An Imperfect Science: Diagnosis of CSF Shunt Malfunction

Clinical scenario: Your patient is a 20 yo male with a history of VP shunt placement as a child for obstructive hydrocephalus. He was brought to the emergency department by his family because of decreased responsiveness over the past day. On arrival to the emergency department, he has aniscoria (L greater than R), no verbal response, and withdraws his extremities symmetrically. An emergent non-contrast head CT shows no change in ventricular size from prior CT scan one year prior and a VP shunt series demonstrates no evidence of fracture of the shunt line. Clearly, something is critically wrong with the patient, but is it his VP shunt to blame?

Clinical question: What is the spectrum of shunt complications? What is the sensitivity of clinical exam and various imaging modalities in detecting shunt malfunction?

Literature Review: There are multiple forms of CSF shunts, the most common of which is the Ventriculo-Peritoneal shunt (as opposed to ventriculo-atrial & ventriculo-pleural) which shunts CSF into the peritoneal cavity. A CSF shunt is composed of a proximal catheter, reservoir, valve and distal catheter [1]. The proximal catheter starts in the frontal horn of the lateral ventricle and exits through a burr hole to connect to the reservoir which is located in the subcutaneous tissue (this is what is accessed when neurosurgery taps a shunt). Flow from the reservoir to the distal catheter is regulated by a one way valve. Programmable shunts allow for the setting of a specific pressure above which fluid drains through a valve. This is sometimes adjusted in one direction or another for VP shunt patients who experience headaches, lightheadedness or other symptoms related to the pressure when their evaluation is negative for obstruction, infection etc. For VP shunts, the distal catheter is then tunneled into the peritoneum

Image Source: Cancer Research UK / Wikimedia Commons

As an emergency physician, one must be familiar with the presentation and diagnosis of shunt complications because they are relatively common; incidence of VP shunt failure is close to 40% at one year and 50% at two years from initial shunt placement, at least in the pediatric population where it has been most actively studied[2]. There are multiple types of shunt malfunctions leading to increased intracranial pressure, including but not limited to:

1. Mechanical Obstruction - Most proximally, the catheter can be obstructed by blood, debris or in-growth of the choroid plexus. The catheter position within the lateral ventricle can also migrate. Kinking or fracture along the catheter track at any point will also lead to shunt failure, as will distal obstruction which can occur when the catheter adheres to the omentum or erodes into intra-abdominal organs.

2. Infection - This often presents with shunt failure, and occurs most commonly within 6 months of placement due to intraoperative contamination with skin flora. The overall incidence of shunt infection is common (8-10%).

3. Ventricular Loculations - Loculations within the ventricle can create non-communicating pockets of CSF that are not drained by the VP shunt. If these grow, they can cause symptoms of hydrocephalus.

At least in very young children, depressed level of consciousness, nausea/vomiting, headache, irritability, and fluid tracking along the shunt site are highly predictive of shunt malfunction (see positive LR below). However, none of these clinical signs and symptoms are adequately sensitive to rule out shunt malfunction in their absence [2,3]. Some signs like abdominal pain/peritonitis are less commonly seen, but more highly predictive of shunt infection.

LR, Sensitivity, & Specificity for clinical signs and symptoms associated with shunt failure in two large pediatric studies

In addition to overall clinical exam and picture, radiographic imaging plays a central role in the emergency department evaluation of VP shunt malfunction.

CT scans are the most commonly used imaging modality to evaluate for shunt malfunction. While enlarged ventricles (when compared with prior imaging studies) are the canonical feature of shunt obstruction, other CT findings correlated with increased intracranial pressure include effacement of the cortical sulci, loss of the basal cisterns and periventricular edema due to transependymal CSF absorption [4]. Based on multiple retrospective pediatric studies using surgical shunt revision as a "gold standard", CT has a sensitivity for shunt malfunction of anywhere between 53% to 92% [4,5; see Table below]. In one small retrospective study of 174 adults evaluated for shunt malfunction with both shunt series and head CT, head CT had a sensitivity of only 52%, a specificity of 78% and negative predictive value of 88% for shunt malfunction [6]. This study only included patients who had had shunt series performed, so it may have underestimated the sensitivity of CT by excluding patients who were evaluated with CT alone. While this is a wide range of estimations for sensitivity, the important point is that a negative head CT does not completely rule out a shunt malfunction.

Shunt series radiographs are used to identify mechanical shunt defects such as shunt discontinuity or kinking. Studies in both children [4,7] and adults [6] support the conclusion that although the yield and sensitivity of radiographic shunt series is very low (see Table below), it is not zero. Shunt series rarely (~ 1-2%) detect abnormalities not identified on initial CT that prompt surgical revision. Therefore, shunt series are still indicated in the evaluation of potential shunt malfunction.

Table 2 from Boyle and Nigrovic, 2015. Reference 4.

In some cases, more commonly in pediatric institutions, MRI protocols have been instituted to reduce cranial radiation in children [4,8,9]. This has been made possible in part due to advances in MRI technology that have allowed for development of "ultra-fast" or Rapid MRI protocols that can acquire images in a span of ~ 1-4 minutes. Rapid Cranial MRI has been studied in comparison to CT for detection of ventricular shunt malfunction in the pediatric population, and appears to be comparable at least with respect to specificity and accuracy [8]. When considering using MRI in place of CT, the provider should be aware that some VP shunts have a programmable shunt valves that can be affected by the magnetic force of the MRI machine and may need to be readjusted after the exam. For this reason, it is common practice to obtain coned-down radiographs of a small indicator usually located near the proximal portion of the distal catheter to identify the setting prior to MR and then again after MR. If the programmed setting has changed, the neurosurgeon can use a magnet to reprogram the setting. The radiologist uses an indicator that looks like a clockface to determine the settings. 

Image source:
Take home Points: Malfunction and infection are common complications of CSF shunts. No single clinical exam finding or image study is sufficient to rule out shunt malfunction, and clinical management should take into account patient history, overall clinical picture, diagnostic data and neurological assessment.

Submitted by Maia Dorsett @maiadorsett
Faculty Reviewed by Peter Panagos and Richard Griffey

1. Wallace, A. N., McConathy, J., Menias, C. O., Bhalla, S., & Wippold, F. J. (2014). Imaging Evaluation of CSF Shunts. American Journal of Roentgenology, 202(1), 38-53.2.Garton, H. J., Kestle, J. R., & Drake, J. M. (2001). Predicting shunt failure on the basis of clinical symptoms and signs in children. Journal of neurosurgery, 94(2), 202-210.3. Piatt Jr, J. H., & Garton, H. J. (2008). Clinical diagnosis of ventriculoperitoneal shunt failure among children with hydrocephalus. Pediatric emergency care, 24(4), 201-210.4. Boyle, T. P., & Nigrovic, L. E. (2015). Radiographic Evaluation of Pediatric Cerebrospinal Fluid Shunt Malfunction in the Emergency Setting. Pediatric emergency care, 31(6), 435-440.
5.Lehnert, B. E., Rahbar, H., Relyea-Chew, A., Lewis, D. H., Richardson, M. L., & Fink, J. R. (2011). Detection of ventricular shunt malfunction in the ED: relative utility of radiography, CT, and nuclear imaging. Emergency radiology, 18(4), 299-305.
6. Griffey, R. T., Ledbetter, S., & Khorasani, R. (2007). Yield and utility of radiographic “shunt series” in the evaluation of ventriculo-peritoneal shunt malfunction in adult emergency patients. Emergency radiology, 13(6), 307-311.
7. Desai, K. R., Babb, J. S., & Amodio, J. B. (2007). The utility of the plain radiograph “shunt series” in the evaluation of suspected ventriculoperitoneal shunt failure in pediatric patients. Pediatric radiology, 37(5), 452-456.
8.Boyle, T. P., Paldino, M. J., Kimia, A. A., Fitz, B. M., Madsen, J. R., Monuteaux, M. C., & Nigrovic, L. E. (2014). Comparison of rapid cranial MRI to CT for ventricular shunt malfunction. Pediatrics, 134(1), e47-e54.
9. Koral, K., Blackburn, T., Bailey, A. A., Koral, K. M., & Anderson, J. (2012). Strengthening the argument for rapid brain MR imaging: estimation of reduction in lifetime attributable risk of developing fatal cancer in children with shunted hydrocephalus by instituting a rapid brain MR imaging protocol in lieu of head CT. American Journal of Neuroradiology, 33(10), 1851-1854.10.

A Balancing Act

It’s another busy day in the ED when an elderly female comes in from triage with fever, cough, and new oxygen requirement. Even before the patient comes back you are concerned for pneumonia with sepsis. The patient is tachycardic and hypotensive with a shock index greater than one. You institute early antibiotics and fluids and systematically begin to aggressively resuscitate her. The patient requires nearly four liters of normal saline before her blood pressure stabilizes. Your attending suggests that your liberal use of normal saline will induce a hyperchloremic metabolic acidosis, and perhaps you should have used lower chloride containing fluid, like lactated ringers. You perform a brief literature review on the topic of balanced resuscitation using lower chloride containing fluids.

Literature Review:
Strong Ion Difference (Kishen et al)
The main difference between normal saline and balanced fluids, such as lactated ringers, is the strong ions difference (SID), that is, the difference between cations (e.g. Na+) and anions (e.g. Cl-).  Normal saline has a SID of zero (equal parts Na+ and Cl-) where as Lactated ringers has a SID of 28, which is due to the additional cations such as Ca+, K+, and lower anion (Cl-) content.  Importantly, normal plasma SID content ranges from 38-44mmol/L, therefore balanced fluids more closely approximates physiologic SID.  As the SID becomes narrower, as is the case with significant normal saline administration, a non-gap metabolic acidosis develops. [1]

The use of normal saline in large volumes has been shown to produce a reliable drop in serum pH as demonstrated by Scheinraber et al, in a study among patients undergoing elective surgery. [2] However, the development of a hyperchloremic acidosis is of unclear clinical significance. Early animal models in dog kidneys demonstrated that compared to non-chloride fluids, chloride containing solution led to renal vasoconstriction and decline in glomerular filtration rate. Similarly a randomized, double blind crossover study in healthy humans demonstrated a significant reduction in renal blood flow and renal tissue perfusion, after the administration of two liters of normal saline compared to low chloride (98 mEq/L) Plasma-Lyte solution. [3] However, the effect of isotonic saline in acutely ill patients is still not as clear. A prospective cohort study among 175 ICU patients demonstrated that higher chloride levels (109.4 vs 115.1mEq) was an independent factor for increased mortality, although a limitation of this study was they could not distinguish the cause of hyperchloremia (iatrogenic, renal dysfunction, or endogenous hyperchloremia) [4]
Traditional and 'balanced' fluid content (
A large retrospective cohort study of critically ill adults with vasopressor dependent sepsis showed lower in-hospital mortality in patients who received balanced (lower chloride) fluids versus isotonic saline, 19.6% versus 22.8% (RR 0.86; 95% CI,0.78-0.94). A limitation of this study was that patients receiving balanced solutions were younger, less likely to have chronic heart and renal failure, and more likely to receive steroids, colloids and invasive monitoring. [5] A 2014 retrospective study in 109,836 patients that met SIRS criteria and received crystalloid fluid resuscitation, showed that low-chloride loads were associated with lower in-hospital mortality. This mortality difference remained even after adjustment for severity of illness and total fluid volume administered. [6]

Similarly, a before and after study by Yunos et al involving 1644 ICU patients, reported the use of chloride-restricted fluids was associated with lower serum creatinine and decreased rates of renal replacement therapy (6 vs 10%) compared to controls. Like the study by Shaw et al, the difference was independent of severity of illness or total fluid volume administered. However, as mentioned by the authors, determining which component of lower-chloride fluid may have led to the observed effect is difficult, as there was simultaneous administration of lower sodium content, as well as increase in the administration of acetate, lactate, and gluconate. Importantly, this study showed no difference in mortality. [7][8]

Take home points: Administration of large volume of isotonic saline is associated with a metabolic acidosis. Animal models have demonstrated decreased renal perfusion with chloride containing fluids. Several retrospective studies indicate that chloride is an independent risk factor for mortality in acutely ill patients. More and more literature in humans seems to indicate that a ‘balanced resuscitation’ may decrease morbidity, and possibly mortality, in patients receiving large volumes of crystalloids as part of their resuscitation.  A single nonrandomized study demonstrated a correlation between low chloride fluids and decreased use of renal replacement therapy. Blinded, randomized, prospective studies are needed to further elucidate this observed effect.

Expert Commentary:

Dr. Schwarz, an Assistant Professor here at Wash U, and both an Emergency Physician and Toxicologist has provided some of his own thoughts on the topic. 

First, I’d like to thank Louis for picking a great topic and generating discussion about a very important subject.  I initially became interested in this topic a few years ago.  Originally, I was much more interested in the mechanism by which normal saline (NS) caused a non-anion gap metabolic acidosis, and that’s when I learned about the strong ion difference and a ‘balanced resuscitation.’  As a full disclosure while I found the pathophysiology really interesting, I initially didn’t think it had much clinical relevance.  However as more investigators have studied this, I’ve come to believe that my initial impressions were incorrect and changed my practice.

 The last time I reviewed the literature, I didn’t see a randomized, controlled trial comparing resuscitation with NS and lactated ringers in the ED.  However I do believe that there are studies out there that are applicable to the ED.  A retrospective study compared patients undergoing elective or emergent general surgery that received either NS or a ‘balanced fluid.’1  Unadjusted mortality and the number of patients developing major complications were higher in the group that received NS; after adjusting with propensity scoring, the mortality was no longer significantly different between the 2 groups.  However, patients that received NS were 4.8 times more likely to require dialysis. In a meta-analysis of patients with sepsis, patients that received a ‘balanced resuscitation’ had a lower mortality than patients receiving NS.2  The trend, however, was not significant.

In a promise to keep this short, I won’t review all the other literature that has been published on this topic and kept the discussion on the 2 articles that I did include short.  I’ll also concede that the literature is not perfect, and as I mentioned earlier, I’m also still waiting for that perfect ED-based study to be completed.  However the cost of NS or a ‘balanced solution’ such as lactated ringers is nearly equivalent.  I’m also not aware of significant complications from administering lactated ringers in most patients. So when the risks, costs, and benefits of implementing a ‘balanced resuscitation’ verses a standard resuscitation with NS are viewed together, I think there is enough evidence to consider changing your resuscitation strategy.

Now like many EDs, lactated ringers is not kept in our department.  It is on shortage but so is NS.  Neither of those are reasons not to use it.  So what do I do? Since I haven’t been able to convince pharmacy to keep lactated ringers in the ED yet, I do my best to guess early on which patients are going to need large-volume resuscitations.  If I think they are going to likely need more than 2-3 liters of fluid, I order additional lactated ringers from the pharmacy when I place their initial orders. In an hour after the patient has received the first few liters of NS, the lactated ringers should be there from the pharmacy.  If they need further resuscitation I can use it or return if they no longer need it.  For those that are interested to read more about this topic, I’d direct you to the upcoming May 2015 edition of Emergency Physicians Monthly. From my understanding, it’s brilliantly written! (Sorry for my shameless plug)

Jamtgaard References:
 [1] Kishen R, Honoré PM, Jacobs R, et al. Facing acid–base disorders in the third millennium – the Stewart approach revisited. International Journal of Nephrology and Renovascular Disease. 2014;7:209-217. doi:10.2147/IJNRD.S62126.
[2] Scheingraber et al. Rapid Saline infusions produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology 1999;90;1265
[3] Chowdhury A et al. .  A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers.  Ann Surg. 2012;256(1):18-24
 [4] Boniatti MM et al.  Is hyperchloremia associated with mortality in critically ill patients? A prospective cohort study. J Crit Care. 2011;26:175–179. doi: 10.1016/j.jcrc.2010.04.013
[5] Raghunathan K, Shaw A, Nathanson B et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis*. Crit Care Med 2014; 42: 1585–91
[6] Shaw A et al.  Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Medicine. 2014;40(12):1897-1905. doi:10.1007/s00134-014-3505-3.
[7] Waikar SS, Saving the Kidneys by Sparing Intravenous Chloride?.JAMA. 2012;308(15):1583-1585. doi:10.1001/jama.2012.14076.
[8] Yunos N et al. Association between a chloride-liberal vs chloride restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA 2012; 308: 1566– 72.

Schwarz References
1. Shaw et al.  Major Complications, Mortality, and Resource Utilization after Open Abdominal Surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012;255:821-829.
2. Rochwerg et al. Fluid Resuscitation in Sepsis. A Systematic Review and Network Meta Analysis. Ann Intern Med 2014;161:347-355.

Submitted by Louis Jamtgaard +Louis Jamtgaard , PGY-3
Faculty Reviewed by Evan Schwarz @TheSchwarziee 

Does cardiac standstill on bedside echo equal 100% mortality?

You’re in the midst of catching up on notes during a hectic overnight shift when out of the corner of your eye you see a stretcher zoom into the trauma bay – with an EMT leaning over the side performing chest compressions. As the team gathers, the paramedics give report. The patient is a middle-aged male, no known past medical history, who was acting normally about half an hour ago when he suddenly collapsed in front of his family. They started CPR within a couple minutes of the patient collapsing, and called EMS. The paramedics continued CPR, placed a supraglottic airway, and placed the patient on the monitor. He has had a slow, organized rhythm without pulse throughout the arrest. He has received several doses of epinephrine without response. The patient has been pulseless for a little over half an hour by the time he arrives. The ED crew takes over CPR, IV access is obtained, and the patient switched over to the ER monitors, which show a slow, wide-complex, relatively disorganized rhythm. The patient shows no signs of life. Your attending physician calls for the ultrasound, and calls out to the team that if the bedside echo shows cardiac standstill, you will consider terminating further resuscitative efforts.

Clinical Question:

Does cardiac standstill on bedside echo universally predict mortality in OHCA?

Literature Review:

A systematic review of studies investigating the diagnostic accuracy of bedside echo in OHCA was published by a Canadian group in Annals in 2012 [1]. This was a well-done study, with a broad search strategy, rigid but logical inclusion & exclusion criteria, and quality assessment with a modified version of the QUADAS instrument.
Eight studies were included in the final analysis, with a total of 568 patients. Of the 378 patients with cardiac standstill on bedside echo, only 9 (2.4%, 95% CI 1.3% – 4.5%) achieved ROSC. The authors pooled results of the included studies to devise a 2x2 table and determine test characteristics of bedside echo. This revealed a sensitivity of 91.6% (95% CI 84.6% - 96.1%) and specificity of 80.0% (95% CI 76.1% - 83.6%). The positive likelihood ratio is 4.26 (95% CI 2.63 - 6.92) and the negative likelihood ratio is 0.18 (95% CI 0.10 - 0.31). Heterogeneity was minimal (0.0%) for the negative likelihood ratio, but was significant (82.1%) for the positive likelihood ratio. The authors conclude, “While there is insufficient evidence to support using echo in isolation to decide whether or not to continue with cardiopulmonary resuscitations, the presence or absence of VWM in the context of the pretest survival likelihood can provide emergency personnel with further information to assist making that difficult decision whether to stop cardiopulmonary resuscitation with more confidence.”

It is important to note that the outcome of interest in this systematic review was survival to admission, which is not necessarily a good predictor of neurologically-intact long-term survival past discharge, which is the ultimate patient-centered outcome of OHCA. Further limitations included variable inclusion/exclusion of traumatic arrest patients in the included studies, and variability in application of bedside ultrasound. Namely, there were significant differences in training level of examiners, degree of external review of OCHA studies, and definition of “cardiac standstill” between the included studies.
This paper was the focus of a “Systematic Review Snapshot,” authored by our very own Dr. Brian Cohn and published in Annals in 2013 [2].

I attempted a PubMed search using the same search strategy as the authors in the original systematic review (available in the online supplementary material), but I did not discover any further studies on this topic that have been published since that paper in 2012.

Take-home Points:

- Cardiac standstill does not universally lead to failure of resuscitation of OHCA.
- The best-available current evidence does not support the use of bedside echo alone to predict outcomes in OHCA patients.
- Other factors influencing likelihood of neurologically-intact survival (down time, underlying rhythm, patient age/comorbidities, etiology of arrest, etc.) should be taken into account when interpreting bedside echo results.
- More research is needed to determine true prognostic factors associated with survival from OHCA.

Submitted by C. Sam Smith, MD. @CSamSmithMD
Faculty review by Brian Cohn +EMJClub 

[1] Acad Emerg Med. 2012 Oct;19(10):1119-26.
[2] Ann Emerg Med. 2013 Aug;62(2):180-1.

Needle that belly!

An infant female with no significant history presents to your trauma bay after reported accidental blunt trauma to the abdomen, the patient arrives from a referral hospital where plain films demonstrated free air. On arrival the patient show signs of hemodynamic instability and an elevated lactate. The patient was decompressed with "needle peritoneumostomy" prior to going to the OR for exploration. 

Clinical Question:

Can “tension pneumoperitoneum” cause hemodynamic instability?

Literature Review:

The presence of "free air" in the peritoneum is often diagnostically significant; however, the gas itself is rarely of clinical importance. An exception to this rule is in the case of a tension pneumoperitoneum. Tension pneumoperitoneum (TPP), also known as hyperacute abdominal
Example of pneumoperitoneum & football sign
compartment syndrome [1], or abdominal tamponade [2], is a rare, but potentially deadly event. Similar to tension pneumothorax, the underlying mechanism is a tissue flap that acts as a one-way valve for air release, resulting in a progressive increase in intra-abdominal pressure. The increasing peritoneal pressures may rapidly lead to respiratory compromise due to diaphragmatic elevation and a drop in cardiac output resulting from decreased venous return or aortic outflow due to occlusion. [3] This can progress to cardiovascular collapse and respiratory failure and eventually death. [2]

In one of the earliest reported cases in 1913, tension pneumoperitoneum was theorized to be a consequence of gas forming bacteria in the abdominal cavity. [4] Now it is known that tension pneumoperitoneum is usually a consequence of hollow viscus perforation, post-operative complications, positive pressure ventilation or other insulflation-dependent procedures (eg, colonoscopy, endoscopy, cystoscopy or air enema). There has even been reported cases from CPR. [9,10] However, there are few published case reports of TPP as a result of blunt force trauma. [3,6]

Signs and symptoms of TPP include abdominal distension and fullness. The additional presence of a tympanitic, rigid abdomen, hypotension, dyspnea, and jugular vein congestion can be considered as signs of TPP, requiring immediate management.

The diagnosis of tension pneumoperitneum should be based physical exam and supported by imaging of the abdomen. Plain films of the abdomen show large amounts of intraperitoneal air. Lateral supine and left lateral decubitus films show the air best. Elevation of the diaphragm or medial displacement of the liver, called the “saddlebag sign” is suggestive of tension physiology.[1] The viscera may appear more distinct as they are outlined by the air tissue interface as in the double-wall sign (the visualization of the outer wall of bowel loops caused by the presence of extraluminal and intraluminal gas). Another radiographic sign of a large pneumoperitoneum is football sign - the intraperitoneal air outlines the abdominal cavity and the falciform ligament appears like the laces of a football.

With this said, plain films of the abdomen are rarely obtained in the setting of trauma. If hemodynamically stable, the patient is imaged using computed tomography (CT scan) which will show posterior liver compression by superiorly located free air. However, because CT scanning is contraindicated in the hemodynamically unstable patient, the diagnosis may have to rest on the clinical presentation and/or portable plain films. It can be confirmed by needle decompression or paracentesis with a rush of air and improvement of hemodynamic stability. [7]
Treatment of tension pneumoperitoneum depends on the stability of the patient. If the patient is acutely unstable with labile blood pressures and signs of shock, treatment is emergent needle decompression using a 14g angiocatheter. There are no large trials that recommend a specific location based on success and/or safety rates. However, several small case series suggest using the same sites for decompression: two centimeters below the umbilicus in the midline (through the linea alba) or five centimetres superior and medial to the anterior superior iliac spines on either side. [8]. If the patient is stable, a paracentesis catheter/drain can be placed. The definitive treatment is to determine what initially caused the air accumulation, which may necessitate an exploratory laparotomy. It should be noted that a nasogastric tube turned to suction is unlikely to evacuate the pneumoperitoneum due to the ball and valve mechanism that created it initially. [3]

Take-home Points: 
-Pathophysiology and treatment is similarly to pneumothorax, it can lead to cardiovascular collapse, respiratory failure, and eventually death if untreated. Unstable patients should be recognized on exam, however x-ray and CT have utility based on stability. Decompression is the treatment and can be performed with an angiocath placed two centimeters below the umbilicus in the midline. 

[1] Lin B, Tension Pneumoperitoneum. The Journal of Emergency Medicine, Vol. 38, No. 1, pp. 57–59, 2010.
[2] Khan ZA. Conservative management of tension pneumoperitoneum. Ann R Coll Surg Engl. 2002 May;84(3):164-5.
[3] Ogle JW Tension Pneumoperitoneum after Blunt Trauma. The Journal of Trauma: Injury, Infection, and Critical Care. 1996 Nove; 41(5): 909-911.
[4] Falkenburg C. Ein Fall von Gasansammlung in der freien Bauch-Hohle. Dtsch Z Chir 1913;124: 130-6.
[5] Olinde A, Carpenter D, Maher J. Tension pneumo-peritoneum. Arch Surg 1983;118:1347-50.

[6] Ferrera PCChan L. Tension pneumoperitoneum caused by blunt trauma. Am J Emerg Med. 1999 Jul;17(4):351-3.
[7] Yakobi-Shvili RCheng D. Tension pneumoperitoneum--a complication of colonoscopy: recognition and treatment in the emergency department. J Emerg Med. 2002 May;22(4):419-20.
[8] Fu KIshikawa TYamamoto TKaji Y. Paracentesis for successful treatment of tension pneumoperitoneum related to endoscopic submucosal dissection. Endoscopy. 2009;41 Suppl 2:E245.
[9] Williams DTManoochehri PKim HT. Tension pneumoperitoneum. Emerg Med J. 2014 Nov;31(11):943.
[10] Mills SAPaulson DScott SMSethi G. Tension pneumoperitoneum and gastric rupture following cardiopulmonary resuscitation. Ann Emerg Med. 1983 Feb;12(2):94-5.
Submitted by Decompression Danny Kolinsky, PGY-2
Edited by Louis Jamtgaard, PGY-3. @Lgaard
Faculty review by Rebecca Bavolek

Sprinkle on a little ketamine

A middle aged patient with a longstanding history of asthma (multiple intubations and ICU stays) presents with 3 days of worsening dyspnea, refractory to home bronchodilators, speaking in 2 word sentences and in tripod position. As oxygen saturations hover in the low 90s, the patient is transferred to critical care area for BiPAP.  As the patient rolls by you plan on BiPAP, solumedrol, epinephrine, and magnesium, and you and your attending think “why don’t we try some ketamine?” 

Severe Respiratory distress (Source imgkid)

Clinical Question: Can ketamine be used as a bronchodilator improve outcomes in patients with severe asthma?

Literature Review: In the review article from 2013 by Goyat et al, 20 articles were examined looking at ketamine for bronchospasm (case series, RCTs, observational, retrospective studies) 3 of which were in the ED.  Ketamine was used as a rescue agent in all studies; general doses were 0.1-0.2mg/kg IVP followed by infusion at 0.15-0.25mg/kg/hr.  Eighteen articles showed a “favorable response”, and 2 studies showed insufficient response.  No major adverse events were reported.  

To review, ketamine has 2 enantiomers: the S is more potent and faster acting, and the R enantiomer may be associated with more emergence reactions.  Most preparations are 1:1 S:R. Peak onset is at 60 seconds with a duration of 10-15 minutes. The distribution half-life is approximately 7-11 minutes and is cleared via the hepatic route with half life of 2-3 hours.  Several mechanisms have been proposed for its effect on bronchospasm: improved airway mechanics, anti-inflammatory properties, airway relaxation, reduction of nitric oxide, inhibition of reuptake of catecholamines at the synapse, and anticholinergic effects.

The first case report of ketamine use for reactive airway disease was in 1972 of a child who had anaphylaxis during skin testing that improved after ketamine, followed by a non-controlled trial in children intubated for asthma that showed a significant difference in PaO2/FiO2 and dynamic compliance after initiation of ketamine infusion.  The first controlled double blind trial in 1994 showed an improvement in “stethoscopic exam” and in Po2 and PCO2.  While it is worth noting the significant change in these objective data points, they are not exactly patient centered outcomes.

One observational study looked at pediatric ED patients. It enrolled 10 patients who were unresponsive to traditional therapy; no change in peak expiratory flow (PEF) was noted at 1 hour, but a significant change in the patients’Asthma Scores and respiratory rates (RR) was noted. 

The next prospective, double blind RCT (Howton, 1996) showed no benefit with ketamine.  Fifty-three consecutive patients with peak flows less than 40% after 3 does of albuterol were enrolled, all were given continuous albuterol, methylpredisolone and oxygen and then either a 0.2mg/kg ketamine bolus followed by 0.5mg/kg/hr x 3 hours, or an equivalent saline dose.  While there was a significant improvement in PEF, RR, FEV-1 in both groups over time, there was no difference between the groups. 

Similarly, a follow up RCT in kids (Allen, 2005), looked at 62 consecutive patients randomized to saline or the same ketamine doses as above, without improvement in pulmonary scores.

 Take-Home Points:
The conclusions of the above review are that ketamine is cheap, has a physiologic rationale, has few adverse effects and has been shown to improve asthma in case series and observational trials, though this has not been born out in the two small RCTs undertaken.  Their suggestion is that it should remain in the ED physicians armamentarium for refractory status asthmaticus and, as always, “further well-designed studies are warranted”.  It is probably not unreasonable for ketamine to be the induction agent of choice for asthmatics, and should be considered whenever NPPV is considered for status asthmaticus. 

Allen JY, Macias CG. The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Annals of Emergency Medicine 2005, 46 (1): 43-50

Howton JC, Rose J, Duffy S, Zoltanski T, Levitt MA. Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma. Annals of Emergency Medicine 1996, 27 (2): 170-5

Shweta Goyal, Amit Agrawal.  Ketamine in status asthmaticus: A review.  Indian Journal of Critical Care Medicine 2013, 17 (3): 154-61

Submitted by Wes Watkins, PGY-4 
Edited by Louis Jamtgaard, PGY-3 @Lgaard

Faculty Review by Joan Noelker

Hypertensive Encephalopathy

A middle age woman with  a history of chronic kidney disease and hypertension presents with chest pain and altered mental status. Paramedics note that she is having decreased responsiveness, moaning to questions, and stating only that she has pain everywhere.  Her blood pressure is 230/165 on arrival.  She is alert and oriented only to self with an otherwise nonfocal neurologic exam.  Head CT is negative for intracranial hemorrhageAs you work through your differential, you wonder how should the diagnosis of hypertensive encephalopathy be made?  How should it be managed in the emergency department and what is the prognosis for patients who have a hypertensive crisis like this patient?

Literature Review:
In a patient with altered mental status in the setting of severe hypertension (systolic >180 or diastolic >120), a hypertensive emergency needs to be on the differential, which is defined by signs of acute end-organ damage in the setting of severe hypertension.  Examples of end-organ damage include altered mental status, pulmonary edema, elevated troponins, and acute kidney injury.  Approximately 1-2% of people with HTN will have an episode of hypertensive encephalopathy in their lifetime, which may manifest as headache, nausea, vomiting, and confusion [1].

There is little evidence in the management of a hypertensive emergency; differences in medicine choices appear mostly based on symptoms of the crisis.  Initial management of hypertensive encephalopathy is to rule out other causes for encephalopathy (ischemic stroke accounts for 25% of all hypertensive encephalopathy cases), other considerations are intracranial bleed (SAH, IPH), posterior reversible encephalopathy syndrome (PRES) or even carotid or vertebral-basilar dissection. After ruling out other causes focus should be on treating the blood pressure with a IV anti-hypertensive that can be quickly titrated, such as nicardipine or nitroprusside [2].  Blood pressure should be lowered approximately 10-20% in the emergency department, and should not be lowered more than 25% in the first day due to the risk of ischemia from dropping pressures below the brain's autoregulatory range.  Keep in mind that the diagnosis of hypertensive encephalopathy is a diagnosis of exclusion and is only confirmed retrospectively with resolution of symptoms after treating the blood pressure [3]. 

Prognosis for hypertensive emergencies is variable.  In 2009 Katz et al. looked at 1,568 patients presenting with SBP >180 or DBP >110 or those with SAH and SBP >140 to evaluate practice patterns, mortality, and complications. Over 50% required more than one anti-hypertensive for blood pressure control. In-hospital mortality in this group was 6.9%, with 90 day mortality of 11%.  59% had acute worsening of end organ damage during the hospitalization. Hypertension has a high health burden, as 37% of the patients analyzed were re-admitted with-in 90 days, of which over 25% were due to repeat “severe hypertension” [4].  Of course, patients do much better if they can take their blood pressure medicines consistently, and this was demonstrated as far back as 1958 where an old study by Dustan showed that without any anti-hypertensive treatment, the survival at 1 year for those admitted for hypertensive encephalopathy was 10-20%.  However, with adherent treatment, 5 year survival rates were 70% [5].

Take-home Points:

Hypertensive encephalopathy is a diagnosis of exclusion, retroactively diagnosed after symptoms resolve with lowering blood pressure. BP should only be lowered 10-20% in the ED. Patients with HTN encephalopathy have an in hospital mortality between 6-11% at 90 days. Mortality reduction is related to long term compliance with antihypertensives. 


1.  Vaughan C, Delanty N. Hypertensive emergencies. Lancet. 2000;356:411–7.
2.  Price RS, Kasner SE. Hypertension and hypertensive encephalopathy. Handb Clin Neurol. 2014;119:161-7.

3.  Manning L, Robinson TG, Anderson CS. Control of blood pressure in hypertensive neurological emergencies. Curr Hypertens Rep. 2014 Jun;16(6):436.
4.  Katz JN, et al. Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension (STAT) registry.  Am Heart J. 2009 Oct;158(4):599-606.
5.  Dustan HP, Schneckloth RE, Corcoran AC, Page IH. The effectiveness of long-term treatment of malignant hypertension. Circulation. 1958 Oct;18(4 Part 1):644-51.

Submitted by Melissa Kroll, PGY-2

Edited by Philip Chan, PGY-2 & Louis Jamtgaard, PGY3 @lgaard
Faculty reviewed by Joan Noelker

As Low As Reasonably Achievable

Your patient is a 40-something female who has never been to your facility before but reports a history of chronic abdominal pain of undetermined etiology. She has had an appendectomy and a cholecystectomy. She is now presenting with two days of right-sided cramping abdominal pain associated with nausea without vomiting and lightheadedness. Screening labs protocoled by the triage nurse are unremarkable, and a bedside RUQ ultrasound is negative for significant pathology. After two doses of morphine she is still visibly uncomfortable in the stretcher. The team is reticent to pursue further diagnostics, but given the fact that she currently carries no diagnosis for her symptoms and is still in considerable distress, and the lack of any prior imaging in your EMR, the decision is made to order a CT abdomen/pelvis with contrast.

Clinical Question:

Given the fact that the pre-test probability for finding significant pathology in this patient is low, how worried should you be about exposing your patient to further ionizing radiation?

Literature Review:

Several groups of experts, including the American Association of Physicists in Medicine, the National Council on Radiation Protection & Measurements, and the US FDA, all report the median effective dose of ionizing radiation (IR) from an abdomen/pelvis CT (the most common CT ordered in the US) as 8 - 10 millisieverts (mSv) [1]. This is compared to 0.065 mSv for a two-view chest X-ray, and 0.42 mSv for a screening mammography series [12].

At the risk of turning this into a physics lecture, the Sievert is the SI unit of measurement for “dose equivalent” and for "effective dose" of radiation. “Dose equivalent” includes a weighing factor that accounts for the relative biological impact of different types of radiation. “Effective dose” takes this a step further, by utilizing weighing factors to account for the relative effect of radiation on different types of tissues. It represents the probability of cancer induction, and is commonly used in medical research. Conventionally, “effective dose” is used to measure low doses of IR which carry the stochastic (i.e., somewhat random and not entirely predictable) risk of inducing malignancy. This is in contrast to high doses of IR that cause deterministic effects -- what we would consider radiation poisoning -- that are certain to occur with exposure to high levels of IR. These exposures are typically measured in Grays, the SI unit of absorbed dose (simply the mean energy imparted to each unit of mass). For more detailed information on radiation quantities and exposures, click here.

So when should we be concerned? There is no "safe" dose of radiation. We are all exposed to a certain level of "background" radiation which probably leads to a certain rate of malignancy all on its own; any exposure to IR beyond this can only increase this risk. Thus the radiation safety doctrine of "As Low As Reasonably Achievable" governing IR exposure.

The National Academy of Sciences' National Research Council published phase 2 of its Biological Effects of Ionizing Radiation (BEIR) VII report in 2006. In this report, the group gathered available biological and epidemiological data related to human IR exposures. This included survivors of the atomic bomb blasts in Japan during WWII, people who lived close to nuclear power accident sites, workers with occupational exposures, and patients who underwent medical radiologic studies [2]. The breadth of available data suggest that increased cancer risk is associated with acute exposures of 10-50 mSv, and protracted exposures of 50-100 mSv [3]. Data also suggest a "linear, no threshold" dose-response relationship -- again, no "safe" level of IR exposure exists and any exposure, no matter how small, carries a nonzero risk of developing malignancy [2].

It doesn't take a particle physicist to see that the high end of the commonly reported dose of a CT scan overlaps with the low end of the dose range leading to increased malignancy. While the absolute risk of developing malignancy from a single CT scan may be quite low, the sheer number of scans performed would suggest that, from a population standpoint, many new malignancies are being induced by medical imaging.

Indeed, a group of authors used radiation risk models from the BEIR report to estimate incidence of future cancers resulting from the 72 million CT scans performed in the US in 2007 (excluding those scans performed on patients already diagnosed with cancer or those performed in the last five years of a patient's life) [4]. They concluded that approximately 29,000 new cancers (95% CI 15,000 - 45,000) could result from these scans, with the largest contributor being CT scans of the abdomen & pelvis with 14,000 new cancers (95% CI 6,900 - 25,000). About a third of these projected cancers resulted from scans performed on patients aged 35 - 54, and 15% from scans performed on pediatric patients less than 18 years old. Lung cancers were projected to be most common, followed by colon cancer and leukemia. Two thirds of cancers were projected to occur in females.

Projected number of future cancers (mean and 95% uncertainty limits) that could be related to computed tomographic scan use in the United States in 2007, according to age at exposure.
From Reference [4]
From Reference [4]
These were not the only authors to reach such concerning conclusions. Again using BEIR VII data & models, one group estimated that annual chest CT screening for lung cancer in adults starting at age 40 would result in a 1/10,000 estimated excess lifetime risk of radiation-induced lung cancer mortality for men and 3/10,000 for women, which would likely negate any mortality benefit gained by early identification of lung malignancy from such screening [5]. Another group examined risk from CT coronary angiogram, using simulated exposure doses and BEIR VII models, and found a 1/284 lifetime attributable risk for a 40-year-old woman, with risk inversely proportional to age [6]. Several other groups have used calculated doses of common scans and BEIR VII models to conclude that exposure to CT scans likely significantly increases lifetime risk of cancer [7,8,9].

Two chief limitations affect all of these studies. First, they all rely on BEIR VII models of lifetime attributable risk. Unfortunately, accurately quantifying risks directly would require long-term follow-up of very large patient populations. The BEIR VII models are based on direct evidence of the carcinogenic behavior of IR in other populations, such as nuclear accident & atomic bomb survivors. As such, they likely represent the best models we have for estimating long-term risk of IR in medical imaging. In fact, in vitro studies suggest that the form of IR utilized in medical imaging (x-rays) may have even greater potential to damage cellular DNA than gamma rays (the primary form of IR released in atomic bomb blasts) [4].

The second limitation to the prior studies is that they almost universally relied on estimated doses of IR from the various scans, with the majority falling in the previously-suggested 8 - 10 mSv range. Practically speaking, it is nearly impossible to truly quantify the IR absorbed by a human body in a CT scanner. Some degree of estimation & calculation will always be necessary, but most of the aforementioned studies relied on previously-published estimates of dose or dose estimates from "phantom studies," not exams performed on actual patients.

In 2009, a group of authors in San Francisco attempted to more directly quantify the radiation dose of common CT study types, compare intra- and inter-site variability, and determine what impact this variability has on attributable cancer risk [10]. They estimated this effective dose using the Dose-Length Product, which is recorded as part of the CT scan metadata. The DLP is an approximation of the total energy a patient absorbs from the scan, determined by multiplying the energy absorbed from a single slice (the CT Dose Index or CTDI) by the total length of the body scanned. The authors combined the DLP with details of the area imaged and used conversion factors to translate this into an effective dose. This approach is used elsewhere in the literature, and is described in a report by the American Association of Physicists in Medicine's report on The Measurement, Reporting, and Management of Radiation Dose in CT [11]. They also utilized methods & risk estimates published in the BIER report to calculate the lifetime attributable risks of cancer above baseline based on the magnitude of a single exposure.

Based on the study group's data, doses of many scans were significantly higher than the commonly-reported 8 - 10 mSV. Abdomen/pelvic CTs had the highest radiation doses, ranging on average from 15 - 31 mSv. The corresponding median adjusted lifetime attributable risk of cancer was 4 cancers per 1000 patients. For a routine abdomen/pelvis CT with contrast, one attributable cancer would be expected for every 470 scans of 20-year-old females, or for every 870 scans of 40-year-old females. These numbers are even more concerning for multiphase scans (e.g., angiography studies), which impart effective doses up to 90 mSv based on the authors' calculations. At this end of the scale, a 20-year-old female undergoing multiphase abdomen/pelvis CT could face as high as a 1/250 risk of cancer attributable to the scan. One of the takeaways from this study was that the same CT scan type could yield effective dosages with over 13-fold variability between sites, or even between different scans on the same equipment.

From Reference [10]

From Reference [10]

 The American College of Radiology addressed these concerns in their White Paper on Radiation Dose in Medicine in 2007 [13]. In this document, the ACR acknowledges that effective dose of commonly-used CT scans may exceed 10 - 25 mSv. They further state that, while there are no hard data as of yet showing an increased incidence of cancer with CT scans, the boom of CT ordering has just occurred in the past 5 - 10 years, and cancer due to IR usually does not occur until 1 - 2 decades or longer after exposure.

Overall, data suggest that anywhere between 1 - 3% of cancer cases in the US may be due to exposure to IR from medical imaging [4,13]. The ACR White Paper states that the massive increased use of CT scanning in the past decade "may likely result in an increase in the incidence of imaging-related cancer in the US population in the not-too-distant future."

Faculty commentary:
Dr. Richard Griffey, Director of Quality and Safety for Washington University Emergency Medicine and evidence-based diagnostics advocate, had this to add:

“One of the things people often ask/wonder about…is what strategy makes sense on an individual patient level?
  • What is the incremental harm of an additional study?
  • Does the benefit of the study far outweigh the risks?
  • What are the other options – ultrasound, watchful waiting, serial exams, MRI, etc.?
  • If someone has already undergone multiple scans, how much additional risk does one more scan actually incur?
  • Who should we be focusing on in avoiding ionizing radiation?"

- While it is highly impractical to conduct a longitudinal study of cancer incidence based on exposure to medical imaging, based on the best data we have it is highly likely that such exposure will lead to tens of thousands of new malignancies in the future.
- The risk of malignancy is most pronounced in females, and is inversely proportional to age.
- Patients undergoing repeat CT scans are almost certainly exposed to a level of ionizing radiation that increases their risk of cancer above baseline.
- It is our responsibility as patient caregivers to be responsible in our ordering of CT scans and other studies that expose patients to ionizing radiation. They carry a nonzero risk of harm which must be weighed against possible diagnostic yield.

Submitted by C. Sam Smith (@CSamSmithMD), PGY-3
Faculty Reviewed by Richard Griffey 

[1] National Council on Radiation Protection and Measurements, Ionizing Radiation Exposure of the Population of the United States. 2009;NCRP report 160
[2] BEIR VII Phase 2.  Washington, DC National Academies Press 2006.
[3] Proc Natl Acad Sci U S A 2003;100(24);13761-13766.
[4] Arch Intern Med. 2009;169(22):2071-2077.
[5] J Med Screen 2008;15(31):153- 158.
[6] JAMA 2007;298(3):317-323.
[7] Radiology 2004;232(3):735- 738.
[8] Radiology 2009;251(1):175- 184.
[9] AJR Am J Roentgenol 2009;192(4):887- 892.
[10] Arch Intern Med. 2009;169(22):2078-2086.
[11] American Association of Physicists in Medicine, The Measurement, Reporting and Management of Radiation Dose in CT: Report of AAPM Task Group 23 of the Diagnostic Imaging Council CT Committee.  College Park, MD American Association of Physicists in Medicine2008;AAPM report 96.
[12] National Cancer Institute, Radiation risks and pediatric computed tomography (CT): a guide for health care providers. 2009.
[13] J Am Coll Radiol 2007;4(5):272- 284.

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,

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.       1st 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.       2nd gen antipsychotics include:
a.       Olanzapine (Zyprexa), ziprasidone (Geodon), aripiprazole (Abilify) – IM and PO
b.      Risperidone (Risperdal), and quetiapine (Seroquel) – PO only
7.       2nd gen antipsychotics also antagonize dopamine, but also serotonin as well
8.       There have been very few head to head trials of 2nd 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 2nd generation
b.      Oral 1st generation
c.       IM 2nd generation – olanzapine 10 mg or ziprasidone 10- 20 mg
d.      IM or IV 1st 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 2nd 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


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:
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.

In a follow-up study carried out by Wolf et. al  in 1978, the authors fired S. aureus tipped bullets from a sterilized gun into sterilized sand [2]. Cultures were obtained from the gun barrel, sand, and bullets prior to start of the experiment and were all negative. Cultures of the contaminated bullets and gun barrels were positive for Staph aureus after they had been fired.  Thus, the contaminated bullets were not sterilized upon discharge of the gun.

A 1982 study used a dog model (cringe!) in which bacteria (Serratia marcescens)-inoculated cloth was placed on the entrance or exit side of the animal prior to gun discharge[3]. When compared to control animals (no inoculated cloth was placed), bacteriological examination demonstrated primary bacterial contamination of bullet wounds immediately after the shot. It was verified that there were two main mechanisms of primary bacterial contamination: (1) The bacteria were sucked into the wound by negative pressure of the temporary cavity at both entrance and exit sides, and (2) bacteria were carried into the wound tract by contaminated bullet itself.

Question 2: Are low velocity gun shot wounds with corresponding fractures considered open fractures and do antibiotics decrease the risk of infection?

In order to answer this question, one must understand that not all fractures caused by gunshot injuries are created equal. These wounds are classified by bullet velocity which is a function of firearm: low-velocity, high-velocity, or shotguns. Bullets with a muzzle velocity less than 2000 feet per second generally are defined as low-velocity. Bullets with a muzzle velocity greater than 2000 feet per second are classified as high-velocity. Examples of muzzle velocities of firearms are given in the table below. There is a general consensus that fractures caused by high-velocity weapons, shotguns, or intra-articular fractures should be treated with prophylactic antibiotics [4].

  Data source: 
There is a paucity of randomized control trials assessing prophylactic antibiotic use in  gunshot wound - associated fractures.  In one small RCT, patients were randomized to receive IV cefazolin 1g q8 x 24 hours or no antibiotics altogether [5]. Patients that sustained high velocity wounds, wounds caused by shot guns, or required surgical intervention were excluded. A total of 96 patients were enrolled in the study. Only 67 were followed until completed union of the fracture. The 29 who were lost to follow up were equally distributed between study groups. Patients were scheduled to follow up 2 weeks after the original injury and then monthly thereafter. The definition of infection was intentionally broad and included any wound complication including prolonged wound drainage, erythema, localized fluctuance, cellulitis, or expressable drainage. Cultures were sent on drainage. Of the 67 patients with complete follow-up, 32 patients (36 fractures) were treated with antibiotics and the other 35 (37 fractures) were not. A total of 1 infection occurred in each group. Chi-Squared analysis demonstrated no significant difference in infection rates. Thus, it was concluded that prophylactic antibiotics did not significantly reduce the incidence of infection in GSW-related fractures.

A systematic review to address this question was published Papasoulis et al in 2013 [6]. A search of the MEDLINE database yielded 33 studies that pertained to the study goals. Of these only one was a RCT (the aforementioned Dickey et al article) and 9 were considered higher quality and 17 of any quality (including the 9 high quality studies) that addressed the specific question “Are antibiotics needed for the treatment of these fractures?”.

Table 2 from Papasoulis et. al. (Reference 6)
The total percentage of infections in fractures treated with antibiotics was 1.7%, while the infection rate for fractures treated without antibiotic treatment was 5.1%. The difference was not significant with the numbers available (p = 0.17). Inclusion of all studies, including 937 fractures, showed an infection rate of 2.4% when antibiotics were used versus 6.7% without antibiotics. When including the lower quality studies, the difference was significant (p = 0.031). However, in the discussion the authors point out that utilizing the lower quality studies is fraught limitations due to mixed data sets – failure to exclude high velocity injuries, unclear locations of gun shot wound, variable follow up periods.

Papasoulis et. al.  conclude by conceding the fact that infection after gunshot injuries is a rare complication (1.9% of 1156 fractures in the 23 studies that answered this question). Thus, large numbers of patients would have to be enrolled for a study to show a significant benefit with any intervention in terms of reducing infections in gunshot fractures.  Indeed, a post hoc power analysis of the results based on the higher-quality studies demonstrated a power of only 41%.

Clinical take home: Contaminated bullets are not sterilized on discharge of the firearm. Bullets traversing contaminated overlying clothes or skin track bacteria or particulate matter into the body tissues directly and by cavitation with result negative vacuum forces.   Despite this, infection after gunshot injury is a rare complication.  The current literature, however limited, suggests that there is no significant advantage of prophylactic antibiotics for non-operative fractures caused by gun shot wounds and the risks/benefits should be considered on an individual patient basis.

[1] Thoresby, F. P., & Darlow, H. M. (1967). The mechanisms of primary infection of bullet wounds. British Journal of Surgery, 54(5), 359-361.

[2] Wolf, A. W., Benson, D. R., Shoji, H. I. R. O. M. U., Hoeprich, P. A. U. L., & Gilmore, A. L. A. N. (1978). Autosterilization in low-velocity bullets. The Journal of trauma, 18(1), 63-63.

[3]Tian, H. M., Huang, M. J., Liu, Y. Q., & Wang, Z. G. (1982). Primary bacterial contamination of wound track. Acta chirurgica Scandinavica. Supplementum, 508, 265-269.

[4] Simpson, B. M., Wilson, R. H., & Grant, R. E. (2003). Antibiotic therapy in gunshot wound injuries. Clinical orthopaedics and related research, 408, 82-85.

[5] Dickey, R. L., Barnes, B. C., Kearns, R. J., & Tullos, H. S. (1989). Efficacy of antibiotics in low-velocity gunshot fractures. Journal of orthopaedic trauma, 3(1), 6-10.

[6] Papasoulis, E., Patzakis, M. J., & Zalavras, C. G. (2013). Antibiotics in the Treatment of Low-velocity Gunshot-induced Fractures: A Systematic Literature Review. Clinical Orthopaedics and Related Research®, 471(12), 3937-3944.

Submitted by Daniel Kolinsky, PGY-2
Edited by Maia Dorsett @maiadorsett, PGY-3
Faculty Reviewed by H. Phil Moy

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


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.

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

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 


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.

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 failureIn 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 cycleDeath.

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 outputRestoration of right ventricular contractility is one of the mainstays of treatment of acute right heart failureAccording 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

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.

Cardiac arrest, add antibiotics to the kitchen sink?

Clinical scenario:
You get a page out for a 55 yo M in cardiac arrest, EMS reports PEA on their arrival, patient has received 3 rounds of epi prior to arrival, patient achieves return of spontaneous circulation (ROSC) after 5 minutes of ACLS while in the ED. When family arrives they report the patient had been feeling unwell for several days and had a significant cough.  No obvious infiltrate was seen on initial chest xray.  The patient's BP is stable on an epi infusion. You admit the patient to the ICU. Your attending requests drawing blood cultures and starting the patient on broad spectrum antibiotics, and cites data stating antibiotics improves mortality in out of hospital cardiac arrest. You perform a brief literature review. 

Literature Review:
Out of hospital cardiac arrest (OHCA) has a very high mortality rate, where approximately only 23% make it to the hospital alive, and 7.6% survive to hospital discharge. (1) The most common etiology of out of hospital cardiac arrest is presumed to be myocardial in origin. However, several retrospective studies indicate that sepsis and bacteremia may also be a significant contributing factor to OHCA. A study by Coba et al in published in 2014 performed a prospective study to identify the incidence of bacteremia in OHCA patients. They enrolled 173 patients, where all patients had two sets of blood cultures drawn, 77 patients met exclusion criteria (trauma, pregnant, pediatric, single positive culture of skin flora). The overall incidence of bacteremia was 37% (65 patients). The most common bacterial species cultured were streptococcus and staphylococcus and Ecoli and klebsiella for gram positive and gram negative bacteria respectively. Bacteremic OHCA patient had significantly higher lactates, lower pH, and more frequent use of vasopressors. Notably the ED survival was significantly lower in the bacteremic patients (25%) compared to nonbacteremic patients (40%). However, 28 day mortality difference was insignificant in bacteremic vs nonbacteremic patients (93.8 vs 92.6%). The figure below by Coba et al lays out the proposed inter-relationships between bacteremia and sudden cardiac arrest. (1)
Proposed association between bacteremic infection and sudden cardiac arrest. From Coba et al.

Although there is very little data examining pre-existing bacteremia in OHCA, there has been a significant amount of research studying infection following ROSC in OHCA. The most commonly cited sources of post ROSC infection are lung possibly from aspiration during arrest, or gut likely from translocation of flora secondary to low flow state during arrest.  Davis et al performed a retrospective analysis on 138 patients admitted to the ICU following OHCA, and showed that 97.8% had at least one positive mark of infection within 72 hours (positive blood culture, consolidation on cxr, CRP greater than 100 or wbc greater than 11 or less than 4 x10^9 ). In this study approximately 38.4% of patients received antibiotics during the first 7 days of their ICU stay. The authors showed that mortality was significantly lower among those receiving antibiotics versus those not receiving antibiotics (56.6% versus 75.3%). However, highest mortality was within the first three days, and for patients who survived to day 3, there was no difference in mortality between those who received antibiotics already and those who had not. (2)

Take home points:
OHCA is typically presumed to be a primary myocardial event, however there is some data to suggest that sepsis is potentially a significantly under reported cause. Furthermore, there is also data to suggest that following ROSC, infection is quite common, and antibiotics may reduce early mortality. However, caution must be taken, as of yet there are no RTC's comparing prophylactic antibiotics versus placebo in OHCA.

Expert Commentary:

Dr. Holthaus one of our own critical care and sepsis guru's was nice enough to provide some of his own thoughts on this topic, and cardiac arrest in general. 

Things we'd like to see examined in future cardiac arrest RCTs:
1) Antibiotics during arrest - push dose, timing, coverage.
2) Propofol - control for this or exclude as a variable since it has been shown to cause some mitochondrial dysfunction and may be thwarting potential resuscitation benefits.
3) Epi dosing - frequency, continue 1mg push dose vs lower dose vs maximum that is less likely to cause or further exacerbate either ischemic or post-inflammatory cardiomyopathy.
4) Vasopressin-Steroid-Epi- for ED arrest. Link to VSE study in JAMA . VSE (vasopresson-steroids-epi) better than Epi alone for in-hospital arrest Vasopressin (20u, q 3-5min, max 100u, w 1 mg epi pushes)-Methypred (40mg IV x1) w better ROSC (84% vs 66%) and better CPC1/2 survival (14% vs 5%).  Major caveat is time to ACLS was very low at 2 min for both which is way faster than many we see in the ED that are frequently >10 min downtime before EMS.  Hypothesis generating, re-hinting at potential beneficial role of vasopressin and steroids for shock (like sepsis). 
5) ED ECMO for cardiac arrest or refractory/severe shock
6) Remote ischemic conditioning immediately after ROSC- 5 min thigh BP tourniquet to >20mmHg above SBP then deflate, repeat 3-4 times, reportedly induces systemic circulation of a protein that blocks CNS/cardiac opening of the "mitochondrial permeability transition pore" which is the final common pathway for ischemic reperfusion injury).  On recent ED ECMO podcast (Shiner-Bellezo) Link to podcast Remote ischemic conditioning 

Personally since everything (ACLS) isn't getting much results, if I can remember to I will do Vasopressin-Methypred-Epi dosing, I am less excited about a lot of epi (ie 3 pushes tells me if they're trending toward making it or not), I've pushed zosyn and then hung vancomycin in a code (after learning about Coba study). I have generally avoided propofol in past because of known myocardial suppression, and now with concern for mitochondrial insult, I just use fentanyl/versed. In addition I  will try thigh remote ischemic reconditioning, and continue targeted temperature management to 33-36C while hoping for ED ECMO (which I think will be the biggest game changer)  

Submitted and Edited by Louis Jamtgaard PGY-3 @Lgaard
Faculty Review by Chris Holthaus


 1) Coba V et al. The incidence and significance of bacteremia in out of hospital cardiac arrest.
Resuscitation. 2014 Feb;85(2):196-202. d

2)Davies K et al. Early antibiotics improve survival following out-of hospital cardiac arrest.Resuscitation 2013 May; 84 (5) : 616-9.

Subchorionic Hematoma: incidental finding or early risk?

Clinical Scenario:

A 20 yo G1P0 at 6wk1day by LMP presented with vaginal bleeding.  She had onset of bleeding 1 hour prior to arrival, soaked through 1 pad.  She was seen at her OB earlier that day (prior to onset of bleeding) and had an US which showed +FHR.  Transabdominal and transvaginal ultrasound showed an IUP with +FHR of 120 BPM (image below).  Her beta hCG was 72,813 and she was Rh+.  Hypoechoic material was seen surrounding the gestational sac, consistent with subchorionic bleeding.  The patient was given return precautions and instructed to follow-up with her OB in 48 hours.  You wonder if should have given any specific precautions regarding subchorionic hematoma?

Literature Review:
A threatened abortion is diagnosed when vaginal bleeding has occurred but the cervical os is closed and fetal demise has not occurred (if there is fetal demise + a closed os it's then a missed AB).  Subchorionic hematoma is commonly seen on routine obstetric ultrasonography.  It appears as hypoechoic or anechoic area behind the gestational sac in a crescent-shape in the first trimester and behind the fetal membranes in the second trimester.  The reported incidence of subchorionic hematoma has a large range (0.5% to 22%).

A systematic review and meta-analysis published in 2011 by Tuuli et al looked at 7 studies with 1735 women with subchorionic hematoma and 70,703 controls. They found that subchorionic hematoma was associated with an increased risk of spontaneous abortion, with risk increased from 8.9% to 17.6% with a odds ratio (OR) of 2.18 (1.20-3.67).  The number needed to harm was 11 for spontaneous abortion and 103 for stillbirth.  They also found that patients with subchorionic hematoma were at increased risk of abruption, with risk increased from 0.7% to 3.6%, OR 5.71 (3.91-8.33).  Preterm delivery and preterm premature rupture of membranes were also increased. 

There is some thought that the size of the subchorionic hematoma may be associated with risk and pregnancy outcome.  There have been many different methods described to assess hematoma size.  However, many of the articles assessing size and risk have sample sizes that are too small.  One study found that a hematoma size of 2/3rds or greater of the gestational sac circumference was a good predictor of spontaneous abortion, OR 2.9 (1.2-6.8).  Many articles, however, fail to show an association between hematoma volume or size and risk of pregnancy loss.

Take home points:
So what should you advise your patients with early pregnancy bleeding and a subchorionic hematoma on ultrasound?  Give patients the same precautions you would give them for threatened abortion. However, when discussing risk of miscarriage with these patients you should advise them that their risk is higher than patients with a typical threatened abortion; closer to 20% of patients will have a spontaneous abortion.  If the amount of bleeding on ultrasound is large their risk is likely higher, but this has not been as well studied.

Submitted by Alli McGovern PGY-4
Edited by Louis Jamtgaard PGY-3 @Lgaard
Faculty Reviewed by Joan Noelker

Tuuli et al, Perinatal Outcomes in Women with Subchorionic Hematoma: A Systematic Review and Meta-Analysis. Obstetrics & Gynecology. 117(5):1205-1212, May 2011.
Ball RH, Ade CM, Schoenborn JA, Crane JP (1996) The clinical significance of ultrasonographically detected subchorionic hemorrhages. Am J Obstet Gynecol 174: 996–1002. 
Xiang L, Wei Z, Cao Y (2014) Symptoms of an Intrauterine Hematoma Associated with Pregnancy Complications: A Systematic Review. PLoS ONE 9(11):e111676.

Correcting Acidosis or Just adding CO2?: On Sodium Bicarbonate for Metabolic Acidosis

Clinical Scenario:
You are working in the emergency department when an elderly male is brought in by EMS after being found unresponsive at home with an unknown downtime.  The paramedics report a possible seizure.  His finger stick glucose registers as critical high.  Post-intubation for poor GCS,  his initial labs reveal an ABG of  6.8/20/90 and a lactate of 18.   As you are signing out the patient to the ICU the ICU team requests a sodium bicarbonate infusion.  You wonder, will sodium bicarbonate administration improve outcomes or correct acidosis faster when compared to normal saline?

Physiology & Literature Review:
Other than well-defined indications for sodium bicarbonate administration (such as treatment of Na-channel blockade in TCA overdose or to induce alkalinization in salicylate toxicity), one should be skeptical about administering sodium bicarbonate simply for acidosis. On the one hand if a patient is acidotic, it makes intuitive sense that you should try to alkalinize them, which is why sodium bicarbonate has been used so often in the past.  On the other hand, there is evidence to show that administration of sodium bicarbonate shifts the oxygen dissociation curve, increasing hemoglobin affinity to oxygen,  and resulting in paradoxical tissue hypoxia and causes an increase in lactate production. In addition, it causes an intracellular acidosis.  Despite this,  because it tends to be part of the "code cocktail",  it is often administered anyway. 

Rise in EtC02 after bicarb (Dr. Sacchetti video)
The effect of administration of Sodium bicarbonate on the end-tidal CO2 in an intubated patient with severe metabolic acidosis is well demonstrated by  this video by Dr. Alfred Sacchetti. While we disagree in giving a bicarb drip as mentioned in the video, it does demonstrate the acid-base physiology in real time. 

A small randomized-controlled trial published in Critical Care Medicine more than 20 years ago gave either a blinded bolus of saline or sodium bicarbonate to patients with lactic acidosis vasopressor support [1].  They then checked ABGs one hour later.   While sodium bicarbonate did increase the venous bicarb level, improved pH, it did not improve hemodynamics.

Regarding two common metabolic acidosis scenarios seen in the emergency department, Diabetic ketoacidosis, the evidence suggests that sodium bicarbonate has the potential to cause harm:
     1. Diabetic ketoacidosis: A recent retrospective observational cohort study examined the effect of sodium bicarbonate on 86 patients in DKA with a pH less than 7.044 patients received sodium bicarbonate and 42 did not.  There was no difference in time to resolution of acidosis (pH greater than 7.2) or hospital length of stay between the two groups. However, there was a significant increase in insulin and fluid requirements in the sodium bicarbonate group. With regard to pediatrics, the PECARN study examining DKA in the pediatric population found that one of the only risk factors for cerebral edema (once again a retrospective analysis) was administration of sodium bicarbonate [3].

    2. Lactic Acidosis: Regarding lactic acidosis, an article from Korea retrospectively looked at 103 patients with acidosis (CO2 less than 20) and lactate greater than 3.3 mmol and compared those that got bicarb (69) to those that did not (34) [4].  Patients who received sodium bicarbonate had increased mortality, but this was confounded by the fact that these patients had lower initial pH, higher initial lactate, and higher APACHE 2 scoresWhen they ran their regression analysis, the only two things that were independently associated with mortality were Sequential Organ Failure Assessment (SOFA) and bicarb administration (95% CI 1-251).   When the authors did a subgroup analysis by excluding less ill patients (SOFA less than 8), they found again that administration of sodium bicarbonate was  associated with death.  They also found that those that received sodium bicarbonate cleared their lactate more slowly. 

Take home points:
Sodium bicarbonate may increase serum pH, but may worsen rather than improve prognosis.  Other than indications where sodium bicarbonate is the treatment for the acidosis (such as TCA overdose), the treatment for metabolic acidosis is to correct the underlying cause, whatever it may be.

Submitted by Wes Watkins, PGY-4
Edited by Louis Jamtgaard, PGY-3 @Lgaard
Faculty reviewed by Evan Schwarz @TheSchwarziee

1. Mathieu D, Neviere R, Billard V, Fleyfel M, Wattel F (1991) Effects of
bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic-acidosis: a prospective, controlled clinical study. Crit Care Med 19: 1352– 1356.
2. Adeva-Andany, M. M., Fernández-Fernández, C., Mouriño-Bayolo, D., Castro-Quintela, E., & Domínguez-Montero, A. (2014). Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis. The Scientific World Journal, 2014.
3. Glaser N, Barnett P, McCaslin I, et al; Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics: Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med 2001; 344:264–269

4. Kim, H. J., Son, Y. K., & An, W. S. (2013). Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis. PloS one, 8(6), e65283.

Thomboembolic events after cardioversion in afib

Clinical Scenario:
55 year old with past medical history of hypertension presents with sudden onset palpitations and chest pain that awoke him from sleep at midnight.  Patient presents 3 hours later with complaint of palpitations, chest pain, shortness of breath with stable vitals.  EKG demonstrates atrial fibrillation (a.fib).  Patient undergoes successful synchronized cardioversion.

Clinical Question:
In a patient who is electrically cardioverted within 48 hours of symptom onset of new atrial fibrillation, what is the incidence of thromboembolic complications?  Do you still have to anticoagulate?

Literature review:
Based on the Finnish CardioVersion Study, which included 2,481 patients who had a.fib for less than 48 hours and underwent cardioversion and were NOT started on oral anticoagulation nor peri-procedural heparin, there are certain groups who have higher risks for thromboembolic events.  Of the group as a whole, 0.7% (95% CI 0.5-1.0) had thromboembolic events within 30 days with a median of 2 days and mean of 4.6 days.  The three highest risk factors were female gender (OR 2.1 95% CI 1.1 to 4.0), heart failure (OR 2.9 95% CI 1.1 to 7.2), and diabetes (OR 2.3 with 95% CI 1.1 to 4.9).  Those with no heart failure who were younger than 60 years old had the lowest risk of thromboembolism (0.2%). 
Example of Afib

Additionally, when deciding between low molecular weight heparin or unfractionated heparin in cardioversion, based on the ACE trial (Anticoagulation in Cardioversion using Enoxaparin), there is no significant difference between the two with regard to embolic events, death, and bleeding complications.  This study included 428 people, and it was a randomized prospective multicenter trial.  Of the enoxaparin patients 7/216 vs. 12/212 heparin patients had primary end point incidents (p=0.016).

Take home points:
-Consider anticoagulation in patients who have heart failure/diabetes who must undergo electric cardioversion

-Low risk patients do not need anticoagulation when cardioverted within 48 hours of onset of a.fib
-No difference between enoxaparin or heparin

1. Airaksinen KE, Grönberg T, Nuotio I, Nikkinen M, Ylitalo A, Biancari F, Hartikainen JE. Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. J Am Coll Cardiol. 2013 Sep 24;62(13):1187-92.
2. Stellbrink C, Nixdorff U, Hofmann T, Lehmacher W, Daniel WG, Hanrath P, Geller C, Mügge A, Sehnert W, Schmidt-Lucke C, Schmidt-Lucke JA; ACE (Anticoagulation in Cardioversion using Enoxaparin) Study Group. Circulation. 2004 Mar 2;109(8):997-1003.

Submitted by Lydia Luangruangrong, PGY-3.
Edited by  Steven Hung (@DocHungER), PGY-2
Faculty reviewed by Doug Char

Hitting the bottle hard, beyond benzos for AWS.

Clinical Scenario:
It’s the age old story, chronic alcoholic evaluated for an unrelated issue, cleared from that issue only to now have developed alcohol withdrawal. The patient in question is a middle aged male with heavy alcohol use history who was transferred from another center for specialist evaluation. After being cleared by the consultant, he is now 24 hours from his last drink and looks decidedly not well. He is tremulous, tachycardic, anxious, and vomiting. You recognize his alcohol withdrawal, but despite treatment, he rapidly worsens requiring very high doses of benzodiazepines and an ICU admission. What adjunct therapies are available for severe alcohol withdrawal?

Synapse in AWS (© 2015 Cynthia Turner
Alcohol abuse is an exceedingly common problem and alcohol-related ED visits are encountered daily across the country.  Annually, around 500,000 episodes of acute alcohol withdrawal require treatment. The symptoms typically begin to manifest within hours to days after cessation of alcohol and typically peak at 2 – 3 days.  The clinical course of alcohol withdrawal varies widely among patients.  Chronic alcohol use leads to down-regulation of GABA receptors and up-regulation of NMDA glutamate receptors. Additionally, GABA receptor expression is suppressed. In the active drinker, this allows patients to maintain a normal level of consciousness despite blood alcohol levels that would incapacitate a nondrinker. Withdrawal is therefore, associated with a decrease in GABAergic activity and an increase in glutaminergic activity. The increase in excitatory activity and loss of inhibitory activity results in the symptom complex of alcohol withdrawal. Symptoms include autonomic hyperactivity, tremor, insomnia, nausea/vomiting, hallucinations (commonly visual or tactile in addition to auditory), psychomotor agitation, anxiety, generalized tonic-clonic seizures. Benzodiazepines are the standard of care for alcohol withdrawal. Adjunct therapies of old have targeted adrenergic symptoms, not so much the underlying disease. These include beta-blockers and calcium channel blockers. Other more targeted therapies like gabapentin are hindered by prolonged onset of action. Adjuncts that make a bit more sense pharmacologically and are gaining popularity include barbiturates, ketamine, and dexmedotomidine.  Let’s look at some of that data.

Literature Review:

Phenobarbital?! What is this the dark ages? Phenobarbital has a rapid onset and long duration of action, with a half-life of 80 – 120 hours. Barbiturates stimulate the GABA receptor and may augment the efficacy of benzodiazepines – so it makes sense.  A retrospective cohort study by J. Gold et al at Bellevue described success with an alcohol withdrawal treatment protocol that used phenobarbital as the primary adjunct. In this protocol, increasing bolus doses of benzodiazepines (in their case primarily diazepam) were given in a symptom-based manner. If symptoms were not controlled with these measures, phenobarbital was added to the mix. All of their patients were admitted to the ICU specifically for alcohol withdrawal. They found that their 24hour diazepam dose, maximum individual dose and use of phenobarbital increased after protocol initiation. With these increases, they also observed a reduction in the need for mechanical ventilation and non-significant trends towards improved ICU length of stay and nosocomial infections.

What about everyone’s favorite drug of the moment, ketamine? Well, it might be good for this too! (Is there anything it can’t do?) Ketamine is an NMDA antagonist. Remember that this is the other system that has been screwed up by chronic alcohol use. A pharm paper by Wong et al out of UPMC describes a retrospective review of patients treated in their ICU for alcohol withdrawal with ketamine. In their 23 cases, they found that after initiation of ketamine infusions, patients’ benzodiazepine requirement at 12 and 24 hours decreased. Sedation scores and alcohol withdrawal scores were stable despite the decrease in benzodiazepine administration. Their median infusion dose was 0.2mg/kg/hr and on average, was continued for just over 2 days. They do note that ketamine does increase heart rate and blood pressure, which can pose challenges in treatment titration.

Dexmedetomidine, a cousin to clonidine, has anesthetic, anxiolytic, analgesic and sympatholytic effects. A case series of 10 patients with severe alcohol withdrawal treated in the ICU with dexmedetomidine (J DeMuro et al) described improvements in vital signs but these improvements did not reach statistical significance. They noted no change in the rate of adverse events despite addition of dexmedetomidine to multiple other agents including bolus dose benzodiazepines, beta-blockers, antipyschotics and propofol. They also noted that dexmedetomidine allowed lower doses of other agents, thereby reducing the risk of respiratory depression with large doses of benzodiazepines, argue their authors. Additionally, they add to the literature that documents safe use of dexmedetomidine far past the FDA approved 24 hour window. The decreased need for benzodiazepines with dexmedetomidine use was echoed by S. Mueller et al. They performed a randomized, double-blind placebo controll trial comparing high dose dexmedetomidine, low dose dexmedetomidine, and placebo. They noted no difference in sedation scores despite greater reduction in benzodiazepine requirements in the dexemedetomidine group.

An important eye in the sky point to take away from a lot of this literature is don’t be stingy with the benzos. These folks have seriously mucked up their brain chemistry and may need an alarming amount of medication. Just taking the literature we’ve reviewed here, DeMuro describes benzodiazepine dosing in the 10 cases used in his series as 2mg lorazepam Q6hrs or 1mg midazolam Q4 hours and reports an average ICU LOS of 9.3 days. Compare that to the 24 hour totals in the Gold paper of over 500mg diazepam (around 50mg lorazepam) with their average ICU LOS of 3.21 days. Far from an apples to apples comparison, but a striking point.

Take home points:
So we end with another age old story. This time we answered the question we asked in the beginning only to find ourselves with more. Yes there are adjuncts to benzodiazepines that may improve clinically important outcomes like intubation, ICU length of stay, and complication rate. However, each of these has it’s own appeal and downsides, and there is no clear winner. So the next time you approach that patient with severe alcohol withdrawal, think back to some of this literature. Use strategies that have been shown to improve outcomes – symptom based and aggressive early benzodiazepine dosing. Beyond that, use of adjuncts looks like a good idea. Choosing a particular adjunct will likely be a multifactorial decision and include factors like availability, cost, and your own comfort with a particular agent. Plus, if your alcohol withdrawal patient is this sick, it might be time to call your friendly, neighborhood toxicologist.

Submitted by Sara Manning, PGY-3@EM_SaraM
Edited by Louis Jamtgaard, PGY-3 @Lgaard
Faculty reviewed by Evan Schwarz @TheSchwarziee 

DeMuro, JP et al, “Use of dexmedetomidine for the treatment of alcohol withdrawal syndrome in critically ill patients: a retrospective case series” 2012. Journal of Anesthesia. Vol. 26(4); pp. 601-605.
Gold, JA et al, “A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens.” 2007. Critical Care Medicine. Vol. 35(3); pp. 724 – 730.
Goldfrank et al, Goldfranks Toxicologic Emergencies, 8ed. 2006. McGraw-Hill.
Mueller, SW et al, “A Randomized, Double-Blind, Placebo-Controlled Dose Range Study of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal.” 2014. Vol. 42; pp – 1131 – 1139.
Wong, A et al, “Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome.” 2015, Vol. 49(1)pp 14 – 19.

Droperidol the psycho dropper or heart stopper?

Clinical Scenario:
You are working a typical EM-1 shift loaded full of psychiatric patients, EMS brings you another agitated male with a history of schizophrenia. He is shouting absurdities and threatening staff members.  The RN glances over at you, 5/2 doc? You're feeling a little different today and order 10mg of droperidol IM. The drug is administered and the patient calms down. With pride you present the patient to your attending. Your attending is alarmed and immediately requests an EKG and places the patient on a cardiac monitor and tells you the patient is in imminent danger of converting into torsades de pointes (TdP) secondary to prolonged QT.  You perform a rapid review of the literature.

Literature Review:
Droperidol is a butyrophenone that has been used since the mid 1970's primarily for acute agitation but it has also found a role in treating nausea, headaches, and abdominal pain. In 2001, droperidol received a black box warning by the FDA because of its association with QT prolongation and potential fatal arrhythmias.
FDA Black Box warning

There is no consensus as to what degree of QT prolongation is clinically significant, but several papers have cited QT longer than 500ms or delta QT of 60ms as at risk for TdP. (1) Mechanistically, in animal models Droperidol has been shown to both block efflux of myocardial potassium and induce early depolarization in cardiac fibers. Human studies have shown varied results, but lean towards droperidol causing some degree of prolonged QT without clinically significant arrhythmias. (2) 

 Lischke et al performed a randomized, double blind study on 40 patients undergoing cardiac surgery that were given either 7 mg,12.5 mg, or 17.5 mg of droperidol prior to surgery. Serial ECGs were obtained and QT prolongation ranged from 37 to 59ms in all groups in a dose dependent manner, however there were no recorded dysrhythmias or fatal events. (3) Again, Guy et al performed a prospective study in 55 patients who received 0.25mg/kg of droperidol prior to surgery, mean QT increased by 24ms, however no arrhythmias were noted. A 2014 prospective study by Calver involved continuous Holter monitoring for 24hrs in patients who had received 10-30mg IM of droperidol for acute agitation. Four out of 46 patients had abnormal QT greater than 480ms, but only one case was temporally associated with droperidol administration.  No arrhythmias were recorded. (4)  Kao et al reviewed decades of published literature including multiple systematic reviews and randomized controlled trials with outcome measures specifically observing for adverse effects of droperidol, and none cited any cases of fatal arrythmias. (1)

 Kao et al reviewed the FDA surveillance data cited by the FDA as cardiac events related to droperidol administrations, and found that the case reports were plagued by confounders and failed to show causation between droperidol administration and fatal arrhythmias.   Many of the European studies cited by FDA used doses of 50 -100mg IM, significantly higher than doses typically used in the US.  
Kao et al FDA surveillance data

Furthermore, similar case studies are described with haloperidol another commonly used antipsychotic.  

Take home points:
Bottom line is there are no randomized trials that demonstrate that droperidol causes fatal arrhythmias, there is data to show the droperidol prolongs QT in a likely clinically insignificant manner. There are rare case reports that suggest cardiac events might be associated with droperidol administration, but most cases involve confounders and cannot demonstrate causation.  Therefore it is likely reasonable to administer droperidol in most cases without any type of cardiac monitoring. However use of droperidol in this manner falls outside of FDA approval, therefore it is likely reasonable to take some precations (EKG or cardiac monitoring) in high risk groups (ESRD, severe cardiac disease) or consider alternative agents.  

Submitted by Louis Jamtgaard PGY-3 @Lgaard
Faculty reviewed by Evan Schwarz @TheSchwarziee

  1. Kao LW Droperidol, QT prolongation, and sudden death: what is the evidence? Ann Emerg Med. 2003 Apr;41(4):546-58.

  1. JM Guy, X Andre-Fouet, J Porte, et al. Torsades de pointes and prolongation of the duration of QT interval after injection of droperidol [in French] Ann Cardiol Angeiol (Paris), 40 (1991), pp. 541–545

  1. V Lischke, M Behne, P Doelken, et al. Droperidol causes a dose-dependent prolongation of the QT interval Anesth Analg, 79 (1994), pp. 983–986

  1. Calver LBr J Clin Pharmacol. 2014 May;77(5):880-6. doi: 10.1111/bcp.12272. High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings.

When What Goes Up Does Not Come Down ... Priapism Management in the ED

Priapus: son of Zeus & Amphrodite, rustic fertility god, protector of flocks, fruit plants, bees and gardens and star of the Priapeia.
Clinical Scenario: A 42 year old man with a history of hypertension presented with approximately 12 hours of priapism. He woke up and noticed his erection would not go away, even with ice, and is has been increasingly painful.  He denies any history of erectile dysfunction medication, sickle cell disease, malignancy or recreational drug use.  Urology was consulted, and after performing a penile ring block, two 18-gauge needles were inserted into the corpora cavernosa.  A few mL of blood were aspirated, and then approximately 100mcg of phenylephrine were injected bilaterally with resolution of the patient’s pain and erection.  Notably, he presented several days later with the same symptoms. 

Clinical question: What are the potential causes of priapism, and how should it be managed?

Review: Priapism is defined as an undesired erection lasting more than 4 hours, and can be divided into ischemic (low flow), non-ischemic (high flow) and stuttering (i.e. recurrent or intermittent) etiologies.  Prolonged ischemic priapism results in erectile dysfunction, corporeal fibrosis, and tissue necrosis.  Ischemic priapism results in a fully erect, painful penis; whereas non-ischemic priapism (which is less commonly seen) typically presents with a partially erect penis without persistent pain.   Sickle cell disease, thalassemia, leukemia, multiple myeloma, and medication side effects (intracorporeal injections, antidepressants, antihypertensives, and recreational drugs such as cocaine) are all potential risk factors for ischemic priapism; whereas non-ischemic priapism is usually attributable to congenital or traumatic arterio-venous malformations.  Stuttering priapism has been less studied but its etiology is thought to be related to ischemic priapism, and is seen more commonly in men with sickle cell disease, or more rarely with neurological disorders.  Overall incidence of priapism is low (1.5 per 100,000 person-years in all comers) but much higher in some populations (89% of males with sickle cell anemia will have an episode of priapism by age 20).

Diagnosis of priapism is clinical, but the differentiation between ischemic and non-ischemic can be confirmed with cavernosal blood gas analysis and Doppler ultrasonography.  Ischemic priapism will result in dark blood that is acidotic, hypoxic, and hypercarbic, and ultrasound will demonstrate minimal or absent flow.

Ischemic priapism is an urologic emergency, and along with analgesia, urologic consult should be obtained.  Oral systemic sympathomimetics such as terbutaline or pseudoephedrine can be initial
Image source: Reference 3
adjuncts, but clinical efficacy is estimated to be only 28-36% in one study, thus it is not standard of care.  Aspiration of the corpora, which is considered definitive care, involves inserting a 19 or 21 gauge butterfly needle into each corpora cavernosa.  Withdrawing about 5mL of blood should decompress the corpora.  100mcg of phenylephrine in 1mL of normal saline can then be injected into the corpora, and this can be repeated every 3-5 minutes until detumescence.  Vital signs should be measured continuously.   Should repeated aspiration and phenylephrine fail, shunt surgery can be performed, which involves creating a fistula between the corpus spongiosum and corpus cavernosum.

Non-ischemic priapism (because of maintenance of oxygenated blood) is non-emergent and can be followed up as an outpatient for arteriography with embolization of any offending fistulas.  Treatment of stuttering priapism focuses on prevention of future episodes through the use of hormonal therapies or PDE5 inhibitors, which paradoxically seem to aid in prevention in idiopathic and sickle-cell related cases.     

Submitted by Phil Chan, PGY-2
Edited by Maia Dorsett (@maiadorsett), PGY-3
Faculty reviewed by Joan Noelker, Clinical Instructor

Visual learner?  Here is great 5 min review of priapism by EM in 5 and a youtube video by Larry Mellick.

1. Deveci S.  Priapism. UpToDate.  2014 Jan 22.  Accessed 2014 Oct 30.

2.Huang, Y. C., Harraz, A. M., Shindel, A. W., & Lue, T. F. (2009). Evaluation and management of priapism: 2009 update. Nature Reviews Urology, 6(5), 262-271.
3. Vilke, G. M., Harrigan, R. A., Ufberg, J. W., & Chan, T. C. (2004). Emergency evaluation and treatment of priapism. The Journal of emergency medicine, 26(3), 325-329.

4. Salonia A, et. al. European Association of Urology Guidelines on Priapism.  Eur Urol. 2014 Feb; 65(2): 480-9. 

Submitted by Phil Chan, PGY-2
Edited by Maia Dorsett (@maiadorsett), PGY-3
Faculty Reviewed by Joan Noelker, Clinical Instructor