More than haldol

Clinical Scenario:

You are working in the ED when you see EMS roll in with the all too common "SNF" patient. An 83 yo M with the alphabet soup of co-morbid conditions. HTN, dCHF, OSA, COPD, V-tach s/p AICD, non IDDM, CKD stage III who presents the the ever ubiquitous chief complaint of altered mental status.   The patient was reported to be "off" by staff at the nursing facility, he was seen by a psychiatrist who was concerned about delirium and advised the patient be reevaluated in the ED.  Upon arrival the patient is AOx3, conversant, and pleasant.  He gets a delirium workup that is fairly unremarkable with the exception of a UA showing weak evidence of UTI. The patient is admitted to the medicine but boards in the busy ER overnight.  During his stay he becomes agitated and uncooperative.  He is now AOx1 (person) and cannot be redirected.  His thoughts are incoherent and the patient will not return to his gurney.  You make the decision to administer IV haloperidol.  The patient relaxes, is able to be redirected. 

A few hours later several family member approach you about the decision to use Haldol. They are educated, with a large amount of experience in the psychiatric field.  They ask if you are aware of the neurotoxic effects of haloperidol and emphasize the use of newer atypical antipsychotics which are neuroprotective.  You admittedly aren't that up to date on this topic, but assure them that haloperidol is used frequently at our institution for acute delirium.  You perform a brief literature review. 

Limited literature review:

You read the reference provided by the family member, which is an editorial from an online psychiatry journal citing that 28 different studies have shown neurotoxic effects of older antipsychotics based on animal models, cell culture, and post-mortem human tissue.  The author instead calls for the use of the 9 atypical antipsychotics to be used as they have reported neuroprotective properties such as neurogenesis. (1) The main difference you note is that the author comes from the perspective of using antipsychotics for long term care, while in the ED we want safe and rapid control for delirium or agitation in the short term. 

Haldol structure, wikipedia.org

In your review you find the American Association of Emergency Psychiatry released a consensus statement/guidelines on the treatment of acute agitation in the ED.  

Here are some highlights:
1.       Prior to giving meds consider verbal redirection and nicotine replacement

2.       1^st gen antipsychotics inhibit dopamine and is structurally similar to GABA

3.       When using haloperidol remember it can prolong QT (rare), cause extrapyramidal side effects (possibly as high as 20%,why it is often given with lorazepam which reduces to 6% incidence).

4.       Haloperidol is not FDA approved for IV administration (PO, IM only), although it is commonly administered this way.
5.       Second generation antipsychotics have long been preferred by outpatient psychiatrist for long term management of various psychiatric conditions. 

6.       2^nd gen antipsychotics include:

a.       Olanzapine (Zyprexa), ziprasidone (Geodon), aripiprazole (Abilify) – IM and PO

b.      Risperidone (Risperdal), and quetiapine (Seroquel) – PO only

7.       2^nd gen antipsychotics also antagonize dopamine, but also serotonin as well

8.       There have been very few head to head trials of 2^nd generations versus Haldol.  
a.      However one double blind, placebo study compared both IM olanzapine and IM Haldol for agitation and showed that IM olanzapine reduced agitation significantly more than IM Haldol 15, 30, and 45 minutes following the first injection (2)

10.   Two studies have been conducted comparing PO risperidone and lorazepam versus IM haloperidol and lorazepam.  Data showed similar benefits to both regimens.  However, both were conducted at Psychiatric emergency centers and not typical EDs. (3)
11.   Their final recommendation for agitation associated with delirium:

a.       Oral 2^nd generation

b.      Oral 1^st generation

c.       IM 2^nd generation – olanzapine 10 mg or ziprasidone 10- 20 mg

d.      IM or IV 1^st generation

12.   Peak concentration for PO meds is fairly similar to IM with exception of olanzapine (6h for PO)

13.   IM meds peak concentration is approx. 15-45 minutes for both classes

The consensus statement does not discuss the “neurotoxic” effects of haloperidol previously mentioned in the editorial citing non-living human studies. 

Take home points:

So which agent do you use? The theoretical neurotoxic effects of haloperidol seems to be more of a potential issue for long term psychiatric disease.  ED concerns should focus on causing extrapyramidal side effects or excess sedation.  The data for 2^nd generation antipsychotics use in the ED  is limited, however there is some data to show their efficacy in controlling of acute agitation. 

Expert Commentary:

Dr. Holthaus Comments: Nice summary Dr. Miller!  The one additional consideration I wanted to share about carte blanche 5/2 (Haldol/Ativan) for all comers is the potential clinical “down time” (ranging anywhere from 3-6+ hours depending on comorbidities/age/habitus/co-ingestants) and its impact on prolonging ED LOS while “waiting” for the patient to recover enough to allow a formal psychiatric interview and then to make the final disposition decision (all compounding time in series). 

     Potential alternate ways around this in my opinion are to 1) Ask psychiatry to evaluate them while acutely psychotic (if available/present and safe) then administer the 5/2 and get labs/etc. allowing an earlier psychiatric disposition to be made as medical etiologies are ruled out in parallel.  2) If psychiatry is unavailable or it's unsafe then consider giving something else that has less back side down time but can achieve a similar up front clinical effect: adequate onset time/calming-sedating enough to allow restraints/seclusion/redirection and at least 1-2 hours for lab-imaging acquisition/results, is safe (and titratable if more is needed), and allows a potentially earlier metabolic window for mental clarity/off set that is amenable to a formal psychiatric interview.  This is in my mind, preferably midazolam (or diazepam if no midazolam) with an IV onset less than 5min, can be quickly/safely titrated to effect, and can also be given IM.  Granted bezodiazepines can potentially worsen delirium but generally if they’re shorter acting and less likely to be hanging around this makes this less likely to persist.  I agree benzos do not directly address their psychosis like the anti-psychotics but my counter-argument would be that these could be administered later if still needed.  Don’t get me wrong, I have no problem with 5/2 but I like it best after a disposition is made (and it also carries the added advantage of making the nurses happier in regards to behavior management and puts people out of their misery while waiting forever for a bed).  However, I will think twice now after Dr. Miller’s analysis and consider more second generation use if using antipsychotics for acute agitation management.

Submitted by Christopher Miller,  PGY-2
Edited by Louis Jamtgaard, PGY-3 @Lgaard
Faculty Reviewed by Chris Holthaus

References:

1) http://www.currentpsychiatry.com/specialty-focus/schizophrenia-other-psychotic-disorders/article/haloperidol-clearly-is-neurotoxic-should-it-be-banned/194f71df8139c102e153b6839a066424.html

2) Wright P, Birkett M, David SR, et al. Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. Am J Psychiatry. 2001;158:1149-1151.

3) Wilson et al. The psychopharmacology of agitation: consensus statement of the american association for emergency psychiatry project Beta psychopharmacology workgroup. West J Emerg Med. 2012, 13(1), 26-34.

Additional References:

Currier et al. J Clin Psychiatry. 2004, 65(3), 386-94.

Wilson et al.  Despite expert recommendations, second-generation antipsychotics are not often prescribed in the emergency department.  J Emerg Med. 2014, 46(6), 808-13.

Hot bullet, dirty wound?

Clinical scenario:  You are working in the emergency department when a car pulls up, dropping off an otherwise healthy male who has suffered a gun shot wound (GSW) to left shoulder.  He says that he was in the rear passenger seat driving around with friends and "minding his own business" when he heard multiple gun shots.  He felt immediate pain in his left shoulder.  A full exam reveals two wounds to the left shoulder and nowhere else.  The patient has bilateral breath sounds and his left arm is neurovascularly intact.  X-rays demonstrate no pneumothorax, but the patient has a comminuted left scapular fracture:

You update the patient's tetanus,  administer pain control, and call Orthopedics.  The orthopedist on call asks that the patient receive prophylactic antibiotics. An ardent defender of antibiotic stewardship, you wonder if antibiotics are necessary.  Is it possible that the heat exposure that comes with firearm discharge sterilizes a contaminated bullet?  Do prophylactic antibiotics decrease the chance of infection?

Literature Review:
Question 1:  Does the heat of firearm discharge sterilize a contaminated bullet?

Image source: http://pixshark.com/

A study by Thoresby and Darlow from 1967 simulated GSWs  using a series of gelatin models, contaminated bullets, and contaminated overlying “clothes”[1].   There were 3 “series” of testing. The first fired bullets contaminated with Serratia marcescens into a gelatin block. The second fired sterile bullets shot through pieces of military fatigues inoculated with Serratia overlying the entrance or exits side of the gelatin (with a piece of foil in between the cloth and gelatin to avoid direct transmission). The third fired bullets through an aerosolized cloud of Serratia in front of the gelatin block.  Significantly, there was bacterial growth along the bullet track in the gelatin in all three series (except for their respective controls). This suggests that bullets are not sterilized by heat upon discharge of the gun. Furthermore, it demonstrates that bacteria were drawn into the cavitation space via vaccum forces in series in which inoculated cloth was placed on the exit site.

EKG Challenge No. 10 Case Conclusion: Heartbreaker

You are working in the emergency department when you get a pre-arrival for "abdominal pain, hypotensive".  You follow EMS into the room when they arrive and are confronted with an elderly female who appears very pale and quite sick.  Per the paramedics and the patient,  she has had upper abdominal pain, nausea and weakness for the last two days.  Her initial blood pressure is 80/60 with a heart rate of 112, and you start working her up for all the badness that causes hypotension and abdominal pain in the elderly.  Everyone gets cracking on some IV access,  and you head for the ultrasound to help you better evaluate the cause of this patient's hypotension.  You start with the cardiac views of your RUSH exam, and see this:

 

Given these findings, you order an EKG:

On review of the EKG you note ST elevation that is most prominent in V2 and V3 (although it can also be seen in I, II, V4, V5) without significant reciprocal ST depression:

Given the apical akinesis and ST elevation in the precordial leads, the patient is sent for an emergent cardiac catheterization, which identifies no coronary artery disease.  

Normal Coronary arteries

                                        
The cardiologist notes apical akinesis of the patient's left ventricle, which during systole resembles a Japanese pot for catching an octopus.   He diagnoses the patient with Takatsubo's Cardiomyopathy.

EKG Challenge No. 10: This one looks sick ...

You are working in the department when you get a pre-arrival for "abdominal pain".  You follow EMS into the room and are confronted with a middle-aged to elderly female who appears very pale and quite sick.  As she is placed on the monitor, you speak with her and she endorses some diffuse abdominal pain and nausea for the last two days.  Her initial blood pressure is 80/60 with a heart rate of 112, and you start working her up for all the badness that causes hypotension and abdominal pain in the elderly.  Everyone gets cracking on some IV access,  and you head for the ultrasound to help you better evaluate the cause of this patient's hypotension.  You start with the cardiac views of your RUSH exam, and see this:

 Given these findings, you order an EKG:

What is your differential?  What do you do next?  Please leave your comments.  Click here to read the case conclusion.

Thank you to Dr. Chris Holthaus for the echo video.

Is it in? Well, flush the line

Clinical Scenario: 

You are working in the TCC when an ESRD patient presents with fever and hypotension, RN’s are able to attain a small IV, but knowing the patient will need abx and IVF, you prepare to place a central venous catheter (CVC). Under ultrasound guidance you place a triple lumen catheter.  You aspirate dark red blood and are confident it is venous. The follow up chest xray shows a cvc with an awkward course to the heart. You send off a blood gas, and are setting up to tranduce the line.  While waiting, you wonder is there another method to confirm CVC placement?

Literature Review:
Approximately three million CVC’s are placed every year in the US. Complication rates vary by source but the most commonly cited rate is around 10%, including arterial puncture, hematoma, pneumothorax, chylothorax, arrhythmia and air embolus . The use of ultrasound during CVC placement has reduced the complication rate to around 3%.  (1) In 2010 Liu et al described the novel use of bedside ultrasound (2D) and a saline flush,to confirm catheter placement in the SVC. The method involves flushing 10ml saline throught the most distal CVC port, while performing a cardiac ultrasound either in the subxiphoid or parasternal view. 

Horowitz et al 

Flushing of the saline causes immediate turbulence in the right atrium and ventricle, that is easily viewable on ultrasound.(1) Prekker et al also reported on using this technique with success, adding that saline can be flushed immediately after venous puncture but before the guide wire or CVC is placed. (2) In 2014 Horowitz et al performed a prospective blinded study testing whether flushed saline under cardiac US could accurately confirm femoral line placement.  In their study, all patients had an arterial line and a femoral CVC placed, then a blinded EM physician performed subxyphoid cardiac ultrasound while a provider flushed either the arterial line or venous CVC. The EM physician would either say "venous" or "arterial" based on the presence of a + flush sign (See image) . The study results showed 100% sensitivity and 90.3% specificity. (3) In other words, the presence of +flush test was always associated with venous CVC. There were zero incidences of an arterial flush being identified as venous. However, approx 10% of venous CVC's were incorrectly identified by negative flush test (specificity 90.3%). 

Take home points:
Rapid assessment of CVC placement can be achieved by saline flush and cardiac ultrasound. A +flush sign has been shown to be 100% sensitive for a venous CVC. However more studies are needed at this time as most literature is focused on case series, with only one prospective randomized study. 

Submitted by Louis Jamtgaard, PGY-3 @Lgaard
Faculty Reviewed by Deb Kane

References

1) Liu et al. Evaluation of proper above-the-diaphragm central venous catheter placement: the saline flush test. Am J Emerg Med. 2011 Sep;29(7):842.e1-3. doi: 10.1016/j.ajem.2010.06.025. Epub 2010 Sep 25.

2) Prekker ME Rapid confirmation of central venous catheter placement using an ultrasonographic "Bubble Test".Acad Emerg Med. 2010 Jul;17(7):e85-6. doi: 10.1111/j.1553-2712.2010.00785.x.

3) Horowitz R¹The FLUSH study--flush the line and ultrasound the heart: ultrasonographic confirmation of central femoral venous line placement. Ann Emerg Med. 2014 Jun;63(6):678-83. doi: 10.1016/j.annemergmed.2013.12.020. Epub 2014 Jan 15.

Hippocratic Medicine No. 2: Between a Rock and a Hard Place

Clinical Scenario:
You are working in the emergency department on a typical busy day. There are fifteen boarding patients waiting for their bed upstairs, another thirty-plus in the waiting room.  You walk into a room to assess a 75 yo female with confusion. Family says that she has been confused: forgetting to put on one shoe, unable to finish her crossword puzzles, and no longer able to bowl without throwing a gutter ball. Amazingly, the urinalysis is negative. Concerned that she may have had a subacute stroke, you order a head CT without contrast which shows “a large amount of vasogenic edema concerning for neoplasm.” The radiologist recommends a follow up MRI for further evaluation. The consulting neurologist instead asks for a Head CT (HCT) with contrast, reasoning they would not be the admitting service if the patient is found to have a mass. Neurosurgery recommends an MRI to evaluate for a suspected mass, and you learn that it will be 8 hours before the patient can go to MRI. With the pressure of the waiting room, the full rooms, and the boarding patients in the ED, you reluctantly order the HCT with contrast, which shows a right parietal neoplasm. Having rarely, if ever, ordered HCT with contrast, you ask- What are the indications for HCT with contrast in a patient with subacute onset of focal neurological deficits?

Literature Review:
The American College of Radiology (ACR) publishes evidence-based guidelines to help direct the efficacious use of radiologic studies. Their 2012 Appropriateness Criteria for Focal Neurologic deficits discusses the use of HCT vs. MRI. HCT without contrast is recommended for initial evaluation in this case. While contrast can provide additional information, “some pathology is difficult to visualize with CT under any circumstances,” and “MRI is more sensitive than CT for detecting primary and secondary brain lesions and for defining extent of disease.” Additionally, MRI spares the patient exposure to ionizing radiation and “provides information that…approaches the accuracy of a neuropathologic diagnosis” [1].  Specifically, for our patient with subacute onset of neurological deficits, the ACR recommends a HCT without contrast for acute screening. The highest rated imaging for further evaluation is an MRI head with and without contrast, rated an 8/9 for “usually appropriate.” A HCT with contrast was rated a 4/9, for “may be appropriate,” with the typical indication being inability to get an MRI. This patient had no contraindications to MRI and should not have had the contrasted HCT. Eight hours later she had a MRI to more appropriately plan her operative course. 

Orolingual Angioedema follow r-tPA administration: Pathophysiology and Risk Assessment

Clinical Scenario:  You are working a typical shift in the emergency department when a right-handed middle aged female with a history of hypertension presents with right sided hemiparesis which had an acute onset 45 minutes prior to arrival in the emergency department.  Her head CT is negative for acute ICH, her FSBS is normal, and after running through the contraindications to tPA administration, she is deemed a tPA candidate.  When discussing the risks and benefits of tPA, you include the risk of life-threatening, including intracranial, hemorrhage.  The patient and her husband express understanding and opt for tPA administration.   Approximately 40 minutes into the infusion, the patient begins to develop lip swelling.  She has no wheezing and no urticaria. Steroids and diphenhydramine are administered without effect.  You review her medications and see that she takes lisinopril. After she develops significant tongue swelling and airway compromise, you decide rapidly that this patient needs her airway secured.  Fortunately, the airway is secured smoothly.

As your heart rate makes its way from 220 to resting, you search on google scholar for "angioedema" and "alteplase".  (Honestly) having never heard of alteplase-induced angioedema until the Neurology resident murmured it over the phone as you update him on the patient's status, you have lots of questions about this sphincter-tightening syndrome. What is the incidence of this potential dramatic complication?  Are there any risk factors for developing it?  Should you be counseling patients about this risk as part of your shared decision making regarding alteplase administration?

Literature Review:
Most emergency physicians are well-aware of the potential complications of ACE-inhibitor induced angioedema.  ACE-inhibitors can lead to angioedema by inhibiting the break down of bradykinins, which are potent vasodilators.  Interestingly, alteplase plays into this pathway as well:

Image source: Hill et. al. (Reference 1)

As per its name "Tissue Plasminogen Activator", tPA is a serine protease that cleaves plasminogen into plasmin.  Plasmin then cleaves thrombus-bound fibrin, leading to the fibrinolytic effect desired in acute ischemic stroke.   However, plasmin also can activate the complement cascade and kinin pathway leading to increased bradykinin levels, and therefore vasodilation and risk of angioedema [1].  If angioedema develops, it tends to do so within an hour of receiving r-tPA and resolves within 3-24 hrs [2].

So what is the overall incidence of this complication?  Several retrospective and prospective studies have examined this question in predominantly the Caucasian and Asian populations.  A recent retrospective study and systematic review calculated an overall incidence of 1.9% (95% CI 1.3 - 2.6) with a relative risk of 12.9 if a patient is already taking an ACE inhibitor (95% CI 4.5 - 37) [3].

Image Source: Lin et. al. (Reference 3)

It is important to note that the majority of these patients did not require intubation for airway protection (for example, out of 5 patients developing angioedema in a retrospective review of 559 patients, only one required intubation) [3].  No deaths from airway compromise were reported in any of the studies.

In our own institution (Barnes Jewish Hospital), we took care of approximately 240 patients who received r-tPA for stroke in 2014  (110 administered IV tPA in the emergency department + 130 "drip and ship" patients admitted directly to the inpatient wards).  Among these 240 patients, there were no reported cases of angioedema.

Clinical Takehome:  Orolingual angioedema is a rare complication of r-tPA administration.  However, patients who take ACE inhibitors are at significantly increased risk.  It is therefore important to specifically ask about ACE inhibitors in patients who are tPA candidates and include this in your discussion of potential rare complications of tPA administration in this subset of patients.  Patients who receive r-tPA should have close monitoring for this complication during and in the first hour following the infusion.  Finally, secure the airway as soon as the angioedema begins to progress from lips to tongue, because no one wants to perform a surgical airway in a patient who just received r-tPA.

Submitted by Maia Dorsett (@maiadorsett), PGY-3
Faculty Reviewed by Peter Panagos

References:
1.  Hill, M. D., Barber, P. A., Takahashi, J., Demchuk, A. M., Feasby, T. E., & Buchan, A. M. (2000). Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke. Canadian Medical Association Journal, 162(9), 1281-1284.
2.  Lekoubou, A., Philippeau, F., Derex, L., Olaru, A., Gouttard, M., Vieillart, A., & Kengne, A. P. (2014). Audit report and systematic review of orolingual angioedema in post-acute stroke thrombolysis. Neurological research, 36(7), 687-694.
3.Lin, S. Y., Tang, S. C., Tsai, L. K., Yeh, S. J., Hsiao, Y. J., Chen, Y. W., ... & Jeng, J. S. (2014). Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior
angiotensin‐converting enzyme inhibitor use. European Journal of Neurology, 21(10), 1285-1291.
4. Correia, A. S., Matias, G., Calado, S., Lourenço, A., & Viana-Baptista, M. (2015). Orolingual Angiodema Associated with Alteplase Treatment of Acute Stroke: A Reappraisal. Journal of Stroke and Cerebrovascular Diseases, 24(1), 31-40.

Assess the pipes, Carotid VTI and fluid responsiveness

Clinical Scenario:

You are working in the ED when a 75 yo F hx of CHF, DM presents with fever, cough, and hypoxia and hypotension. You are concerned for sepsis with presumed pneumonia as the source. You initiate volume resuscitation and start broad spectrum antibiotics.  Your  patient's BP initially responds to fluids, but now after your 3L your patient is still hypotensive. You perform bedside US of the inferior vena cava (IVC) with equivocal findings. You wonder, is there another way to perform rapid bedside ultrasound for volume responsiveness?  You remember a recent paper about carotid velocity time integral (VTI) , and begin to investigate

Literature review:
It seems that predicting volume responsiveness is the never-ending tale in critical care medicine, as numerous methods have been proposed over the past several years with varying degrees of success. With the expansion of ultrasound, measuring IVC collapsibility has been one of the more popular methods utilized in the emergency department. However, measuring the IVC can often be limited by body habitus, excessive intra-abdominal gas, respiratory variation, and operator experience. (1) Measuring IVC collapsibility at greater than 50% has been shown to correlate with a CVP of less than 8mmhg, and a lower CVP has been associated with volume responsiveness, but a higher CVP does not exclude volume responsiveness. (1) A recent paper by Marik et al described the novel use of Carotid VTI and passive leg raise (PLR) as a marker of volume responsiveness in hemodynamically unstable patients.  The benefit of  PLR is that it produces a hemodynamic response similar to a 200-300ml bolus, is relatively easy to perform, and is rapidly reversible.

 Courtesy Ultrasound Podcast

 By combining PLR with dynamic ultrasound, Marik et al sought to create the ideal non-invasive method of determining volume responsiveness.  They demonstrated that a 20% increase in carotid VTI had a sensitivity and specificity of 94% and 86% respectively for predicting volume responsiveness (a patient with a stroke volume increase of greater than 10% was considered volume responsiveness). This study was limited in that it was nonrandomized, nor blinded, and complete data was available for only 34 patient. (2)  Mike and Matt from the Ultrasound podcast provide an excellent review and explanation on how perform VTI that you can find here @ Ultrasound podcast

Take home points:
Studies have shown that only 50% of hemodynamically unstable patients are volume responders. Appropriate fluid resuscitation in sepsis is associated with improved outcomes, while excessive fluid administration is associated with increased ICU LOS and mortality. Determining fluid responsiveness is difficult but VTI combined with PLR appears to have both a high specificity and sensitivity for predicting volume responsiveness.  More studies will be needed to demonstrate validity of this method. 

Submitted by Louis Jamtgaard, PGY-3 @Lgaard
Faculty Reviewed by Deb Kane 


References

1)Nagdev A et al . Emergency department bedside ultrasonographic measurement of the caval index for noninvasive determination of low central venous pressure. Ann Emerg Med. 2010 Mar;55(3):290-5. doi: 10.1016/j.annemergmed.2009.04.021. Epub 2009 Jun 25.

2) Marik P et al. The use of bioreactance and carotid Doppler to determine volume responsiveness and blood flow redistribution following passive leg raising in hemodynamically unstable patients.
Chest. 2013 Feb 1;143(2):364-70.

EKG Challenge No. 9 Case Conclusion: I'll take chest pain with a side of syncope

You are working a typical shift in the ED when an otherwise healthy 33 yo male presents with 2 hours of chest pain. He reports  ~3-4 episodes of vomiting over past few days as well as myalgias & subjective fevers.  Two hours prior to arrival, he awoke with mid-sternal chest pain.  The chest pain is burning in quality, non-radiating, worse with deep inspiration. He denies any current nausea or SOB, prior history of similar episodes or calf swelling or pain. You are general unimpressed, attributing his pain to musculoskeletal strain, gastritis, GERD or viral syndrome.  You then get the EKG:

Your eyes are immediately drawn to leads V1 and V2 which demonstrate the incomplete RBBB and coved-shaped ST elevation typical of  Type 1 Brugada syndrome:

Coved-type ST elevation of Type 1 Brugada - Don't you just want to ski down it?

On further history, the patient denied any recent syncope or pre-syncope but reported having 5 prior syncope episodes throughout his lifetime (most during adolescence and last episode 2 years ago on an airplane). These episodes were without any associated prodrome, such as dizziness, blurred vision, chest pressure or palpitations. He reports that his mother’s cousin died suddenly at the age of 40 while mowing the lawn and had no known cardiac disease.The EKG finding was discussed with EP fellow and close follow-up was arranged. Since patient was in ED for likely unrelated complaint, his risk of sudden cardiac death was thought to be relatively low.

Brugada syndrome (BS) is often the result of a Sodium channelopathy but since many patients are found without mutations, it is now also believed to be influenced by gender, drugs, and an imbalance in autonomic tone (and unidentified underlying genetic mutations may not yet have been identified). The overall prevalence of Brugada type 1 is estimated to be 0.05%. It is most common in Southeast Asia but has been reported in every ethnic group. BS is typically seen in those younger than 50 years of age.

Diagnosis of Brugada syndrome requires both the characteristic EKG findings plus at least 1 other risk factor for sudden cardiac death:
                     - documented V-fib or polymorphic V-tach
                     -  a family history of sudden cardiac death in someone < 45 years old
                     -  an EKG demonstrating Type I morphology in family members
                     - inducibility of arrythmmias on programmed electrical stimulation
                     - history of syncope or nocturnal agonal respirations.

The unifying morphology is incomplete RBBB with ST elevation (2 mm at the J-point) in the right precordial leads, occasional with 1st degree AV block.  This morphology can occur spontaneously or be brought on by Na-channel blockade (see EKG challenge No. 6 on Na-channel blockade - inducing medications). There are three separate characterized morphologies of Brugada syndrome:

Image source: Li and Behr (Reference 1)

1) Type 1: RBBB with coved type ST-elevation and T wave inversion.
2) Types 2 : "Saddle back" ST elevation without coving  or T wave inversions
3) Type 3: morphology of Type 1 or Type 2 but with less than 2 mm of ST elevation.

In studies in both Europe and Japan, the estimated prevalence of Type 1 Brugada EKG findings (as seen in our patient) in an otherwise healthy population is  .05 - 0.1%.   The saddleback type is much more common (estimated prevalence of  2-6%),  but is also much less specific or predictive of true Brugada syndrome.  Some proportion of those recorded as "Type 2" Brugada are likely benign J-point elevation.

In one of the largest registries of Brugada patients to date (Probst et al. 2010), 1029 patients across 4 European countries with EKG findings of Type1 Brugada syndrome were followed over median duration of 31.9 (14 to 54.4) months.   A small proportion of these patient has been asymptomatic, but a fair proportion had a history of sudden cardiac death (SCD) or syncope.  Over this time period, 51 cardiac events occurred (44 patients received appropriate ICD shocks, 7 died suddenly).  The annual cardiac event rate per year was the following based on initial presentation was:

                                History                         Annual cardiac event/year
                                 SCD                                           7.7%
                                 syncope                                    1.9%
                                 asymptomatic                         0.5 %

 Based on this information, the annual risk of death in my patient would be somewhere between 0.5 – 1.9%.

The only treatment proven to be effective for Brugada syndrome is implantation of an Automated Internal Cardiac Defibrillator (AICD). AICD implantation is a Class I recommendation for any patients who have suffered aborted cardiac death and for any patients who have suffered seizure, syncope, or had nocturnal agonal respirations without an obvious noncardiac cause. Implantation of an AICD is otherwise considered a Class II recommendation in the following patients: 1.) those who have had a syncopal, seizure, or agonal respiration event AND who had only drug-induced (via Na-channel blocker) Type 1 Brugada EKG, 2.) Asymptomatic patients with a family history of SCD and a spontaneous OR drug-induced Type 1 Brugada EKG.

Lastly, in the setting of acute illness and Brugada pattern findings, make sure to replete electrolytes (if patient has GI illness), and treat fevers with antipyretics. You should also investigate to see if patient is on any possibly exacerbating drugs such as tricyclics, psychotropics, or other sodium channel blockers and consider discontinuation of these drugs.

So what happened with out patient?  He returned three weeks later for elective ICD implantation. He was discharged home the following day.

Take Home Points: In conclusion, any patient seen in the ED for recent syncope, seizure or (of course) sudden cardiac arrest and has Type 1 Brugada EKG findings should absolutely be admitted to high-risk telemetry bed. Otherwise discharge with close follow-up can be considered but should ideally be arranged with careful discussion with patient, primary physician, and a cardiologist.

Submitted by Anah Ali, PGY-4 and Kevin Cullison, PGY-3
Edited by Maia Dorsett (@maiadorsett), PGY-3
Faculty Reviewed by Douglas Char

References:

1.Li A, Behr ER. Brugada Syndrome: an update. Future Cardiology. 2013. 9(2): 253-271.

2.Marx JA, Walls RM, et al., eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. Philadelphia, PA: Mosby/Elsevier; 2010

3.Probst V, et al. Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry. Circulation. 2010. 121(5): 635-43.

4.Vohra J. Diagnosis and management of Brugada Syndrome. Heart Lung Circ. 2011 Dec;20(12):751-6

5.Wylie JV, Garlitski AC.Brugada syndrome. In: UpToDate, Downey BC (Ed) UpToDate, Waltham, MA (Accessed January 15, 2015)

6. Hermida, J. S., Lemoine, J. L., Aoun, F. B., Jarry, G., Rey, J. L., & Quiret, J. C. (2000). Prevalence of the Brugada syndrome in an apparently healthy population. The American journal of cardiology, 86(1), 91-94.

7.  Miyasaka, Y., Tsuji, H., Yamada, K., Tokunaga, S., Saito, D., Imuro, Y., ... & Iwasaka, T. (2001). Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan. Journal of the American College of Cardiology, 38(3), 771-774.

Want to learn more?:

Read more about Brugada syndrome here at Life in the Fast Lane and listen to Amal Mattu's excellent episodes 1 and 2.

For more about Can't Miss EKG findings in Syncope, read the case conclusion to EKG challenge No. 4 here. 

Break on Through to The Other Side: On Management of Acute Right Heart Failure

Clinical Scenario:  You are working in TCC when EMS brings in a patient with respiratory distress.  She is a middle aged-female breathing 40 times per minute,  with bilateral crackles, and edema from her legs all the way up her anterior chest.  You think to yourself, "acute heart failure" and place the patient on BiPAP.  You are about to order the nitro drip when you see a subcutaneous infusion device anchored to the patient's abdomen.  As you examine it more closely, you realize that it is a infusion of not insulin as you first thought, but Treprostinil, a pulmonary vasodilator.  You look the patient up and find that she has a history of severe pulmonary hypertension secondary to interstitial lung disease.  Shortly after being put on BiPAP, the patient's blood pressure tanks from a SBP of 150 to 70.  You realize, in a panic, that this patient does not have bread and butter left heart dysfunction but acute right heart failure.   What do you do now?

Clinical question:  What is the pathophysiology of right ventricular failure?  Given this pathophysiology, what are the treatment goals and therapeutic options when managing acute right ventricular failure?

Literature Review:  
Just like the left ventricle is adapted to be the work horse of systemic perfusion, the right ventricle has an anatomy and physiology uniquely suited to its function of optimizing venous return and providing sustained low-pressure perfusion through the lungs [1].  Unlike the left ventricle which generates high pressure pulsatile flow, the right ventricle (RV) ejects blood quasi-continuously from the right atria to the lungs.  This sustained low pressure perfusion is possible because of the low resistance of the pulmonary vascular bed, intimately coupling RV output with pulmonary vascular resistance.  

RV failure (RVF) [defined as reduced cardiac output and an elevated right ventricular filling pressure] has many underlying etiologies [2].  As emergency medicine residents, we can think of acute right heart failure in two situations that have specific and reversible causes: acute inferior MI and massive PE.  While these certainly are important etiologies for RVF,  it is also important to realize that RV failure is the most common cause of death in patients with preexisting pulmonary hypertension [2].  Indeed, in most cases, acute RV failure is a combination of established pulmonary vascular disease complicated by an acute derangement such as pneumonia, sepsis or ARDS [3]. Unlike the relatively reversible causes of acute RV failure such as MI or PE,  management of RV failure in the face of underlying pulmonary arterial hypertension (PAH) is a much more complicated business.  Indeed, pulmonary hypertension patients experiencing acute heart failure necessitating inotropic or vasoactive drugs have a documented mortality of 40-60% [4].

When it comes to management of acute right heart failure in the emergency department, there are couple things to acknowledge right off the bat: 
                                       

 1. Right ventricular failure is pathophysiologically different from left ventricular failure:  In the ED, we are comfortable taking care of left ventricular failure or fluid overload in the emergency department.  Acute volume overload?  BiPAP, nitro, diurese.  Cardiogenic shock?  Pick your inotrope.  While severe left ventricular failure leads to back-up and subsequent right heart dysfunction because of pulmonary congestion, the cause and management of respiratory distress in this patient population is different.  Remember, right ventricular failure causes peripheral but not pulmonary edema and fluid balance is a lot trickier to discern. 

2. Not all Right Ventricular Failure is the same, and treatment depends largely on whether there is an afterload problem:  Primary RV failure is usually due to a problem with the lungs.  Across a broad cohort of critically ill patients, pulmonary hypertension and RV dysfunction are going to occur in the setting of 1) PE; 2) pre-existing pulmonary hypertension; 3) ARDS; 4) sepsis.  In the instance that RV failure is primarily cardiac (i.e. acute MI), there is no impedance to forward flow in the system and so fluid management is more straightforward in that usually increased RV preload is necessary to maintain systemic perfusion [3].  However, in the setting of an acute increase pulmonary vascular resistance/right ventricular afterload, increased fluid resuscitation leads to RV dilation with nowhere for the fluid to go (i.e. not able to get through the pulmonary vasculature to the left atrium and improve stroke volume in the left ventricle).  This not only leads to increased free wall tension in the RV and resultant ischemia, RV dilation can lead to impingement of LV filling because of dynamic septal bulging and further drop in systemic blood flow.  The further drop in systemic blood flow leads a decreased RV perfusion and worsening RV failure.  The end of this viscous cycle?  Death.

With these thoughts in mind, the management of acute right heart failure depends on the underlying etiology, but generally can be broken down into four main treatment goals [1,2,3]:

a. Alleviate Congestion and Manage Preload: As discussed above, fluid balance is tricky in patients with RVF because you want just enough preload to promote an efficient fill but not too much which will cause the RV to stretch further and impede LV function.  This is where physical exam and bedside cardiac US can help you.  Peripheral edema > consider diuresis. 

b. Decrease Right Ventricular Afterload: RV afterload is determined by the pulmonary vascular resistance (PVR), which may be altered chronically in pulmonary hypertension (such as interstitial lung disease or COPD) or acutely in conditions such as pulmonary embolism or ARDS.  Because it is adapted to sustained perfusion in a low pressure system, the RV is poorly adapted to acute increases in PVR.  The first line treatment for decreasing pulmonary vascular resistance is to correct hypoxia, hypercarbia and acidosis by treating the underlying exacerbating condition (i.e. pneumonia, sepsis).  If these measures have failed, you can consider pulmonary vasodilators such as NO or prostacyclin.  In the ED, the most commonly inhaled pulmonary vasodilators such as nitric oxide and flolan (esoprostenol) can be initiated.  NO is significantly more expensive and can only be used in ventilated patients.  Flolan can be used with a mask temporarily but only a small amount is reaching the pulmonary vasculature.

Image source: Reference 3

c. Optimize cardiac output:  Restoration of right ventricular contractility is one of the mainstays of treatment of acute right heart failure.  According to several recent reviews, low dose dobutamine  (in the realm of 5-10 mcg/kg/min) is the treatment of choice[1,2,3,4].  There are not any large clinical studies in patients with acute right side heart failure secondary to pulmonary hypertension.  However, in a dog model of RV failure secondary to acute rise in pulmonary artery pressures, dobutamine restored cardiac output, increased heart rate and restored arterial pressure better than norepinephrine [5].   

d. Optimize Right Ventricular Perfusion: Other than inferior MI, where restoration of coronary perfusion requires PCI or lysis, maintaining right ventricular perfusion is accomplished through support of the systemic blood pressure.  The ideal vasoactive medication would increase systemic arterial pressure and RV contractility without increasing pulmonary vascular resistance.  Norepinephrine seems to be the agent of choice for this purpose. In one small study of 10 ICU patients with right ventricular dysfunction in context of septic shock, norepinephrine infusion was associated with increased myocardial oxygen delivery by maintaining systemic perfusion pressure, although pulmonary vascular resistance was also slightly increased [6].  Low dose vasopressin has also been considered an alternative agent for this purpose [3]. Vasopressin use does make some physiologic sense, as there are no V1 receptors in the lung, so PVR will not increase.

So what if you gave the nitroglycerin?  Nitroglycerin is very useful in management of left heart dysfunction/hypertensive urgency because it functions to reduce afterload and preload, thus improving pulmonary edema and promoting forward-flow through the system.  But what is the effect of this intervention on the right heart?  In right heart dysfunction in acute MI, nitroglycerin is contraindicated because forward flow is preload dependent and nitro administration can lead to significant hypotension.  If there is a right heart afterload problem,  multiple studies of patients with stable  pulmonary hypertension have  demonstrated that at low doses (30 mcg/min), nitroglycerin can have a beneficial vasodilatory effects on the pulmonary vasculature [7,8,9].  However, given the risk of increased hypotension and decreased right ventricular perfusion during acute RVF, some may argue that nitroglycerin is relatively contraindicated and has the potential for harm. 

Clinical Takehome:  The right ventricle reacts poorly to acute rises in pulmonary vascular resistance.  RVF may be seen in a wide-variety of critically ill patients in the ED, including those with prexisting pulmonary hypertension, PE, sepsis, ARDS, and acute MI. Acute management of most right heart failure involves optimizing preload, maximizing RV perfusion and contractility, and decreasing afterload.  You should probably throw the cardiac US probe on these patients to evaluate the cause of their hypotension and the effectiveness of your interventions.  Even with aggressive intervention, acute RV failure carries a poor prognosis. 

Submitted by Maia Dorsett (@maiadorsett), PGY-3
Faculty Reviewed by Enyo Ablordeppy and Brian Fuller

References:
1. Mebazaa, A., Karpati, P., Renaud, E., & Algotsson, L. (2009). Acute right ventricular failure—from pathophysiology to new treatments. In Applied Physiology in Intensive Care Medicine (pp. 261-272). Springer Berlin Heidelberg.
2. Hoeper, M. M., & Granton, J. (2011). Intensive care unit management of patients with severe pulmonary hypertension and right heart failure. American journal of respiratory and critical care medicine, 184(10), 1114-1124.
3. Green, E. M., & Givertz, M. M. (2012). Management of acute right ventricular failure in the intensive care unit. Current heart failure reports, 9(3), 228-235.
4. Sztrymf, B., Günther, S., O’Callaghan, D. S., & Humbert, M. (2014). Acute Right Heart Failure in Pulmonary Hypertension. In The Right Heart (pp. 261-275). Springer London.
5. Kerbaul, F., Rondelet, B., Motte, S., Fesler, P., Hubloue, I., Ewalenko, P., ... & Brimioulle, S. (2004). Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure*. Critical care medicine, 32(4), 1035-1040.
6. Schreuder, W. O., Schneider, A. J., Groeneveld, A. B., & Thijs, L. G. (1989). Effect of dopamine vs norepinephrine on hemodynamics in septic shock. Emphasis on right ventricular performance. CHEST Journal, 95(6), 1282-1288.
7.Cockrill, B. A., Kacmarek, R. M., Fifer, M. A., Bigatello, L. M., Ginns, L. C., Zapol, W. M., & Semigran, M. J. (2001). Comparison of the Effects of Nitric Oxide, Nitroprusside, and Nifedipine on Hemodynamics and Right Ventricular Contractility in Patients With Chronic Pulmonary Hypertension*. CHEST Journal, 119(1), 128-136.
8.Morley, T. F., Zappasodi, S. J., Belli, A., & Giudice, J. C. (1987). Pulmonary vasodilator therapy for chronic obstructive pulmonary disease and cor pulmonale. Treatment with nifedipine, nitroglycerin, and oxygen. CHEST Journal, 92(1), 71-76.
9.  Brent, B. N., Berger, H. J., Matthay, R. A., Mahler, D., Pytlik, L., & Zaret, B. L. (1983). Contrasting acute effects of vasodilators (nitroglycerin, nitroprusside, and hydralazine) on right ventricular performance in patients with chronic obstructive pulmonary disease and pulmonary hypertension: a combined radionuclide-hemodynamic study. The American journal of cardiology, 51(10), 1682-1689.

EKG Challenge No. 9: A generally unimpressive case of chest pain ...

You are working a typical shift in the ED when an otherwise healthy 33 yo male presents with 2 hours of chest pain. He reports  ~3-4 episodes of vomiting over past few days as well as myalgias & subjective fevers.  Two hours prior to arrival, he awoke with mid-sternal chest pain.  The chest pain is burning in quality, non-radiating, worse with deep inspiration. He denies any current nausea or SOB, prior history of similar episodes or calf swelling or pain. You are general unimpressed,  but of course get the EKG anyway:






















What do you think is going on?  What would you do next?  Click here to read the Case Conclusion.