Tag Archives: shock

PEM Playbook – Approach to Shock

Originally published at Pediatric Emergency Playbook on June 1,
2016 – Visit to listen to accompanying podcast. Reposted with permission.

Follow Dr. Tim Horeczko on twitter @EMTogether

Do we recognize shock early enough?

How do we prioritize our interventions?

Are we making our patient better or worse?

World wide, shock is a leading cause of morbidity and mortality in children, mostly for failure to recognize or to treat adequately.

So, what is shock?

Simply put, shock is the inadequate delivery of oxygen to your tissues.  That’s it.  Our main focus is on improving our patient’s perfusion.

Oxygen delivery to the tissues depends on cardiac output, hemoglobin concentration, the oxygen saturation of the hemoglobin you have, and the environmental partial pressure of oxygen.

At the bedside, we can measure some of these things, directly or indirectly.  Did you notice, however, that blood pressure is not part of the equation?  The reason for that is that blood pressure is really an indirect proxy for perfusion – it’s not necessary the ultimate goal.

The equation here is a formality:

DO2 = (cardiac output) x [(hemoglobin concentration) x SaO2 x 1.39] + (PaO2  x 0.003)

Shock CAN be associated with a low blood pressure,

but shock is not DEFINED by a low blood pressure.

Compensated Shock: tachycardia with poor perfusion.  A child compensates for low cardiac output with tachycardia and a increase in systemic vascular resistance.

Decompensated Shock: frank hypotension, an ominous, pre-arrest phenomenon.

 

Shock is multifactorial, but we need to identify a primary cause to prioritize interventions.

How they “COHDe”: Cardiogenic, Obstructive, Hypovolemic, and Distributive.

Cardiogenic Shock

All will present with tachycardia out of proportion to exam, and sometimes with unexplained belly pain, usually due to hepatic congestion.  The typical scenario in myocarditis is a precipitous decline after what seemed like a run-of-the-mill URI.

Cardiogenic shock in children can be from congenital heart disease or from acquired etiologies, such as myocarditis.  Children, like adults, present in cardiogenic shock in any four of the following combinations:warm, cold, wet, or dry.

“Warm and Dry”

A child with heart failure is “warm and dry” when he has heart failure signs (weight gain, mild hepatomegaly), but has enough forward flow that he has not developed pulmonary venous congestion.  A warm and dry presentation is typically early in the course, and presents with tachycardia only.

“Warm and Wet”

If he worsens, he becomes “warm and wet” with pulmonary congestion – you’ll hear crackles and seesome respiratory distress.  Infants with a “warm and wet” cardiac presentation sometimes show sacral edema – it is their dependent region, equivalent to peripheral edema as we see in adults with right-sided failure.

“Warm” patients – both warm and dry and warm and wet — typically have had a slower onset of their symptoms, and time to compensate partially. Cool patients are much sicker.

“Cold and Dry”

A patient with poor cardiac output; he is doing everything he can to compensate with increased peripheral vascular resistance, which will only worsen forward flow.  Children who have a “cold and dry” cardiac presentation may have oliguria, and are often very ill appearing, with altered mental status.

“Cold and Wet”

The sickest of the group, this patient is so clamped down peripherally that it is now hindering forward flow, causing acute congestion, and pulmonary venous back-up.  You will see cool, mottled extremities.

Cardiogenic Shock: Act

Use point-of-care cardiac ultrasound:

Good Squeeze? M-mode to measure fractional shortening of the myocardium or anterior mitral leaflet excursion.

Pericardial Effusion? Get ready to aspirate.

Ventricle Size? Collapsed, dilated, or normal.

Careful with fluids — patients in cardiogenic shock may need small aliquots, but go quickly to a pressor to support perfusion.

Pressor of choice: epinephrine, continuous IV infusion: 0.1 to 1 mcg/kg/minute.  The usual adult starting range will end up being 1 to 10 mcg/min.

Avoid norepinephrine, as it increases systemic vascular resistance, may affect afterload.

Just say no to dopamine: increased mortality when compared to epinephrine.

 

Obstructive Shock

Mostly one of two entities: pulmonary embolism or cardiac tamponade.

Pulmonary embolism in children is uncommon – when children have PE, there is almost always a reason for it – it just does not happen in normal, healthy children without risk factors.

Children with PE will either have a major thrombophilic comorbidity, or they are generously sized teenage girls on estrogen therapy.

Tamponade — can be infectious, rheumotologic, oncologic, or traumatic.  It’s seen easily enough on point of care ultrasound.  If there is non-traumatic tamponade physiology, get that spinal needle and get to aspirating.

Obstructive Shock: Act

Pulmonary embolism (PE) with overt shock: thrombolyse; otherwise controversial.  PE with symptoms: heparin.

Tamponade: if any sign of shock, pericardiocentesis, preferentially ultrasound-guided.

 

Hypovolemic Shock

The most common presentation of pediatric shock; look for decreased activity, decreased urine output, absence of tears, dry mucous membranes, sunken fontanelle.  May be due to obvious GI losses or simply poor intake.

Rapid reversal of hypovolemic shock: may need multiple sequential boluses of isotonic solutions. Use 10 mL/kg in neonates and young infants, and 20 mL/kg thereafter.

Hypovolemic Shock: Act

Tip: in infants, use pre-filled sterile flushes to push fluids quickly.  In older children, use a 3-way stop cock in line with your fluids and a 30 mL syringe to “pull” fluids, turn the stopcock, and “push them into the patient.

Titrate to signs of perfusion, such as an improvement in mental status, heart rate, capillary refill, and urine output.

When concerned about balancing between osmolality, acid-base status, and volume status, volume always wins.  Our kidneys are smarter than we are, but they need to be perfused first.

 

Distributive Shock

The most common cause of distributive shock is sepsis, followed by anaphylactic, toxicologic, adrenal,and neurogenic causes.  Septic shock is multifactorial, with hypovolemic, cardiogenic, and distributive components.

Children with sepsis come in two varieties: warm shock and cold shock.

Distributive Shock: Act

Warm shock is due to peripheral vascular dilation, and is best treated with norepinephrine.

Cold shock is due to a child’s extreme vasoconstriction in an attempt to compensate.  Cold shock is the most common presentation in pediatric septic shock, and is treated with epinephrine.

Early antibiotics are crucial, and culture everything that seems appropriate.

 

Shock: A Practical Approach

“How FAST you FILL the PUMP and SQUEEZE”

 

Sometimes things are not so cut-and-dried.  We’ll use a practical approach to diagnose and intervene simultaneously.

Look at 4 key players in shock: heart rate, volume status, contractility, and systemic vascular resistance.

How FAST you FILL the PUMP and SQUEEZE

First, we look at heart rate — how FAST?

Look at the heart rate – is it sinus?  Could this be a supraventricular tachycardia that does not allow for enough diastolic filling, leading to poor cardiac output?  If so, use 1 J/kg to synchronize cardiovert.  Conversely, is the heart rate too slow – even if the stroke volume is sufficient, if there is severe bradycardia, then cardiac output  — which is in liters/min – is decreased.  Chemically pace with atropine, 0.01 mg/kg up to 0.5 mg, or use transcutaneous pacing.

If the heart rate is what is causing the shock, address that first.

Next, we look at volume status.

How FAST you FILL the PUMP and SQUEEZE

Look to FILL the tank if necessary.  Does the patient appear volume depleted?  Try a standard bolus – if this improves his status, you are on the right track.

Now, we look at contractility.

How FAST you FILL the PUMP and SQUEEZE

Is there a problem with the PUMP?  That is, with contractility?  Is this in an infarction, an infection, a poisoning?  Look for signs of cardiac congestion on physical exam.  Put the probe on the patient’s chest, and look for effusion.  Look to see if there is mild, moderate, or severe decrease in cardiac contractility.  If this is cardiogenic shock – a problem with the pump itself.  Begin pressors.

And finally, we look to the peripheral vascular resistance.

How FAST you FILL the PUMP and SQUEEZE

Is there a problem with systemic vascular resistance – the SQUEEZE?

Troubleshoot

Look for signs of changes in temperature – is the patient flushed?  Is this an infectious etiology?  Are there neurogenic or anaphylactic concerns?  After assessing the heart rate, optimizing volume status, evaluating contractility, is the cause of the shock peripheral vasodilation?  If so, treat the cause – perhaps this is a distributive problem due to anaphylaxis.  Treat with epinephrine. The diagnosis of exclusion in trauma is neurogenic shock.  Perhaps this is warm shock; both are supported with norepinephrine.  All of these affect systemic vascular resistance – and the shock won’t be reversed until you optimize the peripheral squeeze.

 

Summary

The four take-home points in the approach to shock in children:

  1. To prioritize your interventions, remember how patients COHDe: Cardiogenic, Obstructive, Hypovolemic, and Distributive. Your patient’s shock may be multifactorial, but mentally prioritize what you think is the MAIN case of the shock, and deal with that first.
  2. To treat shock, remember: How FAST You FILL The PUMP and SQUEEZE: Look at the heart rate – how FAST.  Look at the volume status – the FILL.  Assess cardiac contractility – the PUMP, and evaluate the peripheral vascular tone – the SQUEEZE.
  3. In pediatric sepsis, the most common type is cold shock – use epinephrine (adrenaline) to get that heart to increase the cardiac output. In adolescents and adults, they more often present in warm shock, use norepinephrine (noradrenaline) for its peripheral squeeze to counteract this distributive type of shock.
  4. Rapid-fire word association:
  • Epinephrine for cardiogenic shock
  • Intervention for obstructive shock
  • Fluids for hypovolemic shock
  • Norepinephrine for distributive shock

References

Agha BS, Sturm JJ, Simon HK, Hirsh DA. Pulmonary embolism in the pediatric emergency department.Pediatrics. 2013 Oct;132(4):663-7.

Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41:580-637.

Jaff MR et al. for the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011; Apr 26;123(16):1788-830.

Levy B et al. Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study. Crit Care Med. 2011; 39:450.

Micek ST, McEvoy C, McKenzie M, Hampton N, Doherty JA, Kollef MH. Fluid balance and cardiac function in septic shock as predictors of hospital mortality. Crit Care. 2013; 17:R246.

Osman D, Ridel C, Ray P, et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med. 2007; 35:64-8.

Ventura AM, Shieh HH, Bousso A, Góes PF, de Cássia F O Fernandes I, de Souza DC, Paulo RL, Chagas F, Gilio AE. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med. 2015;43(11):2292-302.



This post and podcast are dedicated to Natalie May, MBChB, MPHe, MCEM, FCEM for her collaborative spirit, expertise, and her super-charged support of #FOAMed.  You make a difference.  Thank you.



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Undifferentiated Shock

Powered by #FOAMed — Tim Horeczko, MD, MSCR, FACEP, FAAP

Pediatric; Emergency Medicine; Pediatric Emergency Medicine; Podcast; Pediatric Podcast; Emergency Medicine Podcast; Horeczko; Harbor-UCLA; Presentation Skills; #FOAMed #FOAMped #MedEd

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.
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  48. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010 Feb 6;375(9713):463-74.
  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.
  50. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012 Oct 16;60(16):1581-98.
  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.
  53. Thygesen K, Mair J, Giannitsis E, et al. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012;33:2252–7.
  54. Reichlin T, Hochholzer W, Bassetti S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009;361: 858–67.
  55. Kelley, W. E., J. L. Januzzi, and R. H. Christenson. Increases of Cardiac Troponin in Conditions Other than Acute Coronary Syndrome and Heart Failure. Clinical Chemistry 2009;55(12):2098-112. Web.
  56. Korff, S. Differential Diagnosis of Elevated Troponins. Heart 2006;92(7):987-93.
  57. Court O, Kumar A, Parrillo JE, Kumar A. Clinical review: Myocardial depression in sepsis and septic shock. Crit Care 2002;6:500-508.
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  60. Bouhemad B, Nicolas-Robin A, Arbelot C, et al: Acute left ventricular dilatation and shock-induced myocardial dysfunction. Crit Care Med 2009; 37:441–447.
  61. Wilhelm J, Hettwer S, Schuermann M, Bagger S, Gerhardt F, Mundt S, Muschik S, Zimmermann J, Amoury M, Ebelt H, Werdan K. Elevated troponin in septic patients in the emergency department: frequency, causes, and prognostic implications.Clin Res Cardiol 2014 Jul;103(7):561-7.
  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.
  2. Sheyin O, Davies O, Duan W, Perez X. The prognostic significance of troponin elevation in patients with sepsis: a meta-analysis. Heart Lung 2015 Jan-Feb;44(1):75-81.
  3. Landesberg G, Jaffe AS, Gilon D, Levin PD, Goodman S, Abu-Baih A, Beeri R, Weissman C, Sprung CL, Landesberg A. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Crit Care Med 2014 Apr;42(4):790-800.
  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.
  6. Cheng H, Fan WZ, Wang SC, Liu ZH, Zang HL, Wang LZ, Liu HJ, Shen XH, Liang SQ. N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study. J Crit Care 2015 Jun;30(3):654.e9-14.
  7. Courtney D, Conway R, Kavanagh J, O’Riordan D, Silke B. High-sensitivity troponin as an outcome predictor in acute medical admissions. Postgrad Med J 2014 Jun;90(1064):311-6.
  8. de Groot B, Verdoorn RC, Lameijer J, van der Velden J. High-sensitivity cardiac troponin T is an independent predictor of inhospital mortality in emergency department patients with suspected infection: a prospective observational derivation study. Emerg Med J 2014 Nov;31(11):882-8.
  9. Skibsted S, Jones AE, Puksarich MA, Arnold R, Sherwin R, Trzeciak S, et al. Biomarkers of endothelial cell activation in early sepsis. Shock 2013 May; 39(5): 427–432.
  10. Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001; 29:S21–7.
  11. Shapiro NI, Schuetz P, Yano K, et al. The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Critical Care 2010; 14:R182.
  12. Becker KL, Nylen ES, White JC, Muller B, Snider RH, Jr. Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004;89(4):1512–25.
  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.
  14. Struck J, Tao C, Morgenthaler NG, Bergmann A. Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients. Peptides 2004;25(8):1369–72.
  15. Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Muller B. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 2005;9(6):R816–24.
  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.
  19. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, Lewis SA, Macfarlane JT. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003 May;58(5):377-82.
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natriuretic peptide. J Am Coll Surg 2011;213:139–46.
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Sepsis Care – What’s New? The CMS Guidelines for Severe Sepsis and Septic Shock have arrived

Author: Krystal Baciak, MD (EM Resident Physician, Jacobi/Montefiore EM) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF)

Every minute a patient presents to an emergency department with severe sepsis or septic shock; the mortality for this condition ranges from 25-50%.1,2 As of October 1, 2015 CMS has issued new benchmarks for the care of severe sepsis and septic shock that all hospitals in the U.S. must meet. The new CMS criteria are as follows:

Table 1 – Definitions
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Table 2 – Treatment Benchmarks

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The Definitions

The definition of severe sepsis is derived from the surviving sepsis guidelines published in 2012 and is based on the International Sepsis Definitions Conference in 2003.1 While the SIRS definition is one commonly used in practice, the definition of organ dysfunction may by unreliable in certain patients. Every end-stage renal or cirrhotic patient would meet the criteria of severe sepsis based on this definition and may be overtreated. We all can agree that a patient experiencing acute kidney or liver dysfunction secondary to sepsis should be treated much more aggressively than an end-stage renal patient who meets SIRS criteria for a viral URI or strep throat. This new criteria does not leave much room for clinician judgment or individualized patient care which is likely more appropriate than a shotgun approach. The definition of septic shock included in the CMS guidelines is currently a conglomerate of the previous definitions of severe sepsis and septic shock. The previous definition of septic shock did not include a lactate level of ≥4; this was part of the definition of severe sepsis. This definition is consistent with the inclusion criteria for the original EGDT, ProMISe, ProCESS, and ARISE trials; we should all be familiar and comfortable with these criteria.2-5 Whether the criteria should be used to define septic shock is debatable.

The Treatment Guidelines

Lactate

The lactate level > 2 is an unexpected criterion for definition of severe sepsis. The EGDT inclusion criteria for severe sepsis or septic shock is a patient who meets 2 or more SIRS criteria, a SBP <90 despite fluid challenge of 20-30 cc/kg, or a lactate ≥4.2 These criteria were used in the Rivers trial and again in the inclusion criteria for the ProMISe, ProCESS, and ARISE trials that have recently been published.2-5 The surviving sepsis campaign states there is no randomized trials using a lactate cutoff for severe sepsis below 4; however, they acknowledge that some institutions may be using a lower lactate cutoff1. Additionally, in the ProMISe, ProCESS, and ARISE trials, the repeat lactate was obtained only if the initial lactate levels were ≥4.3-5 The surviving sepsis campaign suggests targeting our resuscitations to normalize the lactate (level 2C recommendation)1. While there is literature to suggest a lactate between 2 and 4 is associated with an increased risk of death independent of organ dysfunction,6,7,9 there is currently no major study using a lactate cutoff between 2 and 4 as inclusion criteria for EGDT or their protocol-derived care. At this time, the new CMS lactate parameters are not based on any available evidence; nor are they consistent with the current surviving sepsis discussion surrounding serial lactate levels.

Blood cultures and Antibiotics

The surviving sepsis campaign suggests obtaining appropriate cultures prior to antibiotic administration if they do not cause significant delay in treatment which is defined as longer than 45 minutes (grade 1C recommendation).1 In contrast, the new CMS guidelines state you must have two blood culture sets drawn prior to antibiotic administration and do not mention an exception for a significant delay in treatment. The surviving sepsis guidelines state blood cultures are rapidly sterilized within hours of the initial dose of antibiotics, and therefore, they should be drawn prior to giving antibiotics.1 Weinheimer et al. demonstrates the utility of drawing 2 sets of blood cultures stating two separate cultures will pick up 99% of all bloodstream infections.10 They also noted that if the first culture grew a contaminant, the likelihood of the second culture growing the same contaminant was very low.10,11 This study supports the recommendation that two separate blood cultures be obtained prior to antibiotic administration. Positive cultures will aid in the de-escalation of therapy that is crucial to appropriate inpatient care, consistent with the surviving sepsis guidelines,1 and has shown a mortality benefit in severe sepsis and septic shock patients.15 That being said, the advantages of drawing appropriate cultures prior to antibiotic administration must be weighed against the evidence showing that delaying appropriate antibiotic therapy causes an increase in mortality. One study shows that for every hour delay in antibiotic administration for a hypotensive septic shock patient, the mortality rate increases by 7.6% per hour.13 Another study confirms that there is a significant mortality benefit in giving antibiotics within one hour of recognition of septic shock.12 While generally it is possible to draw the required cultures and start the appropriate antibiotics in a timely fashion, it is not difficult to imagine how antibiotics may be given prior to obtaining all of the cultures in a busy emergency department. The new CMS regulations leave little room for physician judgement in this regard, and the data clearly shows that timely dosing of antibiotics is very important for the sickest patients.

Resuscitation

The surviving sepsis guidelines suggest the use of an initial crystalloid bolus of 30cc/kg for resuscitation of severe sepsis and septic shock (grade 1B recommendation).1 They also recommend maintaining a MAP >65 with vasopressors, if appropriate (grade 1C recommendation).1 There is a body of research suggesting that a MAP lower than 65 is associated with an increase in mortality among septic shock patients, which is consistent with the CMS benchmark and surviving sepsis guidelines.20 In a 70 kg patient, 30 cc/kg amounts to roughly 2L of fluid prior to reassessment, which seems reasonable in most patients. This number is similar to a study showing that the optimal amount of fluid is approximately a 3L positive fluid balance at 4 hours after the initiation of resuscitation.17 However, there is literature showing that fluid overload is detrimental to septic shock patients and can cause an increase in mortality independent of other risk factors such as their APACHE II scores.16-18 Another study demonstrated up to 64% of patients at their institution with septic shock have significant LV dysfunction.19 As we all know with our CHF patients, fluid overloading patients with myocardial dysfunction can lead to increased intubation, ICU days, morbidity and mortality. I’m not suggesting we withhold fluids from patients who desperately need them, but a one-sized fits all resuscitation of 30 cc/kg may not be the best option for every patient. Unfortunately, the CMS guidelines are firm on the 30 cc/kg fluid resuscitation.

Reassessment

The CMS guidelines now require documentation of volume status reassessment via physical exam and any two of the four additional studies shown in Table 2. First, of course you are going to reassess your patient in septic shock; I have yet to meet a provider who ignores one of these patients. The specific requirement to reassess one’s patient seems completely unnecessary. As for the required additional testing, both the RUSH exam and passive leg raise or fluid challenge exam seem appropriate in this setting. The RUSH exam can be a critical part of the evaluation of undifferentiated shock and allows one to evaluate “the pump, the tank, and the pipes.” Bedside ultrasound is gaining ground in many clinical settings and allows a non-invasive way to evaluate the fluid status of a patient. For more information regarding the RUSH exam, see http://www.emdocs.net/rush-protocol/. Additionally, passive leg raise or fluid challenge can be a useful way to evaluate the fluid responsiveness of a shock patient. The passive leg raise has a 95% accuracy rate to determine if a patient remains fluid responsive.16 It is easy to perform, costs no money, and garners results within 3 minutes. As for the CVP and SvO2 measurements, both require central venous access. Not every patient with an initial lactate of 4 requires central venous access, and central lines are not without their own complications. A study by Jones et al. shows that lactate clearance was equivalent to SvO2 measurements in determining the mortality of septic shock patients.21 Lastly, CVP will likely be elevated in patients with underlying right heart failure or pulmonary hypertension;22 thus, using it as a marker for fluid resuscitation may not be accurate for these patients. It is not in the best interest of the patient to insert unnecessary central lines when equivalent information can be gathered via non-invasive methods. At the end of the day, we are already reassessing our septic shock patients; CMS has now dictated how we document our reassessments.

The new CMS guidelines have caused some controversies within the emergency medicine community.  Many providers have voiced their concerns that we will be harming patients with antibiotics and fluids they do not need.23,24 Furthermore, there is little to no evidence to suggest any clinical improvement based on these new guidelines, and an abundance of research to suggest the new guidelines will be harmful for certain patients. As for the guidelines, for the time being they are here to stay. Hopefully as more research is published the guidelines will be aligned more appropriately to be in the best interest of our patients.

Further Reading/References

  1. Dellinger et al (2013). Surviving sepsis campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Critical Care Medicine 41(2): 580-637.
  2. Rivers et al (2001). Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. New England Journal of Medicine 345(19): 1368-1377.
  3. Mouncey et al (2015). Trial of Early, Goal-Directed Resuscitation for Septic Shock. New England Journal of Medicine 372(14): 1301-1311.
  4. Peake et al (2014). Goal-Directed Resuscitation for Patients with Early Septic Shock. New England Journal of Medicine 371(16): 1496-1506.
  5. Yealy et al (2014). A Randomized Trial of Protocol-Based Care for Early Septic Shock. New England Journal of Medicine 370 (18): 1683-1693.
  6. Trzeciak et al (2007). Serum lactate as a predictor of mortality in patients with infection. Intensive Care Medicine 33:970-977.
  7. Puskarich et al (2012). Prognostic Value of Incremental Lactate Elevations in Emergency Department Patients with Suspected Infection. Academic Emergency Medicine 19(8): 983-985.
  8. Reddy et al (2015). Lactic Acidosis: Clinical implications and management strategies. Cleveland Clinic Journal of Medicine 82(9): 615-624.
  9. Mikkelsen et al (2009). Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Critical Care Medicine 37(5): 1670-1677.
  10. Weinstein et al (1983). The Clinical Significance of Positive Blood Cultures: A Comprehensive Analysis of 500 episodes of Bacteremia and Fungemia in Adults. Laboratory and Epidemiologic Observations. Reviews of Infectious Diseases 5(1): 35-53.
  11. Weinstein et al (1997). The Clinical Significance of Positive Blood Cultures in the 1990s: A Prospective Comprehensive Evaluation of the Microbiology, Epidemiology, and Outcome of Bacteremia and Fungemia in Adults. Clinical Infectious Diseases 24: 584-602.
  12. Gaieski et al (2010). Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Critical Care Medicine 38(4): 1045-1053.
  13. Kumar et al (2006). Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine 34 (6): 1589-1595.
  14. Garnacho-Montero et al (2015). Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality. Critical Care 19(1): 302.
  15. Garnacho-Montero et al (2014). De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Medicine 40: 32-40.
  16. Podcast 111 by Dr. Paul Marik. Fluids in Sepsis, A New Paradigm. http://emcrit.org/podcasts/paul-marik-fluids-sepsis/.
  17. Boyd et al (2011). Fluid resuscitation in septic shock: A positive fluid balance and elevated central venous pressure are associated with increased mortality. Critical Care Medicine 39(2): 259-265.
  18. Kelm et al (2015). Fluid overload in patients with severe sepsis and septic shock treated with early goal-directed therapy is associated with increased acute need for fluid-related medical interventions and hospital death. Shock 43(1): 68-73.
  19. Pulido et al (2012). Clinical spectrum, frequency, and significance of myocardial dysfunction in severe sepsis and septic shock. Mayo Clinic Proceedings 87(7): 620-628.
  20. Leone et al (2015). Optimizing mean arterial pressure in septic shock: a critical reappraisal of the literature. Critical Care 19: 101.
  21. Jones et al (2010). Lactate Clearance vs Central Venous Oxygenation Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial. Journal of the American Medical Association 303(8): 739-746.
  22. Doepp et al (2008). Internal jugular vein valve incompetence in COPD and primary pulmonary hypertension. Journal of Clinical Ultrasound 36(8): 480-484.
  23. http://emcrit.org/blogpost/current-state-of-severe-sepsis-quality-measures/. We are Complicit – A glimpse into the current state of Severe Sepsis/Septic Shock Quality Measures. Posted June 11, 2015.
  24. Weingart and Faust (2015). News: Future of ED Sepsis Care May be Out of Our Hands – Unless We Agitate. Emergency Medicine News 37(9): 31-32.

RUSH (“Rapid Ultrasound for Shock”) Protocol

Introduction

  • One of multiple described ultrasound protocols for evaluation of patients presenting to ED with undifferentiated hypotension
  • Provides a framework for rapid and systematic evaluation of cause of hypotension
  • Three categories
    • Pump – Cardiac evaluation
    • Tank – Volume status
    • Pipes – Vascular system
  • Equipment: Ultrasound machine with phased array (3.5-5MHz) and linear probes (7.5 – 10MHz)

Pump: Cardiac Evaluation

Determine the Presence of Pericardial Effusion

  • Appears as anechoic fluid surrounding the heart
  • Possible pitfall is to misdiagnose an effusion
    • Distinguish pericardial fat pad from pericardial effusion by mild echogenicity of fat pad and know that fat pads tend to move in concert with myocardium
    • Pericardial effusion appears anterior to descending aorta in parasternal long axis view as opposed to pleural effusion that appears posterior to descending thoracic aorta
  • Look for evidence of cardiac tamponade
    • Right ventricle and atrium may have diastolic collapse, plethoric IVC

Assess LV Contractility

  • Assessing LV ejection fraction – hyperdynamic, normal, moderately or severely decreased
    • Visual assessment by emergency physicians generally accurate
    • E point Septal Separation (EPSS; distance of E wave of anterior MV leaflet from septum in M mode) or calculating fractional shortening may allow more objective assessment

Assess RV Strain

  • Normal RV/LV ratio is 0.6:1
  • RV/LV ratio >0.9 suggestive of right heart strain, may suggest acute pulmonary embolism
  • Parasternal short axis may underestimate size of RV, use other views
  • Bowing of septum into LV suggests elevated right heart pressure (“D sign”)
  • Thickened RV wall suggests chronic right heart strain (e.g. pulmonary htn, COPD)

Tank: Volume Status

“Tank Fullness” – IVC Evaluation

  • Measure IVC 2cm distal from cavoatrial junction or immediately superior to insertion of hepatic veins
  • IVC diameter < 2cm with >50% collapse correlates with CVP < 5mmHg and suggests fluid responsiveness
  • IVC diameter > 2cm with < 50% collapse correlates with CVP > 10mmHG, argues against fluid responsiveness

“Tank Leakiness” – FAST Exam and Lung Ultrasound

  • Evaluates peritoneal compartment for free fluid
  • In non-traumatic setting and depending on the clinical scenario, presence of free fluid may suggest ruptured AAA, ectopic pregnancy, or ruptured hemorrhagic cyst

“Tank Overload” – Assessment for Pleural Effusion and Pulmonary Edema

  • As part of the FAST exam, the views of the RUQ and LUQ should include views above the diaphragm to assess the presence of pleural effusion
  • To assess for pulmonary edema, use the phased array probe in the anterolateral chest, between the 2nd and 5th intercostal spaces
    • Presence of multiple B lines (vertical reverberation artifact extending from the pleural line to the far field) suggests pulmonary edema
    • Finding of poor LV contractility, multiple B lines, and plethoric IVC is suggestive of cardiogenic shock

“Tank Compromise” – Assessment for Pneumothorax as Cause of Obstructive Shock

  • Place linear probe in mid-clavicular line between 3rd and 5th intercostal spaces
  • Assess for normal lung sliding or “waves on a beach” pattern on M mode
  • Lack of lung sliding or “bar code” sign is suggestive of pneumothorax

Pipes: Circulatory System

Aorta (AAA)

  • Measurement of the aorta should begin at epigastrium and extend distally to bifurcation of iliac arteries
  • Measurement of the aorta should be from outer wall to outer wall; abnormal if >3cm
  • In a hypotensive patient with AAA > 3cm, acute rupture should be considered

Aortic Dissection

  • Thoracic aortic dissection may be detected on parasternal long axis view with aortic root measuring > 3.8cm
    • Aortic root best seen in parasternal long axis. You may see an intimal flap if dissecting

“Clogged Pipes” – Deep Vein Thrombosis

  • Compression US of lower extremities using linear probe
  • Should be performed at the level of the common femoral vein to the bifurcation of the deep and superficial femoral veins and at the popliteal vein extending to the trifurcation of the calf veins

The RUSH exam provides a framework for approaching the non-traumatic patient in the emergency department presenting with undifferentiated hypotension.  While the exam generally should start with the cardiac exam, the clinician’s judgment and clinical context should guide the progression through the different components of the exam.

References

  • Weingart SD, Duque D, Nelson B. Rapid ultrasound for shock and hypotension (RUSH-HIMAPP). 2009; http://emedhome.com/.
  • Perera P, Mailhot T, Riley D, Mandavia D. The RUSH exam: rapid ultrasound in shock in the evaluation of the critically ill. Emergency Medicine Clinics of North America. 2010; 28(1): 29–56.
  • Seif D, Perera P, Mailhot T, Riley D, Mandavia D. Bedside ultrasound in resuscitation and the rapid ultrasound in shock protocol. Crit Care Res Pract. 2012; doi: 10.1155/2012/503254.
  • Liteplo A, Noble V, Atkinson P. My patient has no blood pressure: point of care ultrasound in the hypotensive patient-FAST and RELIABLE. Ultrasound. 2012; 20: 64–68.
  • Moore CL, Rose GA, Tayal VS, et al.  Determination of left ventricular function by emergency physician echocardiography of hypotensive patients.  Academic Emergency Medicine. 2002; 9(3): 189-193
Edited by Adaira Landry, MD

Bleeding in the Patient with Renal Failure

Introduction

  • Over 10% of US population has some form of chronic kidney disease (CKD), and more than 350,000 persons require hemodialysis for end stage renal disease (ESRD) annually.1
  • Within the next decade, the incidence of CKD is expected to nearly double.1
  • Uremic bleeding is a well-known consequence of CKD and can result in significant morbidity and mortality.

Why Do Uremic Patients Bleed?

  • No one substance has yet to be identified as the cause of uremic bleeding and the bleeding is likely to be multifactorial.
  • Uremic toxin accumulation causes a disruption of von Willebrand Factor (vWF), which leads to platelets’ inability to bind.
  • This means that typical coagulation studies on uremic bleeding patients (PT, PTT) will be normal.
  • Bleeding time is an indirect measure of platelet function and is almost always elevated.
  • Stage of kidney disease does not correlate well with bleeding risk.2

Why is Bleeding a Concern in this Population?

  • A normocytic normochromic anemia is present as early as stage 3 CKD and is almost universal by stage 4.1 An anemia of chronic disease picture may also be seen.
  • These anemias are mainly due to the diseased kidney’s inability to adequately produce erythropoietin (EPO).
  • Despite the defective nature of platelets described above the platelet count is usually normal.

Presentations of Uremic Bleeding

Arranged in order of frequency:3
Petechiae
Epistaxis
Bleeding following invasive procedure (such as catheter placement): Dialysis access site hemorrhage typically occurs in the setting of aneurysms, anastomosis rupture, or over-anticoagulation.4
Hemorrhagic pericarditis
Hemorrhagic pleural effusion
GI hemorrhage: Hemorrhage of the upper gastrointestinal tract is the second leading cause of death in patients with acute renal failure.3
Intracranial Bleed: Subdural hematomas can mimic dialysis disequilibrium syndrome
Retroperitoneal bleed: Consider hemorrhage into renal cysts in the undifferentiated hypotensive ESRD patient
Spontaneous subcapsular hematoma of the liver
Ocular hemorrhage
Uterine hemorrhage

Treatment

General goals for treatment

  • A patient’s dialysis access is their lifeline and its compromise should only occur if their life is in jeopardy.
  • Patients with ESRD on dialysis have very delicate fluid balance and fluid overload may be apparent on aggressive resuscitation.

Direct pressure

  • Avoid placing a suture into a graft or fistula unless absolutely necessary.
  • A single stitch will often work better if there is a linear tear in the access site versus a puncture.
  • A tourniquet will stop the flow from a bleeding access site on the extremity but will most surely result in thrombosis of the graft or fistula.

Dialysis

  • Difficult in the actively bleeding patient
  • Avoid heparin
  • Corrects bleeding time in 65-85% of patients
  • In general, peritoneal dialysis patients have less bleeding risk than hemodialysis patients.

**Desmopressin / DDAVP

  • Mechanism of action not fully known: likely increases the release of factor 8 VWF polymers from the vascular endothelium => improves platelet aggregation.
  • Effective in about 50% of patients
  • Dose: 0.3 mcg/kg SC or IV; onset: 1 hour; duration: 4-8 hours
  • 1 dose can lead to tachyphylaxis secondary to depletion of factor VIII and vWF from endothelial stores.3
  • Contraindications: polydipsia, unstable angina, or severe congestive heart failure due to its antidiuretic effect
  • Special considerations: if no IV access DDAVP can be administered intranasally at a dose of 3 mcg/kg, however IV dose is preferred.

Protamine

  • Heparin is frequently used during dialysis. The half-life of heparin is short (1.5 hours), thus Protamine will only be effective during the first few hours.
  • Dose: 1 mg of Protamine for every 100 units of heparin given. If the heparin dose is unknown, 10-20 mg of protamine can be given.4
  • Contraindications: Avoid in fish allergy, caution if prior vasectomy and caution in pulmonary hypertension

Estrogen

  • Rarely useful in ED setting, onset: 1 day

Topical Hemostatic agents

Helpful when bleeding from dialysis access site.

Gelatin products
  • Provide a physical matrix for clotting to occur
  • Do not require clotting cascade5
  • Gelfoam and Surgifoam
Thrombin
  • Provides structure for fibrin clot following activation of coagulation cascade.
  • Requires intact coagulation cascade to be effective.
  • Floseal

Cryoprecipitate

  • Contains Factor VIII, fibrinogen, Factor XIII, vWF, and fibronectin
  • Dose: Use 10 bags of Cryoprecipitate over 30 mins; should see an effect within 4-12 hours6

Platelet Transfusion

  • Only in cases of uncontrolled hemorrhage
  • Platelets become dysfunctional shortly after entering uremic environment
  • Use in combination with other agents (i.e. desmopressin, cryoprecipitate, and packed red blood cells).3

*Packed RBCs

  • Transfuse to a level of around 10mg/dl; ensure that this is given along with DDAVP and platelets +/- cryoprecipitate.
  • Remember, anemia worsens bleeding

For an algorithm on the management of uremic bleeding, check out “Evidence-based treatment recommendations for uremic bleeding” published in Nature.2

Further Reading

  1. Bargman J.M, Skorecki K. Chronic Kidney Disease In: Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2011:2308
  2. Hedges, S.J ET al. Evidence-based treatment recommendations for uremic bleeding. Nature Clinical Practice Nephrology 2007 March; 3(3):138-153
  3. Venkat A., Kaufmann K.R., Venkat K.K., Care of the end-stage renal disease patient on dialysis in the ED. The American Journal of Emergency Medicine  (2006) 24, 847 – 858
  4. Larsen, C., Weathers B, Schwartzwald, M, and Barton, M.A. Focus On: Dialysis Emergencies. American College of Emergency Physicians 2010 October
  5. Berry G.W., Griffin D.L., and Schraga E.D. Topical Hemostatic Agents. Medscape 2013 May
  6. Cryoprecipitate @ Life in the Fast Lane
  7. Salsman S. Uremic Bleeding: Pathophysiology, Diagnosis, and Management. Hospital Physician 2001 May; 76 45-50.
  8. Mannucci, M. Desmopressin (DDAVP) in the Treatment of Bleeding Disorders: The First 20 Years. Blood 1997 October 90(7): 2515-2521.
  9. Spontaneous retroperitoneal hemorrhage in a dialysis patient.
Edited by Alex Koyfman, MD

Intubating the Critically Ill Patient

Intro / Main Questions

The following is a review of the most recent literature regarding intubation of critically ill patients. Specifically, the following questions will be addressed:

What is the safest way to intubate a hypotensive patient?

Which patients are at risk for peri-intubation hypotension and cardiac arrest?

What other special circumstances should be considered in intubating critically ill patients?

Recap Basics

  • Prep: Assess for difficult airway, have backup plan
  • Pre-oxygenation: NRB vs NIPPV or manual ventilation (if SpO2 <91%) and passive O2 w/ 5L NC.
  • Pre-treatment (optional): Atropine for <1yr, lidocaine for reactive airway and increased ICP, fentanyl for increased ICP and CV emergency
  • Induction: Etomidate, ketamine, propofol, thiopental, or midazolam/fentanyl
  • Paralysis: Succinylcholine 45 sec, rocuronuim 60 sec
  • Placement: Most skilled personnel, minimize # of attempts
  • Post procedure: Lung-protective vent settings, confirm placement, ABG, HOB to 30-45 to improve lung mechanics, in-line suction, NG/OG, humidify air, sedation/analgesia

What’s New

Cardiac arrest complicating endotracheal intubation (ETI)1

Two independent variables associated with post-ETI arrest:

  1. Pre-induction shock index (SI = HR/SBP) > 0.9: OR increases 1.16 for every 0.1 increase in SI
  2. Weight: OR increases 1.37 for every 10kg increase in weight

Predicting post-intubation hypotension (PIH)2

  • SI > 0.8 associated with increased risk
  • PIH associated with increased in-hospital mortality

How to intubate the hypotensive patient3

  • Pre-treat scopolamine if able: 0.4mg IVP induces amnesia, decreases secretions
  • Have crystalloid (sepsis) or blood/FFP (trauma) infusing
  • Norepi BEFORE intubation to get MAP >80, can use PIV until CVC can be placed post-intubation
  • Have bolus dose pressor ready: epi 5mcg 1:100,000 (not phenylephrine)
  • Midazolam/fentanyl takes too long to act (3-5 min); don’t use it for induction
  • Decrease dose of induction agent: e.g. 10% of normal propofol dose or middle ground dosing ketamine 0.25-0.5 mg/kg, but actually need more of etomidate
  • Paralytic is cardiac output-dependent, therefore pt in shock requires higher dose: succinylcholine 2mg/kg or rocuronium 1.6mg/kg
  • Vent: low and slow (+pressure will drop BP); low PS/PEEP, start tidal volume (Vt) 6ml/kg

Delayed Sequence Intubation (DSI)3

  • For delirious patient with hypoxia, this is alternative to bagging the patient
  • Requires having vent immediately available
  • Ketamine (1-2mg/kg then aliquots of 0.5mg/kg) to disassociate patient
  • Ketamine keeps airway reflexes and does not suppress respirations
  • Vomiting happens during EMERGENCE, not sedation
  • Wait 3 minutes while patient breathes through NRB or NIPPV (if not saturating well on NRB then has shunt physiology and needs PEEP)
  • Paralytic then wait 45 seconds
  • Intubate

Avoiding complications during ETI/PPV4

Hypotension
  • Local anesthesia only if possible or
  • Small titrated dose of sedative (0.3mg/kg propofol based on ideal weight)
  • Begin volume resuscitation before ETI
  • Have pressor ready
  • Start w/ PEEP 5 (0 for COPD) and Vt = 6 ml/kg then titrate up for plateau pressure (Pplt) = 20-30
Acid-base complications
  • Avoid hypotension as above
  • Choose initial setting similar to the pt’s respiratory status prior to ETI (but RR <30 to avoid auto-PEEP)
  • ABG in 15 minutes
  • If complicated by seizure (lactic acidosis) hyperventilate 25-30/min and give bicarb if unstable or insufficient time to document acidosis as cause
Asthmatic
  • Permissive hypercapnea
  • Reduce RR
  • Reduce Vt
  • Reduce iTime / increased expiratory time (promote full exhalation)
  • Keep Pplt <30cm H2O
  • May need sedation / muscle relaxation to decrease RR
Dyspnea / hypoxemia despite high FiO2 (ARDS)
  • Begin w/ Vt 6ml/kg
  • Titrate Vt to maintain Pplt <30
  • Incr PEEP by 3-5 q2-3min and decr Vt to keep Pplt 25-30 until SpO2 >90% on FiO2 = 60%
  • Ensure patient-ventilator synchrony
Traumatic Brain Injury
  • Pre-treatment optional (not evidence-based): Lidocaine 1.5 mg/kg 3 min prior then fentanyl 3 mcg/kg if not hypotensive
  • Induction: Etomidate 0.3 mg/kg or ketamine 1-2 mg/kg if hypo or normotensive
  • Paralysis: Succinylcholine preferred (rocuronium is ok too)
  • Hyperventilate temporarily if patient continues to deteriorate after osmotic agents

Bottom Line / Pearls & Pitfalls

  • BVM with PEEP valve and NC at 10L is “poor man” CPAP
  • Don’t bag before or in between attempts if SpO2 >90%
  • All induction agents can induce hypotension, but ketamine generally causes a sympathetic “surge” with middle ground dosing
  • Be wary of ketamine in patients with CAD, cardiac emergency, hypertension and tachycardia
  • Absolute contraindications to ketamine: age <3months and history of schizophrenia
  • Shock patient requires lower dose of induction agent (except etomidate) and higher dose of paralytic
  • Succinylcholine contraindications: FH of malignant hyperthermia, hyperkalemia, burns > 24h, crush injuries > 3 days, sepsis after 7 days, congenital / acquired myopathies, denervation illness, chronic neuropathy
  • Apply pressure to cricoid, not the thyroid cartilage for Sellick
  • Start low and slow with the vent, +pressure will drop BP even further
  • Have post-intubation checklist

Sources / Further Reading

  1. Heffner A, et al. Incidence and factors associated with cardiac arrest complicating emergency airway management. Resuscitation 84 (2013) 1500-1504.
  2. Heffner A, et al. Predictors of the complication of postintubation hypotension during emergency airway management. Journal of Critical Care (2012) 27, 587–593.
  3. Weingart S. Preoxygenation, Reoxygenation, and Delayed Sequence Intubation in the Emergency Department. The Journal of Emergency Medicine April 2010.
  4. Manthous, CA. Avoiding Circulatory Complications During Endotracheal Intubation and Initiation of Positive Pressure Ventilation. The Journal of Emergency Medicine, Vol. 38, No. 5, pp. 622–631, 2010.
  5. Griesdale D, et al. Airway Management in Critically Ill Patients. Lung (2011) 189:181–192.
  6. Heffner A, et al. The frequency and significance of postintubation hypotension during emergency airway management.  Journal of Critical Care (2012) 27, 417.e9-417.e13.
  7. Reynolds S. Airway Management of the Critically Ill Patient Rapid-Sequence Intubation. Chest Vol 127, Issue 4 (April 2005).
  8. Green SM, et al. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Ann Emerg Med. 2011;57:449-461.
  9. Sehdev RS, et al. Ketamine for rapid sequence intubation in patients with head injury in the emergency department. Emergency Medicine Australasia (2006) 18, 37–44.
  10. Price B, et al. Hemodynamic consequences of ketamine vs etomidate for endotracheal intubation in the air medical setting. American Journal of Emergency Medicine 31 (2013) 1124–1132.
  11. Robinson N. In patients with head injury undergoing rapid sequence intubation, does pretreatment with intravenous lignocaine/lidocaine lead to an improved neurological outcome? A review of the literature. Emerg Med J 2001;18:453–457.
  12. Orebaugh SL. Succinylcholine: Adverse Effects and Alternatives in Emergency Medicine. Am J Emerg Med 1999;17:715-721.
  13. MacLennan N. Anesthesia for Major Thermal Injury. Anesthesiology 1998; 89:749-70.

Discussion Questions / Future Exploration

  1. Therapeutic intervention aimed at optimizing pre-intubation hemodynamics
  2. Optimal drugs for intubating hemodynamically unstable patients
  3. Optimal drug combinations for intubation of other subsets of critically ill patients
Edited by Alex Koyfman, MD

Push-Dose Pressors

General Info/Intro

Vasopressors are medications well known to the critical care and emergency medicine communities. Useful for raising blood pressure and cardiac contractility and therefore improving cardiac output and tissue perfusion, they are used in the treatment of severe sepsis and other forms of shock. In treating shock, continuous infusions of these medications are required, and when refractory, multiple and/or large doses of vasopressors may be necessary. Due to the vasoactive properties of these drugs, they can only be safely delivered through a central line. However, if a patient’s hypotension is expected to be transient, placing a central line and starting an infusion of vasopressors may be undesirable and unnecessary.

In the field of anesthesiology, there currently exists a large amount of literature supporting the use of bolus-dose, or push-dose, pressors in the operating room. Most of the literature examines boluses of ephedrine and phenylephrine to reverse or prevent transient and recurrent hypotension induced by spinal anesthesia during caesarean delivery.1,2,3,4 The literature generally shows excellent response in patients with regard to improvement in blood pressure and prevention of hypotension when used prophylactically.

Despite the multitude of studies, the excellent results, and the commonplace use by anesthesiologists for decades, the use of push-dose pressors has not yet made its way into standard emergency medicine practice. There currently are no studies that show the benefit of push-dose pressors in the emergency department. However, Scott Weingart, MD, an emergency department intensivist, advocates for their use in the ED.5

Recap Basics

Indications for push-dose pressors include transient hypotension — when the clinician anticipates that the patient’s blood pressure will improve if given some time — but the current blood pressure is dangerously low, as may occur post-intubation or during procedural sedation. Another indication is as a temporizing measure until a central line can be placed, infusion vasopressors can be mixed up and received, or patient adequately resuscitated with crystalloid fluids.

How to Prepare Push Doses of Vasopressors

Epinephrine
  • Obtain a 10 mL syringe and fill it with 9 mL of sterile normal saline
  • Into the syringe, draw up 1 mL of epinephrine 1:10,000 (from a cardiac arrest amp)
  • Concentration of epinephrine 1:10,000 is 100 mcg/mL (or 1 mg in 10 mLs, which is one amp)
  • The concentration of epinephrine in the syringe is now 1:100,000, or 10 mcg/mL

Dose: 0.5-2 mL every 2-5 minutes (5-20 mcg). This is equivalent to dose of epinephrine given via infusion (5-20 mcg/min).
Onset: 1 minute
Duration: 5-10 minutes

  • Epinephrine has both α- and β-adrenergic activity and will therefore stimulate the heart in addition to causing vasoconstriction. Consider phenylephrine if patient has significant tachycardia or any tachyarrhythmia.
Phenylephrine
  • Draw up 1 mL of phenylephrine from a vial (contains 10 mg/mL) into a 3 mL syringe
  • Inject this into a 100 mL bag of normal saline; bag now contains 100 mcg/mL of phenylephrine
  • Draw up 10 mLs of this solution into 10 mL syringe

Dose: 0.5-2 mL every 2-5 minutes (50-200 mcg). This is equivalent to dose of phenylephrine given via infusion (50-200 mcg/min).
Onset: 1 minute
Duration: 5-10 minutes

  • Phenylephrine solely has α-adrenergic activity and therefore has no effect on the heart. Use when patient is tachycardic. May cause reflex increase in parasympathetic tone and therefore cause a decrease in heart rate.

Bottom Line/Pearls & Pitfalls

  • Ensure you use the correct dosage of epinephrine.
  • Do not bolus cardiac arrest doses of epinephrine (1:10,000) unless the patient is pulseless.
  • The concentration of push-dose epinephrine, properly mixed up, will be the same as that contained in lidocaine preparations used in local analgesics — 1:100,000. Knowing this, if the push-dose epinephrine were to extravasate, it would be equivalent to injecting 0.5-2 mL of lidocaine with epinephrine subcutaneously.

Further Reading

  1. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesthesia and Analgesia. 2002 Apr;94(4):920-6, table of contents. UI/MI:PMID: 11916798 ISSN:0003-2999; 0003-2999
  2. Ngan Kee WD, Khaw KS, Lau TK, Ng FF, Chui K, Ng KL. Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective caesarean section. Anaesthesia. 2008 Dec;63(12):1319-1326. UI/MI:PMID: 19032300; ANA5635 [pii] ISSN:1365-2044; 0003-2409
  3. Doherty A, Ohashi Y, Downey K, Carvalho JC. Phenylephrine infusion versus bolus regimens during cesarean delivery under spinal anesthesia: A double-blind randomized clinical trial to assess hemodynamic changes. Anesthesia and Analgesia. 2012 Dec;115(6):1343-1350. UI/MI:PMID: 23011562; ANE.0b013e31826ac3db [pii] ISSN:1526-7598; 0003-2999
  4. Siddik-Sayyid SM, Taha SK, Kanazi GE, Aouad MT. A randomized controlled trial of variable rate phenylephrine infusion with rescue phenylephrine boluses versus rescue boluses alone on physician interventions during spinal anesthesia for elective cesarean delivery. Anesthesia and Analgesia. 2013 Dec 2 UI/MI:PMID: 24299932 ISSN:1526-7598; 0003-2999
  5. Weingart S. EMCrit Podcast 6 – Push-Dose Pressors. EMCrit Blog. Retrieved December 14, 2013
Edited by Alex Koyfman, MD