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COVID-19: Physiology and Critical Care Management D e p a r t m e n t o f A n e s t h e s i o l o g y a n d C r i t i c a l C a r e

Timothy G. Gaulton MD, MSc

3.31.2020

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Learning Objectives‣ Describe the clinical epidemiology of COVID-19‣ Understand the physiologic effects of COVID-19 ‣ Explain the steps for providing critical care to a COVID-19 patient

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What is COVID-19?‣ Coronavirus Disease (COVID-19) is a respiratory tract infection ‣ It is caused by the virus: SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus-2‣ Binds via the angiotensin-converting enzyme 2 (ACE2) receptor located on type II alveolar cells

and intestinal epithelia

Source: Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, Goor H van. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology. 2004;203(2):631–7.

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How is COVD-19 Defined?‣ Suspect case:

• A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease (e.g., cough, shortness of breath), AND with no other etiology that fully explains the clinical presentation AND a history of travel to or residence in a country/area or territory reporting local transmission of COVID-19 disease during the 14 days prior to symptom onset.

• A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID19 case (see definition of contact) in the last 14 days prior to onset of symptoms;

• A patient with severe acute respiratory infection (fever and at least one sign/symptom of respiratory disease (e.g., cough, shortness breath) AND requiring hospitalization AND with no other etiology that fully explains the clinical presentation

Source: World Health Organization

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How is COVD-19 Defined?‣ Probable case

• A suspect case for whom testing for COVID-19 is inconclusive. • Inconclusive being the result of the test reported by the laboratory

‣ Confirmed case• A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and

symptoms.

Source: World Health Organization

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What are the initial symptoms of COVID-19?

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When would COVID-19 symptoms manifest after exposure?

Source: Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Eurosurveillance [Internet]. 2020 Feb 6 [cited 2020 Mar 19];25(5). Available from: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.5.2000062

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Source: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Feb 15;395(10223):497–506.

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Source: Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020 Mar 11 [

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What are the clinical syndromes associated with COVID-19? ‣ Uncomplicated upper respiratory tract viral

infection or pneumonia‣ Severe Pneumonia ‣ Acute Respiratory Distress Syndrome

(ARDS)‣ Sepsis and Septic Shock

Timing Within 1 week of a known clinical insult or new or worsening respiratory symptoms

Chest imaging Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules

Origin of edema

Respiratory failure not fully explained by cardiac failure or fluid overload.Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema

Oxygenation Impairmento Mildo Moderateo Severe

200 mmHg < PaO2/FIO2 ≤300 mmHg 100 mmHg < PaO2/FIO2 ≤200 mmHg PaO2/FIO2 ≤100 mmHgWith PEEP or CPAP ≥5 cmH2O

Source: The ARDS Definition Task Force JAMA. 2012;307(23):2526-2533

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What is the severity spectrum of COVID-19?

81%

14%

5%

Non-Severe Severe, Non-critical Critical

Sources: (1) Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24; (2) World Health Organization

Mortality • Overall - 2-3%• Non-severe - 0.1%• Severe, non-critical - 8%• Critical – 40-60%

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Who is at risk of severe COVID-19 illness?

Source: Center for Disease Control and Prevention

Older Age

ImmunosuppressedHeart Disease, Hypertension,

Diabetes

Chronic Lung Disease

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What are the lab abnormalities associated with COVID-19?

Source: Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020 Feb 28;0(0):null.

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Source: Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020 Feb 28;0(0):null.

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Source: (1) Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020 Mar 111. (2) Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Feb 18;

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What are the imaging abnormalities associated with COVID-19?

Source: Silverstein WK, Stroud L, Cleghorn GE, Leis JA. First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia. The Lancet. 2020 Feb 29;395(10225):734.

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What does lung ultrasound look like in COVID-19?

Source: (1) Chinese Critical Care Ultrasound Study Group (CCUSG), Peng Q-Y, Wang X-T, Zhang L-N. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019–2020 epidemic. Intensive Care Med. 2020 Mar 12; (2) Internet Book of Critical Care

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Source: Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. The Lancet Infectious Diseases [Internet]. 2020 Feb 24 [cited 2020 Mar 19];0(0)

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Source: Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. The Lancet Infectious Diseases [Internet]. 2020 Feb 24 [cited 2020 Mar 19];0(0)

1-2 weeks from symptom onset

Before symptom Onset

≤ 1 week from symptom onset

2-3 weeks from symptom onset

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What happens to the lung in COVID-19?

Source: Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. New England Journal of Medicine. 2017 Aug 10;377(6):562–72.

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What happens to the lungs in COVID-19?

Source: (1) https://webpath.med.utah.edu/HISTHTML/NORMAL/NORM160.html; (2) Zhang H, Zhou P, Wei Y, Yue H, Wang Y, Hu M, et al. Histopathologic Changes and SARS–CoV-2 Immunostaining in the Lung of a Patient With COVID-19. Ann Intern Med. 2020 Mar 12

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Why does COVID-19 cause respiratory distress?

Paw

PALV

Resistance

Lung compliance

Chest wall compliance

DiaphragmAbdomen

Source: Nunn’s Respiratory Physiology

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Why does COVID-19 cause respiratory distress?‣ Work of Breathing: P x V

P: 1/CRS * V + RAW * V’

‣ Work of Breathing can also be increased in CNS impairment, diaphragm weakness, and increased alveolar dead space

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Anatomic VD

Alveolar VD

+

Source: Nuckton, T. J. et al. N Engl J Med 2002;346:1281

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Alveolar flooding/consolidationAtelectasis

Baby Lung

Source: Nunn’s Respiratory Physiology

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What does COVID-19 cause hypoxemia?

Source: Radermacher P, Maggiore SM, Mercat A. Fifty Years of Research in ARDS.GasExchange in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017 Apr 13;196(8):964–84.

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What does COVID-19 cause hypoxemia?‣ Mean Airway Pressure ∞ Oxygenation

• Can increase inspiratory time, inspiratory pressure, and PEEP on the ventilator

‣ Don't Forget About Perfusion‣ Be Mindful of Alveolar

Overdistention‣ Consider Microthrombi and

Embolization

Evaluation and Diagnosis of COVID-19

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How is COVID-19 Diagnosed?‣ Clinical suspicion is paramount

• Obtain contact and travel history ‣ PCR assay

• Upper respiratory sample (e.g. nasopharyngeal swab) is recommended • In patients who are intubated, lower respiratory samples can be sample through endotracheal aspirate;

bronchoscopy should be avoided due to risk of aerosolization• Consider resampling if assay is negative but clinical suspicion remains high

‣ Refer to UPHS guidelines: http://accesspoint.uphs.upenn.edu/sites/preparedness/coronavirus‣ Refer to CDC Guidelines: https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html

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How is COVID-19 Diagnosed?‣ Do not forget about other causes of respiratory disease

• There are a number of circulating respiratory viruses, particularly influenza • Evaluate for bacterial infections• Consider non-respiratory causes (e.g. cardiac disease)

Critical Care Management of COVID-19

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What are the guidelines for COVID-19 management?

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What is the most important part of COVID-19 treatment?‣ All confirmed or suspected cases

require isolation and airborne and contact precautions

‣ Providers need to use personal protective equipment, particularly with aerosolizing procedures (e.g. intubation, bronchoscopy, non-invasive ventilation)

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What is the next most important part of COVID-19 treatment?

Respiratory Support Hemodynamic Support

Until immune response to the virus and

recoveryMay take 10-14 days

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How do we manage COVID-19 related respiratory failure?‣ Management of severe COVID-19 is not different from management of most viral pneumonia

causing respiratory failure‣ The principal feature of patients with severe disease is ARDS‣ Follow evidence-based treatment guidelines for ARDS

Source: Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill Patients With COVID-19. JAMA. 2020 Mar 11

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How do we manage COVID-19 related respiratory failure?

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What are the evidence-based treatment for ARDS?

Source: Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill Patients With COVID-19. JAMA. 2020 Mar 11

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What are lung-protective ventilation strategies?

Source: ARDS Net: http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf

General targets: Spo2 90-95%, pa02 60-80 mmHg, Pplat ≤ 30 cmH20, pH > 7.25

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Why is lung-protective ventilation important?

0

10

20

30

40

50

Mortality (Percent)

`

6 ml/kg IBW

12 ml/kg IBW Source: ARDS Net. NEJM 2000

Reduces STRAIN: tidal volume in relation to the functional residual capacity

Reduces STRESS: airway pressure in relation to pleural pressure

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What are the consequences of lung-protective ventilation?‣ Hypercarbia

• Lower Minute Ventilation• Ineffective ventilation – increased

alveolar dead space• Ineffective ventilation – AutoPEEP from

high RR‣ Ventilator dyssynchrony

• Potential need for increased sedation‣ Potential for atelectasis


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What if the plateau pressures are too high?


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How we can treat alveolar collapse and shunt?

PEEP = 0 cmH20 PEEP = 12cmH20

Pre-recruitment Post-recruitment

Recruitment Maneuver

PEEP

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Where should we set PEEP?

Be mindful of the potential adverse effects of PEEP: hypotension, hypoxemia, dead space

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What other maneuvers are helpful to improve outcomes?

Start with lung-protective ventilation

Titrate PEEP/RM to optimize oxygenation + compliance

If oxygenation remains low, consider with

consultation

Prone Position

ECMO

Inhaled Vasodilators

Neuromuscular Blockade

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Why would prone position be beneficial?

Source: (1) Guérin C et al. N Engl J Med 2013;368:2159-2168;(2) UpToDateProne ventilation for adult patients with acute respiratory distress syndrome

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What are other management decisions for COVID-19?

ASSESS: tolerance of SBT based on hemodynamics and respiratory mechanics

CAUTION: Improvements in oxygenation may not correlate with stabilization of inflammation

CONSIDER: extubation to helmet CPAP to limit aerosolization and maintain recruitment if available

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• Deeper sedation may be required during initiation resuscitation to facilitate ventilator tolerance

• Use of sedation protocols allows quicker liberation from the ventilator

Source: DJonghe et al Crit Care 2005; 33: 120-127

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• If persistent hypotension, be mindful that COVID-19 may cause cytokine storm syndrome and subsequent cardiogenic shock.

• Maintain high suspicion and use echocardiography along with EKG, lactate, capillary refill time and central venous oxygenation saturation

Ultrasound for IVC measurementCentral Venous Pressure

Dynamic Parameters (e.g. PPV) if appropriate

General targets: MAP 60-65 mmHg, Lactate < 2mmol/L, CRT < 3 secs

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‣ Consultation with Infectious Disease‣ Low threshold for initiation of empiric

antibiotics in severe disease‣ Anti-viral therapy as dictated by ID protocols ‣ Follow microbiology studies


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