covid-19 and acute respiratory distress syndrome · • pharmacists: rose, jace, mikka, lucy. what...
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COVID-19 and Acute Respiratory Distress Syndrome (ARDS)
Lucy Stun, PharmD, BCCCPClinical Coordinator: Critical Care, Emergency MedicineContact: [email protected] 9th , 2020
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COVID-19 and Critical Illness
• It is estimated that 4.9-11.5% of proven COVID-19 infections will develop severe disease requiring intensive care
Murthy S, Gomersall C, Fowlder R. Care for Critically Ill Patients with COVID-19. JAMA; 3/11/2020Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. CDC Website.
Risk Factors Requiring Critical CareAge ≥ 60 40% exhibit comorbidities • Diabetes
• Hypertension • Cardiac disease• Underlying pulmonary disease (ie asthma, COPD)• Obesity • CKD• Cancer
Onset of symptoms Needing ICU admission8-10 days
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ARDS: Clinical Features
• 2/3 of COVID-19 ICU patients meet criteria for ARDS
Diffuse inflammatory
lung injury
Progressive dyspnea
Increased O2requirements• Mechanical
Ventilation
Bilateral infiltrates on CXR or
CT
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ARDS: Clinical Diagnosis
Thompson BT et al. Acute Respiratory Distress Syndrome. N Engl J Med. 2017 Aug 10;377(6):562-572
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Screen shot of ICU Rounding Report (EPIC®)
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ARDS Pathogenesis Timeline
Early Exudative
StageFibroproliferative
stageFibrotic Stage
Day 7-10 Day 10-14 Day >14
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Early Exudative Stage
• LEFT: Healthy Patient• RIGHT: Exudative Phase• Day 7-10• Interstitial edema• Acute and chronic
inflammation
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Proliferative & Fibrotic Stages
• LEFT: Proliferative Phase • RIGHT: FIBROTIC Phase• Fibroproliferative stage
• Between 7-10 days up to 2 weeks
• Persistent hypoxemia, low lung compliance, may have progressive pulmonary HTN
• Fibrotic stage• Loss of normal lung
architecture; fibrosis and cyst formation
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General ARDS Critical Care Management
Fan E, et al. American Thoracic Society Documents. Mar 2017. Murthy S, Gomersall C, Fowlder R. JAMA; 3/11/2020PETAL Network Clinical Trials. Neuromuscular Blockade in ARDS NEJM 2019http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf
ARDS Management Principles Conservative IV fluid management Consideration of ECMOEmpiric bacterial pneumonia coverage Prone positioning
• Improves oxygenation • Enhances lung recruitment• May reduce mortality
Lung protective mechanical ventilation strategies (ARDSnet trial)
Use of neuromuscular blockade• Not routinely used unless other
indications (ex: ventilator dys-synchrony and refractory hypoxemia)
Permissive Hypercapnia
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General ARDS Critical Care Management
Fan E, et al. American Thoracic Society Documents. Mar 2017. Murthy S, Gomersall C, Fowlder R. JAMA; 3/11/2020PETAL Network Clinical Trials. Neuromuscular Blockade in ARDS NEJM 2019http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf
ARDS Management Principles Conservative IV fluid management Consideration of ECMOEmpiric bacterial pneumonia coverage Prone positioning
• Improves oxygenation • Enhances lung recruitment• May reduce mortality
Lung protective mechanical ventilation strategies (ARDSnet trial)
Use of neuromuscular blockade• Not routinely used unless other
indications (ex: ventilator dys-synchrony and refractory hypoxemia)
Permissive Hypercapnia
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ExtraCorporeal Membrane Oxygenation
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General ARDS Critical Care Management
Fan E, et al. American Thoracic Society Documents. Mar 2017. Murthy S, Gomersall C, Fowlder R. JAMA; 3/11/2020PETAL Network Clinical Trials. Neuromuscular Blockade in ARDS NEJM 2019http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf
ARDS Management Principles Conservative IV fluid management Consideration of ECMOEmpiric bacterial pneumonia coverage Prone positioning
• Improves oxygenation • Enhances lung recruitment• May reduce mortality
Lung protective mechanical ventilation strategies (ARDSnet trial)
Use of neuromuscular blockade• Not routinely used unless other
indications (ex: ventilator dys-synchrony and refractory hypoxemia)
Permissive Hypercapnia
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Prone Positioning- Nursing Services & Respiratory Therapy Services (Lippincott Procedure)
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General ARDS Critical Care Management
Fan E, et al. American Thoracic Society Documents. Mar 2017. Murthy S, Gomersall C, Fowlder R. JAMA; 3/11/2020PETAL Network Clinical Trials. Neuromuscular Blockade in ARDS NEJM 2019http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf
ARDS Management Principles Conservative IV fluid management Consideration of ECMOEmpiric bacterial pneumonia coverage Prone positioning
• Improves oxygenation • Enhances lung recruitment• May reduce mortality
Lung protective mechanical ventilation strategies (ARDSnet trial)
Use of neuromuscular blockade• Not routinely used unless other
indications (ex: ventilator dys-synchrony and refractory hypoxemia)
Permissive Hypercapnia
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Critical Care NMB Management Principles
• Most common agents• Cisatracurium
• 0.5-10 mcg/kg/min• Not affected by organ dysfunction
• Rocuronium• 3-12 mcg/kg/min• Rapid onset; short duration. Ideal for
intermittent NMB• Vecuronium
• 0.6-1.7 mcg/kg/min• Longer onset than rocuronium
• Titration parameters• Control of respiratory effort• Train-of-four (TOF)
• 4 sequential stimuli are administered to assess level of neuromuscular blockade
www.anesthesiologyhub.com
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Critical Care Sedation Management Principles
• RASS • Most ICU patients will titrate sedation to a
RASS of 0 to -2 • If requiring NMB, titrate RASS to -3 to -5
• Choice of sedative• Propofol or dexmedetomidine typically first
line• Ketamine• Avoid benzodiazepines if possible
www.researchgate.netDevlin et. al. CCM 2018; 46(9);e826-873.
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Critical Care Sedation Management PrinciplesDrug Typical Dosing Regimen Contraindications/Warning Common Adverse
EffectsComments
Propofol 10-100 mcg/kg/minUsual max 150 mcg/kg/min
Bolus dosing not typically used
Hypersensitivity to eggs or soy
May exacerbate pre-existing pancreatitis
Hypotension ● WIth high doses (> 60 mcg/kg/min) or prolonged use (> 48 hrs) monitor for PRIS and pancreatitis including periodic Trig. Trig > 500 should prompt consideration of alternative sedation
Dexmedetomidine 0.2-1 mcg/kg/hrMax: 1.5 mcg/kg/hr
Bolus dosing not typically used
BradycardiaHypotension
● With prolonged use consider slower titration to avoid withdrawal. Consider addition of clonidine to facilitate titration off
● Does not required MV
Ketamine 0.5-2 mg/kg/hr Hypertension/tachycardia CV disease
ArrhythmiasEmergence reactionsCan cause hypertensionHypersalivation
● Doses > 0.5 mg/kg/hr MV recommended
Midazolam 1-5 mg/hr Renal impairment Hypotension ● At sedation doses typically hemodynamically neutral● Continuous infusion requires MV● Caution in renal impairment as drug and its active
metabolite can accumulate
mcg- microgram; kg- kilogram; min- minutes; PRIS- propofol related infusion syndrome; Trig- triglycerides; hr- hour; MV- mechanical ventilation; mg- milligram; CV- cardiovascular
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Critical Care Pain Management Principles
• Use of validated pain scales• 0-10 self-reported scale• CPOT - used in critically ill sedated or non-
responsive patients• Score ranges from 0-8• 0-2 : Minimal to no pain present• > 2: Unacceptable level of pain present
• Use of adjuvant therapies• Acetaminophen• Gabapentin• Ketamine• Topical agents
Devlin et. al. CCM 2018; 46(9);e826-873.
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COVID-19/ARDS Critical Care Management
Murthy S, Gomersall C, Fowlder R. JAMA; 3/11/2020
COVID-19 ARDS Management Principles PPE as appropriate Glucocorticoid therapy
• Role in treating COVID-19 unknown; not routinely used for ARDS management
• Currently not part of TUKHS treatment guidance document
Primarily Supportive Septic shock and organ dysfunction (ex: AKI) occur in significant portion of critically ill patients
Avoid high-flow nasal cannula or non-invasive ventilation strategies• Increased exposure risk
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TUKHS Critical Care Surge Plan • Ongoing development and subject to change• Members: Dr Williamson, Dr Flynn, Dr Satterwhite, Adam Olberding (RN-
Director), Courtney Ash (RT-Director)• Cambridge will likely house traditional MICU patients and no positive COVID
patients• Current State (as of 3/28/20):
– COVID(+) 61 then 63 then 65– COVID(-) HC9– COVID Triage 66– Future MICUs? Bell PP, CA PP
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TUKHS Other Initiatives and On-Goings• Inventory Management
– http://departments.kumed.com/rx/home/COVID19%20Info/COVID-19%20Acute%20Care%20Pharmacy%20Inventory%20Tracker.xlsx
• Recurring Wednesday morning meetings to discuss:– New COVID-19 literature– New medication mgmt. options– All updates can be found on the abx sharepoint
• Trials– Losartan (TUKHS;Dr Salathe)– Remdesivir (Gilead; looking into enrolling TUKHS into an expanded use program)– Remdesivir vs HCQ/Azithromycin vs Supportive Care (TUKHS; pending; Dr Pitts)
• Pharmacy– Staffing/Training – Standardization of Pain, Sedation, Paralysis
• Physicians: Dr Thomas, Nazir, Postigo, Spikes, Duthuluru• Pharmacists: Rose, Jace, Mikka, Lucy
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What Is Our Ask of You?!• Keep informed• Ask questions• Identify patient clinical trends and share that information!• Be judicious in our resources
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References• Murthy S, Gomersall C, Fowlder R. Care for Critically Ill Patients with COVID-19. JAMA; 3/11/2020.• Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak
in China. JAMA. Published online February 24, 2020. • Thompson BT et al. Acute Respiratory Distress Syndrome. N Engl J Med. 2017 Aug 10;377(6):562-572• Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–
March 16, 2020. CDC • http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf• Fan E, Del Sorbo L, Goligher E, et al. An Official American Thoracic Society/ European Society of Intensive Care
Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adults with Acute Respiratory Distress Syndrome. American Thoracic Society Documents; March 2017.
• National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Moss M, Huang DT, et al. Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Eng J Med 2019;380:1997.
• Artigas A, Bernard GR, Carlet J, et al. The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome. Am J Respir Crit Care Med 1998; 157:1332.
• Devlin et. al. CCM 2018; 46(9);e826-873. • PETAL Network Clinical Trials. Neuromuscular Blockade in ARDS NEJM 2019• http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf
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Acknowledgment• Mikka Soukup, PharmD, BCCCP• Angela Miller, PharmD, BCPS
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Questions?Lucy Stun, PharmD, BCCCPClinical Coordinator: Critical Care, Emergency MedicineContact: [email protected] 9th, 2020
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Surviving Sepsis Campaign• Guidelines on the Management of Critically Ill Adults with Coronavirus
Disease 2019 (COVID-19)• NOT all based on COVID-19 literature
– Guidelines based on available literature to support any critically ill patient including any COVID-19 literature available.
• Final version will be published ccmjournal.org• Next few slides are summaries from the guidelines
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Expansion in Treatment of COVID-19 Patients
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Supportive Care Index• Hemodynamic
– Fluid Management– Vasoactive Agents– Shock
• Prevalence of 1-35%– Cardiac Injury
• Prevalence of 7-23%
• Ventilator Support
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COVID-19: Hemodynamic Support
• Estimated shock prevalence: 1-35%
• Elevated cardiac markers: 7-23%
• Risk factors associated with shock development:• Older age• Co-morbidities (DM, CV disease including HTN)• Lower lymphocyte count• Elevated D-dimer level• Cardiac injury
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COVID-19: Hemodynamic Support
Fluid Therapy- Crystalloids preferred- Driven by dynamic parameter evaluation
- Non-invasive cardiac output monitoring (NICOM)- Passive leg raise- Fluid bolus challenge- Fluid responsive defined as > 10% change in stroke volume
- Capillary refill time- Lactate measurement- Skin temperature
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Fluid Management
• Conservative fluid management based on dynamic assessment– Reduce mortality– Reduce mechanical
ventilator support days of therapy
– Early clearance-directed therapy was associated with a reduction in mortality, shorter ICU length of stay and shorter duration of mechanical ventilation
• Buffered/balanced crystalloids over unbalances crystalloids
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Vasoactive AgentsFirst Line Agent NOREPINEPHRINE Recommend against
dopamine if NE is available
First Line Alternative Vasopressin Epinephrine
Second Line (distributive shock) Vasopressin
Second Line (evidence of cardiac dysfunction) Dobutamine
Refractory Shock Add hydrocortisone 50mg IV q6h
MAP Goal= 60-65 mmHg
OR
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Ventilator Support• 19% - prevalence of hypoxic respiratory failure in COVID-19• 14% - develop severe disease requiring oxygen therapy• 5% - require ICU admission and mechanical ventilation• Risk Factors for Respiratory Failure
– >60y/o– Male– Co-morbidities: DM, Malignancy, Immunocompromised
• Start oxygenation if SpO2<90-92% (NTE 96% on supplementation)
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Expanded ARDS from SCCM Guideline
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ARDS Management Expansion• Recommend against the use of nitric oxide • Last ditch effort: inhaled pulmonary vasodilator
– Taper off if no rapid improvement to avoid rebound pulmonary vasoconstriction
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COVID-19 Therapy• Cytokine Storm in COVID-19 reminiscent in secondary hemophagocytic
lymphohistiocytosis (HLH)• Suggest AGAINST IVIG