Category Archives: practice updates

Medical Malpractice Insights: Learning from mistakes and dodging bullets

Author: Chuck Pilcher, MD, FACEP (Editor, Med Mal Insights) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Thanks for allowing me to share excerpts from my free monthly opt-in email newsletter, Medical Malpractice Insights – Learning from Lawsuits. The goal of MMI-LFL is to improve patient safety, educate physicians, and reduce the cost and stress of medical malpractice lawsuits.

These posts will appear periodically on emDocs.net for reader enlightenment (and occasionally entertainment).

The first example below is from the September, 2016, issue which highlighted 3 cases of probable negligence that did not result in lawsuits – in the case below, only because the plaintiff (the deceased patient’s wife) died before the case could be filed. Being lucky is no substitute for being smart.

– Chuck Pilcher MD, FACEP, Editor, Med Mal Insights

 

Learning from mistakes and dodging bullets

When it’s CHF and not “walking pneumonia

Patient dies 20 hours after clinic visit for SOB and chest pain

Facts: An ARNP working in a rural Eastern Washington hospital clinic sees a 69 yo male diabetic, hyperlipidemic smoker who c/o SOB, chest tightness, and fatigue for the past 7 days. Other risk factors include peripheral vascular disease w/ fem-pop bypass, sleep screen-shot-2017-01-15-at-4-51-27-pmapnea, prior TIA, and CVA. He is on an ARB, ACE inhibitor, and Lipitor. Orthopnea is not documented. Exam shows a BP of 98/56 (low compared to prior clinic records) and HR 110 (high compared to prior clinic records.) No temperature is recorded. He also has a moist cough with scattered rhonchi but no wheezing. He is diagnosed with “walking pneumonia” and “SOB,” and is prescribed Augmentin and an Albuterol MDI. A brief differential listed does not include CHF. An x-ray done after leaving the clinic is reported as possible “early CHF.” The x-ray results are called to the patient by an MA and an appointment made for a F/U visit in 7 days. Twelve hours later the patient experiences a cardiac arrest. He is returned to the hospital via EMS and dies. Autopsy reveals coronary atherosclerosis and an MI “about 24 hours old.” An attorney is consulted by the surviving spouse.

Plaintiff: I had multiple risk factors for heart disease and an ACS, but you assumed my problem was related to my smoking. You didn’t address my chest tightness, low BP, or tachycardia. You didn’t even do an EKG because you didn’t consider CHF in your differential. You called it “pneumonia” yet didn’t even take my temperature. Besides, Augmentin is a poor choice for “walking pneumonia,” even if you were right. You didn’t even reconsider your diagnosis after you got the x-ray results, so why did you even bother to order one?

Defense: This case was reviewed prior to filing a lawsuit so no defense position is available.

Result: After review by two experts, the patient’s care was felt to be substandard for an ARNP or other primary care provider in a similar situation. A lawsuit was felt to have merit. However, the plaintiff (the surviving spouse) died before the case could be pursued and the attorney had no other reason to pursue it. A bullet was dodged.

Takeaway: Many steps were missed and assumptions made in this case. Keep an open mind in older patients with chest tightness and SOB.

  • Don’t anchor to one element of history, exemplified by the ARNP’s note that includes this: “As I walked into the room the air was impregnated with stale smoke.”
  • Review x-ray results with an open mind and be willing to reconsider your diagnosis.
  • Compare prior vital signs for significant changes.
  • Have a low threshold for getting an EKG in patients with “chest tightness.”
  • “Scattered rhonchi” are common in CHF.
  • Missing the diagnosis of “Walking pneumonia” is rarely life-threatening. Missing an acute coronary syndrome and/or new onset CHF can be rapidly fatal.
  • In the ED, there are a variety of pneumonia mimics: CHF, PE, aspiration, atelectasis, TB, septic emboli, foreign body, ARDS, and many others. The ED provider must consider and evaluate for these mimics. For more on this, please see this post: http://www.emdocs.net/pneumonia-mimics-pearls-and-pitfalls/

 References:

http://emedicine.medscape.com/article/223609-overview 

http://emedicine.medscape.com/article/163062-overview 

http://www.emdocs.net/pneumonia-mimics-pearls-and-pitfalls/

“We learn from failure, not from success.” Bram Stoker, Dracula

TOX CARDS: CIWA-AR

Author: Brian P. Murray, DO (@bpatmurray Senior EM Resident Physician, Resident Brooke Army Medical Center) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital), and Brit Long, MD (@long_brit)
screen-shot-2017-01-08-at-11-30-27-pm
Case Presentation:

A 53-year-old man presents to the Emergency Department with a history of 12 alcoholics drinks daily. His last drink was 24 hours ago, and he is feeling anxious and jittery. Vital signs: HR 90, BP 135/90, RR 18, T 98.9oF, SpO2 97% room air.  

Question:

How can you determine the severity of withdrawal and the need for inpatient versus outpatient management?

Pearl:

The use of the 10 item CIWA-AR score is a rapid and effective tool that can help objectively rate the level of alcohol withdrawal. [1]

  • Alcohol withdrawal syndrome is a spectrum of disorders ranging from mild symptoms to life threatening seizures and delirium tremens. [2]
  • The CIWA-AR score cannot differentiate the different types of alcohol withdrawal syndromes nor between delirium tremens and medical causes of delirium. [3]
  • The score ranges from 0 (no withdrawal) to 67 (severe withdrawal) and can be easily repeated for evaluation of worsening or improving withdrawal.
  • The score incorporates the scores from the categories “Nausea and Vomiting” (0-7), “Tremors” (0-7), “Paroxysmal Sweats” (0-7), “Anxiety” (0-7), “Agitation” (0-7), “Tactile Disturbance” (0-7), “Auditory Disturbance” (0-7), “Visual Disturbance” (0-7), “Headache of Fullness” (0-7), and “Clouding of Sensorium” (0-4).
  • A score of 0-9 is considered mild withdrawal and can be managed as an outpatient with supportive can with or without medical management, at the discretion of the physician.
  • A score of 10-19 is considered moderate withdrawal and should be considered for admission for acute medical detoxification.
  • A score of >20 is considered severe withdrawal and the patient should be admitted to a high acuity unit, such as an ICU, for close monitoring and medical detoxification.
  • If the CIWA-AR score remains high even after adequate medical management, the patient likely has a comorbid medical delirium. [4]
  • A similar 20 item CIWA-B score is also available for use with acute benzodiazepine withdrawal. [5]
Main Point:

The CIWA-AR score is an effective tool that can be employed in less than 5 minutes to objectively score the level of withdrawal. It can also be repeated to assess efficacy of treatment of progression of withdrawal. The tool can be useful in determining the ultimate disposition of the patient; whether they can be discharged to outpatient care (score 0-9), require floor admission (10-19), or ICU admission (score >20).

 
References:

1.      Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA‐Ar). British journal of addiction. 1989 Nov 1;84(11):1353-7.

2.      Kattimani S, Bharadwaj B. Clinical management of alcohol withdrawal: A systematic review. Industrial psychiatry journal. 2013 Jul;22(2):100.

3.      Chabria SB. Inpatient management of alcohol withdrawal: A practical approach. Signa Vitae. 2008;3:24–9.

4.      Bharadwaj B, Bernard M, Kattimani S, Rajkumar RP. Determinants of success of loading dose diazepam for alcohol withdrawal: A chart review. Journal of Pharmacology and Pharmacotherapeutics. 2012 Jul 1;3(3):270.

5.      Busto UE, Sykora K, Sellers EM. A clinical scale to assess benzodiazepine withdrawal. Journal of clinical psychopharmacology. 1989 Dec 1;9(6):412-6.

Tox Cards: Narcan (naloxone)

Author: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

 screen-shot-2017-01-08-at-11-30-27-pm

Case presentation:

25-year-old M brought in by EMS after being found not breathing, pupils are pinpoint. HR 61, BP 109/40, RR 6, T98, O2 Sat 70% RA. You ask for Narcan (Naloxone).

Question:

What dose Narcan should you give?

Pearl:

Start with small doses, i.e. 0.04 mg, and not the standard dose of 0.4 mg IV/IM.

  • The use of copious amounts of naloxone can precipitate opioid withdrawal.
  • Precipitated opioid withdrawal to an opioid-dependent person does not only cause patient distress and complicate care, but it can be life threatening.
  • Patients with precipitated opioid withdrawal (unlike regular opioid withdrawal) are at risk of seizures and arrhythmias.
  • The often referenced ‘standard dose’ and the dose usually given by EMS is 0.4 mg via the IV or IM route.
  • Although this ‘standard dose’ will reverse opioid-induced respiratory depressant effects in non-opioid-dependent patients, it can precipitate withdrawal in opioid-dependent persons.
  • Life-threatening complications like tonic-clonic seizure, and significant hypotension have occurred with IV/IM doses of 0.2 mg – 1.2 mg.[1, 2, 3]
  • Although severe life-threatening reactions after naloxone administration are relatively rare, it usually occurs when the ‘standard’ naloxone dose of 0.4mg IV/IM is given.

 Main Point:

Naloxone can be lifesaving. However, given the high prevalence of opioid addiction and the rare but potentially dangerous complication of precipitated opioid withdrawal, the use of initial small escalating doses of naloxone can avoid the development of precipitated opioid withdrawal. An appropriate strategy is to start with 0.04 mg and titrate up every 2-3 minutes as needed for ventilation to 0.5 mg, 2 mg, 5 mg, up to a maximum of 10-15 mg.[4, 5]

 

References

  1. Buajordet I., Næss A., Jacobsen D., Brørs O. Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. Eur J Emerg Med. 2004;11: 19–23.
  2. Osterwalder J. Naloxone – for intoxications with intravenous heroin and heroin mixtures – harmless of hazardous? A prospective clinical study. Clin Toxicol. 1996;34: 409–416.
  3. Yealy DM, Paris PM, Kaplan RM, Heller MB, Marini SE. The safety of prehospital naloxone administration by paramedics. Ann Emerg Med. 1990; 19(8): 902-5.
  4. Boyer EW: Management of opioid analgesic overdose. N Engl J Med. 2012; 367:146-155).
  5. Kim HK, Nelson LS. Reversal of Opioid-Induced Ventilatory Depression Using Low-Dose Naloxone (0.04 mg): a Case Series. J Med Toxicol. 2016; 12(1):107-10.

 

 

Sepsis Biomarkers: What’s New?

Author: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 43-year-old female presents with cough, congestion, wheezing, fever, and myalgias. She has a history of hypertension and recurrent UTI. She tried to overcome her symptoms with acetaminophen and oral fluids, but her symptoms have worsened. Her vital signs include RR 23, HR 102, BP 102/63, T 101.2, and Saturation 94% on RA. She has right-sided crackles on exam and appears ill, with dry mucosa. You start one liter of LR, while ordering CBC, renal panel, lactate, urinalysis, and chest Xray. Her chest Xray and urinalysis are negative, but after 1L LR, she still appears ill. The lactate returns at 4.2, and you start IV antibiotics with concern for septic shock. Your medical student on shift asks about using procalcitonin to rule out a bacterial cause of sepsis. You know about lactate, but are there other markers you can use in sepsis?

Sepsis is common in the ED and a major cause of morbidity and mortality. The body’s response to an infectious source in sepsis often results in dysregulated immune response, and current diagnosis relies on physiologic criteria and suspicion for a source of infection with laboratory and imaging studies. The host response triggered by the infection can be measured using several biomarkers.1-4

Biomarkers are defined by laboratory assessments used to detect and characterize disease, and they may be used to improve clinical decision-making. Through the years, complete blood cell count (CBC), troponin, creatine kinase (CK), lactate, C-reactive protein (CRP), ESR, and myoglobin have been advocated as biomarkers for a long list of conditions. However, what do biomarkers offer in sepsis? Some argue these biomarkers lack sufficient sensitivity outside of history and exam, while others state these markers can drastically improve medical decision making. In sepsis, diagnosis may not be easy, and a reliable biomarker may be able to improve early diagnosis, risk stratification, assessment of resuscitation, and evaluation.4-8

The post will evaluate several key biomarkers including lactate, procalcitonin, troponin, and novel lab assessments.

Lactate

Lactate can be used in sepsis for resuscitation and severity stratification. It is normally produced in tissues due to pyruvate and NADH metabolism. There are several causes of lactate elevation, and not all are due to shock. Excess beta activity, inflammatory mediators, and liver disease may increase lactate.8-13  The table below demonstrates types and sources of lactate production.

Type A Type B1

Associated with disease

Type B2

Drugs and Toxins

Type B3

Associated with inborn errors of metabolism

Tissue Hypoperfusion

 

Anaerobic muscular activity

 

Reduced tissue oxygen delivery

 

 

Leukemia

 

Lymphoma

 

Thiamine deficiency

 

Pancreatitis

 

Hepatic or renal failure

 

Short bowel syndrome

Phenformin

Metformin

Epinephrine

Norepinephrine

Xylitol

Sorbitol

Lactate-based dialysate fluid

Cyanide

Beta-agonist

Alcohols: Methanol, Ethylene Glycol

Salicylates

Nitroprusside

Isoniazid

Fructose

Paracetamol

Biguanides

Anti-retroviral agents

Pyruvate carboxylase deficiency

 

Glucose-6-phosphatase deficiency

 

Fructose-1,6-bisphosphatase deficiencies

 

Oxidative phosphorylation enzyme defects

Screening

The Surviving Sepsis Campaign recommends lactate for screening.1 Point of care (POC) lactate can be used for this screen, with specificity of 82% for lactate > 2 mmol/L. However, POC lactate has sensitivity of 30-40%, thus physicians must consider the clinical picture and patient appearance.11-16 Arterial blood is not required for this screening, and a venous blood gas (VBG) is fast and easily obtainable. As long as analysis occurs within 15 minutes of sampling, no effect from tourniquet or room temperature is observed.16,17 Lactate is not as reliable if the sample is run over 30 minutes from the time the sample is obtained.

Prognostication

As lactate elevates, mortality increases. In patients with lactate greater than 2.1 mml/L, mortality approximates 14-16%. If lactate reaches 20 mmol/L, mortality approximates 40% or higher.20 Lactate is an independent marker for mortality, no matter the patient’s hemodynamic status. Lactate greater than 4 mmol/L meets criteria for septic shock, and levels greater than 2 mmol/L are associated with increased mortality and morbidity.1,21-26

What about cryptic shock?

Cryptic shock is defined by sepsis in the patient with normal vital signs. A patient who is hemodynamically stable but with elevated lactate is at increased risk for mortality, as end organ damage occurs soon after lactate production. Thus, lactate serves as an early marker for shock and provides valuable diagnostic information. 9,11,20,21

What to do with the intermediate lactate level…

Lactate > 4 is associated with high mortality, but intermediate levels are as well (2.0-3.9 mmol/L).1,20-26 In fact, levels in this range meets Centers for Medicare and Medicaid Services (CMS) criteria for severe sepsis following SSC guidelines.Importantly, mortality can reach 16.4% for patients in this range, and ¼ of these patients with an intermediate level progress to clinical shock.22 Lactate levels greater than 2 warrant close monitoring and aggressive treatment with IV fluids and antimicrobials. The table below provides recommendations based on lactate level.

Lactate Level CMS Measure Resuscitation Recommendation
< 2 mmol/L None Lactate levels may be negative in over half of patients with sepsis. Clinical gestalt takes precedence over markers.
2-4 mmol/L Severe Sepsis Resuscitation with intravenous fluids, antimicrobials and reassessment of lactate within 60 minutes.
> 4 mmol/L Septic Shock Aggressive resuscitation warranted regardless of vital signs.

Clearance

Lactate clearance is an important target in sepsis resuscitation. Many target a clearance of 10%, as early lactate clearance is associated with improved outcomes. Arnold et al. found 10% clearance to strongly predict improved outcomes.28 Delayed or no clearance is associated with high mortality, some studies showing 60% mortality rates.28-21 Lactate can be substituted for ScvO2, which requires invasive, specialized equipment.4,28-31

 Pitfalls

Lactate does not always elevate in sepsis, as 45% of patients with vasopressor-dependent septic shock demonstrate a lactate level of 2.4 mmol/L.32 Hernandez et al. suggested 34% of patients with septic shock did not have elevated lactate, though patients with no lactate elevation had a mortality of 7.7%, while those with lactate elevation 42.9% mortality.33 Lactate should not be used in isolation for assessing presence of shock or as a marker for clinical improvement. Rather, other measures such as mental status, heart rate, urine output, blood pressure, and distal perfusion in combination with lactate is advised.5-7,11

 

Procalcitonin

A great deal of literature has evaluated procalcitonin, a calcitonin propeptide produced by the thyroid, GI tract, and lungs with bacterial infection. This biomarker is released in the setting of toxins and proinflammatory mediators, while viral infections inhibit PCT through interferon-gamma production. These levels increase by 3 hours and peak at 6-22 hours, and with infection resolution, levels fall by 50% per day.5-7,34-40 This biomarker can be specific for bacterial infection, decreases with infection control, and is not impaired in the setting of immunosuppressive states (such as steroid use or neutropenia). However, other states including surgery, paraneoplastic states, autoimmune diseases, prolonged shock states, chronic parasitic diseases (such as malaria), certain immunomodulatory medications, and major trauma can increase PCT levels.34-37

Antibiotic Stewardship

Most of the literature evaluating PCT has been published in ICU studies for lower respiratory tract infections (LRTI) and sepsis. The literature suggests algorithms guided by PCT may be able to reduce antibiotic exposure and treatment cost, though with little to no effect on outcomes.37-49

In COPD and bronchitis, it can be difficult to differentiate viral versus bacterial infection. PCT may hold promise in assisting in this differentiation. The ProResp trial randomized patients to two arms, one guided by PCT and the other not.40 If PCT levels were greater than 0.25 mcg/L, antibiotics were given. Ultimately, the group based on PCT demonstrated less antibiotic use (44% in the PCT group, versus 83%), but no difference in length of stay or mortality.40 The ProHOSP trial was a similar trial with the same cutoff. This trial found similar results to the ProResp trial.41

Diagnosis

PCT may be useful in sepsis diagnosis, but ultimately, the clinical context and picture must be considered.43-47 Source of infection, illness severity, and likelihood of bacterial infection should take precedence over a lab marker such as PCT, which may not return while the patient is in the ED. If concerned for sepsis, antimicrobials and resuscitation should be started.

 PCT can identify culture positive sepsis and may help in prognostication. Bacterial load may also correlate with level of PCT.34-47 PCT levels of < 0.25 mcg/L indicate that bacterial infection is unlikely, with levels greater than 0.25-0.50 mcg/L indicating bacterial source.38,45-49 However, sensitivity in one meta-analysis was 77%, with specificity of 79%.45

The PRORATA trial evaluated ICU patients admitted with sepsis.48 In this trial, antibiotic use was guided by PCT levels of 0.5 mcg/L. Similar to the prior studies discussed, decreased antibiotic use was found, but the all-important patient mortality benefit was not found. This level of 0.5 mcg/L was recommended as the cutoff for bacterial sepsis diagnosis in a 2015 meta-analysis.49  The following table depicts the PCT levels used in two key studies.

ProHOSP and PRORATA trial PCT Use41,48

Antibiotic Use PCT Level
< 0.1 mcg/L 0.1-0.25 mcg/L 0.25-0.5mcg/L 0.5-1mcg/L > 1.0 mcg/L
ProHOSP antibiotic use (respiratory infection only) No No Yes Yes Yes
PRORATA antibiotic use (sepsis patients in ICU) No No No Yes Yes

Ultimately, PCT should not influence provider decision to diagnose, resuscitate, and manage patients with criteria for sepsis.50,51 This lab may assist ICU providers, specifically when to discontinue antimicrobial therapy. Levels of 0.5 mcg/L strongly suggest bacterial sepsis. Providers in the ICU may be able to trend PCT levels in regards to decision of when to discontinue antimicrobials.  If the clinical picture suggests bacterial source, severe local infection (osteomyelitis, endocarditis, etc.), patient hemodynamic instability, PCT greater than 0.5 mcg/L, or no change in PCT level while on therapy, antimicrobial therapy should continue.37-49

Troponin

Yep, that’s right, troponin. Troponin is most commonly used to diagnose acute MI, with the AHA stating elevation above the 99th percentile in healthy population meets criteria for ACS.50,51 Troponin can also be used to risk stratify patients entered into the HEART pathway, and high sensitivity troponin can increase sensitivity.50-54 Cardiac troponin consists of two forms: I and T (these are regulatory proteins). Injury of cardiac tissue results in these proteins entering the bloodstream. However, troponin can elevate in multiple settings, shown below.55-59

Cardiac Causes Noncardiac Causes
Acute and Chronic Heart Failure

Acute Inflammatory Myocarditis Endocarditis/Pericarditis

Aortic Dissection

Aortic Valve Disease

Apical Ballooning Syndrome

Bradyarrhythmia, Heart Block

Intervention (endomyocardial biopsy, surgery)

Cardioversion

Direct Myocardial Trauma

Hypertrophic Cardiomyopathy

Tachycardia/Tachyarrhythmia

Acute Noncardiac Critical Illness

Acute Pulmonary Edema

Acute PE

Cardiotoxic Drugs

Stroke, Subarachnoid hemorrhage

Chronic Obstructive Pulmonary Disease

Chronic renal failure

Extensive Burns

Infiltrative Disease (amyloidosis)

Rhabdomyolysis with Myocyte Necrosis

Sepsis

Severe Pulmonary Hypertension

Strenuous Exercise/Extreme Exertion

Risk Stratification

Troponin elevation is associated in worse patient outcomes, particularly mortality, as well as increased length of stay. In sepsis, anywhere from 36-85% of patients may demonstrate troponin elevation. 58-68  This elevation is associated with septic shock and mortality, with almost two times the risk of death.58-64,69 Troponin elevation may be due to several factors including demand ischemia, direct myocardial endotoxin damage, cytokine and oxygen free radical damage, and poor cardiac oxygen supply due to microcirculatory dysfunction. 57,60,61,63,65,69 LV diastolic and RV systolic dysfunction are also associated with increased troponin and mortality.64

Troponin elevation in sepsis allows for prognostication and predicts a patient who is sicker. Resuscitation is essential with elevated troponin in sepsis. However, troponin’s role in resuscitation, the assay used, and the cut-off level need to be determined. If an elevation occurs, an ECG should be obtained, along with bedside echo to evaluate for wall motion abnormalities. Sepsis cardiomyopathy can cause diffuse hypokinesis, but focal wall abnormalities require emergent cardiology consultation.56-61

 

Novel Biomarkers

Sepsis has a complex pathophysiology, which results in a multitude of biomarkers released. These biomarkers are currently under study, and we will discuss several here.5-8

Endothelial Markers

Sepsis results in endothelial changes, associated with modifications in hemostatic balance, change in microcirculation, leukocyte trafficking, vascular permeability, and inflammation.

Measuring this endothelial dysfunction may allow earlier diagnosis of sepsis, as well as prognostication. These include vascular cell adhesion molecule (VCAM-1), soluble intercellular adhesion molecule (ICAM-1), sE-selectin, plasminogen activator inhibitor (PAI-1), and soluble fms-like tyrosine kinase (sFlt-1).5-8,70-73

Proadrenomedullin (ProADM)

This is a precursor for adrenomedullin, a calcitonin peptide. It likely functions in a similar fashion as PCT in the setting of acute cytokine release with bacterial infection. This peptide works as a vasodilator, though it has immune modulating and metabolic effects as well, and it is elevated in renal failure, heart disease, and cancer. ProADM may be able to risk stratify patients with sepsis and pneumonia into different categories based on level.73-79

One study evaluated an algorithm utilizing CURB-65 and ProADM levels.79 CURB-65 is a validated prognostic score for community-acquired pneumonia that consists of BUN > 19 mg/dL (>7 mmol/L), respiratory rate > 30, systolic blood pressure < 90 mm Hg or diastolic blood pressure  < 60 mm Hg, and age > 65 years.80 The algorithm combining CURB-65 and ProADM did not change patient outcome, though it did decrease patient length of stay.79 This marker could assist in prognostication and early discharge, but further study in the ED is needed.

Acute-Phase Reactants

Cytokines are released in response to inflammation, especially sepsis. There are multiple markers including IL-6, IL-8, IL-10, sTREM01, suPAR, CD-64 index, Lipopolysaccharide-binding protein (LBP), ICAM-1, and pentraxins. The greater the elevation in these markers, the worse the prognosis. However, these require further study before regular use can be recommended.8,81

Cardiac Biomarkers

Commonly utilized for heart failure and coronary disease, NT-proBNP and BNP may be associated with worse outcomes in sepsis. Higher levels can predict longer hospital stay and mortality. Obtaining these biomarkers may help predict cardiac dysfunction in sepsis and the need for inotropic medications, though these require further study.67,82-86 Providers must remember that NT-proBNP and BNP lack specificity, as valvular heart disease, Afib, PE, COPD, and hyperthyroidism can elevated these markers, while obesity may decrease levels. 81-85

 

Key Points:

  • Biomarkers cannot replace the bedside clinician, but they may assist clinical decision making, risk stratification, and prognostication. Lactate has the best evidence in sepsis.
  • Lactate is useful for assessing severity, screening, and resuscitation. However, it is not always elevated in sepsis. Venous POC levels are recommended.
  • Procalcitonin is a marker of bacterial versus viral It is not associated with mortality benefit, but may reduce antibiotic usage. PCT requires further study in the ED.
  • Troponin can be elevated in many conditions and is associated with worse prognosis in sepsis. Sepsis cardiomyopathy is more common than many providers realize.
  • Biomarkers on the horizon include endothelial activators, acute-phase reactants, BNP/NT-proBNP, and proadrenomedullin.

 

References/Further Reading

  1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165–228.
  2. Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE.
Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 2010;38:1276–1283.
  3. Strehlow MC, Emond SD, Shapiro NI, et al. National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med 2006;48:326–31.
  4. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368.
  5. Clerico A and Plebani M. Biomarkers for sepsis: an unfinished journey. Clin Chem Lab Med 2013; 51(6): 1135–1138.
  6. Rivers EP, Jaehne AK, Nguyen HB, Papamatheakis DG, Singer D, Yang JJ, Brown S, Klausner H. Early biomarker activity in severe sepsis and septic shock and a contemporary review of immunotherapy trials: not a time to give up, but to give it earlier. Shock 2013 Feb;39(2):127-37.
  7. Schuetz P, Aujesky D, Mueller C, and Mueller B. Biomarker-guided personalised emergency medicine for all – hope for another hype? Swiss Med Wkly 2015;145:w14079.
  8. Di Somma S, Magrini L, Travaglino F, Lalle I, Fiotti N, Cervellin G, et al. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department. Clin Chem Lab Med 2013;51:1167–75.
  9. Jones AE. Lactate Clearance for Assessing Response to Resuscitation in Severe Sepsis. Acad Emerg Med 2013 August;20(8): 844–847.
  10. Marik PE, Bellomo R. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. OA Critical Care 2013 Mar 01;1(1):3.
  11. Puskarich MA. Emergency management of severe sepsis and septic shock. Curr Opin Crit Care 2012 Aug;18(4):295-300.
  12. Gibot S. On the origins of lactate during sepsis. Crit Care 2012 Sep 10;16(5):151.
  13. Anderson LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc 2013 Oct; 88(10): 1127–1140.
  14. Shapiro NI, Howell MD, Talmor D, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005; 45:524–8.
  15. Trzeciak S, Dellinger R, Chansky ME, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007; 33:970–7.
  16. Singer AJ, Taylor M, Domingo A, Ghazipura S, Khorasonchi A, Thode HC Jr, Shapiro NI. Diagnostic characteristics of a clinical screening tool in combination with measuring bedside lactate level in emergency department patients with suspected sepsis. Acad Emerg Med 2014 Aug;21(8):853-7.
  17. Jones AE, Leonard MM, Hernandez-Nino J, and Kline JA. Determination of the Effect of In Vitro Time, Temperature, and Tourniquet Use on Whole Blood Venous Point-of-care Lactate Concentrations. Acad Emerg Med 2007;14:587–591.
  18. Adams BD, Bonzani TA, Hunter CJ. The anion gap does not accurately screen for lactic acidosis in emergency department patients. Emerg Med J 2006;23:179-82.
  19. Iberti TJ, Leibowitz AB, Papadakos PJ, Fischer EP. Low sensitivity of the anion gap as a screen to detect hyperlactatemia in critically ill patients. Crit Care Med 1990;18:275-7.
  20. Puskarich MA, Trzeciak S, Shapiro NI, Albers AB, Heffner AC, Kline JA, Jones AE. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest 2013 Jun;143(6):1548-53.
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  47. Freund Y, Delerme S, Goulet H, et al. Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection. Biomarkers 2012;17:590-596.
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  49. Hoeboer SH, Van der Geest PJ, Nieboer D, Groeneveld AB. The diagnostic accuracy of procalcitonin for bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2015;21:474–481.
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  51. Newby LK, Jesse RL, Babb JD, et al. ACCF 2012 expert consensus document on practical clinical considerations in the interpretation of troponin elevations: a report of the American College of Cardiology Foundation task force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2012;60:2427–63.
  52. Mahler SA, Riley RF, Hiestand BC, Russel GB, Hoekstra JW, Lefebvre CW, et al. The HEART Pathway Randomized Trial Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge. Circ Cardiovasc Qual Outcomes March 2015;8 (2):195 – 203.
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  1. Bessière F, Khenifer S, Dubourg J, Durieu I, Lega JC. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med 2013 Jul;39(7):1181-9.
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  4. Clemente G, Tuttolomondo A, Colomba D, Pecoraro R, Renda C, Della Corte V, Maida C, Simonetta I, Pinto A. When sepsis affects the heart: A case report and literature review. World J Clin Cases 2015 Aug 16;3(8):743-50.
  5. Klouche K, Pommet S, Amigues L, Bargnoux AS, Dupuy AM, Machado S, Serveaux-Delous M, Morena M, Jonquet O, Cristol JP. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality. J Intensive Care Med 2014 Jul-Aug;29(4):229-37.
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  13. Elsasser TH, Kahl S. Adrenomedullin has multiple roles in disease stress: development and remission of the inflammatory response. Microsc Res Tech 2002;57(2):120–9.
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  16. Christ-Crain M, Morgenthaler NG, Stolz D, Muller C, Bingisser R, Harbarth S, et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]. Crit Care 2006;10(3):R96.
  17. Schuetz P, Wolbers M, Christ-Crain M, Thomann R, Falconnier C, Widmer I, et al. Prohormones for prediction of adverse medical outcome in community-acquired pneumonia and lower respiratory tract infections. Crit Care 2010;14(3) R106.
  18. Albrich WC, Dusemund F, Ruegger K, Christ-Crain M, Zimmerli W, Bregenzer T, et al. Enhancement of CURB65 score with proadrenomedullin (CURB65–A) for outcome prediction in lower respiratory tract infections: derivation of a clinical algorithm. BMC infectious diseases 2011;11:112.
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natriuretic peptide. J Am Coll Surg 2011;213:139–46.
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Acute Valvular Emergencies: Pearls and Pitfalls

Authors: Jessica Zack, MD (EM Chief Resident at SAUSHEC, USAF) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 64-year-old male presents with sudden onset subjective fever/chills, dyspnea, weakness, and mild hemoptysis that began 2 hours prior to arrival. His VS include HR 104, BP 103/62, RR 24, O2 Sat 84% on RA, and T 99.6. On exam, you note bilateral rales R > L, a 4/6 diastolic murmur consistent with his known history of aortic regurgitation, and JVD without peripheral edema. His EKG is only significant for sinus tachycardia. You send labs that include a BNP and troponin and order a stat portable CXR which is pictured below. You subsequently order a CT scan of the chest and start him on NIPPV. You are initially considering PE, ACS, multi-lobar pneumonia, and acute heart failure syndrome … but is there something else you’re missing?

 screen-shot-2017-01-04-at-8-23-14-pm

The prevalence of valvular heart disease in the United States is estimated to be about 2.5% and increases in prevalence with age.1 Though patients with clinically evident valvular heart disease have a 3.2-fold increase risk for stroke and 2.5-fold increase risk for death,2 most valvular heart disease encountered in the emergency department is chronic and does not require emergency stabilization.3 This is vastly different than the rare patient presenting with an acute valvular emergency. Symptoms of an acute valvular emergency may include dyspnea, tachycardia, pulmonary edema, and rapid development of cardiogenic shock. Many of these symptoms are seen with various other diagnoses, and the biggest pitfall clinicians may experience is leaving acute valvular emergency off the differential for patients presenting with acute dyspnea.

Valvular emergencies can be broken down by type of valve: native or prosthetic.  Native valve emergencies are almost always the result of regurgitation, while acute prosthetic valve dysfunction may be the result of either regurgitation or stenosis.4  

Valvular Structure and Function:

The heart is composed of four valves: the mitral and tricuspid valves (atrioventricular valves) and the pulmonic and aortic valves (semilunar valves). These valves all open and close passively in response to changes in pressure and volume. The right side of the heart functions similarly to left except that these valves experience much lower pressures. Since most native valve emergencies involve the mitral and aortic valves, we will focus our discussion here.  Inscreen-shot-2017-01-04-at-8-23-01-pm a normally functioning heart, the aortic valve is open during ventricular systole. This allows blood to flow from the left ventricle into systemic circulation. Once the aortic root pressure supersedes that of the left ventricle, the three cusps of the aortic valve fold in, and valve closure occurs. This marks the beginning of ventricular diastole. During this phase of the cardiac cycle, the mitral valve opens allowing flow from the left atrium to the left ventricle. Filling of the left ventricle is completed after the atrial “kick” which provides 10-40 % of the left ventricular end-diastolic volume.5 This is followed by closure of the mitral valve, and the cycle begins again with ventricular contraction. The anterior and posterior leaflets of the mitral valve are supported by the papillary muscles and chordae tendinae during ventricular contraction and aid in the prevention of reverse flow in the left atrium.6

 

Acute Aortic Regurgitation

Pathophysiology:  Acute aortic insufficiency is typically the result of either acute aortic dissection or endocarditis.7 It has also been reported in the case of blunt chest trauma.8 In acute aortic regurgitation (AR), the left ventricle (LV) pathologically fills during ventricular diastole preventing forward flow from the left atrium (LA). This greatly reduces stroke volume and causes a compensatory tachycardia to maintain cardiac output. In the acute setting, this regurgitation is met by a relatively stiff LV and causes increased LV pressure. The increased pressure in the LV stifles flow from the left atrium (LA) and may cause pulmonary congestion.  In severe AR, increased LV pressure may cause early closure of the mitral valve prior to atrial systole and exacerbate pulmonary congestion as the atria contracts against a closed valve.9,10 When AR is severe enough, the decreased cardiac output leads to progressive hypotension, peripheral vasoconstriction, and cardiogenic shock.

History/Exam: These patients will typically present with sudden onset of dyspnea. Other significant historical features may include those associated with the underlying cause of their AR such as tearing chest pain in aortic dissection or fevers in the setting of endocarditis. Physical exam may reveal evidence of pulmonary edema and cardiogenic shock such as rales, JVD, hypotension, pallor, and diaphoresis.3,13  Don’t be fooled by the absence of the typical blowing diastolic murmur in this patient. Murmurs are created by the velocity of blood flow over the valve. This velocity is largely determined by pressure gradients. In the acute AR versus chronic AR, the LV is less compliant which lends to equalization of end diastolic pressure in the aorta and LV.10 With a decreased pressure gradient, your murmur will likely be softer and shorter. Throw in a noisy ED, tachycardia, tachypnea, and rales, and your murmur may be completely inaudible.

Treatment: Definitive treatment for severe acute AR is immediate surgical intervention. Mortality for acute type A aortic dissection is as high as 1-2% per hour for the first several hours.11 So, how do we keep them alive until the OR?

-Intubate if necessary

-Nitroprusside: Yes, their blood pressure is probably already low. Stay with me. Nitroprusside causes afterload reduction, decreased LV preload, and results in reduced regurgitant volume.12 If your patient is going downhill, consider simultaneously starting dobutamine.

-Dobutamine: This ionotropic agent helps to increase contractility and stroke volume. In combination with nitroprusside, you may be able to achieve increased forward flow and temporize the patient.4,13

-Don’t forget antibiotics in the setting of suspected endocarditis.

Treatment Pitfalls:
-Beta blockers: I know, they’re tempting. Especially if your patient is dissecting. Beta blockers are relatively contraindicated in the case of acute AR.4 Beta blockers will decrease reflex tachycardia, but that tachycardia is currently maintaining their cardiac output. Additionally, that decrease in heart rate will increase the time spent in diastole and cause more aortic regurgitation.4

-Aortic Balloon Counterpulsation: This is absolutely contraindicated.4,13 Remember, the balloon pump will inflate during diastole and definitively make the problem worse.

Acute Mitral Regurgitation

Pathophysiology: The most common cause of acute mitral regurgitation (MR) is rupture of chordae tendinae or papillary muscles from ischemia and is typically seen within the first week following a myocardial infarction.13 However, other causes include leaflet perforation from infective endocarditis, blunt chest trauma, and leaflet tethering in acute cardiomyopathies.3,4,14  In acute MR, blood flows back across the mitral valve during ventricular systole. This causes a precipitous decrease in cardiac output. Additionally, blood is flowing into an atrium with normal compliance. This often results in rapid onset of pulmonary edema. In some cases, unilateral pulmonary edema may be seen. Most commonly, this unilateral edema is isolated to the right side or right upper lobe due to the regurgitant jet, particularly from a posterior flail leaflet, being directed towards the right pulmonary vein.15,16

History/Exam: Like acute AR, acute MR frequently leads to overt cardiogenic shock. One key historical difference is that these patients typically present 2-7 days after acute MI.13  Patients with acute MR present with sudden onset of dyspnea from rapidly amassing pulmonary edema, as well as tachycardia.13  Since the atria has not had time to develop additional compliance like in chronic mitral regurgitation, expect left atrial pressures to be high. Again, without a significant pressure gradient across the valve, don’t be surprised if the typical high-pitched holosystolic murmur is absent. This is particularly true if your regurgitant jet is aimed posteriorly and you are auscultating anteriorly.

Treatment: In addition to treating any underlying ischemia if present, definitive treatment is operative management.

Similar temporizing measures as used in acute AR may be useful here, with a few differences.

-Positive pressure for respiratory failure.3

-Nitroprusside or nitrates for afterload reduction.3,4,13 Often other afterload reducing agents, such as nicardipine, are more readily available in the ED. There is little data available directly evaluating whether other afterload reducing agents have similar clinical effects as nitroprusside.

-Dobutamine for inotropic effects.3,13

-Aortic Balloon Counterpulsation: A balloon pump may provide some benefit here if surgical intervention is not readily available.4,13 This will increase forward flow, increase mean arterial pressure, decrease regurgitant volume, and decrease left ventricular filling pressures.3

-Antibiotics if endocarditis is suspected.

Critical Aortic Stenosis

Background: Aortic stenosis (AS) is most commonly caused by age-related calcific changes of a normal valve, calcification of a bicuspid aortic valve, or rheumatic heart disease.17 The difference between AS and the other native valve emergencies discussed in this article is that aortic stenosis develops over many years prior to symptoms onset.18 Even patients with severe aortic stenosis may never develop symptoms, and their estimated risk of sudden cardiac death is still 0.5%-1.0% per year.18 However, once symptom onset does occur, mortality rate rapidly increases. Seventy-five percent of patients will die within 3 years of symptom onset.19

screen-shot-2017-01-04-at-8-22-46-pmPathophysiology: Severe AS is characterized by a fixed outflow obstruction, and cardiac output is preload dependent.  Since severity increases over time, LV hypertrophy develops as a compensatory mechanism to maintain ejection fraction. Patients will often maintain a normal ejection fraction, but this is commonly associated with an overall decreased cardiac output due to decreased end diastolic volumes in the hypertrophied LV.18  LV hypertrophy itself reduces diastolic function and impairs coronary perfusion contributing to angina,19 one of the most common symptoms of AS.  Another common presenting symptom of AS is syncope during exercise. Though not completely understood, it is theorized that the high resistance across the aortic valve prevents the increase in cardiac output required to maintain normotension during exercise when peripheral vasodilation occurs.18 When the AS becomes severe enough, it can lead to severe LV dysfunction and acute heart failure.

History/Exam: The most common symptoms of severe AS are angina, syncope, and dyspnea.17,18 Since severe AS is a disease process that happens over time, you are more likely to appreciate the crescendo-decrescendo systolic ejection murmur. However, it may be absent in the critically ill patient.17 This murmur often radiates into the carotids. Additionally, you may see evidence of LV hypertrophy on EKG and cardiomegaly on CXR.  Occasionally, patients with severe AS will present with acute left ventricular dysfunction and signs and symptoms of acute heart failure such as dyspnea, pulmonary edema, JVD, and even cardiogenic shock.

Treatment: There are two types of AS patients generally encountered in the ED: patients who have the potential to be sick at any time and patients who are currently really sick.

Patients with symptomatic AS (potential to be sick):

-IV Fluids: overall, AS is preload dependent, and these patients may require IVF resuscitation to maintain cardiac output.17

-Inpatient admission for echocardiography and evaluation for surgical aortic valve replacement.17,20

Patients with severe AS and failing LV (currently really sick AS), consider the following:

-Nitroprusside:17,19 There is limited data supporting the use of nitroprusside infusion in patients with severe AS and MAP > 60mm Hg.21 In this subset of patients, there is some evidence to suggest nitroprusside will decrease afterload, improve systolic and diastolic function, and reduce myocardial ischemia.22 This newer data goes against traditional teaching that nitrates will cause decreased blood pressure and decreased coronary perfusion.21 This should be considered in patients who can be closely monitored in an ICU setting and in conjunction with cardiology and/or an intensivist.

-Ionotropic agents such as dobutamine.17

-Early consultation with cardiology: in some cases percutaneous balloon dilation may be performed as a temporizing measure in patients too ill to immediately receive aortic valve replacement.20

 Prosthetic Valve Emergencies

Acute Valve Thrombosis:  During the first three months following surgery, both mechanical and bioprosthetic valves are at the greatest risk for thrombosis and thromboembolic complications.23 However, this risk has a lifelong persistence for patients with a mechanical valve. Thrombosis of a mechanical valve can lead to acute regurgitation, acute stenosis, or both.4 In severe cases, patients will present with acute dyspnea, weakness, and cardiogenic shock. The preferred treatment for patients with acute valve thrombosis is surgery. However, there is some evidence to support the use of intravenous thrombolytics.24 This decision should be made in conjunction with a cardiologist and cardiothoracic surgeon.

Other complications: While acute thrombosis is typically seen with mechanical valves, other complications such as paravalvular regurgitation from suture failure or dehiscence from endocarditis is seen in both mechanical and bioprosthetic valves.4 Up to 6% of prosthetic valves will be complicated by endocarditis within 5 years.3 This finding is associated with an overall poor prognosis, as approximately one third of patients diagnosed with prosthetic valve endocarditis will die within one year of diagnosis.25 If there is suspicion for prosthetic valve endocarditis, blood cultures should be drawn, antibiotics started, and echocardiography and consult with cardiology should be obtained.

screen-shot-2017-01-04-at-8-22-28-pm

Case Resolution:

The patient was admitted to the MICU and was later intubated for worsening respiratory distress.  He had an echo performed and was found to have new severe mitral regurgitation with a flail posterior leaflet, in addition to his known chronic aortic regurgitation. After his echo, he was immediately taken to the operating room and underwent uncomplicated valve replacement of both mitral and aortic valves. He recovered uneventfully and was subsequently discharged home.

 Key Takeaways:

-In patients presenting with sudden onset dyspnea, always keep a valvular emergency on the differential.

-Murmurs may not be audible in the acute setting.

-Definitive management is surgery more often than not, so get consultants on board early.

-If you have a sick patient with a native valve emergency consider nitroprusside +/- dobutamine.

-If present, don’t forget to treat the underlying cause of aortic regurgitation (aortic dissection, endocarditis), mitral regurgitation (ischemia, endocarditis), or prosthetic valve emergency (endocarditis, thrombosis).

 

References/Further Reading

  1. Nkomo, Vuyisile T., Julius M. Gardin, Thomas N. Skelton, John S. Gottdiener, Christopher G. Scott, and Maurice Enriquez-Sarano. “Burden of Valvular Heart Diseases: A Population-based Study.” The Lancet9540 (2006): 1005-011.
  2. Petty, G. W., B. K. Khandheria, J. P. Whisnant, J. D. Sicks, W. M. O’Fallon, and D. O. Wiebers. “Predictors of Cerebrovascular Events and Death among Patients with Valvular Heart Disease: A Population-Based Study.” Stroke11 (2000): 2628-635.
  3. Alley, William D., and Simon A. Mahler. “Chapter 54: Valvular Emergencies.” Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 8th ed. N.p.: McGraw Hill, 2015.
  4. Mcclung, John Arthur. “Native and Prosthetic Valve Emergencies.” Cardiology in Review1 (2016): 14-18.
  5. Alhogbani, Tariq, Oliver Strohm, and Matthias G. Friedrich. “Evaluation of Left Atrial Contraction Contribution to Left Ventricular Filling Using Cardiovascular Magnetic Resonance.” Journal of Magnetic Resonance Imaging4 (2012): 860-64.
  6. Perpetua, Elizabeth M., Dmitry B. Levin, and Mark Reisman. “Anatomy and Function of the Normal and Diseased Mitral Apparatus.” Interventional Cardiology Clinics1 (2016): 1-16.
  7. Roberts, W. C., J. M. Ko, T. R. Moore, and W. H. Jones. “Causes of Pure Aortic Regurgitation in Patients Having Isolated Aortic Valve Replacement at a Single US Tertiary Hospital (1993 to 2005).” Circulation5 (2006): 422-29.
  8. Baek, J. H., J. H. Lee, and D. H. Lee. “Acute Aortic Valve Insufficiency following Blunt Chest Trauma.” European Journal of Trauma and Emergency Surgery5 (2010): 499-501.
  9. Eusebio, Jose, Eric K. Louie, Lonnie C. Edwards, Henry S. Loeb, and Patrick J. Scanlon. “Alterations in Transmitral Flow Dynamics in Patients with Early Mitral Valve Closure and Aortic Regurgitation.” American Heart Journal5 (1994): 941-47.
  10. Rees, J. R., E. J. Epstein, J. M. Criley, and R. S. Ross. “HAEMODYNAMIC EFFECTS OF SEVERE AORTIC REGURGITATION.” Heart3 (1964): 412-21.
  11. Hamirani, Y. S., C. A. Dietl, W. Voyles, M. Peralta, D. Begay, and V. Raizada. “Acute Aortic Regurgitation.” Circulation9 (2012): 1121-126.
  12. Miller, Richard R., Louis A. Vismara, Anthony N. Demaria, Antone F. Salel, and Dean T. Mason. “Afterload Reduction Therapy with Nitroprusside in Severe Aortic Regurgitation: Improved Cardiac Performance and Reduced Regurgitant Volume.” The American Journal of Cardiology5 (1976): 564-67.
  13. Lefebvre, Cedric, James C. O’Neill, and David Cline. Atlas of Cardiovascular Emergencies. New York: McGraw-Hill Education, 2015.
  14. Smedira, Nicholas G., Magued Zikri, James D. Thomas, Michael S. Lauer, John J. Kelleman, and Patrick M. Mccarthy. “Blunt Traumatic Rupture of a Mitral Papillary Muscle Head.” The Annals of Thoracic Surgery5 (1996): 1526-528.
  15. Shin, Jeong Hun, Seok Hwan Kim, Jinkyu Park, Young-Hyo Lim, Hwan-Cheol Park, Sung Il Choi, Jinho Shin, Kyung-Soo Kim, Soon-Gil Kim, Mun K. Hong, and Jae Ung Lee. “Unilateral Pulmonary Edema: A Rare Initial Presentation of Cardiogenic Shock Due to Acute Myocardial Infarction.” Journal of Korean Medical Science2 (2012): 211.
  16. Young, Andrew L., Charles S. Langston, Robert L. Schiffman, and Michael J. Shortsleeve. “Mitral Valve Regurgitation Causing Right Upper Love Pulmonary Edema.” Texas Heart Institute Journal1 (2001): 53-56.
  17. Chen RS, Bivens MJ, Grossman SA. Diagnosis and Management of Valvular Heart Disease in Emergency Medicine. Emergency Medicine Clinics of North America. 2011;29(4):801-810. doi:10.1016/j.emc.2011.08.001.
  18. Carabello BA. Introduction to Aortic Stenosis. Circulation Research. 2013;113(2):179-185. doi:10.1161/circresaha.113.300156
  19. Carabello BA, Paulus WJ. Aortic stenosis. The Lancet. 2009;373(9667):956-966. doi:10.1016/s0140-6736(09)60211-7.
  20. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-2492. doi:10.1161/cir.0000000000000029.
  21. Khot UN, Novaro GM, Popović ZB, et al. Nitroprusside in Critically Ill Patients with Left Ventricular Dysfunction and Aortic Stenosis. New England Journal of Medicine. 2003;348(18):1756-1763. doi:10.1056/nejmoa022021.
  22. Popovic ZB. Effects of sodium nitroprusside in aortic stenosis associated with severe heart failure: pressure-volume loop analysis using a numerical model. AJP: Heart and Circulatory Physiology. 2004;288(1):H416-H423. doi:10.1152/ajpheart.00615.2004.
  23. Carnicelli, Anthony. “Anticoagulation for Valvular Heart Disease.” American College of Cardiology. N.p., 18 May 2015. Web. 05 Dec. 2016.
  24. Özkan, Mehmet, Cihangir Kaymaz, Cevat Kirma, Kenan Sönmez, Nihal Özdemir, Mehmet Balkanay, Cevat Yakut, and Ubeydullah Deligönül. “Intravenous Thrombolytic Treatment of Mechanical Prosthetic Valve Thrombosis: A Study Using Serial Transesophageal Echocardiography.” Journal of the American College of Cardiology7 (2000): 1881-889.
  25. Lalani, Tahaniyat. “In-Hospital and 1-Year Mortality in Patients Undergoing Early Surgery for Prosthetic Valve Endocarditis.” JAMA Internal Medicine16 (2013): 1495-503.

Must Know Antimicrobial Regimens – Adults

Authors: Marina N. Boushra, MD (EM Resident Physician, Vidant Medical Center) and Cassandra Bradby, MD (EM Attending Physician, Vidant Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

A 75-year-old man with a history of diabetes, hypertension, and dementia presents to the emergency department with a complaint of altered mental status. His nursing home caretaker endorses a dry cough for one week that has recently become productive and fevers with a Tmax of 38.9 ºC. She notes that he is not “acting like himself,” and elaborates that he is sleeping more, talking less, and has had multiple episodes of urinary incontinence, which is unusual for him. His vitals on arrival are T 38.5º C, HR 110, RR 30, BP 100/70. His exam is notable for somnolence, increased work of breathing with accessory muscle use, coarse rales at the base of the right lung, tachycardia, and dry mucus membranes.

Bacterial infections are a common diagnosis in the emergency department, and emergency physicians are often tasked with providing antibiotics for outpatient management or beginning antibiotics prior to admission. Antibiotic treatment is not without side effects, and treatment started in the emergency department is frequently empiric. Therefore, an understanding of the most likely causative organisms as well as local patterns of susceptibility and resistance is paramount to adequate treatment, appropriate antibiotic selection, and responsible antibiotic stewardship. Important historical details to elicit include allergies, recent antibiotic use, prior antibiotic failure, dialysis use, use of immunosuppressants or history of immunocompromise, culture results of prior infections, and contact with healthcare facilities, including recent hospitalization, living in a care facility, or recent invasive procedures such as ureteral catheterizations or intubation. These details offer vital information regarding possible bacterial resistance or the presence of opportunistic infection. Because multiple empiric regimens exist for infectious disease in the emergency department, contacting the hospital pharmacy about the local antibiogram may help tailor the empiric regimen to local microbial susceptibilities. Please keep this in mind with the recommendations discussed in each table. The following is a discussion of the most common or most emergent ED-diagnosed bacterial infections, their most likely causative organisms, and current recommendations for empiric treatment.

Pneumonia

Pneumonia is infection of the pleural parenchyma and can be broadly divided into community-acquired (CAP) and hospital-acquired pneumonia (HAP). A third category of pneumonia, healthcare-associated pneumonia, is discussed in more detail later in this paper. The majority of pneumonia is community-acquired but historical details such as recent hospitalization, intubation, or ventilator dependence should raise concern for HAP and multi-drug resistant organisms (MDROs). Travel history may be important for more rare causes of pneumonia. In patients with known or suspected HIV or AIDS, pneumocystis pneumonia should be strongly considered.

Community-Acquired Pneumonia (CAP)

CAP can be caused by a variety of pathogens, with the most common bacterial cause being Streptococcus pneumonia1–3. Other common organisms include respiratory viruses, Haemophilus influenza, and Mycoplasma pneumoniae1–3. In patients requiring ICU admission, S. pneumoniae is still common, but there is increased prevalence of Legionella pneumophila, Staphylococcus aureus, gram-negative bacilli, and influenza4. It is important to remember these differences in etiology and to cover adequately for these serious organisms in patients requiring ICU admission. Patients with risk factors for aspiration pneumonia should receive additional anaerobic coverage. Treatment for CAP has become increasingly more complicated due to rising resistance to antibiotics. Risk factors for drug resistance include age >65, alcoholism, medical comorbidities, immunosuppressive illness or medication use, and use of beta-lactam, macrolide, or fluoroquinolone antibiotics in the last 3-6 months5,6.

Treatment should be initiated as soon as a diagnosis of CAP is made to prevent decompensation. CAP can often be treated on an outpatient basis. Studies have shown that physicians often use inconsistent criteria when making the decision to admit patients for the treatment of CAP and overestimate short-term patient mortality, leading to an increased rate of unnecessary hospitalizations7. The 2007 guidelines for the Infectious Disease Society of America (IDSA) and the American Thoracic Society (ATS) recommend using the CURB-65 score or Pneumonia Severity Index (PSI), both well validated prediction rules and decision aids, to aid in the risk stratification of patients and making the decision to admit for inpatient treatment7–9. Interestingly, a recent article investigating oral vs. intravenous fluoroquinolones for non-critically ill patients with CAP showed no difference in mortality, ICU transfers, or need for vasopressors or intubation10. Studies have shown shorter time to treatment and shorter hospital stays for patients started on oral rather than intravenous antibiotics11. As such, it is important to consider oral therapy in non-critically ill patients with CAP who are being admitted for treatment but are able to tolerate oral medication.

Studies have shown similar efficacy in CAP for fluoroquinolones and macrolides plus a penicillin or cephalosporin12. Importantly, there is a high rate of macrolide resistance in S. pneumoniae in the United States; as such, macrolides should not be used as empiric monotherapy in areas where resistance to macrolides is >25%5,13–15. Recommended regimens are outlined in the Table 1 below. The IDSA is expected to publish new guidelines for the treatment of CAP that better reflect current trends in resistance in the summer of 2017.

Hospital-Acquired (nosocomial) Pneumonia (HAP)

Pneumonia patients with recent hospitalizations present a challenge in antibiotic selection. While the pneumonia may be caused by an MDRO picked up in the healthcare environment, it is also possible that the patient has a simple community-acquired organism. The multi-drug resistant (MDR) score assesses a particular patient’s risk for infection with an MDRO16,17. Patients with a high MDR score should be presumed to have a pneumonia due to a resistant organism and treated accordingly with broad-spectrum coverage as outlined in Table 1 below. Patients with low MDR scores can be treated with the more narrow-spectrum coverage used for CAP, with the possibility of widening the spectrum in the event of treatment failure. The Shorr score is a similar scoring tool to assess the risk of infection by an MDR and tailor empiric coverage appropriately18.  Antibiotic treatment for presumed HAP should cover for Staphylococcus aureus and Pseudomonas aeruginosa19. Local antimicrobial prevalence and susceptibility, especially within the hospital, is helpful to determining a regimen, but can often be deferred to the judgement of the admitting team. Empiric regimens as recommended in the 2016 IDSA/ATS guidelines for empiric management of HAP are outlined in Table 1 below.

Healthcare-Associated Pneumonia (HCAP)

Healthcare-associated pneumonia (HCAP) refers to pneumonia that may have been acquired in healthcare facilities such as nursing homes and dialysis centers. It was formerly grouped with HAP due to presumed increased susceptibility to MDROs. Several studies, however, have shown no increased susceptibility to MDROs in patient with HCAP, and it is conspicuously missing from the IDSA/ATS guidelines on the management of HAP19–24. As such, in the absences of other historical susceptibilities to MDROs such as comorbidities or severe illness, patients with HCAP may be treated as CAP19–24.

Table 1: Empiric Treatment of Pneumonia based on type, setting, and patient-specific factors8,19

Type Setting Patient Factors Regimen
CAP Outpatient No recent antibiotics, co-morbidities, high-rate of resistance -Doxycycline 100mg bid for five days

-Azithromycin 500mg on day 1 followed by 250mg for four days.*

-Clarithromycin 500mg bid for seven days*

Recent antibiotics, co-morbidities, high-rate of resistance -Levofloxacin 750mg daily for five days

-Moxifloxacin 400mg daily for five days

-Gemifloxacin 320mg daily for five days

-Combination therapy with a beta-lactam (amoxicillin 1g tid, amoxicillin-clavulanate 2g bid, cefpodoxime 200mg bid, or cefuroxime 500mg bid) PLUS either a macrolide (azithromycin 500mg on day 1, followed by 250mg for four days, or clarithromycin 500mg bid for five days) or doxycycline 100mg bid for five days.

Inpatient Mild-Moderate disease, managed on general floor -Levofloxacin 750mg IV or po

-Moxifloxacin 400mg IV or po

-Combination therapy with a beta-lactam (cefotaxime 1-2g, ampicillin-sulbactam 1.5-3g, ceftriaxone 1-2g) PLUS a macrolide (azithromycin 500mg IV, or clarithromycin 500mg orally)

Severe disease requiring ICU admission -Combination therapy with a beta-lactam (cefotaxime 1-2g, ampicillin-sulbactam 1.5-3g, ceftriaxone 1-2g) PLUS a respiratory fluoroquinolone (levofloxacin 750mg IV, or moxifloxacin 400mg IV) OR azithromycin 500mg IV.

-If penicillin allergic, a respiratory fluoroquinolone PLUS aztreonam 1g

-If MRSA suspected, add vancomycin 15-20mg/kg IV

HAP Inpatient Combination therapy is warranted, with one from each of the following 3 categories:

1) Piperacillin-tazobactam 4.5 g IV, Cefepime 2 g IV, Ceftazidime 2g IV, Imipenem/cilastatin 500mg IV

2) Azithromycin 500mg IV, Ciprofloxacin 400mg IV, Levofloxacin 750mg IV, or Gentamicin 5-7mg/kg IV

3) Vancomycin 15-20mg/kg IV, Linezolid 600mg IV

*Macrolide antibiotics should not be used as empiric monotherapy in areas of known S. pneumoniae resistance >25% to macrolides. If such resistance exists, pair with a beta-lactam as shown in the table above.

Urinary Tract Infection

Urinary tract infections can involve the lower urinary tract (cystitis) or the upper tract (pyelonephritis). Urinary tract infections are very common in women, with sexually active women being at higher risk. Risk factors for urinary tract infections include recent sexual intercourse, prior urinary tract infections, and recent spermicide use25. When present in men, urinary tract infections are typically associated with underlying anatomical anomalies, recent catheterization, or other risk factors. While not all urinary tract infections in males are necessarily complicated, a search for these risk factors should be conducted when a male is diagnosed with a urinary tract infection.

Uncomplicated Cystitis

Urinary tract infections in women begin by bacterial colonization of the vagina by fecal bacteria, which may ascend via the urethra to infect the bladder and kidneys. Uncomplicated cystitis and pyelonephritis in women is typically caused by Escherichia coli, though Proteus mirabilis, Klebsiella pneumoniae, and Streptococcus saprophyticus are occasionally found26,27. Empiric treatment for uncomplicated urinary tract infections is best tailored to the regional E. coli sensitivities and is outlined in Table 328. Of note, this table may be modified based on local resistance patterns. Sterile pyuria should raise concern for a possible sexually-transmitted infection (STI) and patients who fail to improve despite appropriate antibiotic treatment should be tested for STI.

Complicated Urinary Tract Infection

A complicated urinary tract infection is one which is associated with a condition that increases the risk for therapeutic failure, as outlined in Table 2. The microbial spectrum of complicated UTI is more broad, including not only the typical organisms associated with uncomplicated UTI but also more varied and resistant pseudomonal, staphylococcal, and Serratia species as well as fungi29,30. Complicated lower urinary tract infections may be managed as an outpatient, but indications for hospitalization include inability to tolerate oral therapy or suspected/ documented infection with a resistant organism such as extended-spectrum beta-lactamase producing organisms (ESBLs). Complicated pyelonephritis is the progression of infection resulting in emphysematous pyelonephritis, corticomedullary or perinephric abscess, or papillary necrosis. Complicated pyelonephritis is an indication for admission and intravenous antibiotic treatment.

Table 2: Conditions that increase the risk of treatment failure in UTI (complicated UTI)

Diabetes
Pregnancy
Renal failure
Hospital-acquired infection
Immunosuppression
Renal transplantation
Anatomic abnormality of the urinary tract
Symptoms >7 days prior to presentation
Presence of an indwelling foreign body (ureteral catheter, nephrostomy tube, ureteral stent)
Ureteral calculus

UTI and Asymptomatic Bacteriuria in the Pregnant Patient

Urinary tract infection and colonization in pregnant patients are worth special mention. While asymptomatic bacteriuria in a non-pregnant female does not warrant treatment, studies have shown a high rate of progression to symptomatic cystitis and pyelonephritis in pregnant patients31. As such, current recommendations suggest that any bacteriuria in a pregnant patient should be treated with antibiotics32. Additionally, although urinary tract infection in a pregnant woman is, by definition, complicated, fluoroquinolones, the first-line treatment for complicated cystitis, are a pregnancy class C medication and should be avoided33. Mild urinary tract infections in pregnant females are treated similarly to uncomplicated UTIs, as shown in Table 3 below. Follow-up cultures for resolution are important in this patient population34.

Table 3: Empiric treatment of uncomplicated and complicated urinary tract infections28,31,35.

Urinary Tract Infection Recommended regimen
Uncomplicated cystitis -Nitrofurantoin 100mg bid for five days*

-Trimethoprim-sulfamethoxazole 160/800mg bid for three days

-Cephalexin 500mg BID for 3-7 days

-Fosfomycin 3g in a single dose*

-Ciprofloxacin 250mg bid or Levofloxacin 250mg once per day for three days**

Complicated cystitis Outpatient:

-Ciprofloxacin 500mg bid or 1000mg daily for five to ten days

-Levofloxacin 750mg daily for five to ten days

Inpatient:

-Levofloxacin 500mg IV

-Ceftriaxone 1g IV

-Ertapenem 1g IV

-Gentamicin 3-5mg/kg IV +/- ampicillin 1-2g every 4-6 hours***

-Tobramycin 3-5mg/kg IV +/- ampicillin 1-2g every 4-6 hours***

Uncomplicated Pyelonephritis

 

 

Outpatient:

-Ciprofloxacin 500mg po bid for seven days or 1000mg daily for seven days

-Levofloxacin 750mg po daily for five to seven days

Inpatient:

-Levofloxacin 500mg IV

-Ceftriaxone 1g IV

-Ertapenem 1g IV

-Gentamicin 3-5mg/kg IV

-Tobramycin 3-5mg/kg IV

Complicated Pyelonephritis – Inpatient, mild-moderate disease:

-Ceftriaxone 1g IV

-Ciprofloxacin 400mg IV

-Levofloxacin 750 mg IV

-Aztreonam 1g IV

Inpatient, severe disease:

-Cefepime 2g IV

-Ampicillin 1g IV four times per day plus Gentamicin 5mg/kg IV daily

-Piperacillin-tazobactam 3.375g IV

-Meropenem 500mg IV

-Imipenem 500mg IV

-Doripenem 500mg IV

Asymptomatic bacteriuria and acute cystitis in the pregnant patient -Nitrofurantoin 100mg po bid for five to seven days (in second or third trimester)*

-Trimethoprim-sulfamethoxazole 160/800 mg po bid for three days****

-Fosfomycin 3g po in a single dose*

-Amoxicillin-clavulanate 500mg po tid for three to seven days

-Cephalexin 500mg po bid for three to seven days

-Cefpodoxime 100mg po bid for three to seven days

*Fosfomycin and nitrofurantoin should be avoided if there is concern for early pyelonephritis.

**Fluoroquinolones, if possible, should be reserved for other important uses to avoid resistance against this class of antibiotics.

***Adding ampicillin provides Enterococcus coverage

****Should be avoided in first trimester and at term

Cellulitis and Soft-Tissue Infection

Cellulitis and Erysipelas

Cellulitis and erysipelas are bacterial skin infections that differ in that erysipelas involves the upper dermis and superficial lymphatics while cellulitis involves the deeper dermis and subcutaneous fat tissue. Both manifest with localized skin erythema, edema, warmth, and pain. Because of the more superficial nature of erysipelas, these lesions are typically more raised and better demarcated than cellulitis. Erysipelas also presents more acutely and with more systemic symptoms such as fevers and chills. The most common pathogens in cellulitis are beta-hemolytic streptococci and S. aureus, including methicillin-resistant S. aureus (MRSA)36–38. Beta-hemolytic streptococci are the most common cause of erysipelas36,39.

Lesions consistent with cellulitis should be examined closely for the presence of a drainable abscess. History is particularly important in the patient with possible cellulitis as cellulitis associated with human or animal bites or with water exposure needs different coverage than uncomplicated cellulitis. The presence of an indwelling device near the region of cellulitis is also important, as it is an indication of device infection.

The treatment of uncomplicated cellulitis is based on whether or not there is associated purulence. Current guidelines group erysipelas with non-purulent cellulitis in terms of treatment, as the lesions are often difficult to distinguish from each other and are caused by a similar spectrum of organisms. Patients with purulent cellulitis should receive empiric coverage for MRSA pending culture results40. Patients with non-purulent cellulitis or erysipelas should receive empiric coverage for beta-hemolytic streptococcus and MSSA, although patients with systemic symptoms, recurrent infection, or prior infection with MRSA should receive additional MRSA coverage36. Cellulitis can typically be managed as an outpatient; patients with signs of systemic toxicity, rapid progression, indwelling devices, or failure of outpatient management should be admitted for parenteral antibiotics. In addition to antibiotics, elevation of the affected area is an important aspect of treatment as it helps promotes drainage of edema and inflammatory substances, speeding symptomatic improvement36.

Table 4: Empiric treatment of cellulitis and erysipelas36

Infection Recommended regimen
Uncomplicated nonpurulent cellulitis without MRSA risk factors or erysipelas Outpatient -Dicloxacillin 500mg po qid for 5-10 days

-Cephalexin 500mg po qid for 5-10 days

-Clindamycin 450mg po tid for 5-10 days

Inpatient -Cefazolin 1-2g IV tid

-Ceftriaxone 1g IV every 24 hours

-Oxacillin or nafcillin IV every 4 hours

-Clindamycin 600-900mg IV tid

Uncomplicated purulent cellulitis or nonpurulent cellulitis with MRSA risk factors

 

Outpatient -Clindamycin 300-450mg po 3-4 times per day for 5-7 days

-Trimethoprim/sulfamethoxazole 1-2 DS tablets po bid for 5-7 days

-Doxycycline 100mg bid for 5-7 days

Inpatient -Vancomycin 15-20mg/kg/dose IV bid

-Clindamycin 600mg IV tid 

-Linezolid 600mg IV two times per day

-Daptomycin 4mg/kg/dose IV once daily

Skin abscesses

Skin abscesses are most commonly due to S. aureus (MRSA or MSSA), although polymicrobial infection with flora from the skin or adjacent mucosal tissues is also common36,40–42. Risk factors for MRSA infection include recent hospitalization or antibiotic use, contact with healthcare environments, institutionalization, HIV infection, intravenous drug use, and diabetes. Source control, in the form of warm compresses to promote drainage or incision and drainage, is important. The role of antibiotics following source control is debated. Studies have shown a slightly increased cure rate with the use of antibiotics following incision and drainage of uncomplicated abscesses, but also a higher rate of diarrhea and adverse effects43,44. Antibiotics should be started for large (>2cm) or multiple abscesses, extensive surrounding cellulitis, systemic symptoms, immunocompromise or co-morbidities, the presence of an indwelling device, or in cases where incision and drainage alone fails to achieve adequate clinical response36. Hospitalization and parenteral antibiotics should be considered for patients with extensive skin involvement or signs of systemic toxicity.

Table 5: Empiric antibiotic treatment of abscesses following source control36

Outpatient If suspicion for MRSA:

-Clindamycin 300-450mg po 3-4 times per day for 5-7 days

-Trimethoprim/sulfamethoxazole 1-2 DS tablets po bid for 5-7 days

-Doxycycline 100mg po bid for 5-7 days

If no suspicion for MRSA:

-Dicloxacillin 500mg po bid for 5-7 days

-Cephalexin 500mg po bid for 5-7 days

Inpatient -Vancomycin 15-20mg/kg/dose IV bid

-Clindamycin 600mg IV tid 

-Linezolid 600mg IV two times per day

-Daptomycin 4mg/kg/dose IV once daily

Sexually-Transmitted and Vulvovaginal Infections

Sexually transmitted infections (STI) are a diagnosis of immense public health importance. While the results of lab testing are often not available in the emergency department, physicians should have a low threshold for the initiation of treatment in patients with presentations consistent with STI. Treatment for common STIs is outlined in Table 6 below45. Counseling patients about safe sex practices and urging them to inform their partners is paramount to infection control.

Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is infection of the upper genital tract (uterus, endometrium, fallopian tubes, ovaries) in women. PID may extend to involve adjacent structures, causing periappendicitis, pelvic peritonitis, and perihepatitis (Fitz-Hugh-Curtis syndrome). The majority of PID is caused by ascending sexually-transmitted infections (STI), with Neisseria gonorrhea and Chlamydia trachomatis being the most commonly implicated pathogens in PID45. The diagnosis of PID is often a presumptive one based on presentation. Due to the risk for tubal scarring leading to infertility or risk of ectopic pregnancy, even minimal symptoms without an alternative diagnosis warrant the start of antibiotic therapy to reduce the risk of serious complications due to delay of therapy. Mild to moderate disease can be treated as an outpatient. Indications for hospitalization and intravenous antibiotics include pregnancy, clinically severe disease, complicated PID (pelvic abscess), and intolerance to, noncompliance with, or failure of oral antibiotics. Empiric coverage for inpatient and outpatient management of pelvic inflammatory disease are outlined in Table 646,47.

Table 6: Recommended treatment regimens for select genitourinary infections45–47

Chlamydia -Azithromycin (1g po in one dose)

-Doxycycline (100mg bid for 7 day)

Gonorrhea* -Ceftriaxone (250mg IM or IV in one dose) plus azithromycin (1g po in one dose) or doxycycline (100mg bid for 7 days)
Trichomonas -Metronidazole (2g po in a single dose or 500mg bid for seven days)

-Tinidazole (2g po in a single dose)

Bacterial Vaginosis -Metronidazole (500mg  po bid for seven days)

-Metronidazole vaginal gel 0.75% (5g intravaginally for five days)

-Clindamycin vaginal gel 2% (5g intravaginally for seven days)

Candida Vulvovaginitis Fluconazole (150mg po in one dose)
Pelvic Inflammatory

Disease

Outpatient management -Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)

-Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)

Inpatient management -Ceftriaxone (250mg IM in one dose) plus doxycycline (100mg po bid for 14 days)

-Cefoxitin (2g IM) with probenecid (1g orally) plus doxycycline (100mg po bid for 14 days)

*Patients with gonorrhea should also be treated for chlamydia due to high rates of concomitant infection.

Bacterial meningitis

While meningitis is not as common an emergency department diagnosis as the bacterial infections discussed above, patients with meningitis are often quite ill, and knowledge of appropriate antibiotic coverage can speed time to therapy. The most common causes of community-acquired meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, in older adults, Listeria monocytogenes48,49. Empiric treatment should be initiated as soon as meningitis is suspected. Empiric regimens should include ceftriaxone (2g every 12 hours) or cefotaxime (2g every 4-6 hours) for coverage of N. meningitidis and S. pneumoniae as well as vancomycin due to increasing rates of S. pneumoniae resistance to third-generation cephalosporins50,51. In patients >50 years of age or with immunocompromise, ampicillin (2g every 4 hours) should be added to provide coverage for L. monocytogenes49.

Adverse Effects of Antibiotic Use

A discussion of antibiotic use in the emergency department would be remiss without mention of the adverse effects of antibiotics commonly used in the ED. While the use of certain antibiotics may be unavoidable due to patient allergies or susceptibility patters, knowledge of the adverse effects of antibiotics may help guide therapeutic choices and inform or temper patient expectations.

Clostridium difficile infection should always be a consideration when starting antibiotics. Clindamycin is the most common culprit in antibiotic-associated C. difficile infection, but cephalosporins, penicillins, and fluoroquinolones are also common causes52–56. Aminoglycosides, tetracyclines, metronidazole, and vancomycin are rarely associated with C. difficile infection, though any antibiotic use increases the risk for C. difficile infection57. Other important adverse effects include QT prolongation with arrhythmia associated with macrolide and fluoroquinolone use and the risk of peripheral neuropathy and (the uncommon, but oft-cited) tendon rupture with fluoroquinolone use. Common or serious side effects of antibiotics used in the emergency department are summarized in Table 7 below.

Table 7: Common and serious adverse effects of commonly used antibiotics

Antibiotic Common Adverse Effects Serious Adverse Effects Comments
Beta-lactams C. diff infection, diarrhea Hypersensitivity reactions High risk of C. diff, especially with broader coverage and with ampicillin
Macrolides Diarrhea, nausea, vomiting, abdominal pain QT prolongation (especially with erythromycin)
Clindamycin C. diff infection, diarrhea Serious hypersensitivity reactions Most common cause of C. diff
Fluoroquinolones Anorexia, nausea, vomiting, abdominal pain Tendon rupture, peripheral neuropathy, QT prolongation High C. diff risk
Tetracyclines Nausea, diarrhea, photosensitivity Inhibition of bone growth and tooth discoloration (a concern in children) Low C. diff risk
Vancomycin Abdominal pain, nausea Nephrotoxicity, ototoxicity, Red man syndrome, hypotension Red man syndrome can be prevented with pretreatment with antihistamines
Aminoglycosides Nephrotoxicity, ototoxicity Need frequent monitoring of drug levels
Metronidazole Headache, dizziness, metallic taste Disulfiram-like reaction Low C. diff risk
  • Summary

Table 8: Common and serious bacterial infections and recommended empiric treatment

Infection Important organisms to cover Recommended Regimens
Community-acquired pneumonia S. pneumoniae CAP outpatient: doxycycline, macrolide +/- penicillin or cephalosporin

CAP inpatient, mild: respiratory fluoroquinolone, macrolide + penicillin or cephalosporin

S. pneumoniae, L. pneumophila, S. aureus CAP inpatient, severe: penicillin or cephalosporin+ fluoroquinolone OR azithromycin
Hospital-acquired pneumonia S. pneumoniae, MRSA, P. aeruginosa HAP inpatient: anti-pseudomonal penicillin or cephalosporin, or fluoroquinolone, or carbapenem + vancomycin/linezolid
Uncomplicated cystitis E. coli Nitrofurantoin or fosfomycin or TMP/SMX or ciprofloxacin

 

Complicated cystitis or uncomplicated pyelonephritis E. coli, Pseudomonas sp., Staphylococcus sp. Outpatient: Fluoroquinolone

Inpatient: Fluoroquinolone or aminoglycoside or third-generation cephalosporin or carbapenem

Complicated pyelonephritis E. coli, Pseudomonas sp., Staphylococcus sp. Inpatient, mild-moderate: third-generation cephalosporin or monobactam

Inpatient, severe: anti-pseudomonal penicillin or cephalosporin, carbapenem

Asymptomatic bacteriuria or simple cystitis in the pregnant patient E. coli Nitrofurantoin or TMP/SMX or fosfomycin, or penicillin or cephalosporin with gram-negative coverage
Nonpurulent cellulitis or abscess without MRSA risk factors, erysipelas Beta-hemolytic streptococcal species, MSSA Outpatient and inpatient: staphylococcal penicillin or cephalosporin
Purulent cellulitis, nonpurulent cellulitis or abscess with MRSA risk factors Beta-hemolytic streptococcal species, MSSA, MRSA Outpatient: Clindamycin or TMP/SMX or doxycycline

Inpatient: Vancomycin or clindamycin

Chlamydia C. trachomatis Azithromycin or doxycycline
Gonorrhea N. gonorrhea AND C. trachomatis Ceftriaxone plus azithromycin or doxycycline
Trichomonas Trichomonas vaginalis Metronidazole or tinidazole
Bacterial vaginosis Polymicrobial, anaerobic gram-negative rods Metronidazole oral or intravaginal gel or clindamycin
Candida Vulvovaginitis C. albicans, C. glabrata Fluconazole
Pelvic Inflammatory Disease N. gonorrhea, C. trachomatis Inpatient and outpatient: third generation cephalosporin plus doxycycline
Bacterial meningitis S. pneumoniae, N. meningitidis, L. monocytogenes (if >50 years or immunocompromised) Vancomycin plus third generation cephalosporin +/- ampicillin if age >50 or immunocompromised

 

 References / Further Reading

  1. Johansson, N., Kalin, M., Tiveljung-Lindell, A., Giske, C. G. & Hedlund, J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin. Infect. Dis. 50, 202–9 (2010).
  2. Jain, S. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N. Engl. J. Med. 373, 415–27 (2015).
  3. Gadsby, N. J. et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin. Infect. Dis. 62, 817–23 (2016).
  4. Cillóniz, C. et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 66, 340–6 (2011).
  5. Vanderkooi, O. G. et al. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin. Infect. Dis. 40, 1288–97 (2005).
  6. Ramsdell, J., Narsavage, G. L. & Fink, J. B. Management of Community-Acquired Pneumonia in the Home: An American College of Chest Physicians Clinical Position Statement. Chest 127, 1752–1763 (2005).
  7. Fine, M. J. et al. The hospital admission decision for patients with community-acquired pneumonia. Results from the pneumonia Patient Outcomes Research Team cohort study. Arch. Intern. Med. 157, 36–44 (1997).
  8. Mandell, L. A. et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin. Infect. Dis. 44 Suppl 2, S27-72 (2007).
  9. Lim, W. S. et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58, 377–82 (2003).
  10. Belforti, R. K. et al. Association Between Initial Route of Fluoroquinolone Administration and Outcomes in Patients Hospitalized for Community-acquired Pneumonia. Clin. Infect. Dis. 63, 1–9 (2016).
  11. Cyriac, J. M. & James, E. Switch over from intravenous to oral therapy: A concise overview. J. Pharmacol. Pharmacother. 5, 83–7 (2014).
  12. Ruhe, J. & Mildvan, D. Does Empirical Therapy with a Fluoroquinolone or the Combination of a β-Lactam Plus a Macrolide Result in Better Outcomes for Patients Admitted to the General Ward? Infect. Dis. Clin. North Am. 27, 115–132 (2013).
  13. Low, D. E. What Is the Relevance of Antimicrobial Resistance on the Outcome of Community-Acquired Pneumonia Caused by Streptococcus pneumoniae? (Should Macrolide Monotherapy Be Used for Mild Pneumonia?). Infect. Dis. Clin. North Am. 27, 87–97 (2013).
  14. Daneman, N., McGeer, A., Green, K., Low, D. E. & Toronto Invasive Bacterial Diseases Network. Macrolide resistance in bacteremic pneumococcal disease: implications for patient management. Clin. Infect. Dis. 43, 432–8 (2006).
  15. Jones, R. N., Sader, H. S., Moet, G. J. & Farrell, D. J. Declining antimicrobial susceptibility of Streptococcus pneumoniae in the United States: report from the SENTRY Antimicrobial Surveillance Program (1998-2009). Diagn. Microbiol. Infect. Dis. 68, 334–6 (2010).
  16. Park, S. C. et al. Validation of a scoring tool to predict drug-resistant pathogens in hospitalised pneumonia patients. Int. J. Tuberc. Lung Dis. 17, 704–709 (2013).
  17. Maruyama, T. et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin. Infect. Dis. 57, 1373–83 (2013).
  18. Shorr, A. F. et al. A risk score for identifying methicillin-resistant Staphylococcus aureus in patients presenting to the hospital with pneumonia. BMC Infect. Dis. 13, 268 (2013).
  19. Kalil, A. C. et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin. Infect. Dis. 63, e61–e111 (2016).
  20. Chalmers, J. D., Rother, C., Salih, W. & Ewig, S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin. Infect. Dis. 58, 330–9 (2014).
  21. Ma, H. M., Wah, J. L. S. & Woo, J. Should nursing home-acquired pneumonia be treated as nosocomial pneumonia? J. Am. Med. Dir. Assoc. 13, 727–31 (2012).
  22. Yap, V., Datta, D. & Metersky, M. L. Is the present definition of health care-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens? Infect. Dis. Clin. North Am. 27, 1–18 (2013).
  23. Ewig, S., Welte, T. & Torres, A. Is healthcare-associated pneumonia a distinct entity needing specific therapy? Curr. Opin. Infect. Dis. 25, 166–75 (2012).
  24. Kollef, M. H. Health care-associated pneumonia: perception versus reality. Clin. Infect. Dis. 49, 1875–7 (2009).
  25. Hooton, T. M. et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N. Engl. J. Med. 335, 468–74 (1996).
  26. Czaja, C. A., Scholes, D., Hooton, T. M. & Stamm, W. E. Population-based epidemiologic analysis of acute pyelonephritis. Clin. Infect. Dis. 45, 273–80 (2007).
  27. Echols, R. M., Tosiello, R. L., Haverstock, D. C. & Tice, A. D. Demographic, clinical, and treatment parameters influencing the outcome of acute cystitis. Clin. Infect. Dis. 29, 113–9 (1999).
  28. Gupta, K. et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin. Infect. Dis. 52, e103-20 (2011).
  29. Nicolle, L. E. Catheter-related urinary tract infection. Drugs Aging 22, 627–39 (2005).
  30. Nicolle, L. E. A practical guide to the management of complicated urinary tract infection. Drugs 53, 583–92 (1997).
  31. Smaill, F. M. & Vazquez, J. C. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane database Syst. Rev. CD000490 (2015). doi:10.1002/14651858.CD000490.pub3
  32. Rouse, D. J., Andrews, W. W., Goldenberg, R. L. & Owen, J. Screening and treatment of asymptomatic bacteriuria of pregnancy to prevent pyelonephritis: a cost-effectiveness and cost-benefit analysis. Obstet. Gynecol. 86, 119–23 (1995).
  33. Hooper, D. C., Wolfson, J. S., Hooper, D. C. & Wolfson, J. S. Fluoroquinolone antimicrobial agents. N. Engl. J. Med. 324, 384–94 (1991).
  34. Patterson, T. F. & Andriole, V. T. Detection, significance, and therapy of bacteriuria in pregnancy. Update in the managed health care era. Infect. Dis. Clin. North Am. 11, 593–608 (1997).
  35. Stamm, W. E., Hooton, T. M. & Hooton, T. M. Management of urinary tract infections in adults. N. Engl. J. Med. 329, 1328–34 (1993).
  36. Stevens, D. L. et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin. Infect. Dis. 59, (2014).
  37. Carratalà, J. et al. Factors associated with complications and mortality in adult patients hospitalized for infectious cellulitis. Eur. J. Clin. Microbiol. Infect. Dis. 22, 151–7 (2003).
  38. Siljander, T. et al. Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings. Clin. Infect. Dis. 46, 855–61 (2008).
  39. Eriksson, B., Jorup-Rönström, C., Karkkonen, K., Sjöblom, A. C. & Holm, S. E. Erysipelas: clinical and bacteriologic spectrum and serological aspects. Clin. Infect. Dis. 23, 1091–8 (1996).
  40. Moran, G. J. et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N. Engl. J. Med. 355, 666–74 (2006).
  41. Singer, A. J. & Talan, D. A. Management of skin abscesses in the era of methicillin-resistant Staphylococcus aureus. N. Engl. J. Med. 370, 1039–47 (2014).
  42. Summanen, P. H. et al. Bacteriology of skin and soft-tissue infections: comparison of infections in intravenous drug users and individuals with no history of intravenous drug use. Clin. Infect. Dis. 20 Suppl 2, S279-82 (1995).
  43. Talan, D. A. et al. Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N. Engl. J. Med. 374, 823–832 (2016).
  44. Schmitz, G. R. et al. Randomized Controlled Trial of Trimethoprim-Sulfamethoxazole for Uncomplicated Skin Abscesses in Patients at Risk for Community-Associated Methicillin-Resistant Staphylococcus aureus Infection. Ann. Emerg. Med. 56, 283–287 (2010).
  45. Workowski, K. A., Bolan, G. A. & Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR. Recomm. reports Morb. Mortal. Wkly. report. Recomm. reports 64, 1–137 (2015).
  46. Ness, R. B. et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am. J. Obstet. Gynecol. 186, 929–37 (2002).
  47. Walker, C. K. & Wiesenfeld, H. C. Antibiotic Therapy for Acute Pelvic Inflammatory Disease: The 2006 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. Clin. Infect. Dis. 44, S111–S122 (2007).
  48. Schuchat, A. et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N. Engl. J. Med. 337, 970–6 (1997).
  49. Clauss, H. E. & Lorber, B. Central nervous system infection with Listeria monocytogenes. Curr. Infect. Dis. Rep. 10, 300–6 (2008).
  50. Tunkel, A. R. et al. Practice guidelines for the management of bacterial meningitis. Clin. Infect. Dis. 39, 1267–84 (2004).
  51. Brouwer, M. C., Tunkel, A. R. & van de Beek, D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin. Microbiol. Rev. 23, 467–92 (2010).
  52. Pépin, J. et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin. Infect. Dis. 41, 1254–60 (2005).
  53. Deshpande, A. et al. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. J. Antimicrob. Chemother. 68, 1951–61 (2013).
  54. Johnson, S. et al. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals. N. Engl. J. Med. 341, 1645–51 (1999).
  55. Tedesco, F. J., Barton, R. W. & Alpers, D. H. Clindamycin-associated colitis. A prospective study. Ann. Intern. Med. 81, 429–33 (1974).
  56. Gurwith, M. J., Rabin, H. R. & Love, K. Diarrhea associated with clindamycin and ampicillin therapy: preliminary results of a cooperative study. J. Infect. Dis. 135 Suppl, S104-10 (1977).
  57. Kelly, C. P., Pothoulakis, C. & LaMont, J. T. Clostridium difficile colitis. N. Engl. J. Med. 330, 257–62 (1994).

 

Seizure Mimics: Pearls & Pitfalls

Authors: James L Webb, MD (Internal Medicine, SAUSHEC, USAF) and Brit Long, MD (@long_brit) // Edited by: Erica Simon, DO, MHA (@E_M_Simon) & Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 20 year-old female presents to the ED after a witnessed fall. According to bystanders, the young woman was walking towards a gym treadmill when she collapsed to the floor below, convulsing for approximately1-2 minutes. Upon EMS arrival VS were within normal limits, GCS was noted as 14 (confusion, orientation only to self), EKG revealed NSR, and accucheck demonstrated a blood glucose of 134. Intravenous access was obtained en route to your facility.

As you interview and examine the patient, you note ABCs intact, a GCS of 15, an ample history remarkable only for report of a “rising feeling in the abdomen” prior to the event, and a secondary survey without obvious signs of trauma. ED evaluation, to include a CBC, CMP, EKG, and non-contrasted head CT are all within normal limits. Urine Hcg is negative.

Was this a seizure? What’s the appropriate patient disposition? If you’ve got questions, we’ve got important details on seizures and their mimics.

 

Background

Current data indicate that nearly 2 million U.S. residents are affected by Epilepsy.1-2 In addition to this population, approximately 150,000 Americans (age >18 years) present to healthcare providers annually following an apparent first seizure.1-2 As assigning a diagnosis a seizure or seizure disorder is not without significant health and quality of life implications (employment repercussions, driving restrictions, etc.1-5), emergency physicians must be aware of conditions that may mimic seizure activity: syncope, psychogenic non-epileptic seizures, metabolic derangements, stroke or TIA, sleep disorders, and migraines.

 

Seizures – A Review

Seizures result from abnormal neurologic electrical activity. This abnormal activity can occur in both hemispheres (generalized seizure) or within one hemisphere (focal seizure), which may spread to the entire brain. Generalized seizures are more common than focal seizures, and often have a genetic association.6 Generalized tonic-clonic seizures most frequently occur in adults – the motions of which consist of a tonic phase with muscle stiffening, followed by a clonic phase with rhythmic muscle contractions.6-7 Focal seizures often occur in the setting of cerebral insult.7 Unlike generalized seizures, symptoms of focal seizures vary according to the anatomic location of the abnormal electrical activity.6,8

Seizures can be classified as provoked or unprovoked. Provoked seizures are those with identifiable causes, which can be isolated to the brain, or are thought to occur secondary to a systemic disorder or illness. Such causes include: brain trauma, CNS infection (i.e. meningitis, encephalitis, brain abscess), anoxic brain injury, intracranial hemorrhage or surgery, metabolic disorders, illicit drug abuse or intoxication (most commonly tricyclic antidepressants and isoniazid), or alcohol withdrawal.9,10  Seizures may also occur in the setting of metabolic derangements (hypoglycemia or hyponatremia).9-12

 Unprovoked seizures are those with no discernible cause, or those occurring greater than seven days following precipitating factors or events. What factors or events might the emergency physician identify through the H&P?

  • Pregnant patient with a seizure –>evaluate for eclampsia
  • Child with an recent illness –>evaluate for personal and familial history of febrile seizures
  • In all patients –>inquire regarding a history of recent head trauma (occurring within 1 week prior to presentation)

It is particularly important to perform a thorough H&P in this patient population, as 50% of individuals experiencing an unprovoked seizure will experience a recurrence.11

 

Approach

Patients presenting with altered mental status (AMS)/seizure concern should be quickly assessed10,13-15,17:

  • ABCs
  • Consider obtaining a POC glucose level
  • First line treatment for seizure activity: benzodiazepines (lorazepam 0.1 mg/kg IV)
    • Second line agents: phenytoin, fosphenytoin, levetiracetam, or valproic acid
      • Intubation with propofol or ketamine with contiguous EEG (in consultation with neurology) may be required.14-17
    • After addressing ABCs, perform an H&P, complete a physical examination (PE), and obtain IV access. Consider: CBC, CMP, EKG, serum Hcg, anticonvulsant level if applicable, imaging as appropriate (CT recommended in the setting of new focal deficits, head trauma, continued AMS, immunocompromised state, history of cancer, persistent fever, focal seizures, history of stroke, or anticoagulation), +/- an LP.13,15-19
      • Note: neuroimaging should be performed in patients with suspected new-onset seizures, but may occur in the outpatient setting for those with a first time generalized tonic-clonic seizure with a normal neurologic exam. MRI is preferable with a higher yield of identifying abnormalities in the non-emergent setting.13,15-19
    • Disposition is often determined in conjunction with specialty consultation. Admission may be required in the setting of persistent neurologic deficit, persistent AMS, or poor social situation.13,15-19 Patients who return to mental status baseline, possess a normal neurologic exam, and whose labs and imaging are without pathology, may be discharged with outpatient follow-up.13,19

 For an in-depth discussion of seizure evaluation and management, see:  http://www.emdocs.net/treatment-of-seizures-in-the-emergency-department-pearls-and-pitfalls/

 

Evaluating Seizure Activity in Patients with Return to Mental Status Baseline

 A definitive diagnosis of seizure is made by EEG interpretation during seizure activity. As this is often times impossible in the ED setting, the emergency physician must seek out signs and symptoms commonly associated with seizure activity9,13,20:

  • HPI significant for aura: déjà vu, a rising sensation in the abdomen, abnormal taste or smell, or autonomic changes.
    • Activity commonly associated with a true seizure: witnessed tonic/clonic movements or observed head turning in the setting of a generalized seizure, or the abrupt onset of limb movements, abnormal sensations, or hallucinations in the setting of a focal seizure. 6,7,20
    • A postictal period occurring for minutes to hours with confusion, disorientation, and drowsiness.
  • Physical exam remarkable for tongue biting.

See Table 1 for signs and symptoms related to seizure activity in studies comparing seizures versus syncope. *Urinary incontinence was demonstrated to lack clinical significance.

screen-shot-2017-01-01-at-3-57-34-pm

What about laboratory studies?

 A lactate level may be useful in differentiating seizures from psychogenic non-epileptic seizures and syncope (sensitivity of 88%, specificity 87% for true seizure activity), 24 while an elevated CK is suggestive of epileptic seizures (specificity 85-100%), but demonstrates variable sensitivity (15-88%).25

 

Seizure Mimics

Studies indicate that approximately 20% of patients presenting for evaluation of seizure are misdiagnosed as having epilepsy.26  Conditions most commonly mistaken for epitileptiform seizure activity include syncope and psychogenic non-epileptic seizures.5 Detailed below is a review of seizure mimics with tips and tricks for ED evaluation and disposition.

Syncope

Syncope is a sudden loss of consciousness (LOC) due to decreased cerebral perfusion, resulting in loss of postural tone, with rapid return to mental status baseline. Syncope may be cardiac, orthostatic, or neurocardiogenic (vasovagal) in origin.

Historical evidence favoring a syncopal episode versus a seizure27-34:

  • Presentation –>LOC with rapid return to mental status baseline.
  • History –>Remarkable for precipitating factors: recent illness (emesis/diarrhea – hypovolemia), recent medication changes (i.e. B-blockers and bradycardia, diuretics causing hypovolemia, etc.), LOC following increased vagal tone (coughing, defecation, shaving).  LOC during physical exertion. In obtaining the HPI, it is important to note that myoclonic jerking occurs in up to 90% of patients experiencing syncope.27

Management and Disposition Pearls:

  • Evaluation –> EKG for dysrhythmias, consider a CBC and CMP to assess for anemia and electrolyte derangement, consider cardiac markers as indicated.
  • Disposition–>As appropriate. Referral for tilt-table testing in the setting of neurocardiogenic syncope may be considered after ruling out life-threatening conditions.

Notes on Syncope of Cardiac Origin

Syncope secondary to cardiac dysrhythmias or structural heart disease may present similarly to a seizure, however, the following suggest cardiac origin27-29, 33,34:

  • Presentation –>Most commonly an elderly patient.
  • History –>The absence of a prodrome; ROS positive for palpitations prior to LOC; CP or LOC during exertion.

Management and Disposition Pearls:

  • Evaluation –>PE for murmurs, rubs, gallops and s/s of heart failure (JVD, peripheral edema, hepatojugular reflex, etc.); EKG for dysrhythmias: SVT, VT, Mobitz type II second-degree, or third-degree AV block, bundle branch blocks, Long QT Syndrome, Brugada Syndrome, WPW Syndrome, Right Ventricular Dysplasia, and pacemaker malfunction have all been associated with syncopal episodes.33 Consider bedside POCUS or formal echocardiogram to evaluate for cardiac structural anomalies.
  • Disposition –>As appropriate. In the large majority of cases admission is required for adjunct testing.

 

Psychogenic Non-Epileptic Seizure (PNES) Disorder

PNES, a condition characterized by the presence of seizure-like activity occurring in the absence of EEG changes, is difficult to differentiate from a true seizure in the emergency setting; even more so as nearly 40% of patients with epilepsy suffer from the disorder.35 Characteristics that make PNES more likely include35-39:

  • Presentation –>Patient in their 20s-30s,35 experiencing an event characterized by asynchronous extremity movements, rapid head turning, pelvic thrusting, eye closing, or geotropic eye movements. Clinical clues useful for the provider: the absence of tongue biting, a prolonged duration (>2 mins), a patient who can recall the event, or a patient who was witnessed to have been crying during the seizure-like activity.
  • History –>Approximately 70% have a PMHx of a psychiatric disorder (depression, PTSD, personality disorder).36,37

Management and Disposition Pearls:

  • Evaluation –>When in doubt: treatment as appropriate (ABCs +/- benzodiazepines). Video EEG is the gold standard for diagnosis, therefore specialty consultation is required.
  • Disposition –>In consultation with neurology/neuropsychiatry. Treatment is often targeted to the underlying psychiatric disorder.39

 

Metabolic Derangements

Metabolic disorders are identified in 2.4-8% of patients presenting with first generalized seizure.9,10,13 Hypoglycemia and hyponatremia are the most common, but other disorders may include hypernatremia, hyperglycemia, hypercalcemia, and uremia.9,10,13

 Management and Disposition Pearls:

  • Evaluation –>Accucheck for all patients with AMS/seizure activity. CMP as appropriate.
  • Disposition –>Treatment and admission requirements based upon laboratory findings.

 

Stroke and TIA 

Stroke/TIA can be confused with a seizure when there is resolution of the neurologic deficit previously caused by cerebral ischemia. Characteristics of Stroke/TIA18,40,41:

  • Presentation –>Most commonly a middle-aged or elderly patient. HPI remarkable for negative symptoms: numbness, weakness, or blindness.
  • History –>PMHx significant for HTN, HLD, cardiac arrhythmia, family history of CVA

Management and Disposition Pearls:

  • Evaluation –>PE: focused neurological examination, accucheck, EKG for dysrhythmias, performance of risk stratification to determine the requirement for cerebral vasculature imaging.
  • Disposition –>As appropriate. Inpatient admission may be required for MRI, carotid ultrasonography, echocardiography, and medication optimization.

 

Sleep Disorders

Narcolepsy with cataplexy may present similarly to seizures. Narcolepsy is defined by excessive daytime sleepiness, lapses into sleep, or multiple naps during the same day at least 3 times per week for a duration of 3 months time. Cataplexy is the sudden loss of tone in response to emotion. 42-45

  • Presentation –>Patient suddenly collapses, but rapidly recovers to mental status baseline with complete recollection of the  event. 42-45

Management and Disposition Pearls:

  • Evaluation –>Thorough history-taking often allows differentiation from seizure activity.
  • Disposition –>Specialty referral for overnight polysomnography and sleep latency testing. Driving restriction is often state-mandated if the condition is suspected. 42-45

 

Migraines

 Migraines are recurrent headaches with or without aura (visual or sensory symptoms). Symptoms include throbbing headache, nausea, vomiting, and sensitivity to light and sound. Auras are often positive visual symptoms. Migraines with aura are similar to certain focal seizures with visual symptoms (hallucinations) or generalized seizure prodrome (aura). Signs and symptoms making a diagnosis of migraine more likely19, 50-52:

  • Presentation –>headache characterized by unilateral pain, throbbing pain, moderate-severe pain, and aggravated by physical activity, +/- nausea/vomiting or photo-/phonophobia
  • History –>PMHx significant for migraines.

Keep in mind, complex migraines may present with neurologic symptoms causing weakness, alteration in consciousness, or LOC.

Management and Disposition Pearls:

  • Evaluation –>PE: focused neurological examination. Rule out intracranial pathology as appropriate (CVA/SAH/meningitis/encephalitis – CT, LP, etc.)
  • Disposition –>As appropriate. In the setting of negative imaging (+/- negative LP), neurology consultation is appropriate as prophylactic medications (TCAs, B-blockers, anti-epileptics) may be considered for outpatient therapy.

 

Summary

– Seizures are caused by abnormal neurologic electrical activity resulting in motor, sensory, and behavioral symptoms.
In all patients presenting with AMS or actively seizing: ABCs, accucheck, initiate therapy as appropriate (benzodiazepines first line).
– For patients presenting after return to baseline mental status: a thorough history and physical examination are key to differentiating between a true seizure and its mimic.
– If a seizure is not suspected, consider syncope, psychogenic non-epileptic seizures, stroke or TIA, sleep disorders, and migraines.

 

References/Further Reading

  1. Hauser WA, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia. 2008;49 Suppl 1:8-12.
  2. Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-Based Guideline: Management of an Unprovoked First Seizure in Adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsy Curr. 2015 May-Jun;15(3):144-52.
  3. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998 Apr 2;338(14):970-6.
  4. England MJ, Livermari CT, Schultz AM, Strawbridge LM Institute of Medicine (US) Committee on the Public Health Dimensions of the Epilepsies; England MJ, Livermari CT, Schultz AM, Strawbridge LM, editors. Epilepsy Across the Spectrum: Promoting Health and Understanding. Washington, DC: The National Academies Press; 2012.
  5. Xu Y, Nguyen D, Mohamed A, et al. Frequency of a false positive diagnosis of epilepsy: A systematic review of observational studies. 2016 Aug 23;41:167-174.
  6. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010 Apr;51(4):676-85.
  7. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med. 2003 Sep 25;349(13):1257-66.
  8. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475.
  9. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia. 2010;51(4):671.
  10. Fields MC, Labovitz DL, French JA. Hospital-onset seizures: an inpatient study. JAMA Neurol. 2013 Mar;70(3):360-4.
  11. Riggs JE. Neurologic manifestations of electrolyte disturbances. Neurol Clin. 2002 Feb;20(1):227-39.
  12. D’Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999 Mar 25;340(12):915-9.
  13. Dunn MJ, Breen DP, Davenport RJ, Gray AJ. Early management of adults with an uncomplicated first generalised seizure. Emerg Med J. 2005 Apr;22(4):237-42.
  14. Pillow MT. Seizure Assessment in the Emergency Department. Emedicine: Medscape. http://emedicine.medscape.com/article/1609294-overview. Accessed 11 August 2016.
  15. American College of Emergency Physicians. Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2014 Apr;63(4):437-47.e15.
  16. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011 Oct;134(Pt 10):2802-18.
  17. Brophy, Gretchen M., Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012 Aug;17(1):3-23.
  18. Harden CL, Huff JS, Schwartz TH, et al. Reassessment: neuroimaging in the emergency patient presenting with seizure (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2007 Oct 30;69(18):1772-80.
  19. French JA, Pedley TA. Clinical practice. Initial management of epilepsy. N Engl J Med. 2008 Jul 10;359(2):166-76.
  20. Manford M. Assessment and investigation of possible epileptic seizures. J Neurol Neurosurg Psychiatry. 2001;70(Suppl 2):ii3–ii8.
  21. Brigo F, Nardone R, Bongiovanni LG. Value of tongue biting in the differential diagnosis between epileptic seizures and syncope. Seizure. 2012 Oct;21(8):568-72.
  22. Brigo F, Nardone R, Ausserer H, et al. The diagnostic value of urinary incontinence in the differential diagnosis of seizures. Seizure. 2013 Mar;22(2):85-90.
  23. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol. 2002 Jul 3;40(1):142-8.
  24. Matz O, Zdebik C, Zechbauer S, et al. Lactate as a diagnostic marker in transient loss of consciousness. Seizure. 2016 Aug;40:71-5.
  25. Brigo F, Igwe SC, Erro R, Bongiovanni LG, et al. Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review. J Neurol. 2015 Feb;262(2):251-7.
  26. Smith PE. Epilepsy: mimics, borderland and chameleons. Pract Neurol. 2012 Oct;12(5):299-307.
  27. Chen LY, Benditt DG, Shen WK. Management of syncope in adults: an update. Mayo Clin Proc. 2008 Nov;83(11):1280-93.
  28. Walsh K, Hoffmayer K, Hamdan MH. Syncope: diagnosis and management. Curr Probl Cardiol. 2015 Feb;40(2):51-86.
  29. Huff JS, Decker WW, Quinn JV, et al.; American College of Emergency Physicians. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Ann Emerg Med. 2007 Apr;49(4):431-44.
  30. Grubb BP. Clinical practice. Neurocardiogenic syncope. N Engl J Med. 2005 Mar 10;352(10):1004-10.
  31. Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol 1994 Aug;36(2):233–7.
  32. McKeon A, Vaughan C, Delanty N. Seizure versus syncope. Lancet Neurol. 2006 Feb;5(2):171-80.
  33. Morag R. Syncope. Emedicine: Medscape. http://emedicine.medscape.com/article/811669-overview. Accessed 15 August 2016.
  34. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009). the task force for the diagnosis and management of syncope of the European Society of Cardiology (ESC). Eur Heart J. 2009 Nov;30(21):2631-71.
  35. Alsaadi TM, Marquez AV. Psychogenic nonepileptic seizures. Am Fam Physician. 2005 Sep 1;72(5):849-56.
  36. Panagos PD, Merchant RC, Alunday RL. Psychogenic seizures: a focused clinical review for the emergency medicine practitioner. Postgrad Med. 2010 Jan;122(1):34-8.
  37. Shaibani A, Sabbagh MN. Pseudoneurologic syndromes: recognition and diagnosis. Am Fam Physician. 1998 May 15;57(10):2485-94.
  38. LaFrance WC Jr, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. 2013 Nov;54(11):2005-18.
  39. Siket MS, Merchant RC. Psychogenic seizures: A review and description of pitfalls in their acute diagnosis and management in the emergency department. Emerg Med Clin North Am. 2011 Feb;29(1):73-81.
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The Thromboelastogram (TEG®): A Five-Minute Primer for the Emergency Physician

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC)

It’s three o’clock in the morning on your fourth night shift in a row.  While mustering the courage to rescue your energy drink from the dank, dark depths of the staff mini-fridge, you hear a familiar page: “trauma team to the trauma room.”  As you walk towards the ambulance bay, the trauma surgeon approaches with information regarding the incoming transfer:

  • 17 year-old male – MVC versus pedestrian
  • Seen at OSH where CTs demonstrated: epidural hematoma, grade III liver laceration, grade II splenic laceration, open book pelvic fracture, and extraperitoneal bladder rupture
  • Patient underwent external pelvic fixation and transfusion of blood products (8U PRBCs, 8U FFP and 4U Plts)
  • Most recent VS: BP 136/89, HR 92, RR (intubated/ventilated):14, SpO2 99% (FiO2 70%)

Drawing your attention to a piece of paper in his hand, detailing what appear to be labs from the outside facility, the surgeon points to a colorful figure: “I’m very concerned about this”:

screen-shot-2016-12-20-at-10-18-26-pm

Scanning your mind for intelligent thought, you realize that it’s been some time since you’ve ordered a thromboelastogram (TEG), let alone interpreted one.

If you’re like this physician, take a few minutes to scan the following review – the quick and dirty on TEGs is coming your way.

Thromboelastography – What is it?

Developed in 1948 by Dr. Hellmut Harter, thromboelastography is a mechanism of assessing coagulation based upon the viscoelastic properties of whole blood.2-8  In contrast to traditional, static measurements of hemostasis (PT, aPTT, INR, fibrinogen level, and fibrin degradation products), thromboelastography allows for an assessment of near real-time, in-vivo clotting capacity, providing the interpreter information regarding the dynamics of clot development, stabilization, and dissolution.7  When utilized as a point-of-care assay, graphic interpretation of thromboelastography (the TEG), offers the opportunity for an expedited assessment of coagulopathies (thrombocytopenia, factor deficiency, heparin effect, hypofibrinogenemia, and hyperfibrinolysis).7,9,12,13

How is a TEG performed?

In order to perform a TEG, a citrated-sample of whole blood is placed into a heated sample cup with calcium chloride (to overcome the effects of the citrate), kaolin (a negatively charged molecule known to initiate the intrinsic pathway10), and phospholipids (required for optimal functioning of the extrinsic pathway11) (Figure 2).  As the sample cup oscillates in a limited arc, formation of clot results in the generation of rotational forces on a pin suspended from a torsion wire.  Forces translated to the torsion wire are then, in turn, transmitted to an electrical transducer, creating a characteristic waveform (Figure 3).

screen-shot-2016-12-20-at-10-20-43-pm

screen-shot-2016-12-20-at-10-20-31-pm

I’ve heard of the Rapid TEG (r-TEG), is there a Difference?

When performed by a trained laboratory specialist, an r-TEG may be completed within 15 minutes as compared to the average 30-45 minutes processing time for a standard TEG.4,5,14  In contrast to a TEG, whole blood samples for an r-TEG may be performed with citrated or non-citrated samples.4 Samples utilized for an r-TEG are combined with tissue factor (activating the extrinsic pathway), and kaolin (activating the intrinsic pathway as above) +/- calcium chloride as applicable.4

I’ve also heard of ROTEM, what is it?

Although utilizing the technique developed by Dr. Harter, rotational thromboelastometry (ROTEM) differs from traditional thromboelastography in its mechanical application.  Unlike traditional thromboelastography, which utilizes a sample cup rotating in a limited arc, ROTEM employs a static sample cup with an oscillating pin/wire transduction system.  By comparison, ROTEM is also a more complex diagnostic test as it requires a number of differing reagents.  A complete discussion of ROTEM is outside the scope of this review.  If interested in further reading, see:

Tanaka K, Bolliger D. Practical aspects of rotational thromboelastometry (ROTEM). Available from: https://www.scahq.org/sca3/events/2009/annual/syllabus/workshops/subs/wkshp6pdfs/ROTEM%20-%20Tanaka.doc.pdf

Haemoview Diagnostics. ROTEM analysis: thromboelastometry. Available from http://www.haemoview.com.au/rotem-analysis.html

Haemoview. The 5 ROTEM tests. Available from http://www.haemoview.com.au/uploads/2/5/4/9/25498232/the_5_rotem_tests.pdf

How Do I Interpret TEG and r-TEG Results?

Drs. Semon and Cheatham of the Orlando Regional Medical Center Department of Surgical Education generated an excellent quick reference chart:

screen-shot-2016-12-20-at-10-23-21-pm

*Note: TEG-ACT (rapid) – reported for r-TEG only.

A TEG-Guided Transfusion Strategy

In addressing TEG and r-TEG abnormalities, experts recommend the following3:

screen-shot-2016-12-20-at-10-23-39-pm

The Quick and Dirty: Pattern Recognition

Perhaps most useful for the ED physician is knowledge of qualitative TEG representations:

screen-shot-2016-12-20-at-10-23-52-pm

Some clarification on DIC Stage 1 and 2:

  • Stage 1: Fibrinolysis results in the degradation of fibrin, increasing fibrin degradation products (FDPs). Excess FDPs result in clot de-stabilization.1
  • Stage 2: The cycle of clot formation and breakdown results in platelet and clotting factor consumption.1

Why Might an Emergency Medicine Physician Want to Know about this Test?

Coagulation abnormalities in trauma patients have demonstrated a significant association with infection, multi-organ failure, and death.15-18 Given its ability to quickly detect hematologic pathology, the TEG is becoming a tool for the evaluation of transfusion requirements/coagulopathy post transfusion in this patient population.3,12,13

What does the literature say?

Cotton, et al., 20114:

  • Pilot study to evaluate the timeliness of r-TEG results, their correlation to conventional coagulation testing (CCT – PT, aPTT, INR, platelet count, fibrinogen), and the ability of r-TEG to predict early blood transfusion.
    • 272 patients meeting requirements for major trauma activation
    • Outcomes:
      • All r-TEG values available within 15 minutes vs. 48 minutes for CCTs
      • ACT, r-value, k-time correlated with PT, INR, PTT (r >0.70; p<0.001)
      • MA and a-angle correlated with platelet count (p<0.001, p<0.001)
      • Controlling for demographics and ED vitals: ACT>128 predicted massive transfusion (>10 U) in the first 6 hours of presentation and treatment

Bottom line – r-TEG results were available within minutes, results correlated with conventional coagulation test results, and were predictive of the requirement for early massive transfusion.

Holocomb, et al., 201219:

  • Study to evaluate the reliability of r-TEGs versus CCTs in predicting blood product transfusion
    • 1974 major trauma patients, median ISS 17 (25% meeting criteria for shock; 28% transfused, 6% died within 24 hours)
    • Outcomes
      • When controlling for age, injury mechanism, weighted-Revised Trauma Score, base excess and hemoglobin, ACT predicted RBC transfusion and a-angle predicted massive transfusion better than PT/aPTT or INR (p<0.001).
      • a-angle was superior to fibrinogen for predicting plasma transfusion, and MA was superior to platelet count for predicting platelet transfusion (p<0.001)

Bottom line – r-TEG was more accurate in the prediction of requirements for RBC, plasma, and platelet transfusions as compared to traditional CCTs.

Wikkelso A, et al., 201612:

  • Cochrane Review including 17 current RCTs (n=1493 participants)
    • Per the authors:
      • Low quality studies: numerous biases
      • Limited generalizability: majority of studies center on cardiac patients undergoing surgical intervention

Bottom line – There is growing evidence to suggest that the utilization of TEG and ROTEM reduce transfusion requirements and improve morbidity in patients with bleeding, but additional studies are required.

Back to Our Case

Why was the trauma surgeon concerned? If we interpret our TEG values:

  • R time 20.0 => well above the upper limit of normal (10.0 minutes) = significantly prolonged time for clot formation
  • K time 13.2 => normal: up to 10.0 = prolonged fibrin cross-linking
  • a-angle 16.5 => normal >53.0 = limited clot formation
  • MA 38 => normal platelet function >50 = limited platelet function

More importantly, one quick glance at our TEG and through pattern recognition, we known that aside from his significant traumatic injuries, the patient is in trouble. This waveform is characteristic of DIC Stage 2.

Key Pearls

  • A TEG can be used as a rapid assessment of thrombosis and fibrinolysis.
  • Although additional RCTs are needed, TEGs utilized in trauma patients have been demonstrated to reduce transfusion requirements (important when we consider TACO/TRALI, risk of DIC, and blood-borne pathogens).
  • If nothing else, take a few minutes to review the characteristic TEG waveforms – depending on your laboratory processing time, knowledge of above tracings could allow early identification of coagulopathy and immediate treatment.

 

References / Further Reading

  1. Williams. Haemscope Basic Clinician Training: Fibrinolysis and Hyperfibrinolysis TEG Analysis. Available from: www.medicine.wisc.edu/~williams/TEG5_analysis.ppt
  2. Walsh M, Thomas S, Howard J, Evans E, Guyer K, et al. Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography. J Extra Corpor Technol. 2001; 43(4):162-167.
  3. Semon G, Cheatham M. Thromboelastography in Trauma. Surgical Critical Care Evidence-Based Guidelines Committee. 2014. Available from: www.surgicalcriticalcare.net/Guidelines/TEG%202014.pdf
  4. Cotton B, Faz G, Hatch Q, Radwan Z, Podbielski J, et al. Rapid thromboelastography delivers real-time results that predict transfusion within 1 hour of admission. J Trauma. 2011; 71:407-417.
  5. Teodoro da Luz L, Nascimento B, Rizoli S. Thromboelastography (TEG): practical considerations on its clinical use in trauma resuscitation. Scand J Trauma Resusc Emerg Med. 2013; 21:29.
  6. Bollinger D, Seeberg M, Tanaka K. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev. 2012: 26(1): 1-13.
  7. Thakur M, Ahmed A. A review of thromboelastography. Int J periop Ultrasound Apply Technol. 2012; 1(1):25-29.
  8. Nickson C. Critical Care Compendium: Thromboelastogram (TEG). 2014. Available from http://lifeinthefastlane.com/ccc/thromboelastogram-teg/
  9. Kashuk J, Moore E, Sawyer M, Wolhauer M, Pezold M, et al. Primary fibrinolysis is integral in the pathogenesis of acute coagulopathy of trauma. Ann Surg. 2010; 252: 434-444.
  10. Zhu S, Diamond S. Contact activation of blood coagulation on a defined kaolin/collagen surface in microfluidic assay. Thromb Res. 2014; 134(6): 1335-1343.
  11. Heemskerk J, Bevers E, Lindhout T. Platelet activation and blood coagulation. Throm Haemost. 2002; 88(2):186-193.
  12. Wikkelso A, Wetterslev J, Moller A, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding (Review). Cochrane Database of Systematic Reviews. 2016; 8:1-149.
  13. Luddington R. Thromboelastography/thromboelastometry. Clin Lab Haematol. 2005; 27(2):81-90.
  14. Jeger V, Zimmerman H, Exadaktylos A. Can rapid TEG accelerate the search for coagulopathies in the patient with multiple injuries? J Trauma. 2009; 66:1253-1257.
  15. Niles S, McLaughlin D, Perkins J et al. Increased mortality associated with the early coagulopathy of trauma in combat casualties. J Trauma. 2008; 64:1459-1463.
  16. Brohi K, Sing J, Heron M. Coats T. Acute traumatic coagulopathy. J Trauma. 2003; 54:1127-1130.
  17. Cotton B, Gunter O, Isbell J, et al. Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma. 2008; 64;1177-1182.
  18. Cohen J, Call M, Nelson M, et al. Clinical and mechanistic drivers of cute traumatic coagulopathy. J Trauma Acute Care Surg. 2013; 75:S40-47.
  19. Holocomb J, Minei K, Scerbo M, Radwan Z, Wade C, et al. Admission rapid thromboelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg. 2012