SAEM Clinical Images Series: Found Down

found down

A 67-year-old caucasian male experiencing homelessness was “found down” in a parking lot. EMS reported that he had a GCS of 6 with a systolic blood pressure in the 80’s, finger stick glucose of 100, and no response to intranasal naloxone. He was intubated in the field and arrived to the emergency department unresponsive with a BP of 95/60, HR 125, T 38°C, and O2 Sat 100%. Hemodynamic stabilization was achieved with central venous access, and laboratory and imaging studies for the evaluation of altered mental status ensued.

General: Disheveled male

HEENT: Normocephalic; PERRLA 3-2 mm; dried blood in nares

Skin: Warm; dry; no visible signs of trauma

Cardiovascular: Tachycardic with no murmurs, rubs, or gallops

Respiratory: Bilateral breath sounds on ventilator; diffuse rales

Gastrointestinal: Soft; non-distended; bowel sounds present

Musculoskeletal: No deformities

Neurologic: Unresponsive; GCS 3

COVID-19 rapid antigen: Detected

Complete Blood Count (CBC): WBC 17 k; Hemoglobin 15; Platelets 185

Comprehensive Metabolic Panel (CMP): Na 133; K 4.6; Cl 91; CO2 21; BUN 18; Cr 2.2; Ca 8.4; Alb 2.1; Tbili 0.4; Alk phos 112; AST 242; ALT 68

ABG on FiO2 100%: 6.99/>95/405/23/100%

Lactate: 16.4

Ammonia: 90

CK total: 716

Trop I HS: 809

PT: 14

INR: 1.05

PTT: 45

Urinalysis: Unremarkable

EtOH, Acetaminophen, Salicylate: Negative

UDS: Negative

Chest Radiograph: Diffuse ground-glass opacities

Air embolism to the right ventricle and pulmonary artery. As little as 20 mL or less of air rapidly infused may cause obstruction, ischemia, and hemodynamic collapse.

Risk factors include central venous catheterization, lung trauma, ventilator usage, hemodialysis, surgery (esp. coronary, neurosurgery), childbirth, and scuba diving barotrauma.

Take-Home Points

  • In the appropriate clinical scenario, especially those involving respiratory, cardiac, and neurologic findings where invasive procedures were utilized, the diagnosis of venous air embolism should be entertained.
  • Immediate management of an air embolism involves administration of 100% oxygen by nonrebreather mask (NRM) or ventilator and placement of the patient in the left lateral decubitus (Durant maneuver) and Trendelenburg positions. Hyperbaric oxygen therapy has also been used if there is no clinical improvement.
  • The purpose of the Durant maneuver and Trendelenburg position is to trap air along the lateral right ventricular wall, preventing right ventricular outflow obstruction and embolization into the pulmonary circulation.

  • Gordy S, Rowell S. Vascular air embolism. International Journal of Critical Illness and Injury Science. 2013;3(1):73. doi:10.4103/2229-5151.109428 Malik N, Claus PL, Illman JE, Kligerman SJ, Moynagh MR, Levin DL, Woodrum DA, Arani A, Arunachalam SP, Araoz PA. Air embolism: diagnosis and management. Future Cardiol. 2017 Jul;13(4):365-378. doi: 10.2217/fca-2017-0015. Epub 2017 Jun 23. PMID: 28644058.

Trick of the Trade: A “Fiberbougie” through a supraglottic airway device (King tube)

king tubeResuscitation before intubation is a critical construct in modern emergency medicine. The prevention of peri-intubation arrest by correcting pre-intubation hypoxia, hypotension, and acidosis is often easier said than done. Worse yet, the intubation process itself, especially if difficult, can worsen hypoxia and hypotension which is often unrecoverable [1, 2] Supraglottic devices, such as a King Airway or laryngeal mask airway, can be placed quickly, and they effectively oxygenate and ventilate patients with a high degree of success [3]. Unfortunately, when the King (or similar device) is exchanged for an endotracheal tube, success is far from guaranteed. Ideally the King could be blindly changed over a tube exchanger however it is quite easy to lose the airway completely during this process. We describe a potentially safer and more effective alternative.

Trick of the Trade

After a patient is stabilized after initial resuscitation, the supraglottic King airway device should be exchanged. A disposable, single-patient-use bronchoscope can serve as a bougie-like guide.

equipment fiberbougie king

Equipment Needed

  • Disposable bronchoscope
  • Endotracheal tube
  • 50 mL syringe
  • Laryngoscope (video or direct)
  • Trauma shears
  • Suction
  • Capnography
fiberbougie through supraglottic device king airway

Left: Demonstrating the technique inserting a single-use bronchoscope through a supraglottic King tube in a simulation patient. Right: Corresponding view of the vocal cords through the King side port in a real patient.

Description of the Trick

  1. Insert a disposable bronchoscope through the airway port of the King airway
  2. Guide the bronchoscope to exit through the side port of the King and into the trachea until you approach the carina
  3. Cut the disposable bronchoscope at the level of the handle, leaving a “fiberbougie” in the trachea above the carina
  4. Remove the King airway over the cut fiberscope in a modified Seldinger technique while suctioning airway
  5. Insert the endotracheal tube over the “fiberbougie”
  6. Use video or direct laryngoscopy to visualize the tube sliding over the “fiberbougie” into cords
  7. Confirm placement with capnography and/or with direct visualization and x-ray
bronch bougie equipment

Insertion of the endotracheal tube over the “fiberbougie” with video laryngoscopy confirmation with a simulation patient. The inset image was captured from a Glidescope on a real patient during the exchange.

 

Video Tutorial of the Fiberbougie Technique to Exchange a King Tube

 

 

References

  1. April MD, Arana A, Reynolds JC, et al. Peri-intubation cardiac arrest in the Emergency Department: A National Emergency Airway Registry (NEAR) study. Resuscitation. 2021;162:403-411. doi:10.1016/j.resuscitation.2021.02.039. PMID 33684505
  2. Russotto V, Tassistro E, Myatra SN, et al. Peri-intubation Cardiovascular Collapse in Critically Ill Patients: Insights from the INTUBE Study [published online ahead of print, 2022 May 10]. Am J Respir Crit Care Med. 2022. doi:10.1164/rccm.202111-2575OC. PMID 35536310
  3. Burns JB Jr, Branson R, Barnes SL, Tsuei BJ. Emergency airway placement by EMS providers: comparison between the King LT supralaryngeal airway and endotracheal intubation. Prehosp Disaster Med. 2010;25(1):92-95. doi:10.1017/s1049023x00007743. PMID 20405470 

Trick of Trade: Large-Bore Endotracheal Tube To Suction the Occluded Airway

vomit suction emesis pumpkin

The paramedics just arrived with a new patient to the resuscitation room. You find an altered patient actively vomiting bloody vomitus and food particles. You prepare for a difficult airway. You prepare 2 Yankauer suction catheters, but you are still worried that the food particles may clog up the catheters. Is there a better alternative?

Background

Up to 44% of emergent intubations are complicated by blood, vomit, or food particles in the airway. It has been shown that contaminated airways may lead to multiple intubation attempts and are associated with poor outcomes, such as peri-intubation cardiac arrest [1, 2].

The Yankauer suction catheter is the most commonly available tool in the Emergency Department to remove foreign particles, but performs poorly when compared to larger-bore catheters [3]. The Yankauer was made initially for surgical field management, with small holes at the tip to gently remove (or become clogged with) debris without damaging tissue. Some standard Yankauer designs have a built-in safety vent hole on the shaft, which if unoccluded, renders the device virtually useless [2]. This protective equipment design does not offer maximum help during emergent large-volume regurgitation dirty airway management.

Alternatively, there is the DuCanto suction catheter. It is a specialized and more expensive large-bore version of the Yankauer; however, it is not as readily available and more expensive [1].

Trick of the Trade: Use a large-bore endotracheal tube as a rigid suction catheter

A large-bore, such as a size 10.0, endotracheal tube can serve as a rigid suction catheter. Note the diameter sizes of the Yankauer, DuCanto, and 10.0 endotracheal tube below.

Suction devices (inner diameter):
Yankauer (3.56 mm), DuCanto (6.6 mm), 10.0 endotracheal tube (10 mm)
  • Materials needed
    1. Size 10.0 endotracheal tube (or the largest size you have)
    2. Suction tubing and canister
  • Making the device
    1. Insert the rubber end of the suction tubing over the plastic endotracheal tube adaptor
    2. Attach suction tubing to the canister
    3. Turn suction on

Video Demonstration: Yankauer vs Large-Bore Endotracheal Tube

Editorial Note: If the rigidity of the catheter is less important, you can also insert the soft suction tubing directly into the airway to remove contents.

Read other Tricks of the Trade posts on ALiEM.

References:

  1. Nikolla DA, Heslin A, King B, Carlson JN. Comparison of suction rates between a standard Yankauer and make-shift large bore suction catheters using a meconium aspirator and various sized endotracheal tubes. J Clin Anesth. 2021 Sep;72:110262. doi: 10.1016/j.jclinane.2021.110262. PMID 33839435
  2. Hasegawa K, Shigemitsu K, Hagiwara Y, et al. Association between repeated intubation attempts and adverse events in emergency departments: an analysis of a multicenter prospective observational study. Ann Emerg Med. 2012;60(6):749-754.e2. doi:10.1016/j.annemergmed.2012.04.005. PMID 22542734
  3. Andreae MC, Cox RD, Shy BD, et al. 319 Yankauer Outperformed by Alternative Suction Devices in Evacuation of Simulated Emesis.” Ann Emerg Med. 68(4), S123 [research abstract] doi: 10.1016/j.annemergmed.2016.08.335
By |2021-10-29T19:15:35-07:00Oct 31, 2021|Critical Care/ Resus, Tricks of the Trade|

Pre-Arrest Acidemia and the Effect of Sodium Bicarbonate on ROSC

Background

Sodium bicarbonate during a cardiac arrest is widely debated and used in many cases. In a 2018 PULMCrit post, Dr. Josh Farkas reviews much of the data and concludes that use of sodium bicarbonate is a “source of eternal disagreement.” A 2013 EMCrit article and podcast by Dr. Scott Weingart also details some of the controversy. The 2020 ACLS Guidelines state that routine use of sodium bicarbonate is not recommended in cardiac arrest [1]. Despite this recommendation, sodium bicarbonate is still often administered during resuscitations if a metabolic (or respiratory) acidosis is suspected or after a prolonged downtime. A recent study evaluated the effect of pre-arrest acid-base status on response to sodium bicarbonate and achievement of return of spontaneous circulation (ROSC) [2].

Evidence

This was a retrospective review of in-hospital cardiac arrests (IHCA) in patients with pre-arrest serum bicarbonate levels ≤21 mmol/L compared to >21 mmol/L. Pre-arrest bicarbonate levels were obtained <24 hours prior to the arrest. Similarly, post-arrest bicarb levels were obtained <24 hours following the arrest. Bicarbonate levels were recorded from basic chemistry panels rather than blood gases. All patients received a median sodium bicarbonate dose of 100 mEq. The groups were relatively well-matched, with the only major difference being the time to first bicarb administration was faster in the ‘acidotic’ group (6.9 vs. 9.2 minutes). Initial ECG rhythms were similar between the groups.

  • 102 patients in ‘acidotic’ group with a median pre-arrest bicarb level of 17 mmol/L
  • 123 patients in ‘non-acidotic’ group with a median pre-arrest bicarb level of 27 mmol/L
  • There was no difference in ROSC (53.9% vs 48.8%, p=0.44) or survival to discharge (8.8% vs 5.7%, p=0.36) between the acidotic group versus the nonacidotic group

Thoughts and Limitations

  • A meta-analysis found no difference in sustained ROSC or survival to discharge with sodium bicarbonate (Alshahrani 2021).
  • In the current study, prearrest bicarb levels could have resulted up to 24 hours prior to the arrest and the authors don’t comment on when exactly they were drawn. The timing limits the ability to know true acid-base status just prior to the arrest. And, that really limits applying this to out-of-hospital cardiac arrest where patients may have more significant acidemia if resuscitation is delayed.
  • A median bicarbonate concentration of 17 mmol/L isn’t really that low, relatively speaking, to indicate a potential impact from administering sodium bicarbonate.
  • Retrospective cardiac arrest studies are challenging. Many interventions happen around the same, making it impossible to connect any one of them with a specific outcome.
  • The study that would be more helpful is taking patients with metabolic/respiratory acidosis and giving have bicarb and the other placebo.

Bottom Line

  • In this cohort of IHCA patients, sodium bicarbonate administration did not improve the chances of ROSC or survival to hospital discharge, irrespective of pre-arrest acid-base status. In other words, attempting to correct ‘acidosis’ does not seem to change rate of ROSC.
  • Sodium bicarbonate use in cardiac arrest should be targeted (e.g., hyperkalemia with metabolic acidosis, sodium channel blockade secondary to an overdose).

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: adult basic and advanced life support: 2020 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2020;142(16_suppl_2):S366-S468. doi: 10.1161/CIR.0000000000000916. PMID: 33081529.
  2. Mclean H, Wells L, Marler J. The effect of prearrest acid-base status on response to sodium bicarbonate and achievement of return of spontaneous circulation. Ann Pharmacother. Published online August 5, 2021:10600280211038392. doi: 10.1177/10600280211038393. PMID: 34353142.

Beta-Blockers for Inhalant-Induced Ventricular Dysrhythmias

Background

There are a few unique scenarios when beta-blockers may be indicated for patients in cardiac arrest. Use of esmolol for refractory ventricular fibrillation was summarized in a 2016 PharmERToxGuy post with an accompanying infographic. Another potential use for beta-blockers is in the rare case of a patient with inhalant-induced ventricular dysrhythmias. The term ‘sudden sniffing death’ refers to acute cardiotoxicity associated with inhaling hydrocarbons. Check out this ACMT Toxicology Visual Pearl for more information about the background and diagnosis of inhalant abuse.

It is thought that inhalants causes myocardial sensitization via changes in various cardiac channels (e.g., sodium channels, potassium channels, calcium channels, or gap junctions) leading to prolonged repolarization and conduction [1, 2]. Additionally, chronic inhalant use can lead to structural heart damage. When the above alterations are combined with a sudden increase in catecholamines (e.g., exercise, caught sniffing), a dysrhythmia can develop which is often fatal [2-4].

Evidence

There are no case reports to support the use beta-blockers to treat inhalant-induced dysrhythmias. However, the case reports below include patients that ingested various hydrocarbons who developed ventricular dysrhythmias and improved following the initiation of beta-blockers. As the adverse cardiac effects should be similar between inhaled and ingested hydrocarbons, we can potentially extrapolate this data to patients with inhalant-induced dysrhythmias.

DemographicsAgent(s) Ingested Cardiac EffectsInterventionsResolution of dysrhythmia following BB?
39 yo M [5]TrichloroethylenepVT/VF arrestDefibrillation, Propranolol bolus and infusion

Y

70 yo F [6]TrichloroethyleneBigeminy, Junctional rhythmEsmolol bolus and infusion

Y

23 yo F [7]Chloral hydrateVF arrestEsmolol bolus and infusion

Y

27 yo M [8]Chloral hydrate, Loxapine, FluoxetineStable VTPropranolol bolus and infusion

Y

3 yo M [9]Chloral hydrateSinus tachycardia, Bigeminy, Trigeminy, NSVTEsmolol bolus and infusion

Y

44 yo M [10]Chloral hydrateStable VTPropranolol bolus, Labetalol infusion

Y

BB=beta-blocker; pVT=polymorphic ventricular tachycardia; VT=ventricular tachycardia; VF=ventricular fibrillation; NSVT=non-sustained ventricular tachycardia

Bottom Line

  • Patients presenting to the ED with cardiopulmonary manifestations of inhalant use should have routine electrolytes and an ECG to assess cardiac status
  • A quiet environment is important to decrease stimulation and minimize catecholamine surges
  • For both stable and non-perfusing dysrhythmias, propranolol or esmolol are reasonable choices to counteract the catecholamine effects, in addition to standard care [5-10]
    • Consider avoiding epinephrine and other catecholamines unless necessary, as they may worsen the dysrhythmia

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

References

  1. Nelson LS. Toxicologic myocardial sensitization. J Toxicol Clin Toxicol. 2002;40(7):867–79. doi: 10.1081/clt-120016958. PMID: 12507056.
  2. Tormoehlen LM, Tekulve KJ, Nañagas KA. Hydrocarbon toxicity: A review. Clin Toxicol (Phila). 2014 Jun;52(5):479–89. doi: 10.3109/15563650.2014.923904. PMID: 24911841.
  3. Bass M. Sudden sniffing death. JAMA. 1970 Jun 22;212(12):2075–9. PMID: 5467774.
  4. Baydala L. Inhalant abuse. Paediatr Child Health. 2010 Sep;15(7):443–54. doi: 10.1093/pch/15.7.443. PMID: 21886449.
  5. Gindre G, Le Gall S, Condat P, Bazin JE. [Late ventricular fibrillation after trichloroethylene poisoning]. Ann Fr Anesth Reanim. 1997;16(2):202–3. doi: 10.1016/s0750-7658(97)87204-8. PMID: 9686084.
  6. Mortiz F, de La Chapelle A, Bauer F, Leroy JP, Goullé JP, Bonmarchand G. Esmolol in the treatment of severe arrhythmia after acute trichloroethylene poisoning. Intensive Care Med. 2000 Feb;26(2):256. doi: 10.1007/s001340050062. PMID: 10784325.
  7. Shakeer SK, Kalapati B, Al Abri SA, Al Busaidi M. Chloral hydrate overdose survived after cardiac arrest with excellent response to intravenous β-blocker. Oman Med J. 2019 May;34(3):244–8. doi: 10.5001/omj.2019.46. PMID: 31110633.
  8. Zahedi A, Grant MH, Wong DT. Successful treatment of chloral hydrate cardiac toxicity with propranolol. Am J Emerg Med. 1999 Sep;17(5):490–1. doi: 10.1016/s0735-6757(99)90256-5. PMID: 10496517.
  9. Nordt SP, Rangan C, Hardmaslani M, Clark RF, Wendler C, Valente M. Pediatric chloral hydrate poisonings and death following outpatient procedural sedation. J Med Toxicol. 2014 Jun;10(2):219–22. doi: 10.1007/s13181-013-0358-z. PMID: 24532346.
  10. Wong O, Lam T, Fung H. Two cases of chloral hydrate overdose. Hong Kong Journal of Emergency Medicine. 2009 Jul;16(3):161–7. doi: 10.1177/102490790901600307.

Trick of the Trade: Upsize the IV with the tourniquet infusion technique

peripheral iv catheterThere you are, middle of the night and EMS just brought you one of the sickest of the sick: a septic-looking, chronically ill-appearing, frail, and malnourished patient with low blood pressures. They need vascular access for fluids, antibiotics, and possibly even vasopressors. The patient arrives with only a 22-gauge peripheral IV in the hand. You ask for two large bore IVs. But unfortunately, your best nurses and techs can’t find a vein, and their initial attempts are unsuccessful. Do you move right towards ultrasound-guided placement, intraosseous needle, or a central line? What if the patient only needs a fluid bolus, antibiotics, and admission to the floor?

Trick of the Trade: Tourniquet infusion technique

The tourniquet-infusion technique provides a method to increase the chance of a successfully placed larger bore peripheral IV in the volume-depleted patient.

Technique

  1. Apply a tourniquet to the extremity, proximal to the existing smaller-gauge IV access site.
  2. Rapidly infuse 50-100 mL of IV fluids, causing distension of the venous system between the IV and the tourniquet. This distension creates a larger target for venous cannulation in volume-depleted patients.

trick tourniquet infusion technique dilate upsizing vein arm peripheral IV

Tourniquet Infusion Technique: After applying a tourniquet and instillation of an IV bolus of fluids through a small distal 22-gauge IV, large veins are more visible for a second larger-bore IV

 

Discussion

This technique has been described in the literature for decades [1-3], and has been anecdotally successful in clinical practice. Its methodology capitalizes on pre-existing or easily-placed distal small gauge access (i.e., a 22g IV in the hand) as a stepping stone to larger venous cannulation.

Quinn and Sheikh investigated the employment of this technique for 22 adult patients with an acute abdomen who had been referred from the ED in hypovolemic shock. A peripheral IV had not been obtained in any of these patients using standard cannulation methods. By employing this tourniquet-infusion technique to upsize the IVs, they were able to successfully obtain adequate access for resuscitation in 15 of the 22 patients (68%). They noted no complications secondary to this technique. The authors noted that of the other 7 patients in this small study, 2 died and 5 required ultrasound-guided IJ venous line placement. In total, 15 patients were potentially spared unnecessary central venous catheterization. This technique is a simple, quick, and effective way of establishing a more appropriate line for resuscitation of sicker patients [1].

Pearls

  • For large-bore antecubital IV placement, consider placing a tourniquet in close proximity and just proximal to the elbow joint.
  • Consider the patient’s cardiac and pulmonary history to ensure that an additional fluid bolus is clinically appropriate.

References

  1. Stein JI. A new technique for obtaining large-bore peripheral intravenous access. Anesthesiology. 2005 Sep;103(3):670. doi: 10.1097/00000542-200509000-00041. PMID: 16130004.
  2. Quinn LM, Sheikh A. Establishing intravenous access in an emergency situation. Emerg Med J. 2014 Jul;31(7):593. doi: 10.1136/emermed-2012-202106. Epub 2013 Jun 15. PMID: 23771897.
  3. Williams DJ, Bayliss R, Hinchliffe R. Surgical technique. Intravenous access: obtaining large-bore access in the shocked patient. Ann R Coll Surg Engl. 1997 Nov;79(6):466. PMID: 9422881; PMCID: PMC2502954.
By |2021-05-30T23:44:23-07:00May 31, 2021|Critical Care/ Resus, Tricks of the Trade|

2020 ACLS Guidelines on Medications for Toxicology-Related Conditions

ACLS 2020 toxicology

The 2020 ACLS guidelines provide recommendations on the medication-specific management recommendations for toxicology [1]. Although the name of the guidelines emphasize they are ‘Advanced,’ these are still relatively basic toxicology recommendations and largely apply to patients in cardiac arrest or refractory shock. There are also our 2020 ACLS guideline summaries on vasopressor and non-vasopressor medications used during cardiac arrest and arrhythmia management.

Benzodiazepines

  • Flumazenil if NOT recommended in undifferentiated coma (COR3, LOE B-R)

Cocaine

  • Benzodiazepines, alpha blockers, calcium channel blockers, nitroglycerin, and/or morphine can be beneficial for hypertension, tachycardia, agitation, or chest discomfort (COR 2a, LOE B-NR)
  • Pure beta-adrenergic blockers may be reasonable to avoid, although “contradictory evidence exists (COR 2b, LOE C-LD)

Local Anesthetics

  • IV lipid emulsion may be reasonable (COR 2b, LOE C-LD)

Sodium Channel Blockers (e.g. tricyclic antidepressants)

  • Sodium bicarbonate can be beneficial for cardiac arrest or life-threatening conduction delays, such as QRS >120 msec (COR 2a, LOE C-LD)
  • Extracorporeal membrane oxygenation (ECMO) may be considered for cardiac arrest or refractory shock (COR 2b, LOE C-LD)

Digoxin

  • Antidigoxin Fab should be administered in severe toxicity (COR 2b, LOE B-R)

Carbon Monoxide

  • Hyperbaric oxygen may be helpful in severe toxicity (COR 2b, LOE B-R)

Cyanide

  • Hydroxocobalamin can be beneficial, along with oxygen +/- sodium thiosulfate (COR 2a, LOE C-LD)

Atrioventricular Nodal Blockers

InterventionBeta-adrenergic blockerCalcium channel blockerEvidence (COR/LOE)
High-dose insulinReasonableReasonable2a/C-LD
Glucagon IVReasonableMay be considered2a/C-LD and 2b/C-LD
CalciumMay be consideredReasonable2b/C-LD and 2a/C-LD
ECMOMight be consideredMight be considered2b/C-LD

Table: Medications and interventions in the management of beta-adrenergic and calcium channel blocker toxicity (COR: class of recommendation, LOE: level of evidence, ECMO: extracorporeal membrane oxygenation)

Reference

Panchal AR, Bartos JA, Cabañas JG, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020 Oct 20;142(16_suppl_2):S366-S468. doi: 10.1161/CIR.0000000000000916. Epub 2020 Oct 21. PMID: 33081529.
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