#3400.159 Rev. 10/16

COVID-19 Meeting # 5Medical Staff Updates and Discussion

April 15, 2020

“Failing to prepare is preparing to fail”

Benjamin Franklin

"For internal Lee Health Use Only. Do Not Copy, Forward or Distribute"

Guiding Premise “The one thing we know- We have no idea what is the ideal

management of these patients .” We will continue to learn, modify and adapt our guidelines as more

information and literature is known.

AGENDA

RSI Non-intubated code blue Proning for non-intubated patients- Draft Cytokine Storm and Anticoagulation Medications and COVID-19 Toxicology and COVID-19 Palliative Care update

Thanks to Covid-19 Critical Care TeamTim Dougherty Elena Gatskevich Doug Brust

Marilyn Kole Javaad Khan Sandra Simmons

Dolan Abu Aouf Shyam Kapadia Linda Odnoha

Razak Dosani Ragai Meena Amy Hiteman

Sagar Naik Jordan Taillon Renee McCauley

Ken Tolep Ashley Cubillos Sunil Pammi

Justin Burkholder Rabia Khan Keith Lafferty

Thank YouRSI in sars-2/Covid-19 patients

Dr K. Lafferty

RSI is really 3 procedures in 1

• Pre-oxygenation

• Medications• Induction• Paralytic

• etti

• Only performed in negative pressure rooms• “huddle” outside of room in all case

• Pharmacy stays out of room• One nurse , one RT, one technician • Minimal exposure to patient• Minimal aerosol generation

1 Pre-oxygenation

• NC 6l’s• Nrb• Mask• 30 degree truncal elevation

• If displaying hypoxia, shunting is occurring

• Need peep• Use bvm with peep valve and viral filter• No bagging • Nc 6l’s underneath• 2 person procedure in regards to the seal that must be maintained

2 RSI Meds

No bagging

3 ETTI

• Place ogt• Place u/s guided central line if needed

• May use pocus ett placement assertion

Thank YouCode Blue Updates

Dr S. Pammi

Codes

• Respiratory code• Cardiac arrest on mechanical ventilation• Cardiac arrest in non-intubated patient

Intubation in Covid-19 patient L-type

• No clear guidelines if patient is tolerating hypoxia. May attempt to escalate oxygen therapy under close observation.

• Watch for AMS, inadequate fall in PCO2 for RR, signs of fatigue, elevated lactate

• Avoid aggressive hydration

Concept- Prevent Aerosolization and Transmission

• Wear PPE before entering any code room including N95, mask, eye protection, gown and gloves. PAPR

• Least number of people in the room as needed• Provide oxygenation device• Cover the face with mask or covering before starting any process

1. All first responders will make sure they are wearing appropriate PPE for suspected PUI. This includes N95, protective eye wear, hat, gown and gloves. All further members of code team who enter room will don PPE as noted.

2. First responders place Non-rebreather and HFNC on patient. Cover face with chuck ideally or towel, blanket or covering to prevent dispersion of aerosolized particle from patient. Limit team to only essential number of personal required.

3. If acrylic intubation box available, it may be placed over patient head.4. Initiate CPR per ACLS guidelines. 5. Another team will mobilize code cart to outside of room. COVID-19 MED bag is brought into room with resp bag. Code

leader should initiate ACLS protocols.6. RT team bring glide scope and ventilator to outside of room. If LMA not part of code cart then it should be brought to code

by RT team.7. CCO or ICU team brings and draws meds outside room for RSI kit.8. Intubation team arrives and will include most experienced intubating person. Team should include RT, RN and possibly

second RT on standby to assist with 2-person bagging if absolutely needed.9. Intubation leader will decide when and whether to interrupt CPR to perform intubation or insert LMA. They will then

request all appropriate equipment to be available.10. When all equipment is available intubation team will enter the room with ventilator and all necessary equipment and

supplies. All other responders that are not needed should be away from head of bed and patient is intubate or place LMA. Inflate cuff and connect to ambu-bag with filter and restart CPR and follow normal ACLS protocol for breathing. Avoid any disconnection of circuit after intubation.

11. If patient has ROSC then RT should clear room before disconnecting from ambu-bag to connect to ventilator.

This is an advisory provided during the current National crisis secondary to the current Covid-19 pandemic. Clinical judgement should supersede any specific recommendation in the appropriate setting.

Covid-19 Pandemic Advisory: Cardiac arrest in Non-Intubated Patient

Thank YouProning for Non-intubated Patients

Dr S. Pammi

Non-Intubated Patient ProningOrder set Review

DRAFT

Thank YouCytokine Storm & Anticoagulation

Dr J. Burkholder

What is a cytokine storm? A hyperinflammatory state generated by our immune system usually when

responding to an infection.

It is a severe immune reaction in which the body releases too many cytokines into the blood too quickly

Cytokines play an important role in maintaining a normal immune system but when a large amount is released into the body it can be harmful

It can be life threatening and lead to multi-system organ failure

Cytokine storm (cont.)

SARS-CoV-2

Cytokine storm (cont.)

Cytokine storm clinical treatment Tocilizumab (Actemra) is an IL-6 inhibitor that is theorized to mitigate

inflammatory immune responses in patients with COVID-19 It is FDA-approved for moderate to severe rheumatoid arthritis, as well as

management of cytokine release syndrome with the use of CAR-T cell therapy.

It should be noted that tocilizumab is not an antiviral agent

Qing Ye MD , Bili Wang MS , Jianhua Mao MD , Cytokine Storm in COVID19and Treatment, Journal of Infection (2020), doi: https://doi.org/10.1016/j.jinf.2020.03.037The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like DiseaseAuthor links open overlay panelDennisMcGonagleabKassemSharifacAnthonyO'RegandCharlieBridgewooda

https://www.sciencedirect.com/science/article/pii/S1568997220300926#!

Hypercoaguability

Hypercoaguability (cont.)

PulmCrit Wee: D-dimer cutoffs to predict thrombosis in COVID-19April 10, 2020 by Josh Farkas

Using a D-dimer cutoff >1.5ug/mL to predict VTE Sensitivity = 85%Specificity = 88.5%NPV = 94.7%PPV = 70.8%

Study #1 Study #2

In another study, 81 patients with severe COVID-19 PNA admitted to ICU in China were tested for DVTThey used D-dimer levels to predict if a pt had a DVT – sensitivity, specificity…

https://rebelem.com/covid-19-thrombosis-and-hemoglobin/

https://emcrit.org/pulmcrit/dimer-cutoff-covid/

EMRAP podcast 4/14/2020

https://emcrit.org/author/pulmcrit/https://rebelem.com/covid-19-thrombosis-and-hemoglobin/https://rebelem.com/covid-19-thrombosis-and-hemoglobin/https://emcrit.org/pulmcrit/dimer-cutoff-covid/

Anticoagulation algorithm

American Society of Hematology (Link is HERE)

https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation

Thank YouMedications UpdateJ. Armitstead/Team

Medication Availability

Thank YouToxicology and COVID-19

Dr T. Dougherty

52

Chloroquine

Chloroquine(CQ) Hydroxychloroquine(HCQ)

Form of quinine that was synthesized in Germany by Bayer (1934) For decades, was a front-line drug for the treatment and prophylaxis of malaria Efficacy gradually declined due to chloroquine-resistant P. falciparum

1st synthesized 1946 to ↓ toxicityChloroquine 2-3 x more toxicTx MalariaDiscoid or SLE Rheumatoid Arthritis

Neuropsychiatric Effects

Agitation Insomnia Confusion Mania Hallucinations Paranoia Depression Catatonia

Suicidal ideationDepressionCatatoniaPsychosis

Hypoglycemia

Reduced Insulin Clearance Increased Insulin Sensitivity Enhanced pancreatic insulin release TX

Stop Drug Food/IV glucose Octreotide (50-100 μg IV/SQ every 8h)

Some Proposed Mechanisms of Chloroquine

• Interferes with ACE2 receptor glycosylation, preventing SARS-CoV-2 binding to target cells.

• Limit the biosynthesis of sialic acids that may be required for cell surface binding of SARS-CoV-2.

• Modulate the acidification ( ↑pH) of endosomes thereby inhibiting formation of the autophagosome.

• Inhibit virus replication through reduction of cellular mitogen-activated protein (MAP) kinase activation.

• Alter M protein maturation and interfere with virion assembly and budding.

• Possible other immunomodulatory actions

Int J Antimicrob Agents. 2020 Mar 11:105938.

Possible Treatment (March 18,2020)

A little bit of knowledge…March 24

HEALTH

Arizona man dies, wife critical after ingesting chloroquine phosphate in hopes of preventing COVID-19 Chelsea Curtis Arizona Republic Published 5:45 a.m. ET Mar. 24, 2020 Updated 10:15 p.m. ET Mar. 24, 2020

Benefit? (4/15/20)

HCQNo Studies MortalityProgression to

ARDSMechanical Vent

HCQ + AzithromycinMortality Risk 3.4% (Failed to report Untreated Cohort)Fewer cases of Viral Clearance Failure(?)

No StudiesNeed for Hospital/ICUMechanical Vent

Harm? (4/15/20)2 studies describe ↑QT (10/95 pts)Over 500 msDiscontinuing

HCQ/AZRenal Clearance25% HCQ

Liver MetabolismP450 isoenzymes

2C8,2D6, 3A4

Azithromycin Alone↑QTc, TdP, VT↑risk for sudden cardiac deathHazard ratio 2.71 compared to no antibiotic/amoxicillin

CQ HCQ Toxicity: Very Narrow Therapeutic Window

1-2 tablets of CQ or HCQ can be fatal in a small child (J Emerg Med. 2005 May;28(4):437-43)

>5 gm almost universally fatal in adults (NEJM 1988 Jan 7;318(1):1-6)

Most deaths prehospital or w/in 2.5 hours from ingestion Neuro: △ MS, SZ Cardio: Class 1a anti-dysrhythmic- ↑ QRS/QTc, flattening T, U waves

↓ BP, impaired contractility, conductivity and excitability ↑ Risks of re-entry dysrhythmias

Hypokalemia (shift intracellularly) Skin: SJS GI: N/V/D

EKG of an Acute Hydroxychloroquine

½ Life Concerns

Chloroquine: Up to 5 days Hydroxychloroquine: 22.4 days (has been reported up to 40 days) Azithromycin: Up to 72 hours

Treatment of acute chloroquine poisoning: a 5-year experience

Treatment (↓ Mortality 91% to 9%)

Immediate Intubation

Epinephrine: Start 0.25 μg/kg/min Not NE (not due to peripheral vasoconstriction)

Diazepam 2 mg/kg IV over 30 min then 1-2 mg/kg q24 hours for 2-3 days Thought to act on peripheral benzodiazepine receptors in the myocardium Need to save some for John Armitstead

Judicious K replacement

NaHCO- for wide QRS

Predictors of Mortality QRS >120 msec SBP

Hydroxychloroquine Overdose: Toxicokinetics and Management

Hydroxychloroquine Overdose: Toxicokinetics and Management Peter Jordan; Jennifer G. Brookes; George Nikolic; David G. Le Couteur The Canberra Hospital (PJ, JGB, GN); The Canberra Clinical School of the University of Sydney (DGLC), Garran, Australia ABSTRACT Background: The management and toxicokinetics of hydroxychloroquine overdose are poorly described. Case Report: We report a case of an 18-year-old girl who ingested 20 g of hydroxychloroquine. She developed marked hypokalemia, hypotension, and ventricular tachyarrhythmias but survived with treatment including intubation, adrenaline infusion, high-dose diazepam, and aggressive potassium replacement. Plasma hydroxychloroquine level was 29.40 mol/L (9.87 mg/L) 2 hours after ingestion and the elimination half-life of hydroxychloroquine was 22 hours. Conclusions: The clinical manifestations of this hydroxychloroquine overdose were similar to those reported for chloroquine overdose and the management principles recommended for chloroquine over- dose appeared to be efficacious in this case.

Clinical Toxicology, 37(7), 861–864 (1999)

Use of Lidocaine?

https://www.heartrhythmcasereports.com/article/S2214-0271(20)30057-9/pdf

QT interval in Patients with SARS_CoV-2 Infection with HCQ/Azithromycin- Preliminary Report

Change in QT in 84 consecutive pts treated w/ HCQ+Azithromycin QTc prolonged maximally from baseline btw days 3 & 4 30% Patients had QTc > 40 ms 11% Patients increased QTc > 500 ms Acute Renal Failure (NOT baseline QTc) strong predictor of extreme ↑

QTc No TdP recorded, 4 deaths (multi-organ failure)

https://www.medrxiv.org/content/10.1101/2020.04.02.20047050v1

Brazilian CQ + Azithromycin Study Cut ShortMayla Gabriela Silva Borba et al (Preliminary Report)

Received High dose: CQ 600 mg BID x 10 days (high dose) or CQ 450 mg(low dose) for 5 days [day 1 BID, then 2-5 daily]

+ Ceftriaxone/Azithromycin/Oseltamivir Patients using CQ (irrespective of dosage) failed to present evidence of

viral clearance by the fifth day (Day 4) of positive RT- PCR, even with the concomitant use of azithromycin.

By day 6, 11pt’s died. Halted high dose all switched to low dose 16/41 deaths high dose (2 developed VT prior to death) 6/40 deaths low dose

https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1

Where are we today (4/15/20)…

Lee Health Experience Benefit?

27.6% still progressed to intubation Of the 38 Discharge patients, 9 Deaths (23.7%)

Risk 11.6% stoppage due to adverse effects (including 1 VT) Almost 2/3 who had QTc monitored had a >500ms documented

Lee Health Recommendations (4/15/20)

Hydroxychloroquine 400mg BID x 2 doses, followed by 200mg PO BID x 4 days. Addition of azithromycin is not recommended at this time due to lack of efficacy data and safety concerns. QTc MUST be monitored if concomitant azithromycin is used.

Alternate dosing: hydroxychloroquine 200mg TID x 5 days Recommend QTc monitoring if concomitant QTc-prolonging medications

are active. BPA warning against this combination and providing a safer alternative in

the unlikely scenario that you need to treat with HQC and also cover for atypical pneumonia organisms.

Society Guideline Recommendations

IDSA (4/11/20) Recommends hydroxychloroquine in the context of a clinical trial for

admitted patients with COVID-19.22 Recommends hydroxychloroquine plus azithromycin only in the context

of a clinical trial for admitted patients with COVID-19.22

www.idsociety.org/COVID19guidelines.

Society Guideline Recommendations

ACC, American Heart Association and Heart Rhythm Society joint statementACC Recommends: Hydroxychloroquine use should occur in the context of a clinical trial. If hydroxychloroquine is used in combination with azithromycin, AAC recommends to discontinue azithromycin if QTc increases by >60 msec or absolute QTc >500 msec. Daily QTc monitoring is recommended

(https://www.acc.org/latest-in-cardiology/articles/2020/04/10/15/06/acc-joins-aha-hrs-in-statement-on-exploratory-covid-19-treatment-drug-interactions-on-qtc)

Society Guideline Recommendations

American Thoracic Society-led International Task Force For hospitalized patients with COVID-19 who have evidence of pneumonia, we suggest hydroxychloroquine (or chloroquine) on a case-by-case basis. Requirements include all of the following: a) shared decision-making in which the patient is informed about the possible benefits and potential side effects, b) collection of data in a manner that enables studies that use valid methods for causal inference and control of confounders for the purpose of interim assessment, c) the patient’s clinical condition is sufficiently severe to warrant investigational therapy, and d) there is not a shortage of drug supply.

https://www.thoracic.org/professionals/clinical-resources/disease-related-resources/covid-19-guidance.pdf

https://www.thoracic.org/professionals/clinical-resources/disease-related-resources/covid-19-guidance.pdf

Palliative care in the Covid19 pandemic

LPG Palliative Care presents a Primer on

Rabia Khan & Jonathan von Koenig with special guest Javaad Khan

Which patients?

Frail

End stage organ failure

Incurable metastatic malignant disease

PALLIATIVE CARE POPULATION

WHAT DO WE KNOW ABOUT MORTALITY IN COVID19?

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy Giacomi Grasselli MD et al. JAMA. Published online April 6, 2020. doi:10.1001/jama.2020.5394

"or internal Lee Health Use Only. Do Not Copy, Forward or Distribute"

DEFINITION OF FRAIL ELDERLY

The concept of frailty in the medical literature has evolved from being synonymous to advanced age, disability, or comorbidity to being a distinct biological syndrome defined as a state of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems, and causing vulnerability to adverse outcomes [12]. Sarcopenia, a process that is central in the pathophysiology of frailty, is defined as having lean body mass two standard deviations below the sex-specific mean in a young healthy sample [13]. Several diagnostic and staging criteria of frailty have been proposed, but the criteria proposed by Fried et al have been most widely used and proven clinically useful. According to Fried et al [12], a person is considered frail if three or more of the following criteria are present: weight loss of more that 10 lbs in one year; physical exhaustion by self report; weakness as measured by grip strength; decline in walking speed; and low physical activity.

Murad, K., Kitzman, D.W. Frailty and multiple comorbidities in the elderly patient with heart failure: implications for management. Heart Fail Rev 17, 581–588 (2012). https://doi.org/10.1007/s10741-011-9258-y

DO NOT RESUSCITATE

Remember, it doesn’t mean DO NOT TREAT. We can help all staff understand thisDNR only pertains to cardiopulmonary resuscitation (usually CPR and/or intubation), it

does not cover pressors, antibiotics, fluids, etc. Continue appropriate medical treatment up until the need for CPR and/or intubation. If

you feel something is not going to change the course of disease process (i.e. pressors) you don’t have to order it, but a DNR order does not replace appropriate medical judgement

FLORIDA PROXY LAW

1. Who ever is listed as health care surrogate2. Spouse, legally married (even if separated)3. Majority of adult children you can reasonably get ahold of (eldest doesn’t trump

youngest)4. Parents5. Majority of siblings6. Other close family members7. Close friend, need an 8. Hospital appointed via social worker (must exhaust everything above, takes a

long time)

They are often difficult and uncomfortable conversations (even for Palliative Care)

You will fail if you go into the conversation with an agenda

Patients and families want to know what you think they should do. They want your guidance BUT they need to trust you first

If the conversations hasn’t been started before the patient is dying, it is probably too late even for Palliative Care to change the course of treatment

GOALS OF CARE CONVERSATIONS

What can we do?

ROLE OF PALLIATIVE CARE IN THE COVID19 PANDEMIC

• Help with complicated goals of care discussions

• Have complicated code status discussions

• Symptom management

• Psychosocial support

We are here to help!

WHO ARE THE LPG PALLIATIVE CARE DOCS?

Rabia Khan, DO HPMC

Jonathan von Koenig, DO LH

and Sara Newman MD GCMC

CH- call any one of us if you need help.

You can contact us via Voalte or our cells.

Rabia Khan, DO 954.294.7276

Jonathan von Koenig, DO 239.850.0087

Sara Newman MD 847.703.1351

THANKS FOR BEING OUR FRONTLINE

HEROES!LPG Palliative Care

Thank You

COVID-19 Meeting # 5�Medical Staff Updates and Discussion��Guiding PremiseAGENDAThanks to Covid-19 Critical Care TeamSlide Number 5Slide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Slide Number 222 RSI MedsSlide Number 24Slide Number 25Slide Number 26Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31Slide Number 32Slide Number 33CodesIntubation in Covid-19 patient L-typeConcept- Prevent Aerosolization and TransmissionSlide Number 37Slide Number 38Slide Number 39Slide Number 40Slide Number 41What is a cytokine storm?Cytokine storm (cont.)Slide Number 44Cytokine storm clinical treatmentHypercoaguabilityHypercoaguability (cont.)Anticoagulation algorithmSlide Number 49Medication AvailabilitySlide Number 51ChloroquineChloroquine(CQ) Hydroxychloroquine(HCQ)Neuropsychiatric EffectsHypoglycemiaSome Proposed Mechanisms of Chloroquine �Possible Treatment (March 18,2020)Slide Number 58A little bit of knowledge…March 24Slide Number 60Benefit? (4/15/20)Harm? (4/15/20)CQ HCQ Toxicity: �Very Narrow Therapeutic WindowEKG of an Acute Hydroxychloroquine �½ Life ConcernsTreatment of acute chloroquine poisoning: �a 5-year experience�Hydroxychloroquine Overdose: �Toxicokinetics and Management �Use of Lidocaine?QT interval in Patients with SARS_CoV-2 Infection with HCQ/Azithromycin- Preliminary ReportBrazilian CQ + Azithromycin Study Cut Short�Mayla Gabriela Silva Borba et al (Preliminary Report)�Where are we today (4/15/20)…Lee Health Experience �Lee Health Recommendations (4/15/20)Society Guideline Recommendations Society Guideline Recommendations Society Guideline Recommendations Palliative care in the Covid19 pandemicPalliative Care PopulationWhat do we know about mortality in Covid19?Slide Number 80Slide Number 81Definition of frail elderlyDO NOT RESUSCITATESlide Number 84Florida Proxy LawGoals of care ConversationsRole of Palliative care in the covid19 pandemicWho are the LPG Palliative Care Docs?Slide Number 89Slide Number 90