Respiratory Care in the North Amidst the Pandemic

Curtis Addison MD, FRCPC (Internal Medicine, Respirology)

NOSM COVID-19 Weekly Clinical Rounds

April 17, 2020

Conflicts of Interest

None.

Overview

1. The COVID-19 differential

2. Clinical Presentation

3. Imaging Findings

4. Respiratory Supportive Care

5. Specific Treatments

6. Non-coronavirus lung disease during a pandemic

Northern / Rural Considerations

Purist Pragmatist

Respiratory Symptoms

Dyspnea

Cough

SputumHemoptysis

Wheezing

Chest pain

Airway disease

Pneumonia

Pulmonary embolism

Lung cancer

Sarcoidosis

Tuberculosis

Interstitial Lung Disease

Pulmonary hypertension

Pleural disease

Neuromuscular weakness

Chest wall deformities

Atelectasis

Pulmonary edema

The COVID-19 Differential

Presenting SymptomsFever 99

CoughNonproductiveProductive

905927

Fatigue 70

Anorexia 40

Myalgias 35

Dyspnea 31

Sore throat 17

Diarrhea 10

Nausea 10

Dizziness 9

Headache 7

Vomiting 4

Abdominal Pain 2

Wang, D. JAMA. 2020;323(11): 1061-1069.

Presenting SymptomsSARS-CoV2(Jan 2020)1 H1N1(2009)2 Seasonal influenza A

(2003-2008)2

n 138 75 52

Fever 99 96 75

CoughNonproductiveProductive

905927

91 89

Fatigue 70

Anorexia 40

Myalgias 35

Dyspnea 31 65 71

Sore throat 17 31 39

“GI symptoms” 24 16

Diarrhea 10

Nausea 10

Dizziness 9

Headache 7

Vomiting 4

Abdominal Pain 2

1Wang, D. JAMA. 2020;323(11): 1061-1069.2Riquelme, R. ERJ. 2011 38: 106-111.

Labs

Parameter Value

WBC 6.2 (45% are normal)

Lymphocytes 0.8 (Low in 63%)

Albumin 31.4

TnI 0.0034 ng/mL

LDH 286 (high in 73%)

Procalcitonin 0.1 (high in 69%)

Wang, D. JAMA. 2020;323(11): 1061-1069.

Diagnostic Imaging

Finding Frequency

No ground glass or consolidation 22 %

Ground glass only 34 %

Consolidation and ground glass 41 %

Bilateral opacities 60 % (77% of patients with opacities)

Rounded opacities 54 %

Peripheral distribution 52 %

Bernheim, A. Radiology. 2020; 295(1): 1061-1069.

Infrequent or Absent Imaging Features

Finding Frequency

Consolidation without ground glass 2

Cavitation 0

Peribronchovascular distribution 0

Emphysema 2

Pulmonary Fibrosis 0

Nodules 0

Pleural Effusion 1

Lymphadenopathy 0

Bernheim, A. Radiology. 2020; 295(1): 1061-1069.

Case courtesy of Dr. Jack Ren, Radiopaediahttps://radiopaedia.org/cases/pulmonary-consolidation-with-airbronchograms

Case courtesy of Dr. Tom Foster, Radiopaediahttps://radiopaedia.org/articles/lobar-consolidation?lang=us

Case courtesy of Robin Smithuis, Otto van Delden and Cornelia Schaefer-Prokop, Radiology Assistanthttps://radiologyassistant.nl/chest/lung-hrct-basic-interpretation#high-attenuation-pattern-consolidation

Image from: Bernheim, A. Radiology. 2020; 295(1): 1061-1069.

Respiratory Supportive Care

HypoxemiaNasal cannulaFacemaskAir-entrainment mask (Venturi)Non-rebreather maskHigh flow nasal cannula (AIRVO)CPAPNon-invasive VentilationInvasive mechanical ventilation

Conditions for which there is strong evidence for Non-invasive Ventilation

1. Acute exacerbations of COPD

2. Cardiogenic Pulmonary Edema

3. Neuromuscular weakness

4. Prevention of post-extubation respiratory failure

5. Neuromuscular weakness

Contraindications to NIV

1. Need for emergent intubationa. Cardiac / respiratory arrestb. Inability to protect the airwayc. Severely impaired consciousnessd. Respiratory failure AND

Inability to cooperateInability to clear secretionsLife-threatening nonrespiratory organ failureFacial surgery, trauma, deformityHigh aspiration riskProlonged duration anticipatedRecent esophageal anastamosis

Respiratory Supportive Care

Bronchospasm

Bronchodilators: salbutamol, ipratropiumUse MDIs

May be given in-line during non-invasive ventilation

Treat underlying cause

Acute exacerbation of asthma – steroids

Acute exacerbation of COPD – steroids (+ antibiotics if purulent)

Aspiration – lifestyle modification, assess/treat esophageal disease

ARDS

- Lung protective ventilation

- Match PEEP to FiO2 (ARDSnet protocol)

- Neuromuscular blockade

- Proning

- Conservative fluid management / prevention of hypervolemia

- Treat complications

Respiratory Supportive Care

Specific Treatments

To date, no medications have demonstrated benefit in patient-oriented outcomes in COVID-19.

Investigational treatments:

• Hydroxychloroquine

• Azithromycin

• Remdesivir

• Lopinavir-ritonavir

• Tocilizumab

• Convalescent plasma

Purist

Treatment Mechanism Evidence

Hydroxychloroquine Reduced in-vitro activity1

Small RCT in mild COVID-19: slightly faster time to improvement in cough, fever and CXR.2

+ azithromycin Nonrandomized trial, reduced virus carriage at day 6.2

Remdesivir Nucleotide analogue (prevents viral replication)

in-vitro activity3

Animal studies in SARS and MERS-CoV4

Case series

Lopinavir-ritonavir Protease inhibitors (prevents viral replication)

RCT severe COVID-19, no change in time to clinical improvement, improved mortality trend5

Tocilizumab Anti-IL6Reduced “cytokine storm”

Case reports

Convalescent plasma Antibodies Case series

References for Investigational Treatments

1. Yao et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa237

2. Gautret et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. doi.org/10.1016/j.ijantimicag.2020.105949

3. Wang et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3) 269-271. doi: 10.1038/s41422-020-0282-0

4. Sheahan et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017; 9(396). doi: 10.1126/scitranslmed.aal3653

5. Cao et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020. doi: 10.1056/NEJMoa2001282

Clinical Practice Guidelines

Infectious Diseases Society of America

- Recommends investigational treatments only in the context of a clinical trial1

Public Health Agency of Canada / Canadian Critical Care Society / Association of Medical Microbiology and Infectious Disease Canada

- “Use of investigational anti-COVID-19 therapeutics should be done under ethically approved, randomized, controlled trials.”2

Surviving Sepsis Campaign

- suggests against convalescent plasma, suggests against lopinavir/ritonavir, insufficient evidence to issue a recommendation on other antivirals, hydroxychloroquine/chloroquine, rIFNs, tocilizumab3

1Adarsh et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. [Online]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

2Fowler et al. Clinical Management of Patients with Moderate to Severe COVID-19 - Interim Guidance April 2, 2020. [Online]. https://canadiancriticalcare.org/resources/Documents/Clinical%20Care%20COVID-19%20Guidance%20FINAL%20April2%20ENGLISH(1).pdf

3Alhazzani et al. Surviving Sepsis Campaign: Guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). [Online]. https://www.esicm.org/wp-content/uploads/2020/03/SSC-COVID19-GUIDELINES.pdf.

Clinical Trials Authorized by Health Canada

https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-clinical-trials/list-authorized-trials.html

Strategies to reduce healthcare-related exposures

Patient well-being Infection control

Airway Disease

Pleural Disease

Asthma• Controlled?

• Trigger avoidance

• Medication use

Lougheed, M.D. Can Resp J. 2010, 17(1): 15-24.

COPD

• Dyspnea? (Standardized score)

• Exacerbations?

• Purulent sputum?

• Smoking cessation?

• Goals of Care and Resuscitation Status?

Bourbeau, J. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine.

COPD

• Physical examination adds little value to chronic airway disease management over history

• Some specific findings clearly direct management

Finding Action

Low SpO2 Home oxygen

Clubbing CT-Chest

Lymphadenopathy CT-neck/chest

Volume overload Diuresis / cardiac evaluation

Exam Findings by History?

Personal Oximeter

Nail changes?

New lumps or bumps?

Volume overload

- swelling (describe pitting)

- weight gain

- orthopnea

Site of Care During a Pandemic

Home

Clinic

Emergency Department

Inpatient Ward

Natural History of Malignant Pleural Effusions

Progressive dyspnea

Presentation to Clinic

Presentation to ER

Thoracentesis

Relief

Indwelling Pleural Catheter

(IPC)

AdmissionChest tube

Talc pleurodesis

Images from: Locklin, Jasmine N MD; Taylor, Susan D DO; Thomson, Norman B MD; Keshavamurthy, Jayanth H. Trapped Lung. https://www.eurorad.org/case/13940.

RocketTM IPC

PleurXTM Drainage System

ASEPT® Pleural Drainage System

Aspira® Drainage System

Comparison of Pleural Disease Management StrategiesRecurrent Thoracentesis “Tube and Talc” Indwelling Pleural

Catheter

Dyspnea Managed Prevented Prevented

Location ER / Clinic Inpatient ward Clinic

Number of procedures Variable (e.g. 6 – 26 / year)

1 1

Complications1 Pneumothorax (2%)Hemothorax (1:1000-1:10 000)

PainHemothoraxAcute pneumonitisSIRS

InfectionHemothorax

Cost Effectiveness2

12-week survivalVariable $4303

$2693$4591

$4563

Quality of Life Significantly improved

Lung entrapment Transient benefit Ineffective Benefit

1Wilcox, M.E. JAMA 2014, 311(23):2422-2431.2Olfert, J. A. P. Respirology. 2016, 22(4).

Take-home messages

• The clinical presentation of COVID-19 is nonspecific• Maintain a high index of suspicion and use of PPE in acute respiratory

illness, but careful search for alternative or coexisting diagnoses is critical• There are no contraindications to non-invasive ventilation, rather

indications for emergent intubation• No specific COVID-19 treatments have demonstrated benefit in patient-

centred outcomes; such treatments should be used in the context of clinical trials

• Phone/videoconference for follow-up and optimization of chronic respiratory disease is likely to provide high-value care

• Outpatient interventions can reduce ER visits and hospitalizations, in turn reducing potential exposure to SARS-CoV2.