By Teya Casner MD MPH PGY-3

​References below the fold...

By Teya Casner MD MPH PGY-3

References are below the fold...

By Perry Lee, MD (PGY-3)
 
Advanced airway management is a mainstay of an emergency physician’s armamentarium. Many practitioners establish a routine with personal nuances established either by their training or from prior experiences. Here we examine common techniques and their effectiveness. 
 
The studies selected are not meant to drastically change your systematic practice, but give recognition to the variability in routine that can still achieve a successful intubation. In addition to technique, intubation success also relies on muscle memory from repetitive practice, operator confidence from successful mental visualization, and the ability to calmly troubleshoot a difficult airway. 

1. SNIFFING POSITIONING  
Optimal positioning of the head and neck should allow for improved laryngeal visualization during direct laryngoscopy (DL) and should therefore increase first intubation success.  A 2015 meta-analysis of randomized controlled trials (RCT) concluded that the sniffing position (alanto-occipital extension with head elevation) despite showing NO improvement in glottis visualization, first intubation success, or intubation time compared to a simple head extension position, should still be used as the standard head positioning as it provides easier intubation conditions.[i]



2. VIDEO LARYNGOSCOPY  
Video laryngoscopy (VL) is increasingly being used as a first attempt adjunct when intubating with multiple studies showing improved success when VL is used.[ii][iii][iv][v][vi] However, a 2017 RCT meta-analysis for patients in the emergency department (ED), intensive care unit (ICU), and prehospital settings requiring tracheal intubation showed NO improved first-attempt success when using video laryngoscopy compared to direct laryngoscopy.[vii]  In fact it shows that prehospital intubation success was worse when experienced operators used video laryngoscopy.

3. BOUGIE  
The gum-elastic bougie is a semi-flexible device that allows a seldinger-like technique to intubate a patient.  Rather than a routine device, most physicians use the bougie as a rescue device after a failed intubation attempt.  A SINGLE CENTER RCT study published in 2018 using the bougie as a primary intubation device showed first-pass success greater with bougie use versus endotracheal tube (ETT) and stylet use (98% vs 87%).[viii]

4. BURP  
Improved glottis visualization by backward, upward, and rightward pressure (BURP) on the thyroid cartilage to displace the larynx has been noted in multiple observational studies.[ix][x][xi]w
 
[i]Akihisa Y, Hoshijima H, Maruyama K, Koyama Y, Andoh T. Effects of sniffing position for tracheal intubation: a meta-analysis of randomized controlled trials. Am J Emerg Med. 2015 Nov;33(11):1606-11.
[ii]Mosier, JM, Stolz, U, Chiu, S, and Sakles, JC. Difficult airway management in the emergency department: GlideScope videolaryngoscopy compared to direct laryngoscopy. J Emerg Med. 2012; 42: 629–634

[iii]Sakles, JC, Mosier, JM, Chiu, S, and Keim, SM. Tracheal intubation in the emergency department: a comparison of GlideScope(R) video laryngoscopy to direct laryngoscopy in 822 intubations. J Emerg Med. 2012; 42: 400–405

[iv]Michailidou, M, O’Keeffe, T, Mosier, JM et al. A comparison of video laryngoscopy to direct laryngoscopy for the emergency intubation of trauma patients. World J Surg. 2015; 39: 782–788

[v]Silverberg, MJ, Li, N, Acquah, SO, and Kory, PD. Comparison of video laryngoscopy versus direct laryngoscopy during urgent endotracheal intubation: a randomized controlled trial. Crit Care Med. 2015; 43: 636–641

[vi]Sakles, JC, Patanwala, AE, Mosier, JM, and Dicken, JM. Comparison of video laryngoscopy to direct laryngoscopy for intubation of patients with difficult airway characteristics in the emergency department. Intern Emerg Med. 2014; 9: 93–98

[vii]Abdelgadir IS, Phillips RS, Singh D, Moncreiff MP, Lumsden JL. Videolaryngoscopy versus direct laryngoscopy for tracheal intubation in children (excluding neonates). Cochrane Database Syst Rev. 2017 May 24;5:CD011413.

[viii]Driver BE, Prekker ME, Klein LR, Reardon RF, Miner JR, Fagerstrom ET, Cleghorn MR, McGill JW, Cole JB. Effect of Use of a Bougie vs Endotracheal Tube and Stylet on First-Attempt Intubation Success Among Patients With Difficult Airways Undergoing Emergency Intubation: A Randomized Clinical Trial. JAMA. 2018 Jun 5;319(21):2179-2189.

[ix]Benumof JL, Cooper SD. Quantiative improvement in laryngoscopic view by optimal external laryngoscopic manipulation. Anesthesia and Analgesia Journal of Clinical Anaesthesia 1996;8:136-140.

[x]Takahata O, Kubota M, Mamiya K et al. The efficacy of the Anesthesia and Analgesia 1997;84:419-421.

[xi]Vanner RG, Clarke P, Moore WJ et al. The effect of cricoid pressure and neck support on the view at laryngoscopy. Anaesthesia 1997;52:896-900.

By Perry Lee, MD (PGY-3)

​Tranexamic Acid (TXA) is an antifibrinolytic that inhibits the enzymatic breakdown of fibrin by plasmin.[i]  It was first developed in 1962 by Japanese wife and husband researchers, hoping to find an effective treatment for post-partum hemorrhage which was a leading cause of maternal death in Japan at that time.[ii]  Given its effectiveness and relative cheap cost, TXA has routinely been included on the World Health Organization’s List of Essential Medicines.[iii]  Below is a list of uses for TXA commonly encountered in the emergency department (ED) with supporting research. 
 
TRAUMA
 

• CRASH-2 trial (2010)[iv]and subgroup analysis (2011)[v]

 
The CRASH-2 trial was the first major landmark article that showed improved survival in patients with traumatic injuries with known or suspected significant hemorrhage.  The trial concluded a decrease in all-cause mortality at 4 weeks in the TXA group (14.5% vs 16% in placebo group).  Specifically, there was a decrease in death from hemorrhage in the TXA group (4.9% vs 5.7% in placebo group).  No difference was found in the rate of vascular occlusive events (1.7% vs 2.0% in placebo group)
 
A follow up subgroup analysis of the CRASH-2 data showed the time sensitivity of TXA administration.  The analysis showed that patients who received TXA within 1 hour showed the highest mortality benefit (5.3% vs 7.7% in placebo group).  This mortality benefit extended into patients that received TXA within 3 hours of injury (4.8% vs 6.1% in placebo group).  More importantly, the data showed an increased risk of death due to bleeding when TXA was administered more than 3 hours after injury (4.4% vs 3.1% in placebo group).
 

• Take home:

1. TXA improved all-cause mortality in trauma patients
2. Administration is time sensitive and should be given within 3 hours of injury, ideally within 1 hour
3. Dosing: IV loading dose of 1,000 mg over 10 minutes, followed by 1,000 mg over the next 8 hours

 
 
POST-PARTUM HEMORRHAGE
 

• WOMAN trial (2017)[vi]

 
The WOMAN trial was a study to examine the effects of TXA used in post-partum hemorrhage (PPH). The original primary outcome was all-cause mortality and/or hysterectomy. However the primary outcome was changed to death from bleeding partway through the study as it was found that the decision to perform a hysterectomy was commonly made at time of randomization and therefore could not be affected by the invention of receiving TXA.  The study did show a reduction in mortality due to bleeding (1.5% vs 1.9% in placebo group) with a improved benefit if given <3hrs (1.2% vs 1.7% in placebo group), similarly to the CRASH-2 trial. 
 

• Take home:

• TXA showed benefit in PPH, however with understanding that the primary outcome was changed during trial.
• Dosing (off-label use): IV 1,000 mg over 10 minutes given within 3 hours of vaginal birth or cesarean section; if bleeding continues after 30 minutes or stops and restarts within 24 hours after the first dose, a second dose of 1,000 mg may be given.

 
 
EPISTAXIS
 

• Topical TXA (2013)[vii]

 
This study examines the use of intravenous (IV) TXA as a topical agent in the setting of non-traumatic epistaxis.  It compared TXA (500mg in 5ml) soaked cotton pledget soaked vs anterior nasal packing (ANP) defined as cotton pledget soaked in epinephrine (1:100000) + lidocaine (2%) for 10 minutes, then packing covered with tetracycline which was removed after 3 days.  They concluded an improvement in cessation of bleeding at 10 minutes (71% vs 31.2% in ANP group).  They also found an improved discharge time of 2 hours or less (95.3% vs 6.4% in ANP group) and decreased rebleeding within 24 hours (4.7% vs 11% in ANP group).
 

• Topical TXA for patients on antiplatelet (2018)[viii]

 
This was a follow up study examining the topical use of TXA in the setting of non-traumatic epistaxis, specifically in patients taking antiplatelets including Asprin, Clopidigrel, or both.  The intervention and control were exactly the same as the previous study in 2013. This trial also showed improved cessation in bleeding at 10 minutes in the TXA group (73% vs 29% in the ANP group). Improvement in rebleeding rate at 24 hours was also seen in the TXA group (5% vs 10% in ANP group).  No adverse events reported in either group.
 

• Take home:
  • Topical TXA for epistaxis is a viable option in non-traumatic epistaxis, even if patient is on an antiplatelet
  • Dosing (off-label): cotton pledget soaked in 500mg in 5mL TXA

 
 
NON-MASSIVE HEMOPTYSIS
 

• Nebulized TXA (2018)[ix]

 
This study examined the use of nebulized TXA 500mg TID vs placebo (nebulized 5ml of 0.9% normal saline) in the setting of non-massive hemoptysis. Patients were excluded hemodynamic or respiratory instability or massive hemoptysis (>200ml/24hr).  They found resolution of hemoptysis within 5 days of admission (96% vs 50% in placebo) and shorter hospital length of stay (5.7 days vs 7.8 days in placebo).
 

• Take home:

• Dosing (off-label): Nebulized 500mg in 5mL TXA.

 
 
UPPER GASTROINTESTINAL BLEED
 

• Cochrane Review (2014)[x]

 
This systematic review and meta-analysis compared 8 randomized control trials (RCT) on TXA for upper gastrointestinal bleeding (UGIB) published from 1973 to 2011.  The various studies compared different control groups including placebo, no intervention, and antiulcer mediations.  Overall, the analysis showed an improvement in all cause mortality in patients who received TXA (4.9% vs 8.4% in the control group). 
 

• Take home:
  • Limited conclusion can be drawn from this data, however TXA can be considered in severe UGIB.
  • Look out for the HALT-IT trial in the near future specifically designed to address this question!

 
 
INTRACRANIAL HEMORRHAGE
 

• TICH-2 (2018)[xi]

 
This study examined functional status at 90 days in patients who received TXA in the setting of intracranial hemorrhage from an acute stroke.  They concluded that there were NO significant difference of functional status define by a modified Rankin Score at 90 days (22% vs 21% in placebo group)
 

• Take home:
  • At this time, TXA is NOT clinically recommended in spontaneous hemorrhagic strokes.

 


[i]Geoff Watts (2016). "Obituary Utako Okamoto". The Lancet. 387 (10035): 2286. 

[ii]http://www.txacentral.org/history

[iii]WHO Model List of Essential Medicines (20th List). 2017.

[iv]Shakur H, et al. "Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage". The Lancet. 2010. 376(9734):23-32.

[v]Roberts I, et al. "The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial." Lancet. 2011; 377(9771):1096-10.

[vi]WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 27;389(10084):2105-2116.

[vii]Zahed R, et al. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med. 2013 Sep;31(9):1389-92.

[viii]Zahed R. "Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial". Acad Emerg Med. 2018. 25(3):261-266.

[ix]Wand O et al. Inhaled Tranexamic Acid for Hemoptysis Treatment: A Randomized Controlled Trial. Chest 2018. Chest. 2018 Dec;154(6):1379-1384.

[x]Bennett C et al. Tranexamic Acid for Upper Gastrointestinal Bleeding (Review). Cochrane Database Syst Rev 2014. PMID: 25414987

[xi]Sprigg N et al. Tranexamic Acid for Hyperacute Primary IntraCerebral Haemorrhage (TICH-2): An International Randomised, Placebo-Controlled, Phase 3 Superiority Trial. Lancet 2018. PMID: 29778325

​By Emerson Posadas, MD, MBA (PGY-3)
​
Thromboelastography (TEG) is a tool that measures in real-time clot development, stability, and dissolution.  It not only measures the coagulation cascade, but also shows the interaction of platelets in clot formation. It is a dynamic measurement, that has in recent years, become more readily available in the emergency department. This blog will review the evidence behind its use in the Emergency Department in the setting of shock in both trauma and medical patients. 
 
First, we must review the basics of TEG and its interpretation. Keep in mind that TEG does not necessarily correlate with traditional coagulation measurements such as INR, PT/PTT, and total platelets. The general method of TEG involves measuring the physical properties of the clot by spinning whole blood in a cup with an electrical transducer. The strength of clot formation affects the rotation of the cup, which then generates data that is visualized in real time. There are several different tests available, some of which can measure fibrinogen and others that take into account whether the patient is on heparin. 
 
What may be difficult for many people first trying to interpret TEG results is that they are presented as not only values but also graphically. As emergency physicians, we have been trained to look at numbers and discrete ranges. Analyzing graphical data on the fly is a skillset many of us have not used in quite some time, if ever. What’s important to note, is that approximate normal ranges are also given; in the event one does not want to interpret the graphical data. Below is a very basic interpretation of the different values:
 
In broad terms, what are the indications for TEG? In general, TEG should not be ordered as a screening exam, but should only be used when a physician is considering an intervention, be it transfusing a patient or performing an invasive procedure.  It can also be used to guide resuscitation, especially in the massive transfusion setting.1
 
The utility of TEG in guiding massive transfusions protocols, especially in the setting of trauma, is well studied.2Since the PROPPR trial in 2015, 1:1:1 of FFTP:PLT:PRBC has been a mainstay for trauma resuscitation as it showed that more patients achieved hemostasis and fewer deaths due to exsanguination at 24 hours.3However, transfusions of any type of blood product do pose serious risks. TEG-directed resuscitation has been explored as a tool that allows physicians to target specific coagulation parameters, with the idea that often less is more. In 2016, a randomized control trial compared TEG-directed resuscitation versus conventional coagulation assays in the trauma setting. In this study, with a sample size of 111, they found that TEG-guided massive transfusion protocols improved survival compared to those guided by conventional coagulation assays. TEG-directed resuscitation also resulted in less blood products being used.4However, it is important to note prior to this study the recommendation from a Cochrane systemic review in 2015 stated that there was no evidence on the accuracy of TEG for trauma induced coagulopathy, and strongly suggest that at present these tests should only be used for research. 5Further complicating the issue, studies have since been published either in favor or against TEG-guided management. 
 
While controversy still exists in the trauma setting, there is even less clear evidence for the use of TEG-directed resuscitation in medical coagulopathies.  There is some evidence for its use in post-partum hemorrhage, bleeding cirrhotic patients, GI bleeds, and severe epistaxis. However, currently many published articles regarding its use outside of the trauma setting are for very specific patient populations and/or case reports. In a recent randomized control trial, TEG-guided blood resuscitation was compared with conventional coagulation assays for patients with cirrhosis with nonvariceal bleeding. The study showed a significantly lower use of blood components in the TEG-guided resuscitation with similar mortality between the two groups.6Within OBGYN, TEG has been studied for its use in guiding management of severe postpartum hemorrhage.7The use of TEG to identify coagulation abnormalities in adult patients with sepsis has also been studied, but its exact applications have yet to be established. 8More studies need to be conducted to better understand the efficacy for its use in the emergency department.
 
In summary, TEG-directed resuscitation has been more established in the trauma setting but remains controversial. Studies have only recently started regarding its use in the bleeding medical patient, many of which are not conducted in the emergency department setting. Regardless, TEG-directed therapy seems promising and should at least be considered by emergency department physicians for any patient with serious bleeding that may require transfusion. 
 
 
 
1.         da Luz LT, Nascimento B, Rizoli S. Thrombelastography (TEG(R)): practical considerations on its clinical use in trauma resuscitation. Scand J Trauma Resusc Emerg Med. 2013;21:29. 
2.         Howley IW, Haut ER, Jacobs L, Morrison JJ, Scalea TM. Is thromboelastography (TEG)-based resuscitation better than empirical 1:1 transfusion? Trauma Surg Acute Care Open.2018;3(1):e000140. 
3.         Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.JAMA. 2015;313(5):471-482. 
4.         Gonzalez E, Moore EE, Moore HB, et al. Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays. Ann Surg. 2016;263(6):1051-1059.
5.         Hunt H, Stanworth S, Curry N, et al. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding. Cochrane Database Syst Rev. 2015(2):CD010438. 
6.         Kumar M, Ahmad J, Maiwall R, et al. Thromboelastography-Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial. Hepatology. 2019. 
7.         Jackson DL, DeLoughery TG. Postpartum Hemorrhage: Management of Massive Transfusion. Obstet Gynecol Surv. 2018;73(7):418-422. 
8.         Muller MC, Meijers JC, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014;18(1):R30.

By Emerson Posadas, MD, MBA PGY-3

The use of thrombolysis in the management of pulmonary embolism is controversial. While many physicians will give thrombolytics in patients with massive pulmonary embolism, I have found that many physicians are much more hesitant to utilize thrombolysis for sub-massive pulmonary embolism. While there has been significant evidence behind the use of thrombolysis in CVA and cardiac ischemia, the evidence behind its use in pulmonary embolism is much less clear.  Yet, pulmonary embolism represents a significant disease process that is associated with high morbidity and mortality. The AHA and American Cardiology Association in the past year has advocated for the use of thrombolytics in both massive and sub-massive pulmonary embolism in select patients.1However, ACEP has yet to release a clinical policy regarding the use of thrombolysis in sub-massive pulmonary embolism. In this review, I will discuss the evidence behind the use of thrombolysis in pulmonary embolism, specifically in sub-massive pulmonary embolism. 
 
In this review, we will assume that the patient already has a diagnosis of pulmonary embolism or likely pulmonary embolism. This review is not to go over the PERC, Wells, or Geneva scores in determining the likelihood of pulmonary embolism. This review guides the clinician on what to do now that the diagnosis of pulmonary embolism has been made. 
 
First, it is best to define the different types of pulmonary embolism based on severity.  Standard definitions for sub-massive pulmonary embolism have not been universally accepted. However, on review of the literature many studies share similar clinical features that delineate between the different severities. 2Massive pulmonary embolism is generally characterized as associated with cardiac arrest, sustained hypotension (BP <90 or requiring inotropic support), or persistent and profound bradycardia suggestive of shock. Submassive pulmonary embolism is associated with a SBP >90 but with signs of either right ventricular dysfunction or myocardial necrosis. Signs of right ventricular dysfunction include RV dilation on imaging, elevation of BNP (>500), new complete or incomplete RBBB, anteroseptal ST elevation/depression or TWI on EKG. Elevated troponin is a sign of myocardial necrosis. Thrombolysis in general is not indicated in non-massive or sub-segmental PE, in which patients have no evidence of hemodynamic compromise or RV strain.3In some studies, the use of the Pulmonary Embolism Severity Index can also be used to help guide management.4
 
The MOPETT trial in 2013 studied the use of half dose TPA (0.5 mg/kg max 50 mg) in sub-massive pulmonary embolism. Their main outcome measure was the reduction of pulmonary artery pressure. They found that there was a significant reduction in pulmonary hypertension as well as recurrent pulmonary embolism, however no significant mortality benefit. However, there was no analysis on rates of RV dysfunction or ischemia.5In a separate trial in 2014, the PEITHO trial studied the effect of single dose thrombolysis to reduce mortality or hemodynamic collapse in sub-massive pulmonary embolism at 7 days. They found that fibrinolytic therapy decreased incidence of hemodynamic decompensation, but was associated with up to a 5-fold major bleeding risk. 6
 
While no single study has had the power to conclusively recommend thrombolytics for pulmonary embolism, there have been several meta-analyses done. A meta-analysis in 2014 found that among patients with pulmonary embolism, thrombolytic therapy was associated with lower rates of all cause mortality but also increased rate of increased bleeding and ICH. Those with RV dysfunction, including those that were hemodynamically stable, seemed to benefit the most.  It is important to note that major bleeding was not significantly increased in patients 65 years and younger.7
Absolute contraindications are similar to those seen in the use of thrombolytics for CVA, and are associated with increased bleeding risk. This includes prior intracranial hemorrhage, AVM, suspected aortic dissection, active bleeding, recent neurosurgery, recent trauma with brain injury. 
                                                                  
Once the provider has decided to give thrombolytics, the question becomes how much? Full dose thrombolytics has been studied in multiple trials including the PEITHO trial (tenecteplase), TOPCOAT trial (tenecteplase), MAPPET-3 Trial (alteplase) which showed consistent decrease in hemodynamic compensation but mixed mortality benefit. Further, there was a increase risk of major bleeding in patients >65 years of age in all trials. 7,8While the MOPETT used ½ dose tPA with improvement of pulmonary hypertension at 28 months with no increase in major bleeding. However, mortality was not assessed in this trial. In one 2010 RCT comparing half-dose vs full dose tPA in patients with pulmonary embolism and hemodynamic instability, researchers found no difference in primary outcomes however there was increased bleeding risk in the full dose tPA group. 9
 
While more studies need to be conducted, the clinical bottom line seems to be trending towards the use of low dose/half dose thrombolysis in selected patient populations. The use of low dose systemic thrombolysis in patients with sub-massive pulmonary embolism and impending hemodynamic instability seem to benefit the most. There also may be decreased bleeding risk with low dose systemic thrombolysis versus systemic thrombolysis. While all-cause mortality does not seem to change, several other outcome measures do improve. There is no clear-cut answer, and the use of thrombolysis in patients should be made on a case by case basis and also taking into account functional status. It is clear that a component of shared decision-making should be done when considering thrombolysis. 
 
 
 
 
1.         Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of Pulmonary Embolism: An Update. J Am Coll Cardiol. 2016;67(8):976-990. 
2.         Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788-1830.
3.         Rali PM, Criner GJ. Submassive Pulmonary Embolism. Am J Respir Crit Care Med. 2018;198(5):588-598. 
4.         Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172(8):1041-1046. 
5.         Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M, Investigators M. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013;111(2):273-277. 
6.         Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.
7.         Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421.
8.         Kline JA, Nordenholz KE, Courtney DM, et al. Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost. 2014;12(4):459-468. 
9.         Wang C, Zhai Z, Yang Y, et al. Efficacy and safety of low dose recombinant tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism: a randomized, multicenter, controlled trial. Chest. 2010;137(2):254-262. 

By Elizabeth Chen MD PGY-3

Acute Ischemic Stroke (AIS) in the pediatric population is extremely rare, has many mimics, and often presents with signs and symptoms that differ from a typical “adult” stroke.  Because the goal for diagnosis and treatment of AIS in adults is 4 hours, these differences often lead to delayed recognition and treatment. In a Canadian study, median interval from time of onset to diagnosis was 22.7 hours. When a stroke occurred in hospital, it still took 12.7 hours to diagnose.   When a child had a stroke out of the hospital, it took on average 1.7 hours for patients to present to the hospital, indicating that the time delay to diagnosis was often on the part of the medical staff. Currently, only a handful of large, dedicated pediatric centers have pediatric stroke teams similar to the typical adult “code stroke” teams found in most communities.  These pediatric teams are equipped to diagnosis and potentially treat children with AIS quickly but most hospitals are not. The key to improve care for children in the community is for all emergency physicians to be well trained on how to recognize and evaluate children for stroke.
​
Recent estimate of the incidence of pediatric stroke is 2-13 per 100,000 children per year. Presentation in children less than a year old, may show up as focal weakness, but more likely to present as seizures and altered mental status. In older children, it is somewhat more similar to adults with hemiparesis or other focal neurologic signs like aphasia, visual disturbances, or cerebellar signs.
According to the International Pediatric Stroke study, half of children with AIS have at least one predisposing factor.   In 676 children from ages 29 days to 18 years with AIS, 9% had no risk factors, 53% had arteriopathies, 31% cardiac disorders, and 24% infection.  When assessing patients for stroke, have a higher clinical suspicion when they have any of the following risk factors:

Arteriopathies:
Focal cerebral arteriopathy of childhood—unilateral focal or segmental stenosis of distal carotid arteries and proximal circle of Willis vessels. The cause is unknown but some have had antecedent viral infections which may potentially cause an inflammation vasculitis.  
Postvaricella arteriopathy—Accounts for nearly 1/3 of childhood AIS. Intraneuronal migration from trigeminal ganglion to cerebral arteries. In a study in Canada with children 6 months to 10 years with confirmed AIS, 31%  had Varicella in the preceding year with a mean interval from varicella infection to AIS being 5.2 months. Patients may experience recurrent varicella associated AIS up to 33 weeks after presentations even with antithrombic prophylaxis.
Moyamoya—a disease process that causes progressive stenosis of the distal intracranial internal carotid artery, and less commonly stenosis of the anterior cerebral artery, middle cerebral artery , basilar artery, and posterior cerebral artery. Peak incidence is at 5 years. Recurrent TIA/AIS are common. Typically, the strokes are ischemic in childhood and then convert to hemorrhagic strokes in young adulthood.

Cervicocephalic arterial dissection—Cervicocephalic arterial dissection accounts for 7.5% of all AIS, half of which are due to trauma. Predisposing factors include trauma, connective tissue abnormalities, fibromuscular dysplasia, and anatomic variations. The cause of intracranial dissection is often spontaneous, while extracranial dissections are associated with trauma. This condition presents with headache, vomiting, dizziness, vertigo, diplopia, confusion, neck pain, and recurrent TIA’s.
Sickle Cell Disease (SCD)—These children are at a very high risk of stroke.  Approximately 11% of SCD patients will have had a clinically significant stroke by age 20, and this increases to 24% by age 45. Transcranial doppler is important in predicting risk for stroke; a mean velocity greater than 170 cm/sec places patients at a marginal risk, while values greater than 200 cm/sec in MC/ICA are highly associated with increased AIS risk.  If a patient with SCD presents with AIS, immediately order transfusion therapy and immediate exchange transfusion for a goal of a HbS fraction less than 30% and a hemoglobin level of 10. Hydroxyurea used by patients with sickle cell disease to reduce the incidence of painful crisis and blood transfusions unfortunately does not prevent stroke recurrence.

Congenital heart disease: Stroke is associated with most types of cardiac lesions but complex congenital heart lesions with right to left shunting and cyanosis are particularly prone to cause stroke. Additionally valvular disease, endocarditis, and arrythmias can lead to stroke. Chronic hypoxia leads to a markedly elevated hematocrit which places patients at higher risk for cerebral venous sinus thrombosis. Although the presence of a PFO increases the risk of stroke, it’s presence should not exclude further investigation into other cardiac abnormalities.

Hypercoagulable disorders: Prothrombotic states alone are rarely a cause of AIS; however, combined with other mechanisms such as protein C deficiency, antiphospholipid antibodies, and elevated lipoprotein, the odds ratio increases.   

Vasculitis: Primary vasculitides include Takayasu, giant cell arteritis, polyarteritis nodosa, Kawasaki disease,  and primary angiitis of the CNS. Diseases associated with secondary vasculitides include infection (bacterial meningitis, HIV, varicella, syphilis, fungal infections, CNS tuberculosis), malignancy, and collagen vascular diseases.  

Metabolic: Conditions such as Fabry disease, homocystinuria, and Menkes disease affect the cerebral vessel walls and increase the risk of AIS.

Presentation:
Infants and toddlers may present with headaches, seizures, altered mental status, behavioral/personality changes, sleepiness or decreased level of consciousness. While older children may present more similarly to adults with severe/sudden headache with vomiting and drowsiness, Vision loss/double vision, severe intractable dizziness, loss of balance/coordination, seizures on one side of the body, numbness/weakness on one side of body, difficulty speaking/understanding others.
There are also many stroke mimics in pediatrics that can make the diagnosis difficult.
Stroke Mimics n=287 Children (Mackay, Stroke 2017)

Migraine-28%
Febrile/Afebrile Seizure-15%
Bell’s Palsy-10%
Stroke-7%
Conversion Disorder-6%
Syncope-5%
Headache NOS-4%
Other CNS conditions-10%

Diagnosis:  Because of the difficulty of making the ultimate diagnosis of AIS in children an MRI and MRA of the brain and neck must be done, after an initial CT.  This often increases the time to diagnosis because of the logistics required to provide sedation for an MRI.

Management: The goal of treating children with AIS is to minimize morbidity and mortality and if possible to improve perfusion to the ischemic areas of the brain.  The system for adults is well organized and shown to improve outcomes. Thrombolysis (tPA) is well documented for use in adults, however it is not FDA approved for anyone under 18 years of age.  Attempts have been made to show efficacy and safety in children. There was a large NIH funded study started in 2015, Thrombolysis in Pediatric Stroke Study (TIPS). It was an international multicenter study with a total of 17 different sites.  A total of 93 patients were screened; 43 had a confirmed stroke, but only 1 child was enrolled. Almost half the stroke patients did not meet enrollment criteria because of missing the time limit (4.5 hours) to receive tPA. The study was discontinued because of a lack of enrollment.  Although there are still no large scale trials showing efficacy and safety there are some case reports showing positive results of tPA in teenage patients. Therefore, management to date should include rapid diagnosis and stabilization to minimize morbidity. Thrombolysis should be considered on a case-by-case basis.  

Future of AIS evaluation in children:  We need to improve awareness of stroke signs and symptoms in pediatric patients in order to diagnose and transport more quickly to a Pediatric Stroke Center.

Here is an example of a pediatric stroke evaluation protocol from Boston Children's Hospital:

By Emerson Posadas MD MBA PGY-2

This is the first of a series of blog posts about administrative and management aspects of the Emergency Department. The first blog in this series describes the transition from one electronic medical record (EMR) system to a new one in our own Emergency Department and all the challenges we faced.

As part of the American Recovery and Reinvestment Act, all pubic and private healthcare providers were required to adopt electronic medical records in 2014. There have been multiple articles on the transition from paper charting to EMR. However, not much has been discussed regarding the transition from one EMR system to another one. With an ever-increasing amount of electronic platforms available, EMR transitions are a common challenge faced by many hospital systems. At University Medical Center of Southern Nevada (UMC) we recently transitioned from McKesson software to EPIC software as our primary EMR system. With this, there were multiple opportunities to improve our workflow and operations in the emergency department. However, as with all transitions this was not as seamless as envisioned.

This transition period was preceded by months of preparation, as we customized the EMR system to our needs. We attempted to develop efficient pathways in the EMR to improve patient care and bring efficiency benefits. This involved multiple meetings with the EMR representatives, gathering input from all staff including physicians, nurses, and pharmacists. We received several notifications in the preceding months that we were “going live” on December 1st 2017. Staff was informed that there would be multiple EPIC “Superusers” available to us in the emergency department during the first month of transition period. Luckily, I was scheduled to work the night we went live.

I was in the middle of a busy night shift. We had been informed that at 3:00 am our current EMR system would be disabled, and there would be a downtime before the new EMR went live. However, we found that the downtime started to occur much earlier than we expected, and by 1:00 am our original EMR had gone down. Orders were no longer going through the computer system. Radiology reports were not being received. Further, there was no electronic tracking board to display which patients had been placed in a bed, discharged, or admitted. In the already chaotic environment of the Emergency Department, another layer of disarray had been added.

However, what occurred next was actually a marvelous display of problem solving and teamwork that was a testament to the preparedness of our Emergency Department. We dusted off old containers that held old paper order forms. The clerks got in contact with the radiology reading room to fax over any reads, and the nursing staff constantly printed and brought them to the physicians. The charge nurse created a makeshift tracking board on a white board that was constantly updated. We were going old school, and it was working. I credit the staff and administration for converting what could have been a terrible situation into something that was manageable. Further, I was able to peer into a time before computers and electronics dominated the healthcare environment. It was simple, but it worked. Over the next few hours, our new EMR system slowly started to become “live.”

​Over the next few weeks, there were growing pains with incorporating the new system to our workflow, but I believe the transition has been a good thing. It has been an opportunity to address core issues in the emergency department to increase efficiency, processes, and ultimately deliver the best possible patient care.

By M. Subramanian, MD and J. Haber, MD

​Image by Alessandro M via flickr

With Punxsutawney Phil predicting another 6 weeks of winter, it’s time for a review of literature on resuscitation of the hypothermic patient. Hypothermia can be a source of anxiety for the emergency physician. The risk of malignant arrest or arrhythmia is very high (and should be expected to occur) in any patient with a core body temperature under 32 degrees Celsius, despite rewarming and resuscitation; this is due to a phenomenon called Rescue Collapse or Afterdrop. Morbidity and mortality are very high in these patients, with less than 50-60% of patients survive neurologically intact after experiencing hypothermic arrest. While there are very few studies on hypothermia resuscitation, there exists some interesting opinions on protocols.
Let’s start at the beginning….
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Many of the protocols start with recognizing hypothermia, either by measuring core temperature (which is difficult to do in the field) or by feeling a cold trunk.  Hypothermia is defined as a core temperature of less than 35 degrees Celsius. A few studies show that esophageal measurement of core body temperature is equivocal to rectal and bladder temperature, but rectal and bladders temperatures may lag behind core temperatures during the process of rewarming.
The next step should be assessment of vital signs. Hypothermic patients may have cardiac instability or irritability, which places them at a very high risk of developing a malignant arrhythmia. Initiation of CPR in an altered hypothermic patient with a bradycardic pulse may actually cause cardiac arrest. Many of the protocols recommend gentle handling of the altered hypothermic patient, and one even recommends checking for a plus for 60 seconds before initiating CPR. Staging the degree of hypothermia is important to determine management; the standard scale used is the Swiss Hypothermia Scale. 

Classification depends more on clinical symptoms rather than core temperature. A patient with a core temperature less than 35 degrees Celsius who is alert (Stage 1) can be treated with passive rewarming measures, such as blankets, heat lamp, and active movement. It is important that the patient have a shivering response as this is key to recovery.

For the altered hypothermic patient with a pulse (Stage 2 or 3), many protocols recommend passive and minimally invasive rewarming.  These include blankets/Bair huggers and warm lights. It is generally not recommended to attempt bladder lavage, peritoneal lavage or thoracic lavage in these patients as such practices may aggravate the cardiac membrane and initiate malignant arrhythmia. Warm IV fluids does not substantially contribute to rewarming, but may be used for volume resuscitation as hypothermia may cause cold-diuresis. One protocol recommends normal saline boluses of 500 ml. Other protocols, however, recommend using crystalloids other than normal saline as patients may require massive amounts of fluids and large boluses of normal saline may worsen acidosis. Warmed humidified air has been seen in multiple studies to improve rewarming rates and is recommended by most protocols. Early airway management was also generally recommended as endotracheal intubation had low rates of instigating arrhythmias in hypothermic patients. As providers should expect a fatal arrhythmia to occur, securing the airway, placing of defibrillating pads and adequate IV access is recommended. Different protocols recommended rewarming the patient to 32-34 degrees Celsius, and then following therapeutic hypothermia rewarming protocols over the next 24 hours. Sinus bradycardia is a normal physiological process in the setting of hypothermia. It is not necessary to use atropine or cardiac pacing, as this will resolve with rewarming. Hypotension or ventricular arrhythmias reflect cardiac irritability, and while supportive management is the mainstay, providers must prepare for a probable malignant arrhythmia.

The hypothermic arrest patient provides a challenge to the typical ACLS resuscitation. The physiology of medication metabolism and the cardiac myocyte response to electricity in hypothermia decreases success of current practices. European guidelines recommend trying 3 rounds of epinephrine and cardiac defibrillation before core body temperature is rewarmed to 32 degrees Celsius. Other sources say to only give one round of epinephrine and one defibrillation attempt before core temperature reaches 32 degrees Celsius. Dr. Doug Brown recommends a combination of the two; one dose of epinephrine and one defibrillation attempt (in the setting of a shockable rhythm) at first, then continuous CPR with rewarming. With every 5 degree Celsius increase in core body temperature, he recommends checking for pulse and shockable rhythm, and if pulseless with shockable rhythm, giving another round of epinephrine and defibrillation. If that does not work, continue CPR and rewarming until core body temperature is 32 degrees Celsius, and a last round of epinephrine and defibrillation. If at that point the arrest is not reversed, the patient is presumed dead and CPR may be terminated. As the emergency medicine adage goes- “the patient is not dead, until warm and dead”. This alteration to the typical ACLS process allows for fewer interruptions of CPR and defined end point. Unfortunately, there is no solid evidence defining what is “warm enough”, but consensus appears to settle around 30-32 degree Celsius.

It is in the setting of Stage 3-4 that invasive rewarming techniques is found to be most beneficial. Multiple case reports and series have shown an advantage to patients who received extracorporeal warming. Techniques include continuous venovenous, continuous arteriovenous (which can be done in the ED), hemodialysis and cardiac bypass. Other techniques of invasive rewarming include lavages of the bladder, peritoneum (similar to a DPL) and thoracic cavities. While these latter techniques are recommended by a few protocols, Dr. Weingart of EMCrit discourages against bladder and peritoneal lavage. He states the risk of complications with peritoneal lavage is not worth the benefit of rewarming. Also, bladder lavage rewarming rates are not aggressive enough to justify the intervention. However, given the high mortality of stage 3 and stage 4, it may be reasonable for clinicians to decide to perform these procedures, as a last resort if all else has failed. Almost all protocols agree that extracorporeal warming is the best for rapid rewarming. Mortality rates improve from below 37% survival to 50-60% survival. Unfortunately many community practices do not have facilities to achieve this, and transfer to such facilities may be difficult to ensure. Hemodialysis is more readily available and has rewarming rates of 1.5 degrees Celsius/hour. Dr. Gentilello created a machine that took blood from an arterial line to a level 1 infuser, warming the blood and connecting it to a venous catheter. However it is difficult to find this adapter anymore.

If a patient does not rewarm at the established rates (given the rewarming interventions), providers should consider other causes preventing an increase in core body temperature. Most common causes of failure to rewarm include hypoglycemia, alcohol intoxication, infection/sepsis, Addison’s, malnutrition and myxedema coma. It is important to check a fingerstick glucose as well as labs for CBC, metabolic panel, thyroid function tests and blood cultures.
While there are many case reports of successful return of spontaneous circulation in hypothermic arrest patients, slow or stagnant neurologic recovery is a significant part of morbidity. Stage 1 patients have the best chances of survival with rates up to 100% neurologically intact. Organ failure is common within the first 24 hours of Stage 4 hypothermic patients, with pulmonary edema as the leading cause of death. Resuscitated hypothermic patients have an in-hospital mortality of 40%. However, given the existence of case reports highlighting the rare patient with full neurologic recovery from Stage 3 or 4 hypothermia, it is difficult to counsel family on withdrawing care. One study found that patients with hypothermia that were found indoors had worse outcomes. Other prognostic factors include serum potassium. A significantly elevated serum potassium is indicative of hypoxia and traumatic cell death. One protocol suggested termination if serum potassium was greater than 12 mmol/liter. Another factor is hypothermia from avalanche burial; indications that hypoxia preceded hypothermia (and therefore not likely to respond to CPR) include snow in the airway, asystole and burial time greater than 35 minutes.

While there are multiple protocols addressing the management of the hypothermic patient, there is little evidence to support one protocol versus another. More research is needed to determine the best evidence based approach to hypothermic patients. Therefore, consider contributing your hypothermia cases to the International Hypothermia Registry, and increase available data to help establish a standard of practice.  

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Resources:
Brown DJ, Brugger H, Boyd J, Paal P. Accidental hypothermia. N Engl J Med. 2012;367(20):1930-8.
Gervais J, Sholl M, Holmes J. Accidental Hypothermia Guideline. Maine Medical Center. Jan 2013. < http://www.mainehealth.org/workfiles/mmc_em/Accidental-hypothermia-v2.pdf>
Mulcahy A, Watts M. Accidental Hypothermia: An Evidence Based Approach. Emergency Medicine Practice. 2009;11(1).
Van der ploeg GJ, Goslings JC, Walpoth BH, Bierens JJ. Accidental hypothermia: rewarming treatments, complications and outcomes from one university medical centre. Resuscitation. 2010;81(11):1550-5.
Boue Y, Lavolaine J, Bouzat P, Matraxia S, Chavanon O, Payen JF. Neurologic recovery from profound accidental hypothermia after 5 hours of cardiopulmonary resuscitation. Crit Care Med. 2014;42(2):e167-70.
Roeggla, M., Holzer, M., Roeggla, G., Frossard, M., Wagner, A. and Laggner, A. N. (2001), Prognosis of Accidental Hypothermia in the Urban Setting. Journal of Intensive Care Medicine, 16: 142–149.
Jones AI, Swann IJ. Prolonged resuscitation in accidental hypothermia: use of mechanical cardio-pulmonary resuscitation and partial cardio-pulmonary bypass. Eur J Emerg Med. 1994;1(1):34-6.
Weingart, Scott. "Podcast 66 – …Until They Are Warm and Dead: Severe Accidental Hypothermia." Review. Audio blog post. EMCrit. Scott Weingart, 7 Feb. 2012. Web. 27 Feb. 2014.
Brown, Doug, and Mel Herbert. "Accidental Hypothermia- Part 2." Review. Audio blog post. EM:RAP. Mel Herbert, Jan. 2014. Web. 27 Feb. 2015.
Petrone P, Asensio JA, Marini CP. Management of accidental hypothermia and cold injury. Curr Probl Surg. 2014;51(10):417-31.
Kosiński S, Darocha T, Gałązkowski R, Drwiła R. Accidental hypothermia in Poland – estimation of prevalence, diagnostic methods and treatment. Scand J Trauma Resusc Emerg Med. 2015;23:13.
Gordon L, Ellerton JA, Paal P, Peek GJ, Barker J. Severe accidental hypothermia. BMJ. 2014;348:g1675.
Paal P, Gordon L, Strapazzon G, et al. Accidental hypothermia-an update : The content of this review is endorsed by the International Commission for Mountain Emergency Medicine (ICAR MEDCOM). Scand J Trauma Resusc Emerg Med. 2016;24(1):111.
Walpoth B, Meyer M. International Hypothermia Registry. University Hospital Geneva, Switzerland. Accessed 12/14/17. <https://www.hypothermia-registry.org/>