POTD: Influenza

Clinical presentation

  • Sore throat, fevers, chills, myalgias

  • If severe, will result in hypoxemia and tachypnea.

When to hospitalize

  • Significant dehydration

  • If the patient appears septic: respiratory distress, hypoxemia, impaired cardiopulmonary function, AMS.

Imaging

  • US/CXR show patchy bilateral infiltrates.

  • CT may show bronchial wall thickening, tree-in-bud nodules, multifocal consolidations.

Testing

  • Flu PCR has ~ 90% sensitivity, though is dependent on quality of sample (did the swab go deep enough)

  • Tracheal aspirate or BAL if intubated (gold standard)

  • Procalcitonin. Influenza generally doesn’t increase procalcitonin à be more suspicious of a bacterial cause.

  • General sepsis/pneumonia labs: blood and sputum cultures, MRSA PCR, urine

When to suspect a bacterial superinfection

  • Imaging with lobar consolidations, cavitations, or significant pleural effusion suggests superimposed bacterial PNA, or other diagnosis.

  • A biphasic illness: when the patient initially improves, then deteriorates again.

  • Copious sputum production (generally not a feature of influenza)

Is there a role for antivirals?

  • The evidence is iffy. Cochrane review 2014 of 44 trials, 24,000 patients showed only modest benefits1

    • Reduction of symptoms by ~ 0.5 days average.

    • Does not reduce hospitalization or development of pneumonia.

  • 1st line: Tamiflu (oseltamivir) 75mg BID x5 days (10 days if critically ill). PO only.

    • Most effective within the first 48 hours if the patient is critically ill, give it regardless of illness duration.

  • 2nd line: Peramivir in pt who cannot tolerate oral therapy.

Is there a role for antibiotics?

No… but also yes. There is bacterial superinfection in 1/3rd of patients, and it is generally difficult to exclude bacterial pneumonia until cultures return.

  • Antibiotic choices include beta-lactam + macrolide + MRSA coverage.

  • Beta-lactam:

    • Generally, ceftriaxone.

    • Broaden to pseudomonal coverage for your HCAP/VAP/immune compromised patients, same as your other pneumonias.

  • Macrolide

    • Instead of azithromycin, consider clarithromycin, which has direct antiviral activity against influenza2.

  • MRSA coverage

    • High prevalence of MRSA superinfection among influenza pneumonia 3

    • Linezolid is superior to vancomycin for MRSA pneumonia, unless there is a contraindication4.

A key difference in resuscitation versus traditional sepsis

  • Most mortality in influenza pneumonia is secondary to ARDS5. Avoid large volume resuscitation. I.e. do not follow the Surviving Sepsis 30cc/kg recommendation.

  • For mild hypotension, consider low dose pressors instead of large volume fluid resuscitation.

  • If the patient is normotensive, great. You don’t need to resuscitate blood pressure.

 

References

1.           Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database Syst Rev. 2014;(4). doi:10.1002/14651858.CD008965.pub4

2.           Yamaya M, Hatachi Y, Kubo H, Nishimura H. Clarithromycin inhibits pandemic A/H1N1/2009 influenza virus infection in human airway epithelial cells. Eur Respir J. 2012;40(Suppl 56). Accessed December 11, 2023. https://erj.ersjournals.com/content/40/Suppl_56/P4364

3.           Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019;68(6):e1-e47. doi:10.1093/cid/ciy866

4.           Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;54(5):621-629. doi:10.1093/cid/cir895

5.           Severe influenza. EMCrit Project. Accessed December 11, 2023. https://emcrit.org/ibcc/influenza/

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POTD: Capnography

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2 Types of Measurement:

 

Colorimetric capnography is a qualitative method for measuring expired carbon dioxide (CO2) using a color-changing indicator. It provides a general range of CO2 values, rather than precise measurements, making it primarily suitable for confirming correct endotracheal tube (ETT) placement.

 

The color change ranges from purple (<4 mmHg CO2) to tan (4-15 mmHg CO2) to yellow (20 mmHg CO2). However, it is important to note that colorimetric capnography cannot rule out bronchial mainstem intubation.

 

 

Capnography is a non-invasive method for continuously monitoring the amount of carbon dioxide (CO2) in a patient's exhaled breath. It is measured in millimeters of mercury (mmHg). A normal EtCO2 range is between 35 and 45 mmHg.

EtCO2 is closely correlated with PaCO2, which is the partial pressure of carbon dioxide in arterial blood. However, EtCO2 is typically about 5 mmHg higher than PaCO2 due to the addition of CO2 from the upper airway.

Hypoventilation is suspected if EtCO2 is greater than 50 mmHg or if there is an increase of more than 10 mmHg from baseline.

 

 

 

 

The Waveform

  • Phase 1 [A-B] – Dead Space Ventilation

    • Should contain no CO2

  • Phase 2 [B-C] – Expiratory Upslope

    • CO2 raises from alveoli into upper airway

  • Phase 3 [C-D] – Alveolar Plateau

    • Value at end of this phase (end-tidal) is that which is reported on monitor

    • Provides insight into V/Q characteristics of lung

  • Phase 4 [D-E] – Inspiratory Downslope

    • Physiologic decline in CO2 partial pressure as patient’s inspire

Sample Abnormal Waveforms

  • Obstructive Lung Disease – Increased baseline indicates there is some trapping of CO2 within the lungs while the same amount of CO2 is expired each breath

  • Hypoventilation – Increased amount of CO2 expired each breath, without a change in baseline

  • Apnea – Serially decreasing amounts of CO2 as decreased amount of CO2 expired

 

 

                 

Clinical Applications in the Emergency Department

 

Spontaneously breathing patients

·       Sedated patients

·       Metabolic acidosis

·       Obstructive lung disease

 

Ventilated patients/apneic patients

·       ET tube placement

·       CPR effectiveness/ROSB

 

 

References

 

Tintinalli JE, Stapczynski JS, Ma OJ, Cline D, Meckler GD, Yealy DM. Tintinalli’s emergency medicine: a comprehensive study guide. Eight edition. ed. New York: McGraw-Hill Education; 2016.

 

Marx JA, Rosen P. Rosen’s emergency medicine : concepts and clinical practice. 8th ed. Philadelphia, PA: Elsevier/Saunders; 2014.

 

Long B, Koyfman A, Vivirito MA. Capnography in the Emergency Department: A Review of Uses, Waveforms, and Limitations. J Emerg Med. 2017;53(6):829-42. PMID: 28993038

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POTD: Acute Organophosphate Toxicity

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Today, we will be talking about organophosphate toxicity!

 

Introduction

 

Organophosphate poisonings occur in agricultural heavy communities. Each year, millions of individuals suffer from organophosphate poisoning, and hundreds of thousands succumb to its adverse effects.

 

Agricultural workers can encounter organophosphates through various routes, including inhalation, ingestion, injection, or skin absorption.

 

Furthermore, organophosphate poisonings can exist as nerve agents created for chemical warfare.

 

Depending on the dose and duration of exposure, sufficient amounts of organophosphates can trigger acute toxicity symptoms.

 

 

Mechanism of Action

 

Organophosphates inhibit acetylcholinesterase, causing acetylcholine buildup and overstimulation of nicotinic and muscarinic receptors, resulting in a cholinergic toxidrome. Sympathetic stimulation occurs, but the parasympathetic response dominates.

 

Organophosphates irreversibly bind to acetylcholinesterase, permanently inhibiting its activity through "aging." Aging forms covalent bonds between the agent and acetylcholinesterase and can take minutes to days, depending on the organophosphate. Once aging occurs, it takes weeks to synthesize enough acetylcholinesterase to alleviate symptoms.

 

Clinical Presentation (based on receptor effects)

·      Nicotinic

o   Mydriasis

o   Tachycardia

o   Weakness

o   Hypertension

o   Fasciculations

o   Seizures

·      Muscarinic – parasympathetic findings

o   Acute poisoning (within 8 to 24 hours from exposure)

§  SLUDGE – Salivation, Lacrimation, Urination, Defecation, GI pain/cramping, Emesis

§  Killer Bs – Bradycardia, Bronchorrhea, Bronchospasm

o   Intermediate syndrome

§  Occurs within 1 to 5 days after exposure in 40% of individuals

§  Characteristics

·      Neck flexor muscle paralysis

·      Proximal extremity muscle weakness

·      Respiratory muscle weakness

o   Can lead to respiratory failure

 

Diagnosis

 

The diagnosis of organophosphate poisoning is primarily clinical, relying on a thorough patient history, physical examination findings consistent with a cholinergic toxidrome, detection of a garlic-like or hydrocarbon odor on the patient, or the presence of neuromuscular dysfunction as described earlier.

 

Two assays can be used to confirm the diagnosis of organophosphate poisoning. Low cholinesterase activity levels are indicative of organophosphate poisoning. However, these assays are send-out tests with turnaround times that make them unlikely to influence emergency department management or treatment decisions.

 

Management

 

Prompt intervention is crucial when suspecting acute organophosphate poisoning. Laboratory testing, though valuable, may delay treatment and potentially worsen the patient's condition. The primary objective is to act quickly to prevent aging, alleviate respiratory distress caused by dry secretions, and avert potential cardiopulmonary collapse. Airway management should not be postponed. Intensive care unit (ICU) admission is often necessary

 

Decontamination and Appropriate Personal Protective Equipment (PPE)

To prevent ongoing exposure to the patient and emergency department (ED) staff, it is essential to follow proper decontamination procedures. In cases of dermal exposure, remove the patient's clothing and wash them thoroughly with soap and water. Dispose of contaminated clothing appropriately and wear PPE to prevent personal exposure.

Organophosphates have a tendency to adsorb onto leather goods such as shoes or belts. Therefore, these items should be discarded along with other hazardous waste and not returned to the patient.

Airway Management

Due to the high risk of respiratory failure, which is the most common cause of death in organophosphate poisoning, early airway management should be considered. This may be necessary due to a combination of hypoxemia, hypercarbia, and neuromuscular weakness resulting from uncontrolled bronchorrhea and bronchospasm.

Mainstay Pharmacologic Therapy

Atropine Sulfate

Atropine sulfate is a competitive antagonist of acetylcholine at muscarinic receptors. It is the primary antidote for organophosphate poisoning and works by blocking the effects of acetylcholine, the neurotransmitter that is overstimulated by organophosphates.

Dose

  • Adults: 1-2 mg IV (0.02-0.1 mg/kg pediatrics)

  • Double dose every 5 minutes

  • Titrate up to endpoint of therapy, which may require very large doses

Target Endpoint of Therapy

  • Clear chest sounds

  • Heart rate (HR) > 80 beats per minute (bpm)

  • Dilated pupils

  • Dry axillae

Administration

  • Once the goal is achieved, begin an infusion at 10-20% of the dose required to control secretions in mg/h.

  • Continue therapy until clinically resolved.

 

Pralidoxime (2-PAM)

Pralidoxime (2-PAM) is an oxime that reactivates inhibited acetylcholinesterase that has not undergone the aging process. It is another antidote for organophosphate poisoning and works by reversing the effects of organophosphates on the enzyme acetylcholinesterase.

Dosing

  • Loading dose: 30 mg/kg (max 2 g) IV in 100 mL 0.9% sodium chloride over 15-30 minutes

  • Maintenance infusion: 8 mg/kg/h (max 650 mg) IV

  • Alternate regimen: 1-2 g IV loading dose, then repeat in 1 hour, then continue 1-2 g IV q10-12h

  • Alternate regimen: 600 mg (15 mg/kg pediatric) IM, then repeat q15min for a total 1,800 mg

Administration

  • Pralidoxime should be initiated as soon as possible to prevent organophosphate aging.

  • Therapy can be discontinued once atropine is no longer required to manage secretions.

 

 

REFERENCE

 

Tintinalli, J. E. (2019). Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th Edition. McGraw-Hill Education. Section 15: Toxicology: 1301-1303.

Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784

Cook Matt, Frey Aaron. Pesticides and Cholinergics. In: Mattu A and Swadron S, ed. CorePendium. Burbank, CA: CorePendium, LLC. https://www.emrap.org/corependium/chapter/recdvP3Xjhrp9vbC8/Pesticides-and-Cholinergics. Updated September 14, 2020. Accessed December 14, 2020.

 

 

 

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