what about it?

Clinical question:  What is the mechanism of action for dantrolene? Does dantrolene have any proven effectiveness in the treatment of neuroleptic malignant syndrome? 

Literature Review: 
    Neuroleptic malignant syndrome is a rare, and potentially life-threatening adverse reaction to anti-dopaminergic anti-psychotic medication.  There are multiple established diagnostic criteria - the Levenson Criteria and DSM-IV - that are largely described by the mnemonic above. 

from Guzofski et. al. [2]

The exact pathophysiology of NMS is unknown, but the muscle rigidity (which looks a lot like Parkinsonism) is thought to be secondary to inhibition of dopamine-mediated signalling (as such this can also occur in Parkinson's patients in the setting of dopamine withdrawal).  This muscle rigidity can cause muscle

damage and subsequent rhabdomyolysis.  The hyperthermia may be the result of either (or both) the muscle rigidity or by direct effects of dopamine D2-receptor blockade on the hypothalamus.  Hyperthermia can become life-threatening, and thus the treatment, in addition to cessation of the offending agent, is to pharmacologically relax and cool down the patient.

Bromocriptine, a dopamine agonist, is sometimes used.  But as discussed above, if there is a serotinergic component to the patient's presentation, this could worsen serotonin syndrome.  Benzodiazepines and IV fluids are the mainstay of supportive care. 

            Dantrolene, the mainstay of treatment for malignant hyperthermia, has also been proposed and has been used for the treatment of NMS.  Dantrolene acts as a direct skeletal muscle relaxant by blocking calcium release from the sarcoplasmic reticulum [3].  As such, the main side effect is muscle weakness, but no reports of respiratory or airway compromise have been reported (at least in healthy volunteers) [3].  Given this mechanism, it is unclear why it would be helpful for NMS.  Like most things in toxicology, the majority of data regarding the efficacy (or lack thereof) of dantrolene in the treatment of NMS comes from case series and case reports. In 2007, a study published in Critical Care attempted to pool the results of 271 Case Reports to assess the effectiveness of dantrolene for the treatment of NMS [4].  From these 271 case reports, the authors collected patient data including gender, age, diagnosis, triggering medication, dosage, time of incidence, diagnostic criteria met, other laboratory parameters and whether the patients received dantrolene therapy alone, dantrolene + other medications, only other medications, or only supportive care.  The "other medications" and the scope of "supportive care" was not specified (or necessarily the same) between case reports.  The outcomes of the study were the following: reported improvement within 24 hrs, complete time to remission and overall mortality.  The authors found that dantrolene monotherapy was associated with a higher likelihood of improvement within 24 hrs and shortest time (9.4 +/- 12.7 days) to complete remission than dantrolene+ other medication, other medication or supportive therapy alone.  If this was not confusing enough (for example, why would dantrolene alone be better than dantrolene+other medication), the dantrolene monotherapy also had an overall higher mortality (16.2% vs. 7.3% for d+other, 8.9% for "other", and 2% for supportive care).  Given the innumerable caveats to pooling the data only from case reports and the difficult to interpret results, it is unclear whether dantrolene therapy is effective, helpful or potentially harmful in the treatment of NMS.  It is possible that patients who received dantrolene who were either 1) not very sick and so got better quickly or 2) very sick, in which case they received other medications (therefore the longer time to remission) or mismanaged by giving dantrolene alone leading to higher overall mortality.

Clinical Takehome: Know your hyperthermic toxidromes because they are not made better with antibiotics.  Regarding NMS, dantrolene has unproven effectiveness but lack of rigorous evidence that it causes harm.  Benzodiazepines and fluids will be your mainstay of treatment, give bromocriptine if you are confident in your diagnosis. Boom shaka laka.

References:
[1]Boyer, E. W., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352(11), 1112-1120.
[2] Peralta, M. D. (2006). Neuroleptic malignant syndrome, with attention to its occurrence with atypical antipsychotic medication: a review. Jefferson Journal of Psychiatry, 20(1), 7.
[3] Krause, T., Gerbershagen, M. U., Fiege, M., Weisshorn, R., & Wappler, F. (2004). Dantrolene–a review of its pharmacology, therapeutic use and new developments. Anaesthesia, 59(4), 364-373.
[4]Reulbach, U., Dutsch, C., Biermann, T., Sperling, W., Thuerauf, N., Kornhuber, J., & Bleich, S. (2007). Managing an effective treatment for neuroleptic malignant syndrome. Crit Care, 11(1), R4.

Submitted by Maia Dorsett [@maiadorsett], PGY-3
Faculty Reviewed by Evan Schwarz [@TheSchwarziee] 

EKG Challenge #3 - A Case of the Dizzies

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.

Interpret the EKG.  What is your differential?  What would you do next?
 
See the case conclusion HERE