All Chapters - COVID-19 Protocols

CHAPTER 1
Clinical Course, Prognosis, and

Epidemiology
Section Editors: Benjamin S. Parker MD MBA, Katherine H. Walker MD MSc
Contributors: Ayrenne Adams MD, Dalia Larios Chavez MD, Geneva A. DeGregorio MD,
Sunny Kung MD, Lisa E. Simon DMD, Priscilla Wang MD, Rebecca Zon MD
Updated: April 19, 2020
Clinical Course
Clinical presentation
1. Symptoms:
a. Presentation can be extremely varied; most common is a non-specific flu-like illness.
The majority of patients present with more than one sign/symptom on admission,
although the combination of fever, cough and shortness of breath may be rare.
(Arentz et al, JAMA, 2020; Chen et al, Lancet, 2020; Guan et al, N Engl J Med, 2020;
Li et al, N Engl J Med, 2020; Wu et al, JAMA Internal Medicine 2020; Zhou et al,
Lancet, 2020; WHO-China Joint Mission on COVID-19; Young et al, JAMA, 2020, Yan
et al, Int Forum Allergy Rhinol 2020)
i. Fever, 44-94% (varied temperature cutoffs in literature, no consensus)
1. We recommend using >= 38°C, based on Washington State data (Arentz et al,
JAMA, 2020).
2. Take into account the patient’s age, immune status, medication regimen (steroids,
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2. Take into account the patient’s age, immune status, medication regimen (steroids,
chemotherapy, etc.), and recent use or administration of antipyretics.
ii. Cough, 68-83%
iii. Anosmia and/or ageusia ~70%
iv. Upper respiratory symptoms (sore throat, rhinorrhea, nasal or sinus congestion), 5-
61%
v. Shortness of breath, 11-40%
vi. Fatigue, 23-38%
vii. Muscle aches, 11-15%
viii. Headache 8-14%
ix. Confusion 9%
x. GI symptoms (nausea, vomiting, diarrhea), 3-17%
2. Laboratory abnormalities:
a. Can be present on patient admission; frequencies are not well established. Patients
presenting with severe disease have been noted to have more significant laboratory
aberrations. (Arentz et al, JAMA, 2020; Chen et al, Lancet, 2020; Du et al, Am J
Respir Crit Care Med, 2020; Guan et al, N Engl J Med, 2020; Young et al, JAMA,
2020; Zhang et al, Lancet Gastroenterol Hepatol, 2020; Zhou et al, Lancet, 2020)
i. Lymphopenia
ii. Mild hepatocellular injury pattern (AST / ALT ~200s)
1. GGT often elevated, AlkPhos elevations rare (Zhang et al, Lancet Gastroenterol
Hepatol, 2020).
iii. Anemia
iv. Elevated D-dimer (in absence of known culprit thrombus/embolus)
v. Elevated CK
vi. Elevated LDH
vii. Low/normal procalcitonin, elevated in severe disease and/or superimposed bacterial
infection
viii. Elevated inflammatory markers: LDH, CRP, ESR, ferritin, IL-6
b. Many of these lab findings are associated with more severe disease or death; see
“Prognostication” subsection of this chapter.
3. Imaging findings:
a. Abnormal diagnostic imaging findings are common. See ”Chest Imaging” under
“Diagnostics” in Chapter 2.

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“Diagnostics” in Chapter 2.
4. Coinfection:
a. Respiratory viral co-infection is more common than previously appreciated, ~20% in
Northern California (Kim et al, JAMA 2020; as well as unpublished reports from
Qingdao, China).
i. This will necessarily vary with local epidemiology and season
b. Rates of bacterial coinfection appear to be low (Zhou et al, Lancet, 2020; Young et al,
JAMA, 2020).
Disease course and progression
1. Duration of symptoms (Zhou et al, Lancet, 2020; Young et al, JAMA, 2020):
a. Fever, median 4-12 days in survivors
b. Dyspnea, median 13 days
c. Cough, median 19 days in survivors. Still present in 45% of survivors on discharge
and 72% of non-survivors on death
2. Timing of complications from illness onset (Zhou et al, Lancet, 2020):
a. Sepsis, median 9 days (range 7-13 days)
b. ARDS, median 12 days (range 8-15 days)
i. Anecdotally, respiratory status can decompensate very rapidly
ii. Duration between symptom onset and ventilation ranges from 3-12.5 days, median
10 days
c. Acute cardiac injury, median 15 days (range 10-17 days)
d. AKI, median 15 days (range 13-19.5 days)
e. Secondary infection, median 17 days (range 13-19 days)
i. Time from initiation of invasive ventilation to VAP occurrence, median 8 days
(interquartile range 2-9 days)
3. Severity of disease (Wu, JAMA, 2020):
a. 81% have mild to moderate symptoms (mild symptoms to mild pneumonia)
b. 14% have severe symptoms (hypoxemia, or >50% lung involvement)
c. 5% have critical symptoms (respiratory failure, shock, multiorgan dysfunction)

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ICU admission and critical illness
1. Onset:
a. Median time from symptom onset to ICU transfer, 12 days (Zhou et al, Lancet, 2020).
2. Indication for ICU admission (Arentz et al, JAMA, 2020):
a. Hypoxemic respiratory failure is the most common indication for ICU.
i. Of all hospitalized patients, supplemental O2 initiated in ~41%, mechanical
ventilation in ~6% (Guan et al, N Engl J Med, 2020).
ii. Of critically-ill patients, mechanical ventilation is initiated in 71%.
1. 100% of ventilated patients had or developed ARDS at some point during their
course.
2. 53% of vented, critically-ill patients developed ARDS within 72 hours of initiation of
mechanical ventilation.
3. Extended use of invasive ventilation is common, with median time to extubation
ranging 11-17 days (Chen et al, Lancet, 2020; Ling et al, Crit Care Resusc, 2020).
b. Presentation with shock is rare
i. Vasopressors are eventually used in 67% of critically-ill patients
c. Cardiomyopathy noted in 33% of critically-ill patients
i. Some progress to cardiogenic shock late in course (anecdotal reports)
Death or hospital discharge
1. Cause of death (Ruan et al, Intensive Care Med, 2020):

a. Respiratory failure alone, 53%
b. Circulatory failure alone (in the setting of myocardial damage), 7%
c. Mixed respiratory and circulatory failure, 33%
d. Unknown cause, 7%
2. Time from illness onset to death:
a. Median 18.5 days (interquartile range 15-22 days) (Zhou et al, Lancet, 2020), though
illness severity has been noted to have two peaks at ~14 days and ~22 days (Ruan et
al, Intensive Care Med, 2020).
3. Time of illness onset to discharge:

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a. Median 22 days (Zhou et al, Lancet, 2020)
4. Duration of hospitalization:
a. Median 12 days (Guan et al, N Engl J Med, 2020)
Prognostication
Indicators
1. Exact hazard / odds ratios vary substantially between studies, and a wide range of
demographic, clinical, laboratory, and radiographic findings have been associated with
hospital outcomes and disease severity progression. See Table 1 for a more in-depth
review. Some highlights / points of emphasis include:
2. Age: increased age correlates with more severe disease and increased mortality (Wu
et al, JAMA Internal Medicine 2020; Chen et al, Lancet, 2020; Yang et al, Lancet Respir
Med, 2020; Qin et al, Clinical Infectious Disease 2020).
3. Comorbidities: Common in patients with COVID-19, more prevalent in those with
severe disease and often associated with worse outcomes (Fang et al, Lancet Respir
Med, 2020; Guan et al, N Engl J Med, 2020; Yang et al, Lancet Respir Med, 2020;
Zhang et al, Allergy, 2020; Chen et al, Lancet, 2020; Tang et al, J Thromb Haemost,
2020; Zhou et al, Lancet, 2020; WHO-China Joint Mission on COVID-19; Yu et al,
JAMA Oncology 2020).
a. Hypertension *
b. Diabetes *
c. Coronary Artery Disease *
d. Chronic Lung Disease *
e. Malignancy *
f. * denotes association with worse outcome in the above literature (i.e. increased odds
of more severe disease or in-hospital death)
4. Laboratory Abnormalities: Common in patients with COVID-19 (see ‘Clinical Course’)
(Zhou et al, Lancet 2020; Huang et al, Lancet 2020; Chen et al, Lancet 2020; Wu et al,
JAMA Internal Medicine 2020; Ruan et al, Intensive Care Med, 2020). Overall
highlights of lab abnormalities associated with severe disease (ARDS / ICU admission)
or death include:
a. WBC > 10 K/uL

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b. Lymphopenia < 1.00 K/uL
c. Platelets < 150 K/uL
d. Creatinine > 1.5 mg/dL
e. Albumin < 3 g/dL
f. ALT > 40 U/L
g. CK > 185 U/L
h. hs-TnT > ~20 ng/L
i. CRP > 125 mg/L
j. LDH > 245 U/L
k. Ferritin > 300 ug/L (severe disease); Ferritin > 1000 ug/L (death)
l. IL-6 > 10 pg/mL
m. D-Dimer > 1000 ng/mL
n. Procalcitonin > 0.5 ng/mL
Epidemiology
Background and geographic distribution
1. Initially recognized in December 2019 by Chinese authorities in the setting of cases of

pneumonia that seemed to be clustered around a seafood market in Wuhan, Hubei
Province (Wuhan Municipal Health Commission, 2019).
2. Bronchoalveolar lavage samples collected from affected patients in late December
2019 yielded evidence of a novel betacoronavirus, genetically-distinct from previously
identified SARS-CoV and MERS-CoV but genetically-similar to previously-published
coronavirus strains collected from bats from southwestern China (Zhu et al, N Engl J
Med, 2020), yielding hypotheses of potential zoonotic origin.
3. The first confirmed case in the United States was documented on January 20, 2020, in
Snohomish County, Washington, in a traveler who had returned from Wuhan, China,
five days prior (Holshue et al, N Engl J Med, 2020).
4. The virus has spread broadly. Worldwide case counts are published by teams at the
World Health Organization, Johns Hopkins University, and others.
5. Viral genomes have been published to GenBank from diverse geographies. Reports on
real-time phylogenetic tracking of the viral genome can be found at NextStrain

(Hadfield et al, Bioinformatics, 2018).

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Transmission dynamics
1. Transmission of SARS-CoV-2 is incompletely understood, and new data continue to

emerge. Many of the studies cited below are based on limited data from the early
phase of the pandemic.
2. Route of transmission:
a. Human-to-human (Li et al, N Engl J Med, 2020), following a suspected zoonotic-to-
human initiating event.
3. Droplet, aerosol, and fomite transmission:
a. Most often transmitted by large droplets and fomites; transmission by aerosolized
particles is possible (especially in patients who are coughing or sneezing) (WHO-
China Joint Mission on COVID-19).
a. Viral particles shown to survive < 24h on cardboard, < 72h on plastic or steel;
aerosolized (droplet nuclei, < 5 µm) particles appear to last at least 3h (van
Dorelmalen et al, New Engl J Med, 2020).
b. Virus has been detected in stool and whole blood (Young et al, JAMA, 2020);
however, significance for transmission is unclear (Chen et al, Emerg Infect Dis, 2020).
4. Viral shedding and symptoms:
a. Nasopharyngeal viral load peaks within days of symptom onset followed by decline
(Young et al, JAMA, 2020).
b. Both symptomatic and asymptomatic patients can transmit the virus (Bai et al, JAMA,
2020; Rothe et al, N Engl J Med, 2020), though symptoms are likely associated with
increased frequency of transmission
i. In several patients, SARS-CoV-2 remained detectable in sputum after symptomatic
recovery (Rothe et al, N Engl J Med, 2020) or without detectable virus in serum
(Holshue et al, N Engl J Med, 2020).
c. Duration of viral shedding from illness onset in survivors, median 20 days
(interquartile range 17-24 days) (Zhou et al, Lancet, 2020; Young et al, JAMA, 2020).
i. Virus detectable to death in nonsurvivors
ii. Viral shedding duration longer in more severe disease status
5. Incubation period:
a. Mean of 5 days, median of 3-4 days, with wide range up to 24 days (common range
2-7 days) (Li et al, N Engl J Med, 2020; Guan et al, N Engl J Med, 2020; Velavan and
Meyer, Trop Med Int Health, 2020; Chan et al, Lancet, 2020).

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Meyer, Trop Med Int Health, 2020; Chan et al, Lancet, 2020).
6. Basic reproduction number (R0):
a. R0 is a measure of transmissibility, denoting the theoretical expected number of
secondary cases from any given case during an epidemic period of transmission. An
R0 > 1 is consistent with sustained outbreak.
b. Considering the period of epidemic transmission, R0 estimated at ~2-5, with min/max
mean/median values ranging from 1.4-5.7; as expected, R0 has declined since
outbreak in China and regions of Europe with control measures (Zhao et al, Int J
Infect Dis, 2020; Riou and Althaus, Euro Surveill, 2020; Flaxman et al, Imperial
College London, 2020 preprint; Read et al, medRxiv, 2020 preprint; Shen et al,
medRxiv, 2020 preprint).
c. These estimates are comparable to those estimated for epidemic transmission during
the 2002-2003 SARS outbreak; secondary cases per index declined with case
isolation and contact quarantining (Lipsitch et al, Science, 2003; Bauch et al,
Epidemiology, 2005; Wallinga and Teunis, Am J Epidemiol, 2004).
7. Super-spreading:
a. Refers to events in which individuals directly spread an infection to a large number of
(> 10) others, was noted in the 2002-2003 SARS outbreak (Lipsitch et al, Science,
2003).
b. It is thought that there may be a similar role in the spread of COVID-19 given
population dynamics (Li et al, N Engl J Med, 2020).
i. A COVID-19 super-spread event is believed to have occured at a church in Daegu,
South Korea, where “Patient 31” infected at least 40 others (Ryall J, The Telegraph,
2020).
8. Case fatality rate:
a. This is the percentage of people diagnosed with the disease who will die from it in a
specified period of time
i. CFR is subject to significant lag time bias and may be artificially low early on in
disease (onset of illness to death is around 18d as described above)
ii. CFR is a function both of virulence of disease, but also demographics and the
availability and quality of healthcare services
b. CFR is approximately 2.3% in Italy (Porcheddu et al, J Infect Dev Ctries, 2020) and
China (Feng et al, China CDC Weekly, 2020), though estimates range from 1-4%
depending on data used (Guan et al, N Engl J Med, 2020; Wang et al, JAMA, 2020),
with initial estimates as high as 15% (Huang et al, Lancet, 2020).
i. Conservative estimates may still be an overestimate according to some (Guan et al,

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i. Conservative estimates may still be an overestimate according to some (Guan et al,
N Engl J Med, 2020; Klompas M, Ann Intern Med, 2020).
9. Reinfection and immunity:
a. Possibility or risk of reinfection in humans is not yet known nor are full details around
development of immunity.
i. Preprint studies report evidence of SARS-CoV-2-specific neutralizing antibodies
generated by B-cells of convalescent patients (Ju et al, bioRxiv, 2020 preprint) and
resistance to reinfection after recovery in non-human primates (Bao et al, bioRxiv,
2020 preprint).
10. Pets, zoonotic spread:
a. Preprint data reports evidence of viral replication in inoculated ferrets and cats, with
viral transmission between cats; dogs showed low susceptibility, and pigs, chicken,
and ducks were deemed not susceptible (Chen et al, bioRxiv, 2020 preprint).
b. Virologist cited in Nature News suggests cat owners should not yet be alarmed, noting
deliberate high-dose inoculation of said cats - unrepresentative of day-to-day
pet/owner interactions, and that none of the infected cats developed symptoms in the
aforementioned study (Mallapaty S, Nature News, 2020).
11. Population prevalence
a. Serology testing helps to determine the (sero)prevalence, with ongoing research on
how long those antibodies are detectable after infection. Early reports (preprint) on
Santa Clara, CA have prevalence that ranged from 2.5-4% (Bendavid et al., bioRxiv,
2020 preprint)
b. Prevalence estimates are rapidly expanding as both viral infection and testing
availability spread.
Health Equity
Introduction and Significance
1. Equity focuses on eliminating avoidable, unfair or remediable differences among

groups, whether these are defined socially, economically, demographically or by any
other stratification.
a. Upholding equity in health allows prioritization of fair opportunities for everyone to

attain their full health potential (WHO Health Systems: Equity).
b. Development of equitable health systems during this time is paramount to identify

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b. Development of equitable health systems during this time is paramount to identify
vulnerable populations, ensure equal treatment opportunities, and ultimately curb
global spread.
2. The COVID-19 pandemic has disproportionately affected vulnerable populations in
China (Wang and Tang, Nat Med, 2020) and around the world.
3. In the United States, early release data from the CDC capturing demographics of
hospitalized patients with COVID-19 across 14 states (between March 1-30, 2020) has
shown that black populations are being disproportionately affected by this disease
(Garg S, CDC MMWR, 2020).
a. Growing data (per below) further corroborates the effects this epidemic has had on
minority groups.
Demographics of COVID-19 Patients
1. Black and Latinx groups are disproportionately represented in COVID-19 cases and
COVID-19 deaths compared to their percentage of the population within the United
States.
a. New York has the highest number of reported COVID-19 cases within the U.S.
(accounting for 29.8% of all U.S. cases as of April 12, 2020).
i. As of April 11, 2020, New York City data on COVID-19 fatalities reported by
race/ethnicity demonstrated that 34% of individuals who died from COVID-related
causes identified as Hispanic and 28% identified as Black, despite comprising 29%
and 22%, respectively, of NYC’s population (NYSDOH Fatalities).
ii. In comparison, 27% of individuals identified as While, 7% as Asian, and 4% as
Other, while comprising 32%, 14% and 3%, respectively, of the city’s population
(NYSDOH Fatalities).
b. Similarly, as of April 10, 2020, Boston City data in Massachusetts showed that 42% of
individuals diagnosed with COVID identified as Black despite comprising 25.3% of
Boston’s population. 16% of individuals identified as Latinx, 28% as white, and 4%
Asian/Pacific Islander while comprising 19.7%, 52.6%, and 9.6% of Boston’s
population, respectively (2020 Census Bureau: City of Boston).
2. Studies have demonstrated that racial classifications inadequately describe genetic
variations between people, and that races have relatively uniform genetic identity
(Templeton AR. Stud Hist Philos Biol Biomed Sci. 2013; Tishkoff SA and Kidd KK, Nat.
Genet. 2004). As such, the concept of race is primarily a social construct (Lewontin,
Evolutionary Biology, 1972) and is unlikely to adequately explain clinical outcomes,
which are more often due to structural and social inequalities. .

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which are more often due to structural and social inequalities. .
Vulnerable Populations
1. Skilled nursing facilities (SNF):

a. A single SNF in Kirkland, WA, USA had 167 COVID-19 confirmed cases (101
residents, 50 health care staff, 16 visitors) with respective hospitalization rates of
55%, 6% and 50%; and case-fatality rate of 34% for residents (McMichael et al, N
Engl J Med, 2020).
2. Homeless populations:
a. Homeless populations less than 65 years old have all-cause mortality 5-10 higher
than the general population at baseline (Baggett et al, JAMA Intern Med, 2013). Living
conditions, higher rates of comorbidities (including substance abuse and mental
illness), difficulty for public health agencies to trace homeless individuals and limited
connection with medical services are all likely challenges (Tsai and Wilson, Lancet
Public Health, 2020) but data on the COVID-19 pandemic in the homeless remains
limited.
3. Incarcerated populations:
a. This section is in development.
4. Undocumented immigrant populations:
a. This section is in development.
Addressing Health Equity at the Hospital Level
1. Collect transparent data:

a. In order to identify affected populations and adequately implement targeted solutions
to barriers in care, robust and transparent data collection should be employed and
examined within and between institutions as well as at a population level (e.g. city,
state, nation-wide)
a. Demographics should include at a minimum, age, sex, race/ethnicity, primary
language, and socioeconomic status (or zipcode as a proxy) (Geronimus AT et al, J
Am Stat Assoc, 1995).Other demographics such as sexuality, education level,
religion, country of origin, immigration/legal status, housing status, and disability
status should be collected if possible.
1. Screen for Social Determinants of Health (SDOH):

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a. SDOH are the conditions under which people are born into, grow, live, work, and age
(AAFP's The EveryONE Project). Examples include housing, transportation,
neighborhood safety, access to sanitation/heating/electricity, job security, and
exposure to violence.
b. Evaluation of resources available to individuals and their communities are essential to
identify support strategies that can help alleviate local disparities. Some Boston-area
resources include:
i. Project Bread hunger and food resources
ii. Harm reduction strategies for people who use substances (English)
iii. Boston and Massachusetts community resources (multiple languages)
iv. State-by-state guide to government services available as part of COVID-19 relief
(English)
2. Employ communication tools for patients and employees with limited English
proficiency (LEP):
a. Below are strategies shared by the MGH Disparities Solutions Center:
i. Create and disseminate language-concordant screening and educational materials
based on the languages spoken in your population.
ii. Ensure interpreting services (e.g. in-person interpreters, bilingual phones, and/or
mobile screens such as iPads) are available during clinical interactions.
iii. Employ staff hotlines with people who are multilingual.
iv. Target communication updates to the LEP population in multiple languages and
through multiple platforms (e.g. email, website, text messaging, flyers, etc)
v. Create a registry with clinical staff who are multilingual and deploy them to
applicable sites that care for LEP patients.
3. Develop communications tools for patients with disabilities:
a. Providing hospital staff and disability groups with clear tools to communicate is
essential to delivering proper education and clinical care.
i. Surgical masks with clear windows can enhance communication for those who are
deaf of hard of hearing.
ii. Photos of clinical care team members to share with patients to alleviate anxiety and
isolation and help foster connectedness in a time when medical care is provided with
abundant use of PPE.
iii. Provide trauma-informed care (CDC guide).
4. Involve diverse personnel in the creation and implementation of clinical and
ethical guidelines.

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ethical guidelines.
a. Healthcare institutions should strive to institute diversity and inclusion measures at all
levels in order to mitigate implicit bias and assure that the viewpoints of multiple
stakeholders are incorporated into policy
CHAPTER 2
ED & Inpatient Floor

Management, Triage, Transfers
Section Editor: Katherine H. Walker MD MSc
Contributors: Christopher L. Roy MD, Paul Chen MD MBA, Raghu Seethala MD MSc,
Elizabeth M. Petersen MD MPH, Glen Kim MD, Samuel Y. Ash MD MPH, John C.
Kennedy MD MSc, B. Christian Renne MD, Morgan C. Espérance MD MPH, Herrick N.
Fisher MD MPhil, Cheryl R. Clark MD ScD, Matthew G. Gartland MD
Personal Protective Equipment and Infection Control

Personal Protective Equipment
1. Location-specific PPE guidance: There are location-specific differences (e.g.,

Shapiro SP-ICU versus Tower ICU COVID testing) in place, so refer to your location
guidelines.
a. Easy to read “grid” summarizing PPE here (Partners login required)

b. Partners PPE Guidance (Partners login required)

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2. For aerosol generating procedures: Strict isolation (aerosol) PPE (including N95
masks) are needed during and for 47 mins after these procedures. These should be
preferentially performed in negative airflow rooms:
a. Intubation
b. Extubation
c. Bronchoscopy
d. Sputum induction
e. Cardiopulmonary resuscitation
f. Open suctioning of airways
g. Manual ventilation (e.g. manual bag- mask ventilation before intubation)
h. Nebulization
i. High flow oxygen therapy (15-60 L nasal cannula or mask)
j. Non-invasive positive pressure ventilation (e.g., CPAP, BIPAP)
k. Oscillatory ventilation
l. Disconnecting patient from ventilator
m. Upper airway procedures / surgeries
n. Upper endoscopy (including transesophageal echocardiogram) and lower endoscopy
o. Chest physical therapy
p. Autopsy
q. Thoracentesis/small-bore (pigtail) chest tube placement (due to the increased risk of
cough)
3. To donate PPE: Please use this link for donations of PPE or targeted funding for PPE
ICU Strict isolation manual
1. Step-by-step protocols for working in COVID-19 precaution patient rooms (e.g.,

transporting a patient, lab draws, micro testing like COVID-19 swab, sterile procedures
like central venous catheters) are linked here.
Epic Note and Lab Templates

1. Add the COVID Dashboard to your EPIC patient list (Partners login required)
2. Brigham and Women’s Specific Epic smartphrases

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a. Inpatient COVID admission note (SPUADMITNOTE)
i. IMPORTANT: This is an example of possible templated note/phrase. Smartlinks are
NOT universal across computer systems. This note should not be copied and used
directly for patient care. We are working to make templates available through the
Epic Community Library.
b. Inpatient progress note (PACEPROGRESSNOTE)
c. COVID discharge counseling (SPUCOUNSELING)
d. Discharge instructions for PUI or COVID positive patients
(SPUDISCHARGECOVIDPOSITIVE)
e. Discharge instructions for COVID negative patients
(SPUDISCHARGE COVIDNEGATIVE)
f. Last set of COVID labs (LASTCOVID)

3. Lab ordersets:
a. COVID Admission Orderset (COVID 19 Add On)
Diagnostic Testing
COVID testing
1. This is an area that is actively changing and varies widely by hospital, test availability,
and local epidemiology. Partners criteria available here (Partners login required)
2. Certain ED presentations (i.e. cardiac arrest) are always tested for COVID-19
Laboratory studies and EKGs
On admission CBC with differential

If not obtained in ED, draw BMP, Magnesium
following morning LFTs, Troponin & CPK, NT-proBNP
LDH, CRP, D-dimer, Procalcitonin
PTT/INR, Ferritin
Baseline EKG
Extended Respiratory Viral Panel - only if would

change management (high risk patients such as
transplant, onc, ICU)

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transplant, onc, ICU)
Daily CBC with differential
Can change to every other BMP, Magnesium
day in stable floor patients If ICU: Troponin & CPK, NT-proBNP, PTT, PT,
Fibrinogen
Every other day LFTs, Troponin & CPK, NT-proBNP
LDH, CRP, D-dimer, Ferritin, PTT, PT, Fibrinogen
If on propofol: Triglycerides, lipase
Twice Weekly sIL-2R
Weekly - only in heme Glucan, Galactomannan
malignancy / stem cell +/- additional per primary oncologist
transplant patients
If clinical worsening CBC with differential
BMP, Magnesium, LFTs
Troponin & CPK, NT-pro-BNP
LDH, CRP, D-dimer, Procalcitonin
PTT/INR, Fibrinogen, Ferritin
ABG preferred over VBG
Repeat EKG
Chest imaging
1. Findings: Please see this excellent resource from Radiopedia.

a. Primary features are of atypical pneumonia or organizing pneumonia.
i. Distribution is typically bilateral, peripheral, and basal
1. Bilateral findings in about 85% of patients; 33 - 86% predominantly peripheral and
70 - 80% predominantly posterior (Chung, RSNA, 2020; Song, RSNA, 2020)
b. Parenchymal imaging findings are variable and depend on timecourse (Wang, RSNA,
2020):
i. Days 0-5: ~65% pure GGOs, 24% GGOs with intralobular lines
ii. Days 6-11: ~40% pure GGOs, 22% pure GGO with intralobular lines, 28% GGO with
irregular lines and interfaces
iii. Days 12 - 17: more consolidations (38% show “mixed” pattern of consolidation,
GGOs, and reticular opacities with architectural distortion)
iv. Late findings may include fibrotic changes

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iv. Late findings may include fibrotic changes
c. Small bilateral effusions can be seen in <10% of patients; large effusions are not.
i. Large effusions, cavitations, discrete nodules, lymphadenopathy suggestive of
another process (eg superimposed bacterial infection)
1. Portable CXR: Sufficient in most cases. Avoid routine daily CXR (unlikely to change
management, evaluate case-by-case).
a. May be initially normal in up to ~30% of hospitalized COVID patients, particularly in
early disease (Wong, Radiology, 2019).
i. Sensitivity 59% in one study, as compared to 86% for CT scan (Guan, NEJM, 2020)
2. CT Chest: Often will not change management and is associated with potentially
unnecessary risk (risk to staff of transmission in transit, risk to patient for desaturation
in transit)
a. Avoid unless otherwise indicated: e.g. for abscess or empyema, or other causes of
hypoxemia like pulmonary embolism
i. If chest CT obtained, non-contrast scan (or contrast and non-contrast phases if
concerned for PE)
b. Approximately 50% of CT scans are normal up to 2 days after symptom onset
3. Point of Care Ultrasound: Can be used by experienced providers, but is operator-
dependent. For experienced providers, sensitivity is likely superior to portable chest X-
ray (Mayo, Intensive Care Med, 2019).
a. Findings: Focal or diffuse B lines with sparing of uninvolved areas, irregular thickened
pleural line with “scattered discontinuities”, subpleural consolidations (relatively
avascular on Doppler), alveolar consolidations with air bronchograms
i. May help distinguish cardiogenic pulmonary edema from ARDS. (Mayo, Intensive
Care Med, 2019).

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Other studies
1. Avoid other studies unless truly necessary due to PPE limitations and transmission risk
a. Avoid routine TTEs (see “Cardiovascular Testing”)
Respiratory Escalation Pathways and Intubation

For persons NOT under investigation for COVID-19 (i.e., not COVID-19 PUI or
confirmed)
1. Nasal Cannula, oxymizer, venturi mask:

a. Continue standard practices.
2. Noninvasive ventilation, high flow nasal cannula:
a. Indications remain the same (e.g., continue nocturnal NIPPV for sleep apnea; NIPPV
for reversible causes of respiratory failure like flash pulm edema or COPD
exacerbation).
b. If there is a doubt about the use of NIPPV or HFNC in a patient that is not a COVID-
19 PUI or confirmed, discuss with Biothreats pager.
For Persons Under Investigation (PUI) or with confirmed COVID-19
1. Goals of oxygen therapy:

a. Maintain target SpO2 92-96%
i. Target SpO2 88-94% in patients with oxygen-dependent COPD
b. Maintain stable work of breathing

i. Goal respiratory rate < 24

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ii. Target normal respiratory effort (no signs of accessory muscle use or obvious
increased respiratory work)
2. Supplemental oxygen support:
a. Initial oxygen delivery should be humidified nasal cannula (NC) titrated from 1 to 6
LPM to meet goals of therapy.
b. If goals of therapy are not met at 6 LPM NC then advance to either:
i. Oxymizer mustache:
1. Initiate at 6 LPM
2. Titrate to maximum of 12 LPM to meet goals of therapy
ii. Venturi mask
1. Initiate at 12 LPM and FiO2 40%
2. Titrate to maximum of FiO2 60% to meet goals of therapy
3. Considerations during oxygen support escalation:
a. Clarify realistic goals of care and appropriateness of ICU hospitalization prior to
escalating to ICU transfer and pursuing intubation
b. If patient is nearing intubation threshold, call family again to:
i. Update worsening clinical status,
ii. Double-check realistic goals of care and
iii. Facilitate a conversation between patient and family prior to intubation,
understanding that in emergent situations, this will not be possible.
c. Consider awake proning in selected patients
d. Consider the rate of change of oxygen escalation as well as pre-existing
cardiopulmonary disease in determining threshold for ICU transfer (such as COPD
patient with pre-existing supplement oxygen use at baseline)
e. Consider Pulmonary Consult if there are concerns for other etiologies of hypoxia
4. If appropriate, consult ICU for triage and evaluation:
a. If SpO2 < 92% (<88% in COPD) or unstable work of breathing at
i. Oxymizer at 10 LPM or Venturi mask at FiO2 50%
1. ICU triage (pager #39999)
5. If appropriate, call COVID airway team or ED airway team for intubation:
a. If SpO2 < 92% or unstable work of breathing at:

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ii. COVID anesthesia airway team (pager #39265)
1. Notify team of any known prior difficult intubations, prior head or neck surgery or
radiation therapy, or know airway abnormalities
iii. Call family as above while awaiting anesthesia, but do not delay intubation
b. Pre-oxygenation for patients on advanced supplemental oxygen support:
i. Increase Venturi mask to FiO2 100% or Oxymizer to 15 LPM prior to planned
intubated
c. Avoid NIPPV or HFNC to stave off intubation
i. For patients already on NIPPV/HFNC, transition to Venturi mask or non-rebreather
mask if possible, ideally 45 minutes prior to intubation
d. Rapid Sequence Induction(RSI) should be performed by the most experienced airway
provider without bag-valve masking and using a video laryngoscope (SCCM
COVID19 Guidelines)(APSF Considerations for Airway Manipulation, 3/20/2020).
i. For more detailed instructions, see “Intubation”
6. Noninvasive Ventilation and High Flow Nasal Cannula:
a. NIPPV and HFNC should not be used to delay intubation for Covid-19 ARDS
(rationale detailed in “Respiratory”).
b. Continue nocturnal NIPPV for Obstructive Sleep Apnea or Tracheobronchomalacia:
i. Patients on home nocturnal CPAP or BiPAP should continue nocturnal NIPPV, but
use BWH equipment and must abide by the specifications below.
c. NIPPV is generally not used in Covid-19 confirmed or PUI: Exceptions can be
considered on a base by case basis for rapidly reversible causes of hypoxemia, such
as flash pulmonary edema or COPD exacerbation.
i. For cases where it is unclear whether NIPPV should be used, services (such as the
ED) can consult the SP-ICU triage pager (#39999) and/or biothreats pager.
Examples of this situation could be a presentation of flash pulmonary edema or
COPD exacerbation with a lower pre-test probability of Covid-19 based on
symptoms and/or a negative nasopharyngeal swab
d. If NIPPV used:
1. Use BWH NIPPV machine with dual limb with a HEPA filter and BWH mask without
anti-asphyxia valve
a. Patients may NOT use their home NIPPV mask or nasal pillow or single-limb

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a. Patients may NOT use their home NIPPV mask or nasal pillow or single-limb
machine due to increased aerosol risk.
2. Use under strict airborne precautions, including N95s, strict isolation, and a
negative pressure room.
3. Ensure masks/devices fit well and there is minimal air leak
a. Measured exhaled air distances are minimally increased with CPAP pressures up
to 20 cm H2O and HFNC up to 60 LPM; importantly device/interface leaks cause
significant lateral air travel (Hui et al, Eur Respir J, 2019)
e. HFNC: At present, we do not use HFNC in patients who are COVID-19 PUI or
confirmed due to risk of potential aerosolization (rationale detailed in “Respiratory”).
Medical Management
1. Management is largely supportive. Antiviral and immune-modulating therapies are
investigational. Please see “Therapeutics and Clinical Trials” and “Infectious Disease”
for further details
2. Fluid management should be conservative due to risk of hypoxia/CHF. Please see
“Septic shock” for more information on dynamic fluid management
Considerations for Geriatric Patients

1. Frailty, immunosenescence and multimorbidity placed older adults for increased risk of
adverse outcomes
2. Older patients may present differently:
a. Use lower fever criteria: one oral temp > 37.8C or two oral temps > 37.2C (IDSA
criteria)
b. More likely to present with atypical symptoms such as altered mental status,
decreased appetite, non-focal pain
3. If patient presenting from facility, call facility to notify of COVID-19 positivity
4. Include frailty screen on initial assessment.
a. Perform the FRAIL scale as below
i. If patient screens positive for frailty or has a history of dementia, delirium, or is a
nursing home resident, page geriatrics tele-consult pager (Pager #38251)

Fatigue “Are you fatigued throughout the day?”

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Fatigue “Are you fatigued throughout the day?”
Resistance “Are you unable to walk up a flight of stairs?”
Aerobic “Are you unable to walk a block?”
activity
Illnesses Does patient have > 5 of the following illnesses: HTN, DM, cancer
(> 5) (excluding localized skin cancer), chronic lung disease, MI, CAD, CHF,
angina, asthma, arthritis, CVA or TIA, CKD?
Loss of Has patient lost > 5% body weight in the past 6 months?
weight
Scoring: (each “yes” answer = 1 point)
0=robust; 1-2=prefrail; > 3 = frail)
Early Advance Care Planning

1. In conscious patients, review or sign Health Care Proxy form and discuss and
document goals of care on admission
a. Educate patient and family on disease course and prognosis
b. Focus on desired quality of life and tolerance for ICU measures
c. Early consultation of palliative care if appropriate. See “Palliative Care”
Bedside Procedures
1. 24/7 COVID-specific procedure teams are available to do bedside procedures (pager
#39299). Specific teams, hours of availability, and instructions are outlined in the
respiratory chapter.
Triage to ICU
Consult the ICU triage team EARLY for:
1. Provider concern
2. Respiratory distress
a. Need O2 > 6 LPM to maintain SpO2 > 92% or PaO2 > 65.

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b. Rapid escalation of oxygen requirement.
c. Significant work of breathing.
3. Hemodynamic instability after initial conservative fluid resuscitation
a. SBP < 90, Mean arterial pressure < 65, or Heart rate > 120.
4. Acidosis
a. ABG with pH < 7.3 or PCO2 > 50 or above patient’s baseline.
b. Lactate > 2.
5. Need for intensive nursing care or frequent laboratory draws requiring arterial line.
6. Severe comorbid illness / high risk for deterioration.
Transfer Process
Floor / ED to ICU:
1. ICU RN brings ICU bed to the floor for transfer (to avoid bed transfer in COVID
precautions room and subsequent bed cleaning).
2. Patient wears a surgical mask, with an extra clean gown and sheet on top.
3. Providers wear standard PPE during transport.
4. Security facilitates the shortest and fastest transfer route, walks 6 ft away from patient
and providers, not required to wear PPE
5. Necessary tests (e.g. CT), should be obtained during transfer if possible.
ICU to floor:
1. RN wears standard PPE

2. Patient travels in wheelchair or stretcher
Floor to discharge:
1. RN wears standard PPE

2. Patient travels in wheelchair

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4. Patient is escorted directly into vehicle; contact care management if patient does not
have access to a personal vehicle
Inpatient Discharge Planning

Clinical Discharge Criteria
1. Consider discharge for patients’ who meet the following clinical criteria:
a. Resolution of fever >48 hours without antipyretics
b. Improvement in signs and symptoms of illness (cough, SOB, and oxygen
requirement)
Disposition Options
1. Home with or without support services

a. Post-discharge phone call: ALL PUIs and COVID+ patients admitted to BWH and
BWFH will have a post-discharge phone call with an Advanced Practice Practitioner
(APP) within 24-48 hours of discharge.
b. Partners Homecare: Fully operational and accepting all appropriate PUI and
COVID+ patients in need of visiting nurse services. Patients will be triaged for virtual
and in person visits.
c. Home Digital Monitoring Program: Patients will receive an oximeter, thermometer,
and will record symptoms, O2 saturation, and temperature daily on a mobile device or
computer for 14 days. A nurse (with 24/7 MD backup) will call patients on the day of
discharge and if recorded symptoms or vitals worsen. Contact care coordination for
enrollment.
2. Facility - LTAC, short-term rehab, skilled nursing facility, Barbara McInnis House
(undomiciled), Boston Hope Medical Center (low acute housing facility)
a. CMS has waived the 3-midnight rule for discharge to a facility for all Medicare
patients.
b. Please contact care coordination to assist with screening for all facility discharges and
for the most up-to-date guidance on the need for COVID-19 testing prior to discharge,
which varies by facility.
3. Discharge against medical advice

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3. Discharge against medical advice
a. People are able to sign themselves out of the hospital against medical advice if they
demonstrate decision making capacity. Please see the Psychiatry section on
assessment of capacity.
Confirmed COVID-19 Discharge Checklist
Prior to discharge
❏ Verify and document preferred language of patient and emergency contact in Epic
❏ Verify and document preferred phone number for patient and emergency contact in
Epic and ensure active phone and voicemail service
❏ Confirm patient’s ability to understand and adhere to home isolation instructions
❏ Confirm patient’s ability to manage ADL/iADLs with current level of support at home
❏ Confirm patient has resources/social support to receive food and other necessary
supplies for the duration of quarantine (see community resources below, consider SW
consult)
❏ Perform DME needs assessment and consider sponsorship from hospital if item cannot
be delivered or obtained by patient’s family/support person
Discharge medications/supplies
❏ Provide 90-day supply of all medications, recommend meds-to-bed delivery at BWH

❏ Provide a surgical mask to all infected patients who are discharging home
Transportation
❏ Verify patient has a ride by private vehicle or enlist care coordination assistance to
arrange alternate transportation (infected person should wear mask in vehicle)
Discharge instructions
❏ Counsel patient on voluntary isolation procedures and include COVID discharge

instructions template in discharge summary
Epic Smart Phrases
SPUCOUNSELING
SPUDISCHARGECOVIDPOSITIVE

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SPUDISCHARGECOVIDNEGATIVE
❏ Encourage patients to call 211 or 311 to obtain the most up-to-date resources
❏ Partners infographic discharge instructions (multiple languages)
❏ COVID fact sheets (multiple languages)
Ambulatory follow-up plan
❏ Verify and document patient’s PCP in Epic

❏ Provide Epic in-basket message or warm handoff to patient’s PCP
❏ ALL PUIs and COVID+ patients admitted to BWH and BWFH will have a post-
discharge phone call with an Advanced Practice Practitioner (APP) within 24-48 hours
of discharge
❏ Schedule a telemedicine follow-up visit within 7 days of discharge for all patients with
Partners PCPs
❏ Schedule a telemedicine or in person follow-up appointment for patients with a non-
Partners PCP
Community resources
❏ Project Bread hunger and food resources

❏ Harm reduction strategies for people who use substances (English)
❏ Boston and Massachusetts community resources (multiple languages)
❏ State-by-state guide to government services available as part of COVID-19 relief
(English)
CHAPTER 3
Respiratory and Pulmonology

Section Editors: Steven Keller MD PhD, Bina Choi MD

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Contributors: William Feldman MD D.Phil, Jeremy Weinberger MD, Adam Smith BS RRT-
ACCS, Julie Ng, MD, C. Lee Cohen MD MBA, Kevin Olsen MD, Bradley Wertheim MD,
Anthony Massaro MD, Edy Kim MD, Amanda Scippa RD LDN CNSC, Paul Szumita
PharmD, RPh, FCCM BCCCP BCPS, Majid Shafiq MD MPH
Acute Lung Injury (ALI) and Acute Respiratory Distress

Syndrome (ARDS)
Pathophysiology
1. Histology of COVID-19 associated lung disease shows bilateral diffuse alveolar

damage with cellular fibromyxoid exudates, desquamation of pneumocytes, pulmonary
edema, and hyaline membrane formation. There is also some evidence of direct viral
injury to lung tissue, not just inflammatory sequelae. (Xu et al, Lancet Respir Med,
2020).
2. Anecdotally, patients with COVID-related lung disease have significantly higher
compliance than is typical for their shunt fraction, indicating this may be a very different
phenotype than typical ARDS. The explanation remains unclear, with pulmonary
perfusion dysregulation posited as one possible explanation. (Gattinoni, AJRCCM,
2020)
3. The SARS-CoV-2 virus binds to the ACE2 receptor as its target receptor for cell entry
which may be an explanation for many of the pathophysiological manifestations of
infection. The ACE2 receptor is expressed by select populations of cells including the
pulmonary endothelium, Alveolar Type 2 cells, proximal renal tubule cells,
gastrointestinal epithelial cells, and many other others. The cells that express ACE2 are
likely the cell populations targeted in immune responses to infection. Their subsequent
injury may explain specific manifestations of the disease. Specific, hypothesized
manifestations, include the following:
a. In the pulmonary endothelium, ACE2 acts to downregulate angiotensin II (a potent
vasoconstrictor) while increasing levels of angiotensin (1,7) (a vasodilator). Infection
with SARS-CoV-2 may impair this pathway or may lead to imbalances in the
ACE/ACE2 pathways with uncertain effects on hypoxic vasoconstriction mechanisms.
Impairment of this pathway may induce increased shunt and resultant hypoxia.
b. Alveolar Type 2 cells secrete surfactant. Their selective injury caused by SARS-CoV-2
infection may lead to selective loss of surfactant in a subgroup of patients resulting in
increased derecruitment at low opening pressures and a highly PEEP sensitivity to

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increased derecruitment at low opening pressures and a highly PEEP sensitivity to
maintaining lung function. These patients may experience prolonged recovery periods
dependent on repopulation of Alveolar Type 2 cells and reconstitution of surfactant.
Definition of Acute Respiratory Distress Syndrome (ARDS)
1. Most patients with COVID-19 who require ICU level of care will develop ARDS.
2. The Berlin definition of ARDS requires the following four criteria:
a. Acute (onset over 1 week or less)
b. Bilateral opacities detected on CT or chest radiograph
c. PF ratio <300mmHg with a minimum of 5 cmH20 PEEP (or CPAP)
d. Must not be fully explained by cardiac failure or fluid overload
Severity PaO2/FiO2 (on PEEP/CPAP >5) Mortality (all cause, cohort)

Mild 200-300 27%
Moderate 100-200 32%
Severe <100 45%
Time course
1. Anecdotally, many report that progression of hypoxemic respiratory failure occurs

rapidly (within ~12-24 hours).
2. From onset of symptoms, the median time to:
a. Development of ARDS: 8-12 days (Wang et al, JAMA, 2020; Zhou et al, Lancet, 2020;
Huang et al, Lancet, 2020)
b. Mechanical ventilation: 10.5-14.5 days (Huang et al, Lancet, 2020; Zhou et al, Lancet,
2020)
Management of Hypoxemia for COVID PUI/ Confirmed

Cases
Supplemental Oxygen Support
1. Goals of therapy:

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a. Maintain target SpO2 92-96%
i. Target SpO2 88-94% in patients with oxygen-dependent COPD
b. Maintain stable work of breathing
i. Goal respiratory rate < 24
ii. Target normal respiratory effort (no signs of accessory muscle use or obvious
increased respiratory work)
2. Supplemental oxygen support:
a. Initial oxygen delivery should be humidified nasal cannula (NC) titrated from 1 to 6
LPM to meet goals of therapy.
b. If goals of therapy are not met at 6 LPM NC then advance to either:
i. Oxymizer mustache:
1. Initiate at 6 LPM
2. Titrate to maximum of 12 LPM to meet goals of therapy
ii. Venturi mask
1. Initiate at 12 LPM and FiO2 40%
2. Titrate to maximum of FiO2 60% to meet goals of therapy
3. Considerations during oxygen support escalation:
a. Clarify goals of care and appropriateness of ICU hospitalization prior to escalating to
ICU transfer and pursuing intubation
b. Consider awake proning in selected patients
c. Consider the rate of change of oxygen escalation as well as pre-existing
cardiopulmonary disease in determining threshold for ICU transfer (such as COPD
patient with pre-existing supplement oxygen use at baseline)
d. Consider Pulmonary Consult if there are concerns for other etiologies of hypoxia
4. If appropriate, consult ICU for triage and evaluation:
a. If SpO2 < 92% (<88% in COPD) or unstable work of breathing at
1. ICU triage (pager #39999)
Intubation
1. If appropriate, call COVID airway team for intubation:

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a. If SpO2 < 92% or unstable work of breathing at:
1. COVID anesthesia airway team (pager #39265)
a. Page STAT line if code/ emergent (pager #26555)
2. Notify team if you anticipate needing arterial line or central access, as they
may be able to place the line while in full intubating PPE (see Bedside ICU
procedures)
3. Notify team of any known prior difficult intubations, prior head or neck surgery or
radiation therapy, or know airway abnormalities
2. Pre-oxygenation for patients on advanced supplemental oxygen support:
a. Increase Venturi mask to FiO2 100% or Oxymizer to 15 LPM prior to planned
intubated
3. Avoid NIPPV or HFNC to stave off intubation (see discussion below)
a. For patients already on NIPPV/HFNC, transition to Venturi mask or non-rebreather
mask if possible, ideally 45 minutes prior to intubation
4. Rapid Sequence Induction(RSI) should be performed by the most experienced airway
provider without bag-valve masking and using a video laryngoscope (SCCM COVID19
Guidelines)(APSF Considerations for Airway Manipulation, 3/20/2020).
a. For more detailed instructions, see “Intubation”
5. Intubations outside the ICU should be attended by the Resource RT, who can facilitate
early and appropriate ventilator settings
6. After intubation, see “initial mechanical ventilation” for next steps
Non-invasive Positive Pressure Ventilation (NIPPV) and High Flow Nasal Cannula
(HFNC)
1. We recommend avoiding high-flow nasal cannula (HFNC) and non-invasive

positive pressure ventilation (NIPPV; i.e. CPAP/BiPAP) in most circumstances
a. There is a paucity of data on the increased aerosol risk of these interventions, and
their role in increasing transmission.
i. General consensus suggests that NIPPV increase the risk of viral transmission, but
the degree of aerosolization is poorly understood and data on this is lacking. WHO
interim guidance (published March 13, 2020) recommends use in selected patients

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interim guidance (published March 13, 2020) recommends use in selected patients
while maintaining airborne precautions.
ii. A systematic review on SARS found that NIPPV was associated with increased risk
of viral transmission to healthcare workers (n=2 studies), but HFNC was not (n=1)
(Tran et al, PLoS One, 2012)
iii. Some other centers feel that “helmet” NIPPV has less risk than face mask NIPPV
but there is not clear data.
iv. Whether HFNC increases aerosol risk is more unclear than face mask NIPPV. Other
studies with very limited power exist, such as a post-hoc analysis that found no
secondary infections in medical staff from patients with influenza H1N1 treated with
HFNC (but n=20) (Rello et al, J Crit Care, 2012). A recent non-peer reviewed pre-
print (Iwashyna et al, medRXiv, 2020) tested aerosol levels in healthy volunteers and
concluded that there was no variation in aerosol level among room air, 6L/min NC,
15 L/min NRB, 30L/min HFNC and 60 L/min HFNC regardless of coughing.
Similarly, a randomized, controlled crossover trial of HFNC versus conventional
oxygen mask found no increase in air or contact surface contamination by bacteria
(Leung et al, J Hosp Infect, 2020)
v. Given the rapid progression of disease in most patients, we do not anticipate many
patients would avoid intubation using NIPPV/HFNC, but this remains unknown and
may change as we gain more experience
vi. Case reports from China suggest high failure rates for non-invasive ventilation,
including high-flow nasal oxygen (Zuo et al, Chin Med Sci J, 2020), though there are
some patients who may recover on HFNC.
vii. Generally, NIPPV is thought to stave off intubation only in early ARDS and the data
is inconsistent (Rochberg et al, ERJ, 2016).
2. Continue nocturnal NIPPV for Obstructive Sleep Apnea or
Tracheobronchomalacia:
a. Patients on home nocturnal CPAP or BiPAP should continue nocturnal NIPPV, but use
BWH equipment and must abide by the specifications below.
3. NIPPV is generally not used in Covid-19 confirmed or PUI:
a. Exceptions can be considered on a base by case basis for rapidly reversible causes
of hypoxemia, such as flash pulmonary edema or COPD exacerbation.
b. For cases where it is unclear whether NIPPV should be used, services (such as the
ED) can consult the SP-ICU triage pager (#39999) and/or biothreats pager.
c. Examples of this situation could be a presentation of flash pulmonary edema or

COPD exacerbation with a lower pre-test probability of Covid-19 based on symptoms
and/or a negative nasopharyngeal swab. It is likely that other unique situations could

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and/or a negative nasopharyngeal swab. It is likely that other unique situations could
arise.
4. If NIPPV is used:
a. Use BWH NIPPV machine with dual limb with a HEPA filter and BWH mask without
anti-asphyxia valve
i. Patients may NOT use home NIPPV mask or nasal pillow or single-limb machine
due to increased aerosol risk.
b. Use under strict airborne precautions, including N95s, strict isolation, and a negative
pressure room.
c. Ensure masks/devices fit well and there is minimal air leak
i. Measured exhaled air distances are minimally increased with CPAP pressures up to
20 cm H2O and HFNC up to 60 LPM; importantly device/interface leaks cause
significant lateral air travel (Hui et al, Eur Respir J, 2019)
5. HFNC:
a. At present, we do not use HFNC in patients who are COVID-19 PUI or confirmed due
to risk of potential aerosolization and limited benefit (see above)
i. This is an evolving area and may change in the future. If it does change, patients
would be expected to wear surgical masks and limit flow rate to < 30 L/min
Awake proning
1. This section will be updated shortly
Initial Mechanical Ventilation

Checklist following intubation
1. Set the initial ventilator settings:

a. Initiate ARDS ventilation as described below
b. Determine PEEP and mechanics as described below
c. Assure adequate sedation as described below
2. Obtain STAT portable CXR to confirm endotracheal tube location

a. Prioritize CXR and vent settings over procedures (such as central venous catheter
placement) if possible.

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placement) if possible.
3. Complete the “Mechanical Ventilation with Sedation” orderset in EPIC
4. Obtain an ABG (preferred) or a VBG within 30 minutes
a. Calculate P/F ratio from initial post-intubation ABG. Adjust oxygenation as described
below
b. Goal pH 7.25 to 7.45 adjust ventilation as described below
Use of Single Ventilator Multiple Patients
1. The ASA, SCCM, APSF, AARC, AACN, and CHEST societies have issued a joint
consensus statement against using single ventilator for multiple patients (Joint
Statement On Multiple Patients Single Ventilator). Splitting of ventilators comes with
many risks, including infection transfer between patients, difficulty positioning of
essential equipment, difficulty adjusting set respiratory parameters to meet individual
patients’ needs and different clinical courses, difficulty controlling for sensed
parameters (e.g. spontaneous respiration), alarm failures, measurement error in
ventilator self-checks, and ethical dilemmas in prioritizing different patients’ treatment
plans.
Initial ARDS Ventilation Settings
1. Set mode to volume control (AC/VC)

2. Set Initial tidal volume (Vt):
a. Vt = 6 ml/kg (based on ideal body weight [IBW] from ARDSnet table, see table below)
i. IBW men (kg) = 50 + 2.3 (height in inches – 60)
ii. IBW women (kg) = 45.5 + 2.3 (height in inches – 60)

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3. Set Initial respiratory rate
a. Typical starting rates will be 16-24 titrated to goal minute ventilation of 5-8 L/min
b. Consider starting rates of 24-28 titrated to goal minute ventilation of 8-12 L/min in
setting of acidosis (pH < 7.25) pre-intubation
4. Set an Initial PEEP based on BMI (empirically chosen targets):
a. BMI < 35: PEEP 5
b. BMI ≥ 35: PEEP 10
5. Initial FiO2: 100% on intubation then rapidly wean to SpO2 92-96% (Barrot et al, N
Engl J Med, 2020)
Determining PEEP and mechanics
1. Titrate FiO2 and PEEP for oxygenation

a. Initiate PEEP based on BMI, per above, and then titrate PEEP and FiO2 to target
oxygenation SpO2 92-96% as per the following guidelines:
i. BMI < 35: titrate PEEP and FiO2 as per the ARDSnet LOW PEEP table

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ii. BMI ≥ 35: titrate PEEP and FiO2 as per the ARDSnet HIGH PEEP table
b. If SpO2 < 92% or > 96% then titrate PEEP and FiO2 according to the ARDSnet table
as per BMI
c. Special consideration: anecdotal reports of COVID-19 patients describe a compliant,
highly PEEP dependent phenotype in which PEEP management may not strictly
adhere to specified ARDSnet tables (e.g., FiO2 0.4 - 0.5 but does not tolerate PEEP
<10)
d. Avoid elevated plateau pressures (with goal ≤ 30), particularly if using the higher
PEEP table. Special cases (e.g., morbid obesity, burns) may need extra diagnostics,
such as esophageal balloons, which we do not recommend for routine use given the
likely limited resources.
2. Obtain respiratory mechanics:
a. Plateau pressure (with goal ≤ 30, management below)
b. Static compliance
Sedation and Ventilator Synchrony

Targets
1. Treat Pain, Agitation, and Delirium

a. The BWH Guidelines for Pain Agitation and Delirium in Mechanically Ventilated
Patients provide additional detail (Partners login required)

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Patients provide additional detail (Partners login required)
b. The chart below describes how to assess and treat pain, agitation, and delirium.
i. “Pain first” approach (both assessment and treatment)
ii. Use the lowest dose that can achieve the desired effect
c. Preferred medications may change as drug availability and shortages
i. In general, bolus strategy of benzodiazepines and opioids are preferred to
continuous infusions
1. If continuous infusions are required, boluses should be administered prior to
starting the infusion as well as when infusions are up-titrated
2. Typical bolus dose ranges are 50-100% of continuous infusion rate
2. Achieve ventilator synchrony. This is incredibly important in reducing ventilator
induced lung injury.
i. Following Rapid Sequence Intubation, ensure analgesia/sedation is started as
paralytics may still be active (assume 60 minutes for Rocuronium, 10 minutes for
succinylcholine), target sedatives to a RASS score -2 to -3
ii. After paralytics are worn off, assess patient synchrony with the ventilator (e.g., signs
of breath-stacking, double triggering, other ventilator alarms)
iii. If synchronous, lighten sedation to the lowest level that maintains synchrony, ideally
RASS score 0 to -1.
iv. If not synchronous, escalate sedation as needed to achieve synchrony
regardless of RASS
v. If patient remains dyssynchronous despite deep sedation (RASS -4 to -5), initiate
continuous paralytic
1. Target sedation to RASS - 4 to -5 and BIS 40 to 60 (before initiating paralytic)
2. Titrate neuromuscular blockade to ventilator synchrony
PAD Bundle Pain Agitation Delirium

Assess and Able to self report RASS (-5 to +4) CAM
Document Numeric Rating Scale BIS in patients receiving ICU-modified
(0-10) (NRS) Neuromuscular Blockade (+ or -)
Preferred
Unable to Self Report
Tools
Critical Care Pain
Observation Tool (0-8)

(CPOT)
Frequency At least every 8 hours on At least every 8 hours on At least every

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Frequency At least every 8 hours on At least every 8 hours on At least every
all patients all patients 8 hours on all
If receiving intermittent or If receiving intermittent or patients
continuous analgesia or continuous analgesia or
sedation, every 2 hours sedation, every 2 hours
Interpretation Patient is in significant Sedation/agitation depth Delirium
pain if: defined according to present if:
RASS scale CAM-modified
● NRS > 4
Usual goal RASS is 0 to is positive
● CPOT > 3 -1
Analgesia
1. Pharmacotherapy
a. Use adjunctive therapies (acetaminophen, gabapentin)
b. Goal CPOT < 3 and NRS < 4 (RASS 0 to -1 may be utilized in addition)
c. 1st line – Hydromorphone or fentanyl
i. Fentanyl is preferred for short term or in severe renal dysfunction
1. Use with caution in liver dysfunction, concern for serotonin syndrome, or obesity
(due to lipophilicity)
2. Fentanyl is in short supply - Please consider utilization of hydromorphone infusions
where clinically appropriate. Some populations who may be particularly good
candidates for hydromorphone are patients on longer term fentanyl infusions (over
2-3 days) and/or higher fentanyl infusion doses (roughly over 250 mcg/hr)
ii. Hydromorphone
1. Preferred in ARDS, longer term use, liver dysfunction, obesity, ECMO
a. Use with caution in severe renal dysfunction
d. 2nd line - Morphine
1. Use caution in renal dysfunction and hemodynamic instability
Sedation
1. Pharmacotherapy
a. Assessment and monitoring

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i. RASS goal
1. Patient not paralyzed: ideally 0 to -1, but may target -2 to -3 if needed for ventilator
synchrony
2. Patient paralyzed: BIS 40 - 60 (RASS should not be performed)
b. 1st line – Propofol or Dexmedetomidine
i. Propofol is preferred in renal and liver dysfunction, ARDS
1. Use with caution in prolonged sedation, obesity, bradycardia
2. Monitoring: Triglycerides, CK and Lipase (if triglycerides elevated > 400) every 24-
48 hours
a. If Triglycerides > 500, consider dose-reducing strategies prior to discontinuation
(unless concern for pancreatitis)
b. If Triglycerides > 1000 or signs of pancreatitis, discontinue
ii. Dexmedetomidine is preferred in need for light sedation, nearing extubation,
spontaneous mode of ventilation, and may have some analgesic effect.
1. Use with caution in bradycardia, liver dysfunction,
2. Avoid in ARDS due to lack of respiratory suppression if still targeting ventilator
synchrony
c. 2nd line – Midazolam. Preferred if propofol is contraindicated or as an adjunctive
agent in neuromuscular blockade if needed to achieve goal BIS.
i. Use with caution due to accumulation in obesity, renal dysfunction, liver dysfunction
d. Alternative agents – ketamine, phenobarbital, pentobarbital, lorazepam, diazepam,
antipsychotics
i. Minimal data exist in ICU literature
ii. May be considered on patient-specific basis
Neuromuscular blockade
1. Monitoring
a. Efficacy:
i. Ventilator synchrony
b. Safety:

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i. Train of four (TOF) – goal ≥ 2 twitches. Consider decreasing dose of neuromuscular
blockade if consistently 0-1 twitch out of four. Considerable variability exists and test
is not consistently reliable
ii. Due to severe myopathies, always try to use lowest effective dose of neuromuscular
blockers
1. Concomitant corticosteroids may increase risk of severe myopathy
c. Concurrent analgesia/sedation:
i. Neuromuscular blocking agents have no analgesic or sedative properties. Deep
sedation (RASS -4 or -5 and BIS 40-60 prior to initiation of neuromuscular blockade)
and BIS goal 40-60 at all times while on paralysis
2. Pharmacotherapy
a. 1st line – Cisatracurium. Preferred in Renal dysfunction, Liver dysfunction,
Hemodynamic instability
i. Cisatracurium is in short supply - Please consider utilization of rocuronium
intermittent boluses or continuous infusion where clinically appropriate. Some
populations who may be particularly good candidates for rocuronium are patients on
longer term cisatracurium infusions (over 2-3 days) and/or higher cisatracurium
infusion doses (roughly over 6 mcg/kg/min).
b. 2nd line – If concerns for tachyphylaxis, consider rotating to an alternative agent in this
order of preference: Vecuronium, Rocuronium, Atracurium. Please see chart below for
comparison of pharmacokinetics
Variable Cisatracurium Atracurium Vecuronium Rocuronium
Duration/Recovery 80-180 20-40 30-60 20-30
(min)
Renal excretion Hoffman Hoffman 50 20-30
(%) Elimination Elimination
Effect renal failure No change No change Increased, Minimal
especially
metabolites
Hepatic excretion Hoffman Hoffman 35-50 < 75
(%) Elimination Elimination
Effect hepatic No change No change Variable, mild Moderate

failure
Histamine release No Dose No No

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Histamine release No Dose No No
dependent
Bronchoscopy
Indications
1. Diagnostic bronchoscopy:
a. BAL for COVID testing: Reserved for situations where:
i. COVID-19 diagnosis would significantly alter management, and
ii. Less invasive specimens (e.g., nasopharyngeal swabs and tracheal aspirates) have
been non-diagnostic
b. BAL for secondary bacterial/fungal infection: Reserved similarly as above
c. Inspection for localization of hemoptysis: Reserved for situations where:
i. Radiographic imaging is unable to localize source (or unavailable), and
ii. Localization would significantly alter management
2. Therapeutic bronchoscopy:
a. Respiratory compromise due to:
i. Hemoptysis, or
ii. Intractable mucus plugging (after failing less invasive measures)
Contra-Indications
1. Unavailability of experienced operator

2. High ventilator requirements and/or hemodynamic instability (use clinical judgment)
Preparation
1. All providers:
a. Ensure access to recommended PPE for aerosol-generating procedures
b. Only essential staff should be present (conserve PPE, reduce staff risk)
2. Bronchoscopist:

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a. Obtain informed consent per current institutional policy (i.e., verbal)
b. Order labs
c. Order paralytic agent: Recommend bolus dose based off actual body weight:
cisatracurium 0.3 mg/kg, vecuronium 0.1mg/kg, rocuronium 0.6mg/kg, or atracurium
0.5mg/kg (use atracurium as last resort, and give it over 1-2min as it may cause
hypotension)
3. Nurse:
a. Print specimen labels and place them in a biohazard sample bag
b. Ensure patient is appropriately sedated + relaxed (if BIS available, target 40-60)
i. Verify lack of cough on in-line suctioning
c. A reverse Trendelenburg position (esp. if obese) may help prevent decruitment
4. Respiratory Therapist:
a. Ensure patient is getting mandatory (A/C or CMV) breaths (either VC or PC)
b. Ensure patient has a secure airway (ETT or trach) with cuff inflated
c. Ensure patient is preoxygenated with 100% FiO2 (for 10 min)
i. Team should reconsider risk/benefit if SpO2 still <95% after 10 min
ii. Verify lack of triggering on vent (i.e., adequately sedated + relaxed)
5. Gather materials:
a. 3-way bronchoscope swivel adapter
b. Suction tubing with attachment for wall suction
c. 1 slip-tip 10cc syringe with 1% or 2% lidocaine drawn up
d. 2 slip-tip 50cc or 60cc syringes with sterile saline drawn up
e. Lukens trap or similar sample trap
f. Silicone lubricant
g. A chuck for placement of soiled bronchoscope immediately post-procedure
h. Flexible bronchoscope along with the appropriate video monitor:
i. Recommend disposable bronchoscope (no risk of cross-infection)
6. Perform timeout/safety check
Procedural Steps
1. Regular bronchoscopy:

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a. The most experienced operator should do the bronch, minimizing procedure time
b. A nurse, RT, and dedicated assistant must be present throughout the procedure
2. Technique for rapid bedside BAL (ONLY if patient can tolerate transient apnea):
a. RT sets the vent in standby mode at end-exhalation (i.e., FRC)
b. Bronchoscopist inserts bronch via swivel adapter and directly navigates to the target
subsegmental bronchus, attaining a wedge position
c. Assistant injects 50-60cc of saline
d. Bronchoscopist applies suction to obtain BAL while NOT breaking wedge
e. Assistant removes trap, applies secure cap, and connects suction to bronch
f. Bronchoscopist removes bronch and wraps chuck around its distal portion
g. RT resumes ventilator breaths and team ensures appropriate ventilation and stable
vital signs before preparing to leave the bedside
h. AT ALL TIMES, nurse monitors vital signs and asks team to immediately resume
ventilation for hemodynamic instability, arrhythmia, or hypoxemia (SpO2<85%)
Post Procedure
1. Monitor for pneumothorax post-procedure (esp. in cases with high airway pressures)
2. Make sure the patient remains on a mandatory ventilation mode until paralysis wears
off
3. Place specimens in biohazard bag(s) with labels and call to notify the lab ahead of time
4. If a disposable bronchoscope was used, dispose it off in a biohazard bin
5. Follow standard High-level Disinfection protocol for re-usable bronchoscopes
6. Follow standard disinfection protocol for video monitors and bronchoscopy towers
7. Follow PPE doffing protocol
8. Write procedure note in Epic
9. Routine CXR not needed but may be obtained if desired (use clinical judgment)
Ventilator Adjustments and Daily Management
General management of ventilated patients
1. Consider whether patient requires daily CXR:

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a. CXR clearly indicated for:
i. Clinical change
ii. Concern for displaced ET tube:
1. Sudden increase in peak inspiratory pressure or resistance
2. Decreased, unilateral breath sounds (usually on the right)
3. RN or RT concern for change in depth of ET tube at teeth
2. COVID-19 ICU Bundle:
a. Ventilated patients should all have a daily ICU “Bundle” of best practices. See here for
our COVID-19 ICU Bundle.
3. Ventilator consults:
a. If you need additional assistance managing ventilator choices, you can request a
pulmonary phone/in-person consult (p11957)
Changing ventilation parameters (respiratory rate and tidal volume)
1. Follow ARDSnet ventilation where possible:

a. Starting tidal volume of 6 cc/kg (Tidal volumes should be 4-6 cc/kg using IBW (see
table above) to excessive pressures and ventilator injury).
2. Minute ventilation (respiratory rate x tidal volume) typically drives pH and PCO2:
a. Titrate ventilatory parameters to pH and not PCO2.
i. To achieve low tidal volumes will tolerate hypercapnia (functionally no limitation
unless clinical sequelae) and acidemia (pH > 7.2).
ii. Because tidal volumes are low, the respiratory rate often has to be high to
accommodate; typical RR is 20-35 breaths/minute.
3. pH goal is normally 7.25-7.45:
i. If pH > 7.45, decrease respiratory rate
ii. If pH 7.15-7.30, then increase respiratory rate until pH > 7.30, or PaCO2 < 25
(maximum RR= 35 breaths/minute)
iii. If pH < 7.15, then increase respiratory rate to 35 breaths/minute
iv. If pH still < 7.15, then perform the following:

1. Tidal volume may be increased by 1 mL/kg until pH > 7.15 (until plateau pressure
reaches 30 cm H2O or tidal volume reaches 8 cc/kg)

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reaches 30 cm H2O or tidal volume reaches 8 cc/kg)
2. Deep sedation advancing to RASS -5 if needed
3. If no improvement, initiate continuous paralysis
4. If still no improvement, initiate prone ventilation (may improve V/Q matching and
better ventilation)
Changing oxygenation parameters
1. Minimize oxygen toxicity: PEEP and Fi02 drive oxygenation

i. The goal is to deliver a partial pressure of oxygen to perfuse tissues (PaO2 > 75,
Sp02 >92%) i while limiting lung injury from high distending pressures (Ppl ≤ 30)
and hyperoxia (FiO2 < 60%, SpO2 < 96%). i
1. Lower limit goals for PaO2 / SpO2 are widely debated; PaO2 > 55 and SpO2 >88%
are also commonly used at BWH.
2. PEEP Optimization:
i. COVID-specific data:
1. Preliminary anecdotal reports suggest a common phenotype of high compliance
with PEEP-sensitive hypoxia. The pathophysiology of this phenotype has yet to be
determined but it may reduce the efficacy of the ARDSNET PEEP tables to guide
FiO2 and PEEP management.
ii. PEEP should be set and titrated as explained above using the ARDSNET PEEP
tables to guide FiO2 and PEEP determination
iii. Optimal PEEP methods: significant efforts to determine a physiologically optimal
PEEP are described in the literature but no specific method has demonstrated
improved outcomes in large studies. In the setting of persistent hypoxemia or
deviation from the ARDSNET PEEP tables, there are several methods employed at
BWH for determining optimal PEEP.
1. Best PEEP: BWH employs a “Best PEEP” protocol to optimize PEEP in selected
patients in which the RT iterates changes in PEEP and compliance measurements
to determine the physiologically optimal PEEP. However, to minimize demands on
RT time, we will avoid routine use of “Best PEEP” protocol for COVID-19 ICUs.
2. PV Tool: For patients on the Hamilton G5 ventilator, the Pressure-Volume (PV) tool
may be used to determine the optimal PEEP as described below:

a. Set the Pstart = 0 and Pmax = 40 and Pstop = prior PEEP

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b. Set the time step at 2 seconds with time hold at 0 seconds
c. On completion of the maneuver, a PV loop is displayed demonstrating the
inspiratory and expiratory limbs of the hysteretic loop
i. The optimal PEEP is selected as slightly greater (1 to 2 cm H2O) above the
lower inflection point (considered to reflect alveolar collapse and risk of
“atelectrauma”)
d. Note: test is optimally performed when patients are not making voluntary
respiratory effort (eg deeply sedated or paralyzed).
3. Esophageal balloon: Use of esophageal balloons to measure transpulmonary
pressure will not be routinely performed on COVID patients due to risk to staff.
iv. In other contexts, some patients in severe, fibrotic stage ARDS require very low
PEEP (even <5 occasionally). Anecdotally, this very low compliance phenotype may
be less common in COVID-19, but should not be missed (e.g., by tracking
respiratory mechanics).
3. Adjust FiO2:
i. If using the ARSNET PEEP tables, titrate the FiO2 and PEEP to achieve the target
SpO2 > 92%
ii. If using Optimal PEEP methods above then adjust Fi02 after determining an optimal
PEEP
iii. Goal FiO2 ≤ 60%; if FiO2 >60%; patient requires ventilator optimization. If you need
assistance, pulmonary consultation is available (pager 11957)
1. It is reasonable to put a desaturating patient temporarily on 100% FiO2, but
remember to wean oxygen as rapidly as possible
2. Some at BWH advocate that FiO2 < 75% is a crucial limit, based on animal studies
of hyperoxia.
4. Check plateau pressure:
i. Check plateau pressure with every change in tidal volume, PEEP, or clinical
deterioration (worsening oxygenation) but not as part of routine practice
ii. If plateau pressure is >30 cm H20, then decrease tidal volume by 1 mL/kg (minimum
4 mL/kg)
iii. If plateau pressure is < 25 H20 and tidal volume < 6 mL/kg, then increase tidal
volume by 1 mL/kg until plateau pressure is > 25 cm H2O or tidal volume = 6 mL/kg
iv. If plateau pressure is < 30 cm H20 and patient is breath stacking or
dyssynchronous, then increase tidal volume in mL/kg increments to 7 mL/kg or 8
mL/kg while plateau pressure is < 30 cm H20

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mL/kg while plateau pressure is < 30 cm H20
Airway pressure release ventilation (APRV) and alternative modes of mechanical

ventilatory support
1. There exists significant practice variation around the use of bilevel ventilatory modes
which includes indications for use and role of deep sedation and paralysis and is highly
dependent on expertise and usage at specific centers
2. BWH current practice is to trial use of APRV or bilevel ventilation either as salvage
therapy in patients with persistent hypoxemia not responsive to advanced conventional
therapy who are also not ECMO candidates or in patients with persistent ventilator
dyssynchrony that is impairing weaning and lightening of sedation.
3. There may be a role for bilevel-type ventilatory support for patients with COVID who
require high PEEP pressures but at present, our preference is to use bulk flow
ventilation methods based on local experience and lack of definitive evidence of
superiority of bilevel methods for general use
Refractory Hypoxemia
1. Refractory Hypoxemia pathway:
a. If patient is hypoxic (PaO2 <75) despite PEEP optimization as above); and FiO2 >=
0.6 or PaO2 / FiO2 ratio < 150 then perform the following in this order:
i. Optimize volume status by diuresing or RRT if possible; if no improvement then:
ii. Deep sedation, advancing to RASS -5 if needed; if no improvement then:
iii. Initiate continuous paralysis (cisatracurium bolus 0.2mg/kg followed by infusion at 0-
5 mcg/kg/min titrated to patient-ventilator synchrony); if no improvement then:
iv. Initiate prone ventilation early: Discuss proning when PaO2/FiO2 < 150.
(We prone earlier than typical in non-COVID-19 ARDS)
a. Prone within 12 hours of FiO2 > 75%.

b. Strongly consider early in severe ARDS (<36 hrs from ARDS onset) if no
improvement then:
v. Initiate continuous inhaled epoprostenol (veletri) or inhaled nitric oxide (see
“pulmonary vasodilators” below) if no improvement then:
vi. Consider ECMO consultation (see below) if, despite the above steps:

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1. Persistent PaO2 < 75 requiring FiO2 > 0.75
2. Plateau pressure >30
3. Refractory hypercapnia and pH < 7.2
4. Absence of contra-indications (see ECMO section)
Prone Ventilation
1. Prone early:
a. We recommend early proning in severe ARDS prior to vasodilator trial (a departure
from our typical practice for ARDS not due to COVID-19): < 36 hours from ARDS
onset, start discussion of prone when P:F < 150, prone within 12 hours of FiO2 > 75%
(Guérin et al, N Engl J Med, 2013).
2. Eligibility criteria for proning:
a. The only absolute contraindications are spinal cord injury, open chest or abdomen,
and unstable airway; BMI and patient size are not absolute contra-indications
b. For tracheostomy, patients should typically have their tracheostomy replaced by oral
endotracheal intubation (ETT). In the setting of COVID-19, this intubation procedure is
higher risk and the ICU team and anesthesiology should carefully discuss the risks of
replacing tracheostomy with ETT.
c. RRT can be performed while proned (e.g, by femoral vein catheter) but should be
discussed with renal consultation prior to proning
d. If the RN staff in the SP-ICU is unfamiliar with proning, the SP-ICU charge nurse
should consult with the MICU charge nurse.
3. Managing a proned patient:
a. If you are needing assistance, page the Prone Team (pager #34433, available 24/7).
This team consists of 3+ physical therapists who can help physically prone patients
and provide expertise in positioning and wound prevention.
b. Please see BWH MD MICU proning protocol
i. Detailed instructions can be found in the BWH Nursng MICU proning protocol
(Partners log-in required)
ii. This NEJM video provides brief instruction
c. Prone >16 hrs per 24 hrs. Supine >4 hrs per 24 hrs.
d. 1 hour post-initiation of prone ventilation:
i. Adjust oxygen parameters: re-assess lung mechanics (plateau pressure and re-

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optimize PEEP, see above)
ii. Assess tidal volume and adjust ventilation parameters as in section 6
1. Preferred tidal volume is 6 ml/kg (range 4-8)
2. Goal plateau pressure < 30
e. If patient demonstrates improvement on proning then recommend:
i. Discontinue neuromuscular blockade while maintaining deep sedation to limit risk of
extubation. Resume neuromuscular blockade in setting of patient:ventilator
dyssynchrony.
ii. Consider discontinuing further proning if patient meets these goals after supine for
>4 hrs:
1. PaO2 / FiO2 ratio > 200
2. Ppl < 30
3. pH > 7.25
4. FiO2 < 60%
iii. If patients do not meet criteria for supine ventilation then recommend ongoing prone
ventilation. There is no time limit for maintaining prone ventilation and it should be
continued while beneficial.
Pulmonary Vasodilators
1. There is no evidence of survival benefit of inhaled vasodilators in ARDS, and it can

demand significant respiratory therapist resources (Fuller et al, Chest, 2015; Gebistorf
et al, Cochrane Database Syst Rev, 2016; Afshari et al, Cochrane Database Syst Rev,
2017).
2. Limited in vitro data notes that iNO at high doses inhibits replication of SARS-CoV, but
this has not been studied in vivo (Akerstrom et al, J Virol, 2005; Gebistorf et al,
Cochrane Database Syst Rev, 2016).
3. Instructions for use:
1. Inhaled epoprostenol
a. Exclude contraindications: Alveolar hemorrhage (epo has mild antiplatelet effect), LV
systolic or diastolic CHF (vasodilators cause pulm blood flow LV filling
pressure pulmonary edema & PaO2 consider CHF if pt gets worse after
starting).
b. Measure baseline ABG for PaO2
c. Start continuous nebulization at 0.05 mcg/kg/min based on IBW (MDcalc online

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c. Start continuous nebulization at 0.05 mcg/kg/min based on IBW (MDcalc online
calculator).
d. Do not change ventilator settings, sedation, paralysis, patient position or other care
that could affect oxygenation.
e. Re-check ABG 2 hrs after initiation of inhaled epoprostenol.
f. If PaO2 increased by >10% from baseline, continue inhaled epoprostenol.
g. If less than 10% improvement, consider inhaled nitric oxide (iNO); it is not required to
attempt iNO.
h. Avoid abrupt discontinuation if using for RV failure
2. Inhaled nitric oxide (iNO) (at BWH, iNO is supplied by Respiratory Dept via INO Vent
Device):
a. Exclude contraindications: LV systolic or diastolic CHF (see epoprostenol above).
b. Measure baseline ABG for PaO2
c. Initiate iNO at 20ppm.
d. Do not change ventilator settings, sedation, paralysis, patient position or other care
that could affect oxygenation.
e. Re-check ABG 2 hrs after initiation of iNO.
f. If PaO2 increased by >10% from baseline, continue iNO.
g. If PaO2 not increased by >10%, increase iNO to 80ppm.
h. Re-check ABG 2 hrs later; if PaO2 increased >10% from baseline, continue iNO at
80ppm. If PaO2 increased less than 10% from baseline, wean iNO to off.
i. NO can cause methemoglobinemia ( risk if on nitroglycerin or nitroprusside).
Monitor methemoglobin on ABG Q6 hr for the first 24 hr, Q12 hr for the second 24 hr,
daily thereafter, or PRN if new clinical deterioration or SpO2-PaO2 dissociation.
3. Weaning protocol for inhaled epoprostenol and iNO:
a. Attempt to wean off after 24-48 hrs and daily afterwards.
b. Wean inhaled epoprostenol by decreasing 0.01mcg/kg/min every hour. Wean inhaled
nitric oxide to off by 20ppm per 30 mins or more slowly at 20ppm per 2 hrs if
concerned for right heart failure or pulmonary hypertension. Monitor SpO2 and
hemodynamics.
c. Re-check ABG 2 hrs after weaned off. If PaO2 worsened by >10%, restarted inhaled
epoprostenol or inhaled nitric oxide.
ECMO consultation
1. BWH ECMO guidelines

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a. BWH ECMO consult pager is 35010.
b. BWH ECMO guidelines are linked here (BWH log-in required).
c. BWH participates in the New England ECMO consortium to discuss regionally ECMO
availability and policies during COVID-19.
d. The information below conveys general principles used by many medical centers and
is NOT meant to reflect current BWH specific policies (linked above).
i. Indications:
1. Persistent PaO2 / FiO2 ratio < 75 mmHg despite optimized ARDS management
(optimized PEEP, neuromuscular blockade, proning, inhaled vasodilator).
2. Plateau pressure > 30 cm H2O on ARDSnet ventilation.
3. pH < 7.2
4. No potentially reversible causes (e.g., pulmonary edema, mucus plug, abdominal
compartment syndrome)
2. Contra-indications: Each patient is assessed on a case-by-case basis.
Absolute or relative contra-indications can include:
e. Advanced age
f. Active malignancy
g. Severe shock; high cardiac output state
h. Multi-system organ failure
i. Prolonged ventilation or ARDS with poor chance of pulmonary recovery or severe
chronic lung disease.
j. Severe neurologic injury or intracranial hemorrhage
k. Overall poor life expectancy (e.g., < 6 months); poor functional status at baseline;
poor potential to recover functional status.
l. Active hemorrhage or inability to anticoagulate
m. Thrombocytopenia (plt < 50)
n. Neutropenia (ANC < 500)
o. BMI > 40 / total body weight > 180 kg
Ventilator Weaning and Extubation

1. Clinical goal is to liberate patients from mechanical ventilation as soon as safe and

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1. Clinical goal is to liberate patients from mechanical ventilation as soon as safe and
feasible.
a. Prolonged intubation is associated with ventilator-associated pneumonia (VAP) with
median-time to VAP onset of 8 days in retrospective study of 191 COVID patients in
Wuhan (Zhou et al, Lancet, 2020).
2. All patients with improving or stable respiratory disease should be considered for
weaning from sedation and mechanical ventilation when they meet the following
criteria:
a. Improving or stable respiratory disease
b. FiO2 ≤ 50%, PEEP ≤ 10 with SpO2 >92%
c. Hemodynamically stable (minimal to no vasopressor requirements to maintain target
MAPs)
3. Assess patient readiness for weaning at least once daily
a. A daily spontaneous awakening trial (SAT), consisting of temporary cessation of
sedatives until a RASS of 0 is achieved, is be considered for all patients who meet the
following criteria:
i. Patients are in supine position
ii. Continuous paralytics discontinued for a minimum of 6 hours prior to SAT and has
evidence of spontaneous motor activity and/or train of fours is 4/4 for
neurostimulator test
iii. Hemodynamically stable (defined as HR < 120, MAP > 65, and vasopressor
requirement of levophed gtt < 10 mcg/min)
iv. SpO2 > 92% or PaO2 > 75 with an FiO2 ≤ 50% and PEEP ≤ 10 (and most recent
Ppl < 30)
b. A daily spontaneous breathing trial (SBT) is considered for all patients who meet the
requirements for a daily SAT
i. SBT consists of Pressure Support ventilation mode with a PS = 5 and PEEP = 5
ii. SBT discontinued if the patient develops
1. Evidence of increased work of breathing with RR > 30
2. Hypoxia (SpO2 < 92%)
3. Hemodynamic instability
4. Rapid shallow breathing index (RSBI) = RR/TV > 105

iii. Terminate all SBTs after 30 minutes and return to prior VC settings if patients are
deemed not ready to extubate

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deemed not ready to extubate
4. Extubation readiness:
a. Extubation should be considered if patients meet the following criteria
i. Breathing spontaneously
ii. RASS 0 to -1
iii. Able to follow commands
iv. Intact cough and able to protect airway
v. Requiring airway suctioning for secretion < q2h
b. Other considerations include:
i. FiO2 < 40% at the time of extubation
ii. Optimization of volume status prior to extubation
5. Weaning can fail in the setting of the following conditions (address appropriately) from
Boles et al, ERJ, 2007:
a. Respiratory factors:
i. Ongoing pneumonia or pulmonary inflammation
ii. Bronchoconstriction
iii. Glottic and airway edema, sputum production, impaired cough
b. Cardiac factors:
i. Cardiac dysfunction or shock
c. Neuromuscular factors
i. Weakness and prolonged immobility
ii. Effects of steroids or neuromuscular blockade
d. Neuropsychological factors
i. Delirium
ii. Sedating medications
e. Metabolic factors
i. Malnutrition
ii. Electrolyte disturbances (hypophosphatemia, etc)
6. Place NG tube prior to extubation for patients intubated for >48h
a. Patients should have an NG tube placed prior to extubation given the frequency of
swallowing issues post-extubation in these patients and delayed clearance for

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swallowing issues post-extubation in these patients and delayed clearance for
swallowing due to challenges obtaining video swallow / FEES (fiber-optic) in COVID
patients
i. NGT placement after extubation is also challenging and high-risk for clinicians on
floor services
ii. Exceptions (e.g. in young patients who are A/Ox3) must be discussed by attending
b. Prior to extubation, remove OGT replace with an NGT
i. Regular NG tubes have the advantage of being able to be put to suction and be
used for bolused feeds. However, if the team anticipates long-term enteral access,
consider small bore feeding tube (more challenging to place given need for two-step
chest xray or bronchoscopy to confirm placement)
c. Place SLP consult at time of extubation
7. Extubation process
a. See the ICU extubation guide under “Extubation” (in the Intubation and Anesthesia
chapter)
Bedside ICU Procedures

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1. Procedures should not be performed by the primary team unless necessary: Please
follow the flow chart above to find the relevant dedicated COVID procedure team.
a. The COVID procedure team has in-house staff 24/7 (largely anesthesia, some
surgical)
b. In the event that the primary team does need to do an procedure, please see these
procedure protocols, page 20 for PPE and instructions
2. Exception to flowchart:
a. Please notify anesthesia team at the time of intubation if you anticipate needing
arterial or central access, as they may be able to obtain while in intubation PPE
3. While placement of a nasogastric or orogastric tube is not sterile procedure, it involves
manipulation of the upper respiratory tract and requires the same PPE as for
aerosolizing procedures (An N95 mask + face shield (or PAPR), bouffant hat, gown,
and gloves)
Nutrition in ICU Patients

1. Consult nutrition services if not already done. While awaiting nutrition input, start
enteral nutrition:
2. In most patients:
a. Osmolite 1.5 @10mL/hr., advance by 20mL Q6h to goal 50mL/hr.

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3. If renal failure and high K or phosphorus:
a. Nepro @ 10mL/hr, advance by 10mL Q6h to goal 40mL/hr.
4. If on pressor support:
a. Hold tube feeds for elevated pressors requirements d/t risk of intestinal ischemia
including:
i. Hold tube feeds if on two escalating pressors
ii. Epinephrine > 5 mcg/min
iii. Norepinephrine > 10 mcg/min
iv. Phenylephrine >60 mcg/min
v. Vasopressin >0.04 units/min
b. If unable to tolerate enteral nutrition support given escalating or multiple vasopressors
TPN should be considered.
5. If paralyzed:
a. It is safe to feed while patients are on paralytic agents such as cisatracurium
6. If prone:
a. Patients requiring proning may continue to receive tube feeding.
b. The tube feeds should be held for one hour prior to turning the patient.
c. Prokinetic agents may be beneficial during proning to enhance gastric emptying and
decrease risk of vomiting as per ICU nursing procedure ICU-31.
7. Other:
a. Famotidine 20mg IV BID in intubated patients; Pantoprazole 20-40mg IV daily if
history of GERD or GI bleed
b. MVI with minerals daily
c. Thiamine 100mg daily and Folate 1mg daily x3 days
d. Goal glucose range is 70-180.
ICU Management of Hyperglycemia and Diabetic

Ketoacidosis
1. Hyperglycemia, DKA with concomitant increased insulin requirements are common in
critically ill patients with COVID-19.
2. In an effort to minimize the number of patients on insulin infusions, the Diabetes

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2. In an effort to minimize the number of patients on insulin infusions, the Diabetes
Subcommittee has developed a guideline for COVID-19 patients who are critically ill
and/or in mild-moderate DKA to allow for q 4h monitoring and SC insulin dosing.
a. This strategy will minimize exposure with RN time at bedside and conserve PPE while
maintaining the ability to deliver high dose insulin therapy distributed across multiple
adjustable doses per day.
b. The major difference to highlight is the change to a q 4h interval (as compared to the
q 1h monitoring and insulin dosing with BHIP and q 2h with the SC DKA protocol).
This guideline also expands the use of a SC DKA protocol to include both mild and
moderate DKA and with this in place only severe DKA/HHS will require an insulin
infusion.
3. Guidelines on COVID-specific treatment are available here
4. Additional glucose management assistance is available by paging Endocrine (p11519)
or Diabetes (p34444) Consultation. They can assist with:
a. Adjustment of Insulin Orders and Hypoglycemia Prevention
b. Insulin Management during Transition of Care Planning
CHAPTER 4
Therapeutics and Clinical Trials
Section Editor: Katherine H. Walker MD MSc, Jeffrey C. Pearson PharmD BCIDP
Contributors: Rebecca M. Baron MD, Lindsey Baden MD MMSc, Francisco M. Marty MD

SM, Sigal Yawetz MD, David A. Morrow MD MPH, Jean Connors MD, Sophia Koo MD,
Erin A. Bohula MD DPhil, Richard M. Kaufman MD, Ann E. Woolley MD MPH, Joshua P.
Lang MD, Kevin M. Dube PharmD BCCCP BCPS, William Sauer MD, Alisa A. Mueller MD
PhD, Erin H. Penn MD MSc, Matthew Moll MD, C. Lee Cohen MD MBA, Mathias
Lichterfeld MD PhD, Sheila Bond MD

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Overview
Therapeutics summary
1. The anti-viral and anti-inflammatory section is meant to provide a summary of the

literature. The BWH Infectious Diseases COVID-19 treatment guidelines (Partners login
required) and ID consultation service take precedence over the information provided in
the literature review below. This table is from those treatment guidelines, which mirror
our recommendations laid out in this chapter, but in a more concise format and with
BWH-specific contacts.
Infectious Diseases Consultation
1. The infectious diseases consult teams should be consulted on all inpatients who are
being considered for COVID-19 treatment

2. Separate from the infectious diseases consult teams, the biothreats team can be paged
at any hour for the following situations:

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at any hour for the following situations:
a. Inpatients who may require COVID-19 testing
b. Inpatients who test positive for COVID-19
c. Care questions regarding inpatients who are undergoing COVID-19 testing
d. Urgent need to modify precautions/infection status/risk flag for inpatients with CoV-
risk
e. Inpatients who require urgent procedures for which pre-procedure COVID-19 testing
is indicated
f. Any other questions related to clinical operations affected by COVID-19 that cannot
be answered on the Partners Pulse Coronavirus Update page
g. More information on the biothreats team can be found here
Clinical Trials
1. ID teams are enrolling for ongoing clinical trials of antiviral agents. ID and the PETAL
network are coordinating to enroll for clinical trials of host-response modifying
therapies, such as hydroxychloroquine (see also “Systemic Corticosteroids” and “Anti-
IL6 agents” sections of this chapter).
2. For clinical trial enrollment, the contact person for the trial can be paged or emailed to
discuss further. Preferred methods of contact for each trial can be found here (Partners
login required)
3. Enrollment criteria for each trial can found here (Partners login required)
4. If a patient is enrolled in a COVID-19 clinical trial, verify that other therapeutic regimens
do not add harmful drug interactions with study agents
Antibiotics
Choice of agent
1. Clinical reports indicate that rates of bacterial superinfection with COVID-19 are low,
but when present increase mortality risk. Anecdotal reports suggest less MRSA
superinfection than is often seen with influenza. Unnecessary antibiotics carry risks of
fluid overload and drug-resistance, as well as the possibility that antibiotics may
become a limited resource. (Zhou et al, Lancet, 2020; Yang et al, Lancet Respir Med,
2020; Lippi and Plebani, Clin Chim Acta, 2020; WHO, COVID-19 Interim guidance,
March 2020).

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March 2020).
2. Antibiotics should reflect IDSA guidelines, presumed source, and MDRO risk.
a. For empiric coverage for a presumed pulmonary source of infection:
i. In patients without risk factors for MRSA or Pseudomonas (i.e., living in community,
no prior MDROs), start with ceftriaxone + azithromycin.
ii. In patients with risk factors for MRSA or Pseudomonas (i.e., chronic hospitalization,
prior MDR infections), start with vancomycin + cefepime and consider ciprofloxacin if
high concern for Pseudomonas.
3. For coverage of potential coinfections:
a. If concurrent influenza, treat with oseltamivir.
b. Given prevalence of lymphopenia in clinical presentation of COVID-19, consider
Pneumocystis and treat accordingly.
4. See special dispensations for oncology patients in “Oncology”
Formulation
1. Give oral antibiotics (azithromycin, levofloxacin, ciprofloxacin, etc.) when possible to

reduce volume load, unless concerns for poor oral absorption.
Discontinuation
1. Unnecessary antibiotics should be discontinued as soon as possible (ideally, within 48

hours). Clinical judgement should prevail over any specific lab value, but we suggest
discontinuing when the following criteria are met:
a. Clinical status is not deteriorating
b. Cultures do not reveal pathogens at 48 hours and/or procalcitonin and WBC are
relatively stable from 0 to 48 hours
Nebulizers
1. Nebulization is considered an aerosol generating procedure and may contribute to
disease transmission.
a. Nebulization requires appropriate PPE (e.g., N95) and room (e.g., negative airflow)
b. Laboratory studies on human patient simulators showed increased dispersion of

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particles during jet nebulizations at 6L/min from 0.45 to >0.8m when simulating
normal lung or severe lung injury, respectively. In comparison, there was 0.4m
dispersion with 5L/min nasal cannula and 0.3m with Venturi mask (40%) Hui et al.
Hong Kong Medical Journal. 2020). However, a meta-analysis of aerosol-generating
procedures did not find nebulizer as a risk factor for SARS transmission, unlike
procedures like tracheal intubation (Tran et al. PLOS One. 2020).
Bronchodilator Therapy
1. COVID-19 clinical reports do not indicate wheeze as a common symptom, and not all
patients require bronchodilators. Bronchodilators should certainly be prescribed
whenever indicated but should not be ordered as a default on every patient (Zhou et al,
Lancet, 2020; Yang et al, Lancet Respir Med, 2020; Guan et al, N Engl J Med, 2020;
WHO, COVID-19 Interim guidance, March 2020).
Non-intubated patients
1. If the patient is COVID-19 confirmed or PUI:

a. If possible, use metered dose inhalers (MDIs) + spacer rather than nebulizers.
Nebulizers are an aerosol generating procedure.
b. Because MDI supply is limited, only prescribe when needed. Ask patients / families to
bring in their home inhalers if possible and check in home MDI with pharmacy.
c. However, if the patient requires a nebulizer (e.g., difficulty using MDI),
nebulizers should be used in COVID-19 confirmed or PUI patients.
i. For Covid-19 confirmed or PUI patients, consider a breath actuated nebulizer (BAN),
which may help reduce aerosol generation.
ii. Order breath actuated nebulizer (BAN) as free text in the nebulizer order.
iii. Note: The patient needs to generate flow to trigger the neb; so patients with upper
airway edema/stridor, weakness or inability to cooperate may be poor candidates for
a breath actuated nebulizer (BAN).
iv. If a COVID-19 confirmed or PUI patient requires nebulizers and cannot use BAN,
then a regular nebulizer should be ordered.
2. If the COVID-19 PUI patient is ruled out and considered COVID-19 negative:
a. The patient should use their previously prescribed MDI until it runs out, then switch to
nebulizers.
3. In patients admitted WITHOUT suspicion for COVID-19:

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3. In patients admitted WITHOUT suspicion for COVID-19:
a. Use nebulizers even if on droplet precautions (e.g., influenza) because MDI supply is
limited.
Intubated patients
1. For intubated COVID-19 confirmed or PUI, it is approved to use nebulizers.

a. The in-line nebulizer container is part of a closed ventilator circuit.
Airway Clearance
Secretion thinning
1. Patients can develop thick secretions from Covid-19 itself or secondary bacterial
pneumonia.
2. Nebulized treatments can help with airway secretions
a. Options include:
i. Normal (0.9%) saline nebulizer BID.
ii. N-acetylcysteine (“Mucomyst”) nebulizer BID or TID
1. N-acetylcysteine can cause bronchoconstriction
iii. Nebulized hypertonic (3-7%) saline once daily
1. Hypertonic saline can cause bronchoconstriction. .
2. If using, start with 3% saline to assess response and bronchoconstriction.
3. Pre-treat with albuterol 2.5mg just prior to delivery.
iv. Dornase alfa 2.5mg nebulizer once daily
1. Dornase can cause bronchoconstriction and mucosal bleeding Pre-treat with
albuterol 2.5mg, just prior to delivery
2. Avoid in setting of bloody secretions.
3. Note: Dornase nebulizer can clog the HEPA filter and require intermittent
replacement by RT
4. It would be reasonable to consider other agents, including N-acetylcysteine, first

given the need to change HEPA filters. In addition, a RCT for dornase nebulizer
versus saline will begin shortly at BWH. However, if persistent secretions, it is

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versus saline will begin shortly at BWH. However, if persistent secretions, it is
reasonable to try dornase nebulizer.
v. Although avoided if possible since it is an aerosol generating procedure,
bronchoscopy for pulmonary toilet can be performed if needed on Covid-19
confirmed or PUI patients.
Mechanical airway clearance
1. Avoid oscillating positive expiratory pressure devices (Aerobika or Acapella) and cough
assist (MIE) devices, due to aerosolization risk and unclear benefit in COVID-19
2. Chest PT can be performed if needed
3. Chest PT vests if the patient requires at home (e.g., CF patients) should be continued
with appropriate isolation precautions
Systemic Corticosteroids
Evidence
1. Data on corticosteroids for COVID-19 is mixed.

a. Many studies show negative effects of corticosteroids on similar viruses. There is no
clinical evidence of net benefit from steroids in SARS-CoV, MERS-CoV or influenza
infection, and observational data show increased mortality, more secondary
infections, impaired viral clearance and more adverse effects in survivors (e.g.,
psychosis, diabetes, avascular necrosis) (Lee et al, J Clin Virol, 2004; Stockman et al,
PLoS Med, 2006; Arabi et al, Am J Respir Crit Care Med, 2018; WHO, COVID-19
Interim guidance, March 2020; Wu et al, JAMA Int Med, 2020).
b. However, a retrospective cohort analysis of patients with COVID-19 who developed
ARDS (n=84) noted that methylprednisolone treatment was associated with a
decreased risk of death (Wu et al, JAMA Int Med, 2020).
c. An earlier, non-blinded randomized controlled trial of patients with ARDS (not COVID-
19) suggested a benefit to dexamethasone treatment (Villar et a, Lancet Resp Med,
2020) but this has not been replicated as of yet.
Recommendations
1. At this time, we do not recommend steroids for COVID-19 except as part of a

clinical trial or if treating another indication such as asthma or COPD

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clinical trial or if treating another indication such as asthma or COPD
exacerbation. This is in line with WHO guidance (WHO, COVID-19 Interim guidance,
March 2020).
2. If treating another indication, use corticosteroids at a low dose for a short duration:
a. For asthma or COPD exacerbation, treat with 40mg prednisone PO or 30mg
methylprednisolone IV, once daily x 3-5 days.
b. For any shock with a history of chronic steroid use in excess of 10mg
prednisone daily, treat with 50mg hydrocortisone IV Q6H until improvement in
shock.
c. For multipressor (>2 pressors) shock without history of chronic steroid use,
treat with 50mg hydrocortisone IV Q6H until improvement in shock.
Pulmonary Vasodilators
1. Please see the pulmonary chapter under “refractory hypoxemia”.
Remdesivir
1. If treatment of COVID-19 is being considered, remdesivir trial enrollment should be
discussed with the infectious diseases study team for key inclusion and exclusion
criteria in the use for moderate or severe COVID-19 disease (NCT04292730 and
NCT04292899, respectively)
2. Outside of the currently enrolling clinical trials, remdesivir can only be used for
pregnant patients at BWH through Gilead’s compassionate use protocol
Pathophysiology
1. Remdesivir is a nucleotide prodrug metabolized to an analog of adenosine

triphosphate, which inhibits viral RNA-dependent RNA polymerase, causing premature
termination of RNA transcription.
Evidence
1. Animal models have shown reduced lung viral loads when remdesivir is used for both
SARS-CoV-1 and MERS-CoV (Sheahan et al, Sci Transl Med, 2017; Sheahan et al,

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SARS-CoV-1 and MERS-CoV (Sheahan et al, Sci Transl Med, 2017; Sheahan et al,
Nat Commun, 2020; de Wit et al, Proc Nat Acad Sci, 2020)
2. For the treatment of Ebola, remdesivir did not show favorable outcomes compared to
other investigational agents (MAb114 and REGN-EB3) in a randomized controlled trial
(Mulangu et al, N Engl J Med, 2020)
3. Remdesivir has shown in vitro activity against SARS-CoV-2 (Wang et al, Cell Res,
2020)
4. A case report has been published on the use of remdesivir in a 35-year-old male who
improved one day after remdesivir was initiated, but it is unclear if the use of remdesivir
resulted in this improvement (Holshue et al, N Engl J Med, 2020)
5. A case series of compassionate use remdesivir was able to analyze 53 patients, of
whom 68% had an improvement in their oxygen-support class, 47% were discharged,
and 13% passed away (Grein et al, N Engl J Med, 2020)
a. Without a control group, it is unclear if the use of remdesivir altered the natural
progression of COVID-19 disease in these patients
Recommendations
1. If eligible, patients should be enrolled in the remdesivir clinical trials for COVID-19
moderate or severe disease
2. Gilead’s compassionate use protocol can be used for pregnant patients with severe
COVID-19
3. Outside of BWH, institutions may be able to obtain remdesivir through Gilead’s
expanded access treatment protocol (NCT04323761)
Dosing
1. Remdesivir is only available as an investigational agent through clinical trials or

compassionate use
2. 200 mg IV loading dose, followed by 100 mg IV daily for a total of 5 or 10 days,
depending on the clinical trial arm
Monitoring and Toxicity
1. Elevated liver function tests (AST, ALT), phlebitis, constipation, headache, nausea
2. Remdesivir is co-formulated with sulfobutyl ether β-cyclodextrin (SBECD), so there is a
theoretical risk of accumulation in renal failure promoting further renal injury, similar to

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theoretical risk of accumulation in renal failure promoting further renal injury, similar to
intravenous voriconazole
Hydroxychloroquine and Chloroquine

Pathophysiology
1. Hydroxychloroquine (HCQ) is an anti-malarial 4-aminoquinoline shown to have in vitro

(but not yet in vivo) activity against diverse RNA viruses, including SARS-CoV-1 (Touret
and de Lamballerie, Antivir Res, 2020).
2. HCQ is thought to act against viruses through multiple mechanisms (Devaux et al, Int J
Antimicrob Agent, 2020):
a. Inhibition of viral entry. HCQ inhibits synthesis of sialic acids and interferes with
protein glycosylation, which may disrupt interactions necessary for viral attachment
and entry (Vincent et al, Virol J, 2005; Olofsson et al, Lancet Infect Dis, 2005).
b. Inhibition of viral release into the host cell. HCQ blocks endosomal acidification,
which activates endosomal proteases. These proteases are required to initiate
coronavirus/endosome fusion that releases viral particles into the cell (Yang et al, J
Virol, 2004).
c. Reduction of viral infectivity. HCQ has been shown to inhibit protein glycosylation
and proteolytic maturation of viral proteins. Studies on other RNA viruses have shown
a resulting accumulation of non-infective viral particles, or an inability of viral particles
to bud out of the host cell (Savarino et al, J Acquir Immune Defic Syndr, 2004;
Klumperman et al, J Virol, 1994).
d. Immune modulation. HCQ reduces toll-like receptors and cGAS-STING signaling. It
has been shown to reduce release of a number of pro-inflammatory cytokines from
several immune cell types (Schrezenmeier and Dorner, Nat Rev Rheum, 2020).
Evidence
1. An expert consensus group out of China suggests that chloroquine improved lung
imaging and shortened disease course (Zhonghua et al, CMAPH, 2020). Chloroquine
is included in the treatment guidelines from the National Health Commission of the
People's Republic of China, but the specific data on which this is based is not yet
available (Gao et al, Biosci Trends, 2020)
2. Hydroxychloroquine was found to be more potent than chloroquine in inhibiting SARS-
CoV-2 in vitro (Yao et al, Clin Infect Dis, 2020)
3. One pre-print report of 62 COVID-19+ patients showed improved time to clinical

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3. One pre-print report of 62 COVID-19+ patients showed improved time to clinical
recovery in the hydroxychloroquine treatment arm compared to placebo (Chen et al,
unpublished report, 2020)
4. However, a number of pre-print reports have since shown no difference in outcomes
between hydroxychloroquine and placebo (Tang et al, unpublished report, 2020;
Mahevas et al, unpublished report, 2020) and even showed harm in one unpublished
study (Silva Borba et al, unpublished report, 2020)
5. We will await peer reviewed literature before commenting on any of these studies
further
Recommendations
1. Consideration should be given for use of hydroxychloroquine after weighing the

risks and benefits only in patients who:
a. Are not candidates for other clinical trials AND
b. Require supplemental oxygen OR are inpatients not on supplemental oxygen but at
high risk for progression to severe disease (age >65 years, immunocompromising
conditions, active malignancy, structural lung disease, chronic kidney disease,
hypertension, coronary artery disease, diabetes, or BMI >40)
Dosing
1. Hydroxychloroquine: 400 mg PO BID on the first day, followed by 200 mg q12h (q8h
if concerns for absorption) for a total of 5 days
a. May extend up to 10 days depending on clinical response
b. The half-life of HCQ is over 7 days, so a 5-day treatment course should still yield
therapeutic HCQ levels past day 10 (Yao et al, Clin Infect Dis, 2020).
2. Chloroquine phosphate: 500 mg PO BID for 10 days
a. Not available at BWH
1. Hydroxychloroquine is contraindicated in epilepsy and porphyria. Known adverse
effects include:
a. Gastrointestinal symptoms (nausea, cramps, diarrhea)

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b. Bone marrow suppression
c. Cardiomyopathy and retinopathy
i. Case series and reports have found this to be a long-term (years) and dose-
dependent phenomenon. Given the anticipated short duration in COVID-19, it is not
an expected risk (Nord et al, Semin Arthritis Rheum, 2004; Yusuf et al, Eye, 2017).
d. QT-segment prolongation and therefore torsades de pointes, especially if
administered in combination with azithromycin or other QTc-prolonging agents
2. Given this, the following monitoring is required for patients being treated with
hydroxychloroquine:
a. Obtain baseline ECG, ECG 3.5 hours after first dose, and daily ECG thereafter
b. Discontinue all other QT-prolonging agents
c. Maintain continuous telemetry while under treatment
d. Do not start if QTc > 500 msec (or 550 msec with pacing or BBB)
e. Discontinue if there is an increase in PVCs or non-sustained polymorphic VT.
3. The ACC has published a risk score for drug associated QTc prolongation which may
help in determining those patients in whom these drugs may be dangerous. ACC and
HCQ Risk Assessment
Azithromycin
Pathophysiology
1. Azithromycin is a macrolide antibiotic that inhibits RNA-dependent protein synthesis by

binding to the 50S ribosomal subunit of bacteria, resulting in blockage of
transpeptidation
2. There is no evidence of azithromycin’s direct effects on SARS-CoV-2
3. Theoretical benefit could come in azithromycin’s anti-inflammatory effects seen in other
infectious diseases (Amsden GW, J Antimicrob Chemother, 2005)
Evidence
1. A French study has received international attention over the potential combination of
hydoxychloroquine and azithromycin for the treatment of COVID-19 (Gautret et al, Int J
Antimicrob Agents, 2020, Gautret et al, Travel Med Infect Dis, 2020)
2. A separate French study has shown no benefit of adding azithromycin to

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2. A separate French study has shown no benefit of adding azithromycin to
hydroxychloroquine, directly conflicting the work done by Gautret and colleagues
(Molina et al, Med Mal Infect, 2020)
a. No conclusions can be drawn from these studies and until more conclusive studies
are done, we believe that the risks of QTc prolongation and torsades de pointes
outweigh the potential benefits of combination treatment
Recommendations
1. There is not sufficient supporting evidence to use azithromycin in combination with

hydroxychloroquine for COVID-19, unless concomitant community-acquired pneumonia
is suspected and atypical coverage is desired
Dosing
1. Normal azithromycin dosing for community-acquired pneumonia (for atypical coverage)

is 500 mg daily for 5 days inpatient, or 500 mg x1, then 250 mg for a total of 5 days
1. While not recommended for treatment of COVID-19 at BWH, if azithromycin is used in

combination with hydroxychloroquine, QTc should be monitored as described above
a. In one study of 84 COVID-19 patients, the hydroxychloroquine & azithromycin
combination led to a QTc increase of >40 ms in 30% of patients and overall QTc >500
ms in 11% of patients (Chorin et al, unpublished report, 2020)
Lopinavir/ritonavir
Pathophysiology
1. Lopinavir/ritonavir (Kaletra, LPV/r) has been available since 2000 as an antiretroviral

agent in the treatment of human immunodeficiency virus (HIV)
2. Lopinavir and ritonavir are both protease inhibitors, which by inhibiting HIV-1 protease,
lead to the formation of immature, noninfectious viral particles. Ritonavir specifically is a
CYP3A4 inhibitor that is used to decrease metabolism of lopinavir (a CYP3A4
substrate), thereby increasing serum lopinavir levels
3. Lopinavir may theoretically work against coronaviruses like SARS-CoV-2 by inhibiting

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3. Lopinavir may theoretically work against coronaviruses like SARS-CoV-2 by inhibiting
3-chymotrypsin-like protease (3CLpro)
Evidence
1. Lopinavir was shown to have in vitro activity against both SARS-CoV-1 and MERS-CoV
in some studies (Chu et al, Thorax, 2004; de Wilde et al. Antimicrob Agents
Chemother, 2014), but not in others (Chan et al, J Infect, 2013)
2. Against SARS-CoV-1, LPV/r use (n=75) was associated with a lower overall mortality
and intubation rate in one study. A subgroup analysis showed no difference in overall
mortality or intubation rate however when lopinavir/ritonavir was used as rescue
therapy at a median of 18 days after symptom onset (n=31) (Chan et al, Hong Kong
Med J, 2003)
3. A recent randomized, controlled, open-label trial assessed lopinavir-ritonavir (n=99) vs.
standard of care (n=100) in SARS-CoV-2 patients (Cao et al, N Engl J Med, 2020)
a. Treatment with LPV/r was not associated with a difference in time to clinical
improvement or mortality
b. Randomization didn’t occur until a median of 13 days after symptom onset however,
so the window for benefit may have already closed, as seen in the Chan et al paper in
SARS-CoV-1
4. There are still many ongoing trials for the use of LPV/r in COVID-19, but additional
results are not yet available (Yao et al, J Med Virol, 2020)
Recommendations
1. Lopinavir/ritonavir should not be used at BWH as overall evidence is lacking and we

are unable to obtain supply of the medication
Dosing
1. If LPV/r were to be used at other institutions, the dosing regimen is 400/100 mg by

mouth twice daily for up to 10 days
1. Interactions are an incredibly important aspect of LPV/r use as ritonavir is a potent

CYP3A4 inhibitor, so will interact with CYP3A4 substrates (i.e. apixaban, tacrolimus,

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CYP3A4 inhibitor, so will interact with CYP3A4 substrates (i.e. apixaban, tacrolimus,
amiodarone)
2. Diarrhea, nausea, and transaminitis are common. Other adverse effects include
hyperlipidemia, pancreatitis, asthenia, and hyperglycemia
Nitazoxanide
Pathophysiology
1. Nitazoxanide is an antiprotozoal agent originally approved by the FDA in 2004 for use
in adults for the treatment of diarrhea caused by Giardia lamblia or Cryptosporidium
parvum
2. It is metabolized to its active metabolite tizoxanide in vivo
3. Antiviral activity of tizoxanide is due to interference with host-regulated pathways
involved in viral replication, rather than a particular virus-targeted mechanism
(Rossignol JF, J Infect Public Health, 2016)
Evidence
1. Nitazoxanide’s metabolite tizoxanide has in vitro activity against a variety of viruses,

including influenza (Rossignol et al, J Biol Chem, 2009), hepatitis B (Korba et al,
Antiviral Res, 2008), hepatitis C (Keeffe et al, World J Gastroenterol, 2009), and
Japanese encephalitis (Shi et al, Virol J, 2014)
2. In a randomized, controlled phase 2b/3 trial for uncomplicated influenza, nitazoxanide
dosed at 600 mg twice daily for 5 days reduced the duration of symptoms by ~21 hours
(Haffizulla et al, Lancet Infect Dis, 2014).
a. Other phase 3 trials in the treatment of influenza have been completed
(NCT01610245, NCT02612922, NCT03336619), but results are not yet available.
3. Another randomized controlled trial comparing nitazoxanide to placebo in the treatment
of severe influenza-like illness showed no difference in hospital length of stay (Gamiño-
Arroyo et al, Clin Infect Dis, 2019)
4. Nitazoxanide had been shown to have in vitro activity against MERS-CoV (Rossignol
JF, J Infect Public Health, 2016)
5. Most recently, nitazoxanide has been shown to have in vitro activity against SARS-
CoV-2 (Wang et al, Cell Res, 2020)

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Recommendations
1. Nitazoxanide should not be used at BWH as overall clinical evidence is lacking and
optimal dosing is not yet known
Dosing
1. If nitazoxanide were to be used, the most likely dose regimen would be 600 mg twice
daily of extended release tablets, which was the dosing used for influenza without
major safety concerns. However, the extended release tablets are not currently
available in the United States
1. Common adverse effects of nitazoxanide include:

a. Abdominal pain (6.6%)
b. Diarrhea (4.2%)
c. Headache (3.1%)
d. Nausea (3%)
Anti-IL6 Agents (Sarilumab, Tocilizumab, Siltuximab)

Pathophysiology
1. IL-6 activates T cells and macrophages, among other cell types (see “Cytokine
Activation Syndrome” section in “Shock” chapter). IL-6 inhibitors are approved for
cytokine activation syndrome complications related to Chimeric Antigen Receptor T cell
(CAR-T) therapy (Brudno and Kochenderfer, Blood Rev, 2019; Rubin et al, Brain,
2019).
2. IL-6 levels are reported to correlate with severe COVID-19 (Ruan et al, Intensive Care
Med 2020; Liu et al, unpublished report). While patients have peripheral lymphopenia,
BAL fluid is often lymphocytic, suggesting that IL-6 inhibition and prevention of T cell
activation may be protective.
Evidence
1. A non-peer-reviewed Chinese case series described 21 patients who received

tocilizumab 400 mg once. Three patients received a second dose within 12 hours due

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tocilizumab 400 mg once. Three patients received a second dose within 12 hours due
to continued fevers. All patients presented with fevers, but all defervesced within 24
hours of tocilizumab administration. In addition, oxygen requirement and lymphopenia
seemed to improve post-tocilizumab. (Xu et al, unpublished report, 2020)
a. This was a small, single arm study that didn’t report out on any concomitant therapy
used, so it’s unclear if patients also received steroids and/or antivirals. While thought-
provoking, it isn’t conclusive by any means
2. A similarly sized non-peer-reviewed Italian case series described 21 patients requiring
ventilation (CPAP or NIV) who received siltuximab via compassionate use at a dose
ranging from 700-1200 mg once. Five patients received a second dose 2-3 days after
the initial dose at the clinician’s discretion. Of the 21 patients, the condition of 7
seemed to improve (based on CPAP/NIV settings), 9 seemed to stabilize, and 5
seemed to worsen, including 1 death (Gritti et al, unpublished report, 2020)
3. Neither of these small case series confirm the efficacy or safety of anti-IL6 agents and
large randomized controlled trials are needed, and are currently ongoing
Recommendations
1. The routine use of anti-IL-6 agents is not recommended unless part of a clinical
trial. Sarilumab is the only current active anti-IL-6 clinical trial at BWH, so is the
preferred agent if therapy is warranted.
2. For severe cases of COVID-19 with suspicion of cytokine activation syndrome
(see “Other Guidance” chapter), consider use in conjunction with Infectious Diseases
consultation.
a. Retrospective reviews in patients with rheumatological disease suggest a possible
increase in serious bacterial infection, so use caution if secondary infection is
clinically suspected
i. Tocilizumab is routinely used at BWH (i.e. CRS in patients after CAR-T cell
treatment) without obvious increase in bacterial infection
3. Other immunomodulatory agents have been proposed in the management of COVID-
19 disease (i.e. anakinra, baricitinib, lenzilumab, leronlimab), but none currently have
evidence supporting their use and there are no additional active BWH
immunomodulator trials for COVID-19 outside of sarilumab
Dosing
1. Sarilumab (anti-IL6R mAb): New intravenous formulation and dosing, available only as
part of a clinical trial (NCT04315298).

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part of a clinical trial (NCT04315298).
2. Tocilizumab (anti-IL6R mAb): 400 mg (4-8 mg/kg) IV x1. Dose may be repeated 12
hours later if inadequate response to the first dose, but is not necessary in the majority
of cases. The total dose should be no more than 800 mg. Tocilizumab should not be
administered more than twice.
3. Siltuximab (anti-IL6 mAb): 11 mg/kg IV x1
1. Sarilumab common adverse effects include:

a. Transaminitis (AST, ALT), 28-47%
b. Neutropenia, 7-10%
c. Infusion reactions, 7%
d. Upper respiratory tract infections, 4%
e. Urinary tract infections, 3%
2. Tocilizumab common adverse effects include:

a. Transaminitis (AST, ALT), >22%
b. Infusion reaction, 4-20%
c. Hypercholesterolemia, 20%
d. Upper respiratory tract infection, 7%
e. Neutropenia, 2-7%
3. Siltuximab common adverse effects include:

a. Edema, >26%
b. Upper respiratory infection, >26%
c. Pruritus / skin rash, 28%
d. Hyperuricemia, 11%
e. Lower respiratory tract infection, 8%
f. Thrombocytopenia, 8%
g. Hypotension, 4%
4. Tocilizumab and sarilumab have black box warnings for a risk of serious infections,
including tuberculosis and other opportunistic infections. Patients treated with either
agent should be tested for latent tuberculosis prior to discharge from the hospital and

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agent should be tested for latent tuberculosis prior to discharge from the hospital and
followed up in the TB clinic if that testing is positive.
Convalescent Plasma
Pathophysiology
1. Convalescent plasma originates from patients who have previously recovered from a
viral infection and are now able to donate their immunoglobulin-containing blood
2. The presumed mechanism of action is that antibodies present in convalescent plasma
may suppress viremia
3. In previous viral infections antibody administration is likely more effective as pre- or
post- exposure prophylaxis than treating established infection (Cheng et al, Eur J Clin
Microbiol Infect Dis, 2005)
Evidence
1. A meta-analysis of 32 studies assessing the efficacy of convalescent plasma for the

treatment of severe viral acute respiratory infections (coronaviruses and influenza)
showed a reduction in mortality following treatment (Mair-Jenkins et al, J Infect Dis,
2015)
a. Of note, studies included were of low or very low quality and generally lacked control
groups
2. SARS-CoV-1
a. In one Hong Kong report, patients who received convalescent plasma had a 12.5%
mortality rate (n=80), while the overall mortality rate was 17% in March-May 2003
(Cheng et al, Eur J Clin Microbiol Infect Dis, 2005)
b. Patients treated with convalescent plasma before day 14 (n=48) were more likely to
be discharged than those treated after day 14 (n=32) (58.3% vs. 15.6%, p<0.001),
and the mortality rates in the two groups were 6.3% vs. 21.9% respectively (p=0.08)
3. SARS-CoV-2
a. A case series reported out on 5 critically ill COVID-19 patients who received
convalescent plasma, 4 of 5 who saw temperature normalization within 3 days and 3
of 5 who have been discharged (days 51, 53, and 55), with the other two in stable
condition at the time of the publication (Shen et al, JAMA, 2020)
i. It’s important to note that this study does not show efficacy of convalescent plasma,

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i. It’s important to note that this study does not show efficacy of convalescent plasma,
as the patients in this case series displayed relatively the same clinical course as
many critically ill COVID-19 patients who do not receive the treatment
b. A separate case series reported out on 4 critically ill COVID-19 patients who received
convalescent plasma (including one pregnant woman), all of whom recovered (Zhang
et al, Chest, 2020)
i. The time from transfusion to negative PCR test results ranged from 3-22 days. But
similar to the previous study, without a control group it’s impossible to know if these
patients would have also recovered without convalescent plasma on their own
c. The most recent case series reported out on 10 severe COVID-19 disease patients
who received convalescent plasma and tolerated it well (Duan et al, Proc Natl Acad
Sci USA, 2020)
Recommendations
1. Convalescent plasma is not yet available or recommended at BWH. If it becomes

available, it should only be used under an IRB-approved protocol
2. Outside of BWH, providers can request use of convalescent plasma through a single-
patient Emergency Investigational New Drug (eIND) application if a blood center has
plasma available. The Mayo Clinic is leading the charge for expanded access, more
information can be found on their dedicated website
3. If used, earlier administration is more likely to be effective
4. More detailed information regarding convalescent plasma donation can be found on the
Michigan State University website https://ccpp19.org/
Dosing
1. Optimal therapeutic dosing is not yet known. In one case series vs. SARS-CoV-2, all 5
patients received 400 mL of plasma, but all with varying receptor binding domain
(RBD)-specific antibody titers. In the second study, volumes ranged from 200 to 2400
mL of plasma, and the most recent case series used a volume of 200 mL for each
patient
2. Most ongoing studies are assessing an infusion of 1-2 units (200-500 mL) once
1. Plasma transfusions in general are safe and well-tolerated in most patients. Potential
side effects however include:

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side effects however include:
a. Mild fever
b. Allergic reactions, including serum sickness on rare occasions
c. Transfusion-related acute lung injury (Gajic et al. Am J Respir Crit Care Med. 2007)
d. Potential risk of another infectious disease from donor, although risk is incredibly low
with modern blood bank techniques
2. There is a theoretical concern that convalescent plasma may lower a patient’s INR if on
warfarin, similar to (but to a lesser degree than) fresh frozen plasma
Angiotensin Converting Enzyme Inhibitors (ACE-I) and

Angiotensin II Receptor Blockers (ARB)
Pathophysiology
1. SARS-CoV-2, the virus that causes COVID-19, enters via the same cell-entry receptor
as SARS-CoV, namely angiotensin-converting enzyme II (ACE2) (Paules et al, JAMA,
2020). SARS-CoV-2 is thought to have a higher affinity for ACE2 than SARS-CoV.
2. ACE2 is expressed in the heart, lungs, vasculature, and kidneys. ACE-inhibitors (ACEi)
and angiotensin-receptor blockers (ARBs) in animal models increase the expression of
ACE2 (Zheng et al, Nat Rev Cardiol, 2020), though this has not been confirmed in
human studies. This has led to the hypothesis that ACEi and ARBs might worsen
myocarditis or precipitate ACS. It has also been hypothesized that the upregulation of
ACE2 is therapeutic in COVID-19 and that ARBs might be protective during infection
(Gurwitz D, Drug Dev Res, 2020).
Recommendations
1. For outpatients, we recommend against discontinuing outpatient ACEi/ARBs.

2. For inpatients, we recommend against routine discontinuation of ACEi/ARBs, unless
otherwise indicated (e.g., acute kidney injury, hypotension, shock, etc).
a. This remains an area of investigation and it is unclear how these medications affect
patients with COVID-19. However, the evidence that currently exists favors continuing
these medications unless otherwise indicated to stop them because their abrupt
discontinuation, particularly in those who have heart failure or have had a myocardial
infarction, may lead to clinical instability and adverse outcomes (Vaduganathan et al,
NEJM 2020).

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NEJM 2020).
b. The American College of Cardiology, American Heart Association and Heart Failure
Society of America joint statement recommends against discontinuing ACE-I and
ARBs in patients with COVID-19 (Bozkurt et al, HFSA/ACC/AHA Statement
Addresses Concerns Re: Using RAAS Antagonists in COVID-19, 2020).
Non-steroidal anti-inflammatory drugs (NSAIDs)

Pathophysiology
1. SARS-CoV-2 binds to cells via ACE2. ACE2 is upregulated by ibuprofen in animal

models, and this might contribute to increased pathology (see “Angiotensin Converting
Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB)” section of this
chapter).
Recommendations
1. Reports from France indicate possible increase in mortality with ibuprofen in COVID-19
infection, but these reports have not been corroborated (Fang et al, Lancet Respir Med,
2020; Day M, BMJ, 2020). WHO clarified on 3/20/20 it does not recommend avoiding
NSAIDs as initially stated 3/18/20 (WHO, COVID-19 Interim guidance, March 2020).
a. Concern has been raised that NSAIDs may worsen COVID-19 disease. This has not
been proven clinically to-date, so we cannot make a recommendation for or against
their use at this time.
Vitamin C
1. While this idea has been popular in mainstream media, there is currently no evidence
to support low- or high-dose vitamin C in COVID-19 patients. There is a trial currently
recruiting for high-dose vitamin C trial in COVID-19 patients in China slated to be
complete in the fall of 2020 (NCT04264533).
a. The use of Vitamin C as a treatment for sepsis is beyond the scope of this document.
A 96-hour infusion of vitamin C did not demonstrate significant improvement of organ
dysfunction, vascular injury or alter inflammatory markers in sepsis patients with
ARDS, although a reduction in 28-day mortality was exhibited (Difference -0.17,
p=0.03). (Fowler, et al. JAMA, 2019). This study does not look at COVID-19 ARDS
patients.

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patients.
Blood Products
Considerations
1. In general, treat bleeding rather than numbers.

i
2. We recommend a restrictive transfusion strategy (Hct > 21, Hgb > 7)
3. If hemodynamically stable, transfuse 1 unit at a time and reassess needs.
a. Parsimony is encouraged given risks associated with blood product transfusions,
limited supply (blood drives are limited by social distancing), and volume overload
being of particular concern in COVID patients.
4. FFP or 4 factor-PCC (lower volume) should be given for active bleeding in the setting of
known or suspected coagulation abnormalities.
5. For warfarin reversal, use 4 factor-PCC given longer effect and lower volume.
6. Massive transfusion protocol, as a very limited resource, will need to be activated only
by the ICU attending.
7. Tranexamic acid: only for ongoing oozing/bleeding with over DIC and hyperfibrinolysis.
8. Procedures: If the patient is at high bleeding risk, the most experienced operator
should perform the procedure to minimize trauma.
a. We recommend avoiding subclavian lines when placing central venous catheters in
coagulopathic patients.
Transfusion Thresholds
Patient DVT ppx Transfusion Thresholds

Transfuse 1 unit at a time
RBC Platelets Cryo FFP
No bleeding, LMWH daily or Hgb < 7 n/a Fibrinogen INR
Plts > 30k SC UFH TID If ACS,** < 100 > 10
Hgb > 10
No bleeding, but patient Heparin gtt Plts <
requires anticoagulation PTT goal 30k
depends on
indication
No bleeding, SCDs* Plts <

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Plts < 30k Hold 10k
pharmacologic
Minor Procedures Continue Plts < INR
(a-lines, CVCs) pharmacologic 10k >3
ppx in most
patients
SCDs* if not
using
pharmacologic
Mild Bleeding or Rigors Continue Plts < INR
(increases risk of ICH in pharmacologic 20k >3
thrombocytopenia) ppx in most
patients
SCDs* if not
using
pharmacologic
Intra-Cranial + SCDs* Plts < INR
Hemorrhage Hold 75k >
pharmacologic if 1.7
able
Serious Bleeding#, + SCDs* Transfuse Plts < INR
Trauma or Major Hold for active 50k or >2
Procedure pharmacologic if bleeding higher (INR
(includes LP) able >
1.4
for
LP)
* SCDs = sequential compression devices = “pneumoboots”
** ACS = Acute Coronary Syndrome
# Intracranial hemorrhage and massive bleeding are not included here. The massive
transfusion protocol must be activated by the attending, given blood product shortages.
Blood donation
1. We encourage all staff who are healthy and eligible to donate to make an appointment
to donate blood or platelets at the Kraft Family Blood Donor Center at DFCI and BWH,

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to donate blood or platelets at the Kraft Family Blood Donor Center at DFCI and BWH,
either by phone (617.632.3206) or online.
CHAPTER 5
Infectious Disease
This section is in progress. Content is currently found in “Therapeutics” and “Sepsis”

sections
CHAPTER 6
Cardiology
Section Editor: Joshua P. Lang MD
Contributors: Erin A. Bohula MD DPhil, David A. Morrow MD, Mandeep Mehra MD

(Transplant)
Acute Cardiac Injury

Definition and incidence

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Definition and incidence
1. Definition: The definition differs in studies and is non-specific. More recent studies
define as troponin > 99th percentile upper limit of normal; earlier studies include
abnormal ECG or echocardiographic findings (Zhou et al, Lancet, 2020; Shi et al,
JAMA Cardiology, 2020).
2. Incidence: Incidence of 7-22% in hospitalized patients with COVID-19 in China (Ruan
et al, Intensive Care Med, 2020; Wang et al, JAMA, 2020; Chen et al, Lancet, 2020; Shi
et al, JAMA Cardiology, 2020; Guo et al, JAMA Cardiology, 2020).
Pathophysiology
1. The mechanism is unknown, though several have been proposed, based on very
limited data outside of case series and reports (Ruan et al, Intensive Care Med, 2020;
Hu et al, Eur Heart J, 2020; Zeng et al, Preprints, 2020; Inciardi et al, JAMA Cardiology,
2020)
a. Possible direct toxicity through viral invasion into cardiac myocytes (i.e., myocarditis)
b. Acute coronary syndrome and demand ischemia
c. Stress cardiomyopathy (i.e., Takotsubo’s)
d. Myocardial suppression in the setting of profound inflammatory response/cytokine
storm (Siddiqi & Mehra, Journal Heart Lung Transpl, 2020)
Time course and prognostic implication
1. Troponin rise and acute cardiac injury may be late manifestations of COVID-19.
a. Troponin increased rapidly from ~14 days from illness onset, after the onset of
respiratory failure (Zhou et al, Lancet, 2020).
b. Among non-survivors, a steady rise in troponin I levels was observed throughout the
disease course from day 4 of illness through day 22 (Zhou et al, Lancet, 2020).
2. ACI is associated with ICU admission and mortality
a. ACI is higher in non-survivors (59%, n=32) than survivors (1%, n=1) (Zhou et al,
Lancet, 2020).
b. ACI is higher in ICU patients (22%, n=22) compared to non-ICU patients (2%, n=2)
(Wang et al, JAMA, 2020)
Consultation of Cardiovascular Medicine
1. Cardiology Consultation

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1. Cardiology Consultation
a. The following clinical scenarios should prompt cardiology consultation:
i. Malignant and unstable arrhythmias
ii. A marked rise in cardiac biomarkers (including hsTnT >200 ng/L)
iii. Concern for myocarditis
iv. Concern for ACS
v. New heart failure or new reduction in LVEF
vi. Undifferentiated or suspected mixed or cardiogenic shock
Cardiovascular Testing
1. Cardiac Biomarkers:
a. All patients: check hsTrop, NTproBNP and CPK on admission
b. ICU patients: Check hsTrop NTproBNP, and ScvO2 daily (qOD NTproBNP if stable).
c. Inpatients: Check hsTrop every other day
i. If hsTrop > 200 ng/L, marked elevation in NTproBNP, or ScvO2 <60%
1. Obtain 12-lead ECG
2. Perform point-of-care US (POCUS) to assess for gross abnormalities in LV or RV
function; upload to centricity/PACs
3. If either are abnormal, obtain virtual or bedside cardiology consultation. Consider
formal echocardiogram in discussion with cardiology consultation.
4. If no new ECG or echocardiographic abnormalities, continue to monitor hsTrop,
NTproBNP, and ScvO2
1. Telemetry:
a. Telemetry should be used for all critically-ill patients
b. At BWH, COVID-19 intermediate-care patients also have telemetry.
c. For hospitals, with resource-limitations, telemetry is most important for patients who
meet AHA criteria (Sandau et al, Circulation, 2017).
2. ECGs:
a. Daily ECGs are reasonable for individuals with severe COVID-19.

i. When possible, print ECGs from the in-room monitor to minimize contamination of
equipment

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equipment
3. TTE:
a. Do not order routine TTEs on COVID-19 patients.
b. Indications for POCUS:
i. Marked elevation in troponin or NTproBNP or decline in ScvO2/MvO2
ii. Shock
iii. New heart failure (not pre-existing heart failure)
iv. New persistent arrhythmia
v. Significant ECG changes
c. If abnormalities are identified on POCUS (e.g. new reduction in LVEF < 50%), a
formal TTE should be obtained and cardiology consulted. Where possible order
limited TTEs instead of full TTEs to conserve resources.
4. Advanced CV Imaging (Stress Testing, TEE, CT, CTA, MRI, Invasive Coronary
Angiography)
a. All testing should be limited to cases where the information is thought to be critical to
patient care. Consideration of all advanced imaging should be discussed with
cardiology consultation or individual imaging teams.
b. Specific considerations:
i. Stress testing is likely not expected to be commonly indicated in individuals with
active COVID. If needed, consider pharmacologic nuclear stress testing or coronary
CTA.
ii. TEE
1. Only for absolute necessity
2. Consider alternative noninvasive imaging modalities (e.g. cardiac CT to rule out left
atrial appendage thrombus, cardiac CT or PET/CT for endocarditis complications).
Arrhythmias
Incidence
1. Case series report the occurrence of unspecified arrhythmias in 17% of hospitalized

patients with COVID-19 (n=23 of 138), with higher rate in ICU patients (44%, n=16)
compared to non-ICU patients (7%, n=7) (Wang et al, JAMA, 2020). In one study of
189 hospitalized patients in Wuhan, China, the rate of VT/VF was 5.9% (n=11) (Guo et

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189 hospitalized patients in Wuhan, China, the rate of VT/VF was 5.9% (n=11) (Guo et
al, JAMA Cardiology, 2020).
Workup
1. Telemetry, 12-lead EKG, cardiac troponin, NT-proBNP, TFT

2. ScvO2 if central line present (ScvO2 <60%, trigger for further workup or cardiology
consultation).
3. POCUS to assess LV and RV function with uploaded images
4. Obtain formal TTE and consider cardiology consultation if abnormalities of any of the
above
Management
1. Atrial fibrillation/atrial flutter

a. Beta blockade if no evidence of heart failure or shock
b. If significant heart failure or borderline BPs, use amiodarone. There is no known
increased concern for amiodarone lung toxicity
c. If unstable, synchronized DCCV with 200 Joules biphasic
2. Ventricular tachycardia (VT)
a. Unstable/pulseless: initiate ACLS
b. Stable:
i. Cardiology consult (may represent evolving myocardial involvement)
ii. Amiodarone 150mg IV x 1 or lidocaine 100mg IV x 1
Acute Coronary Syndromes

Incidence
1. There is no current available data on the incidence of ACS in COVID. However, we

presume that due to the presence of ACE2 receptors on the endothelium, and the
known increased risk of ACS in influenza that there is a possible increased incidence of
ACS among COVID-19 patients.

a. The incidence of ACS is about 6 times as high within seven days of an influenza
diagnosis than during the control interval - incidence ratio 6.05 (95% CI, 3.86 to 9.50)

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diagnosis than during the control interval - incidence ratio 6.05 (95% CI, 3.86 to 9.50)
(Kwong et al, NEJM, 2018).
Workup
1. Elevated troponin/ECG changes alone may not be able to discriminate between:

a. Coronary thrombosis
b. Demand-related ischemia
c. Myocarditis
d. Toxic myocardial injury (e.g. sepsis)
2. Determination of ACS will rely on all evidence available:
a. Symptoms (if able to communicate): New dyspnea, chest pain, anginal equivalents
b. Regional ECG changes
c. Rate of change of Troponin changes (i.e., steep rise suggests ACS)
d. Echo findings (e.g., new RWMA): When in doubt, request a cardiology consult.
3. When in doubt, request a cardiology consultation
Management
1. Medical management of ACS should be coordinated with cardiology

a. Treat with full dose aspirin, clopidogrel (if not bleeding), heparin, oxygen (if
hypoxemic), statin, nitrates (if hypertensive), and opioids (if persistent pain during
medical management).
b. Beta blockers should be used with caution given possible concomitant
myocarditis/decompensated heart failure.
2. As of the time of this writing, the cath lab will take COVID-19 patients, even if
ventilated.
a. If resources become constrained and door-to-balloon time is no longer adequate,
cardiology may decide to use lytic medications for COVID-19 STEMI patients in lieu of
PCI.
Pericarditis and Myocarditis

Incidence

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Incidence
1. Myocarditis and pericarditis are potential manifestations of COVID-19 and source of

Acute Cardiac Injury, based on case reports/case series (Ruan et al, Intensive Care
Med, 2020; Zeng et al, Preprints, 2020; Hu et al, Eur Heart J, 2020; Inciardi et al, JAMA
Cardiology, 2020). One case report had cMRI proven myocarditis and a concomitant
reduction in LVEF to 35% with rapid resolution after antiviral treatment and systemic
glucocorticoids (Inciardi, et al, JAMA Cardiology, 2020).
Workup
1. Likely no role for endomyocardial biopsy

2. cMRI should be discussed on a case-by-case basis with a cardiology consult team.
Management
1. Supportive for heart failure and direct viral treatments

2. The use of steroids and anti-inflammatory medications such as Colchicine and
Ibuprofen should also be discussed with the cardiology consult team as this literature is
evolving.
Heart Transplantation
Literature
1. The literature available on COVID-19 in patients with a history of heart transplantation

is limited. Currently, there are two published case series from China (Zong-Li et al,
Journal of Heart Lung Transplantation, 2020; Fei Li et al, Journal of Heart Lung
Transplantion, 2020). In one case series of two patients, one severe and one mild, both
recovered.
Management Principles
1. In heart transplant patients presenting with symptoms, positive for SARS-Co-V-2 and
no pulmonary findings (normal CXR, none to mild CT findings, no hypoxia)
a. Exclude co-infection (e.g. CMV) and bacterial infection (procalcitonin >0.5ng/ml)
b. Maintain baseline immunosuppression (avoid over-immunosuppression)
c. Continue ACEi/ARB//Statins

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c. Continue ACEi/ARB//Statins
d. Do not augment steroids
e. Check troponins and NT-proBNP, monitor CRP and other indices of inflammation
(platelets, LDH, ferritin, d-dimer)
2. In heart transplant patients with proven COVID-19 pneumonia (CT findings and
hypoxemia)
a. Hold MMF/AZA/SRL
b. Consider holding tacrolimus if renal dysfunction or diarrhea (where levels are
expected to rise); in others consider decreasing dose by 50%
c. Use low dose IV steroids as main immunosuppression (do not exceed 0.5-1mg/kg
methyprednisolone)
d. Exclude co-infection as above (including CMV, pneumocystis and fungal infections)
and use empiric antimicrobials in consultation with ID teams
e. It is reasonable to add antiviral therapy via clinical trials (IV remdesivir) or other trial-
based treatments
3. Special circumstances
a. With evidence of hyper-inflammation (d-dimer > 1,000, low platelets, markedly high
CRP, ferritin > 1,000, IL-6 > 40) would strongly consider tocilizumab (8mg/kg IV over
60 minutes) early rather than late in the disease course
b. Follow cardiac allograft function closely (check troponins, TTE for increased LV wall
thickness or decline in allograft function, QRS amplitude decrease, raised filling
pressures clinically, significantly elevated NT-proBNP) and consider tocilizumab with
higher dose steroids (1 mg/kg methylprednisolone); in a case-by-case basis may
consider use of IVIG (10-20 mg/kg over 2-3 days)
4. Recovery
a. Once recovery ensues restart CNI at usual dose and adjunctive (MMF) at 50% of
baseline dose until viral recovery is seen (2 negative NAT), then return to baseline as
tolerated. There is uncertain benefit to switch to mTOR (known benefit in CMV
suppression)
CHAPTER 7
Shock: Septic, Cardiogenic, and

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Shock: Septic, Cardiogenic, and
Cytokine
Section editors: C Lee Cohen MD MBA, Joshua Lang MD
Contributors: Erin Bohula MD, David Morrow MD, Kathleen Haley MD, Bina Choi MD
Updated: March 30, 2020
Undifferentiated Shock in COVID

Overview
1. Definition:
a. Acute onset of new and sustained hypotension (MAP < 65 or SBP < 90) with signs of
hypoperfusion requiring IVF or vasopressors to maintain adequate blood pressure
2. Time course:
a. Patients rarely present in shock on admission
i. Natural history seems to favor the development of shock after multiple days of
critical illness.
3. Etiology:
a. The range of reasons for shock is wide and more variable than for most patients and
may includes:
i. Myocardial dysfunction
ii. Secondary bacterial infection
iii. Cytokine storm
Workup
1. Assess for severity of end organ damage:

a. UOP, mental status, lactate, BUN/creatinine, electrolytes, LFTs

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2. Obtain a FULL infectious/ septic workup, which includes all of the following:
a. Labs: CBC with differential. Note that most COVID patients are lymphopenic (83%).
However, new leukocytosis can occur and left-shift can be used as a part of clinical
picture (Guan et al, N Engl J Med, 2020). Two sets of blood cultures, LFTs (for
cholangitis/acalculous cholecystitis), urinalysis (with reflex to culture), sputum culture
(if safely obtained via inline suctioning, do not perform bronchoscopy or sputum
induction), procalcitonin at 0 and 48h (do not withhold early antibiotics on the basis of
procalcitonin alone), urine Strep and legionella antigens
b. Portable CXR (avoid CT unless absolutely necessary)
c. Full skin exam
3. Assess for cardiogenic shock
a. Assess extremities: warm or cool on exam
b. Assess patient volume status: JVP, CVP, edema, CXR
c. Assess pulse pressure: If < 25% of the SBP, correlates highly with a reduction in
cardiac index to less than 2.2 with a sensitivity of 91% and a specificity of 83%
(Stevenson and Perloff, JAMA, 1989)
d. Perform POCUS, if able, to assess for gross LV/RV dysfunction (upload to
PACS/Centricity)
i. For TTE protocols see “Cardiovascular Testing”
e. Labs: Obtain an SCV02 or MV02 if the patient has central access, troponin x2, NT
proBNP, A1c, lipid profile, TSH
f. EKG (and telemetry)
g. Calculate estimated Fick Cardiac Output
i. MDcalc online calculators: Fick CO, BSA
h. Obtain cardiology consultation if any suspicion of cardiogenic shock
4. Assess for other causes of shock:
a. Vasoplegia:
i. Run medication list for recent cardiosuppressive medications, vasodilatory agents,
antihypertensives
b. Adrenal insufficiency:
i. Unless high pretest probability of adrenal insufficiency, we recommend against

routine cortisone stimulation testing
c. Obstruction:

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c. Obstruction:
i. PE (given the elevated risk of thrombosis)
ii. Tamponade (given elevated risk of pericarditis)
iii. Obstruction from PEEP
d. Cytokine storm (see “Cytokine Activation Syndrome”)
e. Allergic reactions to recent medications
f. Neurogenic shock is uncommon in this context
g. Hypovolemia:
i. Bleeding
ii. Insensible losses from fever
iii. Diarrhea/vomiting
Differentiating Shock
This video is a helpful tutorial.
Type of Shock Cardiac SVR CVP/Wedge ScvO2, Other

Output MvO2 features
Cardiogenic
Distributive
(sepsis,cytokine,
anaphylaxis)
Obstructive
Hypovolemic

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Neurogenic Decreased
HR
/normal
Septic Shock and Secondary Infections

Incidence
1. The reported rates of sepsis and septic shock are not reported consistently in currently
available case series
a. Secondary bacterial infections are reported:
i. 20% of non-survivors (Zhou et al, Lancet, 2020)
ii. 16% of non-survivors (Ruan et al, Intensive Care Med, 2020)
iii. 12-19% In H1N1 epidemic (MacIntyre et al, BMC Infect Dis, 2018)
b. Concurrent Pneumocystis pneumonia has been reported in at least one case
(possibly due to lymphopenia)
Management
1. Antibiosis:
a. Early empiric antibiotics should be initiated within 1 hour (see “Antibiotics”)
2. Pressors and Fluid Management:
a. Goal MAP > 65mmHg
i. While there is emerging data that lower MAP thresholds may be beneficial, we
recommend following this threshold for now.
b. Pressors
i. Start Norepinephrine while determining the etiology of undifferentiated shock
ii. Unless new evidence emerges, standard choices for distributive shock (i.e.,
norepinephrine then vasopressin) are recommended, with high vigilance for the
development of cardiogenic shock, addressed in the next section

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development of cardiogenic shock, addressed in the next section
c. Conservative fluid management:
i. Do not give conventional 30cc/kg resuscitation
1. COVID-19 clinical reports indicate the majority of patients present with respiratory
failure without shock. ARDS is mediated in part by pulmonary capillary leak, and
randomized controlled trials of ARDS indicate that a conservative fluid strategy is
protective in this setting (Grissom et al, Crit Care Med, 2015; Famous et al, Am J
Respir Crit Care Med, 2017; Silversides et al, Int Care Med, 2017)
2. Conservative fluid management is also part of the most recent WHO guidelines.
WHO, COVID-19 Interim guidance, March 2020).
ii. Instead, give 250-500cc IVF and assess in 15-30 minutes for:
1. Increase > 2 in CVP
2. Increase in MAP or decrease in pressor requirement
a. Use isotonic crystalloids; Lactated Ringer’s solution is preferred where possible.
Avoid hypotonic fluids, starches, or colloids
iii. Repeat 250-500cc IVF boluses; Use dynamic measures of fluid
responsiveness
1. Pulse Pressure Variation: can be calculated in mechanically ventilated patients
without arrhythmia; PPV >12% is sensitive and specific for volume responsiveness
2. Straight Leg Raise: raise legs to 45° w/ supine torso for at least one minute. A
change in pulse pressure of > 12% has sensitivity of 60% & specificity of 85% for
fluid responsiveness in mechanically ventilated patients; less accurate if
spontaneously breathing
3. Ultrasound evaluation of IVC collapsibility should only be undertaken by trained
personnel to avoid contamination of ultrasound
4. For further guidance, Conservative Fluid Management protocols are available from
from FACCT Lite trial (Grissom et al, Crit Care Med, 2015).
iv. Corticosteroids
1. See “Systemic Corticosteroids” section
2. Stress dose hydrocortisone should still be considered in patients on > 2 pressors.
Cardiogenic Shock
Incidence and clinical course

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Incidence and clinical course
1. Etiology: See “Acute Cardiac Injury”.

i. Mechanism is unknown, potentially direct viral toxicity, ACS, stress or inflammatory
cardiomyopathy
2. Incidence:
a. Heart failure or cardiogenic shock was observed
i. In 23% (n=44 of 191) of hospitalized patients in one case series (Zhou et al, Lancet,
2020).
1. There were higher rates in non-survivors (52%, n=28) compared to survivors (12%,
n=16),
ii. In 33% of patients admitted to an ICU in Washington State 33% (n=7 of 21) (Arentz
et al, JAMA, 2020).
1. These patients tended to be older with more comorbidities and had a high mortality
(11 of the 21 died).
3. Prognostic implication:
a. Heart failure or myocardial damage contributed to death
i. In 39% (n=29) of deaths in a series of 68 patients in Wuhan. Most (n=22 of 29) had
concomitant respiratory failure (Ruan et al, Intensive Care Med, 2020).
4. Time course:
a. Cardiogenic shock may present late in the course of illness even after improvement of
respiratory symptoms, and manifest as a precipitous clinical deterioration in the
setting of an acute decline in LVEF (see “Acute Cardiac Injury”)
Workup
1. All cardiogenic shock cases require cardiovascular medicine consult

a. PA catheters may be placed bedside by experienced providers, with preference for
use only in mixed shock or complex cases with cardiology guidance
2. Significant concern for cardiogenic shock if any of the following are present with
evidence of hypoperfusion (e.g., elevated lactate):
a. Elevated NT-proBNP, or
b. CvO2 < 60% (PvO2 < 35 mm Hg), or
c. POCUS or echocardiogram with depressed LV and/or RV function

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c. POCUS or echocardiogram with depressed LV and/or RV function
3. Rule out ACS and complete the initial work up as described in “Acute Coronary
Syndromes”.
4. Ongoing monitoring:
a. Labs: Trend troponins to peak, SCvO2 (obtained by upper body CVC) or MvO2 q8-
12h or with clinical change, Lactate q4-6h, LFTs daily (for hepatic congestion)
b. Daily EKGs or prn with clinical deterioration
c. Trend troponin to peak
Management
1. Close collaboration with the cardiovascular medicine consultation service is

recommended.
a. Goals: MAPs 65-75, CVP 6-14, PCWP 12-18, PAD 20-25, SVR 800-1000, SCvO2 >
60%, CI > 2.2
i. Note: Achieving MAP goal is first priority, then optimize other parameters
b. How to achieve goals:
i. Continue titration of norepinephrine gtt for goal MAP 65-75
ii. Initiate diuretic therapy for CVP > 14, PCWP >18, PAD > 25
iii. Initiate inotropic support:
1. Dobutamine gtt for SCvO2 < 60%, CI < 2.2 and MAP > 65. Start at 2mcg/kg/min.
Up-titrate by 1-2mcg/kg/min every 30-60 minutes for goal parameters. Alternative
strategies should be considered once dose exceeds 5mcg/kg/min. Maximum dose
is 10mcg/kg/min.
iv. Ensure negative inotropes such as beta blockers, calcium channel blockers and
antihypertensives are discontinued.
Mechanical Support
1. The benefit of mechanical circulatory support in COVID-19 is not yet clear.

2. Patients who experience the following should prompt an immediate call to the
cardiovascular medicine consult service for consideration of mechanical support:

a. Dobutamine gtt at 5mcg/kg/min (or unable to tolerate dobutamine due to
tachyarrhythmias) and ScvO2 < 60% or CI < 2.2

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tachyarrhythmias) and ScvO2 < 60% or CI < 2.2
b. Lactate > 4 after medical therapy
3. The criteria for VA ECMO and other mechanical circulatory support varies among
centers and are difficult to develop even under typical circumstances. The unclear
trajectory of the COVID-19 pandemic makes these evaluations even more difficult.
a. VA- ECMO guidelines are available here (Partners login required)
b. For the purposes of general education, a hypothetical set of inclusion criteria for VA
ECMO or MCS could cover:
i. Younger age
ii. Expected life expectancy >6 months pre-hospitalization
iii. No evidence of solid or liquid malignancy
iv. Able to tolerate anticoagulation
v. Platelets >50,000
vi. Absence of severe peripheral arterial disease
vii. No evidence of irreversible neurological injury
viii. Able to perform ADLs at baseline prior to illness
ix. Cannot have profound respiratory failure (defined as requiring prone ventilation at
time of consult for MCS or having PaO2:FiO2 ratio < 150) (for MCS other than
ECMO)
Cytokine Activation Syndrome

Pathophysiology
1. A subgroup of patients with severe COVID-19 may have cytokine activation syndrome
and secondary HLH (Mehta et al, Lancet, 2020).
a. Patients who had cytokine activation developed rapid progression to ARDS, shock,
and multiorgan failure (Chen et al, Lancet, 2020)
2. Pathophysiology:
a. Neutrophil activation likely contributes to the pathogenesis of cytokine storm and
ARDS (Wu et al, JAMA Intern Med, 2020). Wu et al found that COVID-19 confirmed
patients with ARDS have higher neutrophil counts, average 7.04 (95% CI: 3.98 to
10.12) vs. those without ARDS, average 3.06 (2.03 to 5.56)
b. Similar patterns of cytokine storm and ARDS have been seen with SARS, MERS (Kim

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b. Similar patterns of cytokine storm and ARDS have been seen with SARS, MERS (Kim
et al, J Korean Med Sci, 2016)
c. Other studies have suggested that increased proinflammatory cytokines in the serum
are associated with pulmonary injury in SARS, MERS, and COVID-19 (Wong et al,
Clin Exp Immunol, 2004)
Workup
1. Suspect if clinical deterioration with shock and multiorgan failure.

a. CBC with diff, PT/INR, PTT, fibrinogen, d-dimer, ferritin, liver function test,
triglycerides, c-reactive protein (CRP), sIL-2R (Ruan et al, Intensive Care Med, 2020)
i. CRP seems to correlate with disease severity and prognosis of COVID-19 (Ruan et
al, Intensive Care Med, 2020; Young et al, JAMA, 2020)
ii. An HScore (MDcalc online calculator) may be helpful in estimating the probability of
secondary HLH in these patients
Management
1. If high suspicion, discuss with ID about the use of IVIG, steroids, cytokine blockade,
particularly IL-6 pathway and perhaps IL-1 (see “Anti-IL6 Agents”). While steroids have
been implicated with worse lung injury and outcomes, they may be beneficial in the
hyperinflammatory state.
1.
CHAPTER 8
Cardiac Arrest
Section Editor: Jordan Anderson MD
Contributors: Raghu Seethala MD, Karen M. Griswold RN MBA CPPS, Anthony Massaro

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MD, David Rubins MD, Bina Choi MD
Preparation
Minimizing Healthcare Worker Risk of Exposure
1. Code Responses to COVID-19 patients are high-risk events for healthcare worker
exposure due to the aerosolization that occurs with chest compressions and intubation
a. Use PPE:
i. CDC guidelines recommend N95 respirator, face shield, gown and gloves be used
by all code responders during code events (CDC Guidelines, 2020) as well as Face
Shield, Gown and Gloves).
b. Minimize personnel:
i. Use an automated compression device where available to minimize personnel.
c. Prepare code equipment:
i. To limit transmission of virus while passing meds/supplies into the patient’s room
from the code cart, consider creating Code Bags inside the Code Cart pre-packed
with necessary code meds (Epinephrine, Bicarbonate, Calcium etc.) and IV/lab
supplies.
Early goals of care conversations
1. To avoid unnecessary codes in patients with an irreversible underlying condition,

patients who are at high-risk for acute decompensation should be identified early and
appropriate steps should be taken to confirm code status and initiate early goals of
care conversations with the patient and family.
Code Management
1. Efforts should be made to minimize the total number of Code responders in the
room to 7-8.
a. Code responders inside the patient’s room who should don full PPE prior to entering
the patient’s room:

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the patient’s room:
i. Code Leader (1)
ii. Code RN (1)
iii. Scribe RN (Primary RN or NIC) (1)
iv. Respiratory Therapist (1)
v. Anesthesiologist (1)
vi. 2 Chest Compressors, resting compressor holds femoral pulse (2)
vii. If needed for surgical procedures, Surgical Responder (1)
b. Code responders outside the patient’s room should not don PPE unless called upon
in the room:
i. Additional unit nurses (2-3) (supplies, meds from omnicell, code cart)
ii. Code Cart
iii. Pharmacist (1)
iv. Additional medical resident/MDs (2) (Medical resident on computer outside the room
placing orders, calling consults, and providing code leader with patient information)
v. Additional Code Responders (3-4) Surgery and Anesthesia team if not needed in the
room
vi. Security
vii. Observer (for PPE observation)
2. Circulation
a. Until a definitive airway is obtained, compression-only CPR should be performed.
Multiple studies have shown that compression-only CPR is non-inferior to standard
CPR (Svensson et al, NEJM, 2010).
b. If the patient has shockable rhythm (VF/VT), defibrillate as soon as possible.
c. If a patient has been proned for ventilatory purposes and they develop cardiac arrest,
a decision should be made by the medical and nursing team whether to de-prone the
patient.
i. If the patient is able to be safely de-proned in an efficient manner, the medical team
should de-prone the patient and begin supine chest compressions.
ii. If the patient is not able to be de-proned due to limited staff, or concerns about
extubation or line/tubing entanglements, the team should proceed with reverse
precordial compressions, also called Reverse CPR (Brown et al, Resuscitation,

2001).
1. Reverse precordial compressions are performed by placing a clenched fist beneath

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1. Reverse precordial compressions are performed by placing a clenched fist beneath
the sternum while administering compressions to the midthoracic spine between
the inferior scapulae (Sun et al, Anesthesiology, 1992).
2. This is optimally performed with one person administering compressions and one
person holding counter-pressure beneath the sternum.
3. Airway
a. Initial Airway Management, Prior to Intubation:
i. Prior to securing a definitive airway, oxygen should be applied via a non-rebreather
mask at 15L/min without humidification
ii. Avoid BVM ventilation, high-flow nasal cannula, and non-invasive ventilation (CPAP,
BiPAP) to minimize aerosolized virus (Cheung, Lancet Resp Med, 2020; Tran et al,
PLoS One, 2012).
iii. If passive oxygen is not available, place a surgical face-mask and a blanket over the
patient’s face prior to chest compressions.
iv. If the patient does not have a shockable rhythm, proceed with Rapid Sequence
Intubation as early as possible to limit aerosolization
b. Endotracheal Intubation
i. Endotracheal intubation is the procedure that subjects the rescuer to the highest risk
of infection during resuscitation. To maximize the success rate for intubation, airway
interventions should be carried out by experienced individuals and chest
compressions should be stopped (Cheung, Lancet Resp Med, 2020). This may
deviate from usual cardiac arrest care leading to a pause in chest compressions,
however this is acceptable to maintain the safety of code responders. Please see
“Intubation” chapter.
ii. Chest compressions should resume once the endotracheal tube (ETT) cuff is
inflated and the ETT is connected to the ventilator.
iii. If the pause in chest compressions is excessive and endotracheal intubation does
not seem likely, consider LMA or other extraglottic airway device.
iv. Code responders should distance themselves from the head of the bed during the
intubation procedure (6 ft distance).
v. Continuous capnography device should be used to monitor ventilation (Cheung,
Lancet Resp Med, 2020).
vi. Depending on institutional policies, anesthesia and respiratory therapy may don
higher levels of PPE including PAPR hoods for the intubation procedure.
4. Etiologies to Consider

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a. Data from a retrospective study in Wuhan (Ruan et al, Intensive Care Med, 2020)
revealed cause of death to be:
i. Respiratory failure (53%)
ii. Heart failure with respiratory failure (33%)
iii. Myocardial damage (7%)
iv. Unknown cause (7%)
b. It is important to attempt to identify and treat reversible causes (5H’s, 5T’s) before
stopping the code.
5. Cardiac Arrest Outcomes
a. Early outcomes from China for in-hospital cardiac arrest with attempted resuscitation
(n=136; 113 in general ward, 23 in ICU) (Shao, Resuscitation, 2020):
i. Did not achieve ROSC: 118
ii. Achieved any ROSC: 18
iii. Of those who achieved ROSC, 14 died in hospital, 4 survived at 30-days
b. Initial rhythm of patients with cardiac arrest was
i. Asystole 89%
ii. PEA 4.4%
iii. VF/VT 5.8%
c. Factors associated with ROSC and 30-day survival were initial rhythm and location of
arrest (ICU patients did better than ward patients).
6. Terminating Resuscitative Efforts
a. Avoid prolonged resuscitation if there is no easily reversible etiology identified.
b. No one factor alone, or in combination, is predictive of outcome during cardiac arrest,
however it is reasonable to stop resuscitation efforts if return of spontaneous
circulation (ROSC) has not been achieved within 30 minutes.
c. In intubated patients, failure to achieve an ETCO2 of greater than 10 mm Hg by
waveform capnography after 20 minutes of CPR should be considered as one
component of a multimodal approach to decide when to end resuscitative efforts
(Mancini et al, Circulation, 2015)
7. Post-Resuscitation Care
a. Dispose of, or clean, all equipment used during CPR. Any work surfaces used for
airway/resuscitation equipment will also need to be cleaned.
b. After the resuscitation has ended adhere to strict doffing procedure to limit exposure.

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b. After the resuscitation has ended adhere to strict doffing procedure to limit exposure.
c. If ROSC is achieved, provide usual post-resuscitation care consistent with current
recommended guidelines including targeted temperature management (Donnino et al,
Circulation, 2015).
CHAPTER 9
Hematology
Section Editor: Matthew Moll MD
Contributors: Jean Connors MD, Katelyn Sylvester PharmD, CACP, BCPS, Marlise Luskin
MD MSCE
Thrombotic Disease
Incidence:
1. In ICU patients, cumulative incidences range from 20% to 40% in patients on varying
levels of prophylactic anticoagulation (Klok et al, Thrombosis Res 2020.; Saskia et al,
Preprint 2020.). i
2. In as-yet unpublished BWH data, Dr. Connors et al found 15% (15 of 103) BWH SP-
ICU patients developed venous thromboembolic events (VTE, largely DVTs), despite
100% compliance with VTE ppx (i.e., enoxaparin 40mg qday for standard patients).
Historic BWH ICU VTE rates for patients on prophylactic anticoagulation are
approximately 7%, indicating that there may be a roughly two-fold increase in VTE in
COVID patients specifically.

a. However, only 1% of SPU (Covid-19 floor) patients developed VTE.

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3. Higher D-dimer and FDP levels track with multi-organ dysfunction syndrome and
poorer prognosis (Wang et al, JAMA, 2020; Zhou et al, Lancet, 2020).
Pathophysiology:
1. The mechanism for VTE are unknown and likely multifactorial:

a. Systemic inflammatory response as seen in sepsis
b. Stasis/critical illness
c. Possibly direct endothelial damage from viral injury/ACE2 binding
2. Colleagues from Wuhan have reported finding microthrombi in pulmonary vasculature
on autopsy (Luo et al, Preprints, 2020 preprint), which could contribute to local V/Q
mismatch or hydrostatic changes causing edema. However these mechanisms remain
entirely hypothetical. Our discussions with pathology colleagues indicate more cellular
debris than microthrombi.
3. There is a theory from the SARS epidemic that SARS-CoV1 Spike protein can be
cleaved by FXa and FIIa. Cleavage of the Spike protein activates it which promotes
infectivity (Du, Biochem Biophys Res Com, 2007). By extension, it is hypothesized that
anticoagulation might inhibit SARS-CoV-2 replication, however this remains unproven.
a. There is a small case series suggesting dipyridamole may be useful, though
anticoagulation and antiplatelet agents require further investigation prior to being used
therapeutically (Liu et al, medRxiv, 2020 preprint; Lin et al, Emerging Microbes &
Infections, 2020).
Prophylaxis Management:
1. For floor patients:

a. Given BWH data do not support significantly increased VTE risk in this population
(1%, see above), prophylaxis for SPU (Covid-19) patients remains the same:
i. If CrCl > 30: Lovenox 40 mg SC daily
ii. If CrCl < 30 or AKI: Heparin 5,000 units SC TID
2. For ICU patients and post-ICU patients:
a. Given the elevated VTE risk relative to baseline (15% relative to 7%, see above), our
recommendation for prophylaxis doses for ICU patients and post-ICU patients is now
higher (see table below)
b. Inclusion:

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b. Inclusion:
i. Covid-19 confirmed and PUI patients requiring ICU level of care during ICU course
and after transfer to the floor
ii. Platelets > 25
c. Exclusion:
i. If Platelets <25,000 or bleeding, hold prophylaxis and start TEDs and SCDs
ii. Other exclusion criteria remain the same (e.g., including but not limited to certain
neurosurgery patients, active hemorrhage etc.).
VTE Dosing Weight Adjustment CrCl ≥ 30mL/min CrCl < 30mL/min
Standard Enoxaparin 40mg BID UFH 7,500 units Q8H
Obese (≥120kg or BMI ≥ 35) Enoxaparin 0.5mg/kg BID* UFH 10,000units Q8H
(max dose 100mg BID)
Low Body Weight (< 60kg) Enoxaparin 30mg BID* UFH 7,500 units Q8H
*Consider anti-Xa monitoring to adjust regimens if additional risk of bleeding or

thrombosis. However, routine anti-Xa monitoring is not required for the average patient.
Goal peak anti-Xa for VTE ppx is between 0.2 and < 0.5 (peak should be taken 4-6 hours
after 3-4 injections)
Therapeutic anticoagulation
1. Recommendations for therapeutic anticoagulation of patients with known DVT or PE

remain the same as prior.
a. While some institutions are considering full dose anticoagulation in severe COVID
disease without known VTE, our interpretation of the data is that the risks outweigh
the benefits at this time, unless documented DVT or PE. i
2. If the patient is on direct oral anticoagulants (DOACs) or Warfarin for Afib or VTE,
switch to full dose anticoagulation (LMWH or UFH, as indicated based on renal function
or clinical scenario).
Speculative use of therapeutic anticoagulation or tissue plasminogen activator

(TPA)
1. While therapeutic anticoagulation has been used empirically in some severe COVID-19
patients in Wuhan given the possible microthrombi in pulmonary vasculature (see
“Pathophysiology” above), our interpretation of the data is that the risks outweigh the

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“Pathophysiology” above), our interpretation of the data is that the risks outweigh the
benefits at this time, unless documented DVT or PE (Hardaway et al, Am Surg 2001).
a. Similarly, TPA has been proposed as a possible therapeutic. We recommend against
TPA for ARDS.
b. If high clinical suspicion of PE, consider TPA for salvage/lysis as per usual indications
Disseminated Intravascular Coagulation (DIC)

Incidence/pathophysiology:
1. Limited data: 16 of 183 hospitalized patients in Wuhan had DIC (Tang et al, J Thromb
Haemost, 2020).
2. Laboratory changes in coagulation parameters and FDP track with multi-organ
dysfunction (Zhou et al, Lancet, 2020).
Time course:
1. Median time to onset of DIC was 4 days into hospital admission (Tang et al, J Thromb
Haemost, 2020).
Workup:
1. Identify and treat underlying condition

2. ISTH DIC score (MDcalc online calculator): If score < 5, no DIC; recalculate in 1-2 days
3. Elevated PT/PTT and D-dimer correlate with worse prognosis: trend PT/INR, PTT, D-
dimer, fibrinogen every 3 days until discharge or death
Management:
1. If not bleeding, supportive care:

a. If fibrinogen < 150: FFP, cryoprecipitate or fibrinogen concentrate (RiaSTAP or
Fibryga)
i. RiaSTAP and Fibryga are less volume, but dose must be discussed with
HAT/pharmacy
2. Transfuse platelets if < 30K

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a. Consider holding anticoagulation if the patient requires blood products for supportive
care, though clinician should weigh risks and benefits.
3. If bleeding, give blood products:
a. For elevated PT/PTT and bleeding, use FFP or 4F-PCC (KCentra is less volume, but
must discuss dose with HAT/pharmacy)
b. Hold anticoagulation for active bleeding.
4. Start systemic anticoagulation only if:
a. Overt thromboembolism or organ failure due to clot (i.e., purpura fulminans)
b. There has been no mortality benefit of therapeutic anticoagulation in DIC (Levi et al,
Blood, 2018).
Prognosis:
1. DIC is associated with worse survival in COVID-19 patients. Out of 183 COVID-19
patients in Wuhan, 71% of non-survivors had DIC (ISTH score ≥ 5; MDcalc online
calculator) compared to 0.6% of survivors (Tang et al, J Thromb Haemost, 2020).
Leukopenia
1. This section is in development
Thrombocytopenia
CHAPTER 10
Nephrology
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Nephrology
Section Editor: Ayman Al Jurdi MD, Bina Choi MD
Contributors: Peter Czarnecki MD, Orhan Efe MD
Acute Kidney Injury

Incidence and Pathophysiology
1. Incidence of AKI in COVID-19 varies widely, but estimates range from 0.5% (Guan et
al, NEJM, 2020) to 27% (Diao et al, medRXiv, 2020). The wide range of estimates of
AKI incidence may reflect different populations included in studies (e.g. floor vs ICU
patients).
2. The most likely etiology of AKI is acute tubular necrosis (ATN). An autopsy series from
China (Diao et al, medRXiv, 2020) found severe ATN and interstitial infiltration with
CD68+ macrophages on histopathologic examination of kidney tissue.
Immunohistochemical staining showed viral nucleocapsid protein staining in tubules
and glomeruli, which may explain proteinuria and microscopic hematuria seen in these
patients. Membrane attack complex protein (C5b-9) deposition was also seen in the
tubules, suggesting that activation of the alternative complement pathway may play a
role in tubular injury as well.
3. Areas for future research: Some have hypothesized that there could direct cellular
injury by the virus via angiotensin converting enzyme II (ACE2). COVID-19 uses ACE2
for cell entry. ACE2 is expressed in proximal renal tubules more than glomeruli (Fan et
al, medRxiv, 2020).
Workup:
1. Monitor serum creatinine at least daily
a. Studies find variable onset of AKI, from 7 days (Cheng et al, medRxiv, 2020 preprint)
to 15 days after illness onset (Zhou et al, Lancet, 2020). Onset of AKI more rapid and
severe in patients with underlying CKD (Cheng et al, medRxiv, 2020 preprint)

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severe in patients with underlying CKD (Cheng et al, medRxiv, 2020 preprint)
2. In patients with AKI, order urine electrolytes (urine Na, urea and Cr) and urinalysis with
sediment
a. Patients may present with proteinuria (44%), hematuria (26.9%) (Cheng et al,
medRxiv, 2020 preprint)
b. For patients with proteinuria, quantify proteinuria with spot urine protein-to-creatinine
and albumin-to-creatinine ratios
3. Consider other common etiologies of AKI that can occur in patients who do not have
COVID-19 (e.g. volume depletion, contrast-associated nephropathy, acute interstitial
nephritis and obstruction)
Management:
1. Discontinue all medications that can contribute to AKI (e.g. NSAIDs, ACE inhibitors,
ARBs and diuretics) and avoid using iodinated contrast with CT imaging
2. Consider a gentle fluid challenge (e.g. 1 liter of isotonic crystalloid fluid) to determine if
there is a pre-renal component to AKI, especially in patients with clinical or laboratory
signs suggestive of intravascular volume depletion (e.g. hypotension, tachycardia, dry
mucous membranes, FENa<1% and/or FEurea<35%). Be cautious with fluid
administration in patients with severe hypoxemia (see “Septic Shock” for conservative
fluid recommendations)
3. Consult nephrology for patients with:
a. Creatinine clearance <30 ml/min/1.73m2
b. Volume overload not responsive to diuretics
c. Hyperkalemia (>5.5) not responsive to dietary K restriction and diuretics
Renal Replacement Therapy (RRT)
1. Estimates for RRT range from 1 to 5% of hospitalized patients. Among critically ill
patients, need for CRRT ranges from 5 to 23%
a. Few studies have reported outcomes of RRT. One case series reported that out of
191 patients, 10 received CRRT, and all 10 died (Zhou et al, Lancet, 2020).
2. Renal will be coordinating RRT continuation and initiation
a. Indications for dialysis in COVID-19 patients are the same as the indications for all
patients.
3. ICU nephrology will determine the need, timing, and modality of renal replacement on a

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3. ICU nephrology will determine the need, timing, and modality of renal replacement on a
case-by-case basis.
Prognosis
1. Increased serum creatine, BUN, AKI, proteinuria, or hematuria are each independent
risk factors for in-hospital death (Cheng et al, medRxiv, 2020 preprint)
a. In two other studies, non-survivors had higher BUN and creatinine and higher rates of
AKI (Wang et al, JAMA, 2020; Yang et al, Lancet Respir Med, 2020).
b. Another study found that higher BUN and creatinine are associated with progression
to ARDS, and higher BUN (though not creatinine) is associated with death (HR 1.06-
1.20) (Wu et al, JAMA Intern Med, 2020).
c. In SARS, AKI correlated with poor prognosis and 91.7% of patients with AKI died (vs
8.8% without AKI, p < 0.0001) (Chu et al, Kidney Int, 2005).
CHAPTER 11
Neurology
Section Editor: Erika Williams MD PhD, Henri Vaitkevicius MD
Authors: Priya Srikanth MD PhD
Contributors: Amrit Misra MD
Neurologic complications of COVID-19
Introduction
Incidence

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Incidence
1. Neurologic manifestations are relatively common: 36.4% of 214 COVID-19 inpatients in

a Wuhan hospital exhibited neurological signs and/or symptoms during the course of
infection (Mao, JAMA Neurology, 2020).
a. The most common neurologic symptoms were dizziness (16.8%), headache (13.1%),
impaired consciousness (7.5%), hypogeusia (5.6%), hyposmia (5.1%)
b. Severely ill patients were more likely to have:
i. Neurologic symptoms (45.5% severe vs. 30.2% non-severe, p = 0.02)
ii. Stroke (5.7% severe vs. 0.8% non-severe, p = 0.03)
iii. Impaired consciousness (14.8% severe vs. 2.4% non-severe, p < 0.001)
iv. Skeletal muscle injury (19.3% severe vs. 4.8% non-severe, p < 0.001)
c. Other published reports of COVID-19 related neurological illness will be included in
disease-specific sections as they become available.
2. Lessons from related coronaviruses:
a. MERS-CoV:
i. In a series of 70 patients, 25.7% developed confusion and 8.6% developed seizures
(Saad, Int J Infect Dis, 2014).
ii. Case reports have described acute disseminated encephalomyelitis, ischemic
stroke, encephalitis (Arabi, Infection, 2015), hemorrhagic stroke, critical-illness
polyneuropathy (Algahtani, Case Rep Neurol Med, 2016), acute inflammatory
demyelinating polyneuropathy / Bickerstaff encephalitis, and possible toxic vs.
infectious neuropathies (Kim, J Clin Neurol, 2017)
b. SARS-CoV-1:
i. In a series of 206 patients, 2.4% developed large-artery ischemic strokes (Umapathi,
J Neurol, 2004)
ii. Case reports have described critical illness polyneuropathy and myopathy, and
rhabdomyolysis (Tsai, Arch Neurol, 2004; Tsai, Acta Neurol Taiwan, 2005)
3. Neurological care is complicated by COVID:
a. Patients with underlying neurological disorders may be vulnerable to infections and
respiratory complications (due to immunosuppression, aspiration, respiratory
weakness, poor cough) and often have impaired communication.
b. Patients with COVID often have impaired communication with providers owing to
oxygen delivery devices, proning, and the need for PPE
4. For additional information, this is an excellent resource from our colleagues at Boston

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4. For additional information, this is an excellent resource from our colleagues at Boston
Medical Center.
Pathophysiology
1. Possible mechanisms of neurologic injury include direct viral invasion of the nervous
system, neuronal pathway transport, hypoxia-mediated injury, sequelae of the systemic
pro-inflammatory state, and possibly binding of SARS-CoV-2 to angiotensin-converting
enzyme 2 (ACE2) causing blood-brain barrier damage (Wu, Brain Behav Immun,
2020).
Workup and management
1. See subsections below for specific guidance by indication.

2. Routine neurologic exams:
a. For floor patients without known neurologic dysfunction, recommend neurologic
exams be done every shift, including:
i. Orientation questions, pupil check, facial symmetry, holding extremities antigravity
for 5 seconds, sensation to light touch in extremities
b. ICU patients intubated and sedated for respiratory failure, unable to tolerate SAT:
given risk of respiratory compromise with holding sedation, recommend pupil checks
to be done each shift
c. If able, CAM or CAM-ICU assessment by RN daily
3. PPE considerations for neurologic patients:
a. See PPE section for standard guidelines
b. Seizure and agitated delirium should be considered aerosol-generating
c. Patients who are unable to be screened due to encephalopathy or neurologic deficits
should be treated as COVID-19 rule-out patients until testing results
Headache
Stroke
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Stroke
Incidence
1. In two case series of patients with COVID-19 from a single center in Wuhan,
2.8%-5.0% had strokes (Mao, JAMA Neurology, 2020; Li, Preprint in Lancet, 2020)
a. Ischemic stroke (5%) more common than intracerebral hemorrhage (0.5%) or cerebral
venous sinus thrombosis (0.5%) (Li, Preprint in Lancet, 2020)
i. TOAST classification of 11 observed ischemic strokes:
1. 5 (45.5%) large vessel stenosis
2. 3 (27.3%) small vessel occlusion
3. 3 (27.3%) cardioembolic
ii. Stroke presentation occurred on average 12 days after SARS-CoV-2 infection
b. Stroke more common in “severe” COVID-19 presentations (Mao, JAMA Neurology,
2020)
c. Stroke was associated with older age, risk factors (hypertension, diabetes, prior
cerebrovascular disease), elevated C-reactive protein, and elevated D-dimer (Li,
Preprint in Lancet, 2020)
Presentation
1. Consider stroke in patients who develop acute focal neurological deficits, including
vision loss, unilateral face, arm and/or leg weakness, unilateral sensory loss, dysarthria
or aphasia.
2. Acute stroke meriting emergent workup and neurology consultation should be
considered if the patient’s last seen well is <24h ago
a. Non-focal mental status changes can be caused by stroke but more commonly are
caused by alternative etiologies (see altered mental status section).
Work-up
1. If acute stroke is suspected:
a. Multiple published guidelines exist addressing how to best manage a code stroke
during the COVID-19 pandemic (Khosravani, Stroke, 2020; AHA/ASA Stroke Council,
Stroke, 2020; Baracchini, Neurol Sci, 2020). An outline of our general management is

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Stroke, 2020; Baracchini, Neurol Sci, 2020). An outline of our general management is
below.
b. Check ABCs, obtain vitals (HR, BP, temperature, SpO2), place on telemetry
i. Blood pressure management should be discussed with neurology. General
recommendations:
1. If tPA/intra-arterial therapy (IAT) candidate, initial goal BP < 185/110
2. If not a tPA/IAT candidate, initial goal BP < 220/120
c. Address stroke mimics:
i. STAT finger-stick blood glucose; correct if < 50, > 400 and reassess
ii. Correct SaO2 < 90% as able and reassess
d. While performing above, page acute stroke pager (BWH ED: p31381; BWH inpatient:
p31382 [stroke fellow] and p30342 [stroke consult resident]).
i. Try to establish accurate “last seen well” time as soon as possible
ii. Perform NIHSS, neurology will also perform on arrival
iii. Code Stroke teams will require rapid access to necessary PPE on the floor to
minimize time to patient evaluation while maximizing provider safety
e. Order STAT non-contrast head CT and CTA of head and neck. Call CT and tell them
the patient is an acute stroke and if COVID-19 positive or PUI. Clarify which scanner
the patient will be going to.
i. Discuss with neurology before ordering MRI given comparative ease of CT scanner
sterilization and sufficient utility of CT for clinical decision-making
f. Ensure the patient has at least one 18 gauge IV in an upper extremity for contrast
scan and prepare patient for transport
i. COVID-19 rule-out and positive patients will be scanned wearing a surgical mask
and cover with a sheet with adherence to standard PPE procedures
g. Draw labs as below if not performed within 24 hours (scan should not be delayed
for lab draw)
h. Keep patient NPO, HOB > 30°, prepare patient for imaging (eg supinate if proned,
place sling under patient if needed)
2. Ischemic Stroke Workup: Discuss with neurology consultant for tailored

recommendations based on clinical presentation
Imaging workup Lab workup
- Vessel imaging: CTA head and neck preferred. If - Finger-stick blood glucose
unable to obtain, consider MRA head and neck or

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unable to obtain, consider MRA head and neck or - CBC w/ differential
carotid US/TCDs
- BMP, LFTs
- Defer MRI unless likely to change short-term
- PT/INR, PTT, D-dimer
management
- Lipid panel
- TTE:
- HgbA1C
- Defer until patient off precautions unless likely to - TSH
change short-term management (eg concern for
- Troponin, NT-proBNP
endocarditis)
- ESR, CRP, fibrinogen,
- Consider with bubble in patients < 60 years old
ferritin, procalcitonin
- Consider with LV contrast particularly if high
- Blood cultures
concern for LV thrombus as embolic source
- EKG - Consider
hypercoagulability workup
- Telemetry while inpatient
in patients < 60 years old:
- If stroke confirmed and mechanism unclear,
- Homocysteine
consider 30 day mobile cardiac telemetry or LINQ
(if no known AFib) - Lupus anticoagulant,
DRVVT
- Anti-cardiolipin Ab (IgG
and IgM)
- Beta-2-glycoprotein Ab
- Protein C, Protein S
- Anti-Thrombin III
- Factor V Leiden
- Prothrombin Gene
Mutation (G20210A)
Management
1. Ischemic stroke:
a. Consult neurology, if not already done
b. Neurology to guide determination of eligibility for tPA and/or intra-arterial therapy
(IAT), as well as further treatment recommendations. General guidelines below.
i. Note: tPA increases D-dimer levels and decreases fibrinogen levels for at least 24
hrs (Skoloudik, J Thromb Thrombolysis, 2010). D-dimer should not be used for
COVID prognostication post-tPA.

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COVID prognostication post-tPA.
ii. If IAT is being considered, strongly consider intubating patient in discussion with
stroke team.
tPA IAT
Inclusion Exclusion criteria Inclusion Extended window inclusion
criteria criteria criteria
- Last see - Use of DOACs - Last seen - Last seen well ≤ 24 h
well < 4.5 within 48h well < 6 h - Life expectancy > 12 mo
h - Current / prior - Age > 18 - Advanced imaging criteria
- Age > 18 intracranial - Large Vessel (with neurology, consider
- Disabling hemorrhage Occlusion MRI, CT perfusion)
neurologic - Hypodensity > (LVO)
deficit cerebral present
- Plt > hemisphere on - NIHSS ≥ 6
100K CT
- MRS ≤ 1
- INR < 1.7 - TBI/stroke/brain (varies)
surgery < 3
- SBP - ASPECTS
months
<185/110 score ≥ 6
- Major surgery <
- SBP <
2 weeks
185/110
- GI hemorrhage
< 3 weeks
- Vascular
malformations
- Intracranial
neoplasm
c. Medications:
i. If tPA not given and not on anticoagulation or at high risk of bleeding: give aspirin
325 mg PO (or 300 mg PR)
ii. High-intensity statin, eg atorvastatin 80 mg PO QHS (ok to defer if no enteral
access), goal LDL < 70
iii. Discuss with neurology ongoing antiplatelet therapy or anticoagulation based on
clinical presentation
iv. Consider fluoxetine 20 mg QD x 90 days, starting 5 days after stroke onset (Chollet,
Lancet Neurol, 2011)

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Lancet Neurol, 2011)
v. Ensure on DVT prophylaxis if clinically appropriate
d. Post-stroke monitoring:
i. If intubation required for IAT, patients will not be extubated in the OR, but in negative
pressure room in intensive care
ii. NPO until RN documents swallow screen, consider nasogastric tube if needed for
enteral access
iii. Neurologic exam and vital signs:
1. Follow existing institutional guidelines regarding frequency of vital signs and
neurologic exams post-tPA or post-IAT
2. If no tPA/IAT:
a. Patient stable: neuro exams and VS Q4H x 24 h then Q8H if remains stable
b. Patient unstable or high-acuity insult (large territory MCA infarct, posterior fossa
stroke): neuro exams and VS Q1-2H x 24H then Q4H if stable
3. Maintain telemetry
4. Blood pressure goals should be discussed with neurology. General guidelines:
a. If given tPA: BP < 180/105
b. If successful IAT: SBP < 140
c. If no tPA/IAT: SBP < 220 x 24 h then decrease by ~20% per day to inpatient goal
SBP < 160
d. Outpatient goal SBP < 130-140
iv. STAT non-contrast head CT for change in neurologic exam
1. If hemorrhage identified < 24 h post-tPA, draw STAT fibrinogen to guide possible
tPA reversal (see intracranial hemorrhage management)
v. Post-tPA considerations:
1. When more frequent exams are clinically indicated (eg q15min post-tPA), as able,
the same provider should remain in the room and perform these exams to
conserve PPE
2. Bedrest x 8 h post-tPA administration
3. Defer if able until 24 h post-tPA: venous / arterial puncture, bladder catheterization,
nasogastric tube placement
4. Hold pharmacologic DVT prophylaxis and antithrombotics until confirmed absence
of intracranial hemorrhage on 24 h post-tPA non-contrast head CT
5. Obtain non-contrast head CT 24 h after administration

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5. Obtain non-contrast head CT 24 h after administration
a. If ICU beds are limited, consider prior to 24 h: check fibrinogen and if > 150 can
expedite post-tPA head CT in order to facilitate floor transfer
b. If no hemorrhage, can start pharmacologic DVT prophylaxis and antiplatelet /
anticoagulation per discussion with neurology
e. General post-stroke care:
i. Recommend PT/OT/SLP consults if appropriate
ii. Goal euthermia, use antipyretics as needed. If unable to control fever consider
cooling blanket
iii. Goal euglycemia (FSBG 80-140)
iv. Magnesium goal >2
v. Smoking cessation counseling and nicotine replacement therapy if needed
2. Intracranial Hemorrhage:
a. Consult neurology. Consider neurosurgical consultation, especially for:
i. Any rapidly expanding hemorrhage
ii. Intraparenchymal hemorrhage in cerebellum or with significant mass effect
iii. Intraventricular hemorrhage
iv. Subarachnoid hemorrhage
v. Subdural hemorrhage > 1 cm or with significant mass effect
vi. Epidural hemorrhage
b. Blood pressure control:
i. Goal SBP < 140 x 24 h then SBP < 160 if stable
ii. Attempt IV pushes:
1. Labetalol 5-20 mg IV Q4H PRN (if HR allows)
2. Hydralazine 5-20 mg IV Q4H PRN
iii. If BP very elevated and/or refractory to IV pushes, consider continuous infusions:
1. Nicardipine 0-15 mg/h, or
2. Labetalol 0-4 mg/min, or
3. Nitroglycerin 0-200 mcg/min
iv. If requiring continuous infusion, place arterial line to facilitate monitoring and
recommend ICU level of care
v. Start and/or up-titrate PO antihypertensives as needed in conjunction with above

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v. Start and/or up-titrate PO antihypertensives as needed in conjunction with above
c. Reverse anticoagulation:
Anticoagulant Reversal Dose

Agent
Warfarin Vitamin K and 10mg IV over 10min
Kcentra INR > 6: 50 IU/kg
INR > 4: 35 IU/kg
INR < 4: 25 IU/kg
or Profilnine INR > 4: 50 IU/kg
SD INR < 4: 25 IU/kg
or FFP 10 cc/kg (~3-5 units for 70 kg)
tPA RiaSTAP fibrinogen > 150: 2 vials
fibrinogen < 150: 2+2 vials
Cryoprecipitate fibrinogen < 150: 20+20 units
fibrinogen > 150: 20 units
Heparin Protamine 1mg/100 heparin units over the last 4 h
Hematology consult recommended
Enoxaparin* Protamine If < 8h: 1mg/mg of enoxaparin
If > 8h: 0.5mg/mg of enoxaparin
Aspirin* Platelets 6 pack; not recommended for all patients,

consider if patient going for cranial surgery or
Plavix*
plt < 100
Rivaroxaban, Andexanet alfa - High dose order panel (800 mg IV followed by
Apixaban, 960 mg over 120 min):
Edoxaban**
- Apixaban dose > 5 mg or unknown and [given
< 8 h ago or unknown time within last 18 h]
- Rivaroxaban dose > 10 mg or unknown and
[given < 8 h ago or unknown time within last 18
h]
- Low dose order panel (400 mg IV followed by
480 mg over 120 min):
- Apixaban dose > 5 mg or unknown and given
8-18 h ago
- Apixaban dose ≤ 5 mg and given < 18 h ago

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- Apixaban dose ≤ 5 mg and given < 18 h ago
- Rivaroxaban dose > 10 mg or unknown and
given 8-18 h ago
- Rivaroxaban dose ≤ 10 mg and given < 18 h
ago
Kcentra 35 IU/kg
Dabigatran Idarucizumab 5g IV x1
FEIBA 100 units/kg
Fondaparinux* Factor VIIa 90 mg/kg
Argatroban* ddAVP 0.3 mg/kg over 30 min
Cryoprecipitate 10 units
Uremia* ddAVP 0.3 mg/kg over 30 min
* Limited data, consider in emergent situations
** Andexanet alfa not currently FDA approved for edoxaban, phase III study ongoing;
would consult hematology
d. Imaging considerations:
i. Recommend CTA head to evaluate for vascular abnormalities (excepti if isolated
subdural hemorrhage)
ii. STAT non-contrast head CT for any change in neurologic exam
iii. Repeat non-contrast head CT 4-6 h after initial scan to assess stability
1. If clinically or radiographically worsening, contact neurology / neurosurgery
consultant
iv. Consider non-urgent MRI brain either during admission or within 3 months if etiology
unclear (eg to evaluate for supporting evidence of cerebral amyloid angiopathy or
underlying tumor)
e. Medications:
i. Antihypertensives as above
ii. Hold all antiplatelets and anticoagulants; discuss timing of resumption with
neurology / neurosurgery
iii. Hold pharmacologic DVT prophylaxis until 48 h after radiographic stability
iv. Prophylactic AED recommended for traumatic subarachnoid hemorrhage and
traumatic subdural hemorrhage

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traumatic subdural hemorrhage
1. If normal renal function, keppra 500 mg x 7 days
2. Adjust dosing for renal impairment in discussion with pharmacy or neurology
f. Monitoring:
i. Patient stable and small hemorrhage: neuro exams and VS Q4H x 24 h then Q8H if
remains stable
ii. Patient unstable or high-acuity insult (large hemorrhage, cerebellar hemorrhage,
significant intraventricular hemorrhage): neuro exams and VS Q1-2H x 24H then
Q4H if stable
iii. Discuss with neurology / neurosurgery when in doubt
iv. Consider transfer to neurosciences ICU if patient: requires neurosurgical
intervention, at high risk of elevated ICP, has rapidly worsening neurologic exam, or
has expanding hemorrhage
g. Post-intracranial hemorrhage care:
i. NPO until RN documents swallow screen, consider nasogastric tube if needed for
enteral access
ii. HOB > 30°
iii. Recommend PT/OT/SLP consults if appropriate
iv. Goal eunatremia
v. Goal euthermia, use antipyretics as needed. If unable to control fever consider
cooling blanket
Seizure and Status Epilepticus

Incidence
1. There is currently little published data regarding the frequency of seizure presentation
from COVID-19 infection
a. SARS-CoV-2: In a series of 214 patients, 1 patient had a generalized seizure lasting 3
minutes (Mao, JAMA Neurology, 2020)
b. MERS-CoV: In a series of 70 patients, 8.6% developed seizures (Saad, Int J Infect
Dis, 2014)
c. Non-SARS non-MERS CoV: In a series of 64 children with HCoV, 7.8% had seizures
(Dominguez, J Med Virol, 2009)
d. Seizures may present as part of a constellation of more fulminant neurological insults,

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d. Seizures may present as part of a constellation of more fulminant neurological insults,
with imaging abnormalities (Li, Intervirology, 2016).
2. Epileptic patients with COVID-19 infection will likely have a higher than normal level of
breakthrough seizure activity given changes in medication adherence, metabolism, and
active infection (Lai, Seizure, 2005). There should be a low threshold to check levels of
home AEDs and check for medication interactions.
Definitions
1. Seizure: generally a sudden change in behavior resulting from uncontrolled

synchronous electrical activity of a neuronal network
2. Status epilepticus (SE): > 5 minutes continuous electrographic or clinical seizure
activity OR recurrent seizure activity without return to neurologic baseline between
seizures
a. Generalized convulsive SE: rhythmic jerking of extremities and impaired
consciousness
b. Focal motor SE: focal jerking of one limb or one side of the body
c. Non-convulsive SE: electrographic seizure activity meeting SE criteria, without clinical
findings consistent with convulsive SE
i. Includes subclinical seizures, depressed mental status associated with seizure, or
subtle clinical findings not consistent with convulsive SE
d. Refractory SE: continued seizures after benzodiazepine and 1 second line AED
e. Super refractory SE: continued seizures despite adequate burst suppression attempt
3. Epilepsy: brain disorder characterized by an underlying predisposition to generate
seizures, including 2 or more unprovoked seizures
4. Self-limited typical seizure in patient with known epilepsy: patient’s typical seizure
semiology with return to neurologic baseline after typical post-ictal period
5. Atypical seizure in patient with known epilepsy: different from prior seizure
semiologies in clinical presentation, duration, post-ictal period, or with persistent new
neurologic deficit(s)
6. Psychogenic Non-Epileptic Seizures (PNES): episodic changes in behavior that
resemble epileptic seizures clinically, but without electrographic correlate
Workup
1. Note that seizure should be considered aerosol generating, providers should don
appropriate PPE

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appropriate PPE
2. Isolated seizure:
a. ABCs and vital signs
b. Initial diagnostics:
i. FSBG
ii. Laboratory tests: CBC with differential, comprehensive metabolic panel, magnesium,
phosphorus, ionized calcium, ammonia, UA/UCx, serum toxicology (including
ethanol), urine toxicology, creatine kinase, lactate, ESR, CRP, ferritin, fibrinogen,
COVID-19 PCR
1. hCG (females)
2. Home anti-epileptic drug (AED) levels (if applicable)
3. Consider ABG/VBG, blood cultures, respiratory viral studies if appropriate clinical
history
4. Consider prolactin; if obtained within 10-20 min after the convulsion, helpful to
differentiate epileptic/cardiovascular event from PNES
iii. EKG, CXR
c. Imaging:
i. Non-contrast head CT
ii. Consider MRI brain with contrast, seizure protocol. Can defer until patient off
COVID-19 precautions unless likely to change short-term management.
iii. Defer imaging for self-limited typical seizure in patient with known epilepsy
d. Consider routine EEG for first seizure or atypical seizure
i. Can defer until patient off COVID-19 precautions unless likely to change short-term
management
e. Consider LP in select circumstances - may discuss with neurology
i. Patient febrile without clear source, has meningeal signs, or has altered mental
status
ii. Immunocompromised patient
iii. COVID-19 positive patients
f. History: Prodrome, triggers (medications, AED nonadherence, infectious symptoms,
substance use or withdrawal, sleep deprivation), timing (duration of seizure and post-
ictal state), psychiatric history, known brain anomalies or structural abnormalities,
history of TBI

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history of TBI
g. Exam: Evaluate for depressed mental status or any focal neurologic deficit
h. Consult neurology if no clear trigger (eg alcohol withdrawal, AED nonadherence) or if
uncertain regarding workup/management
3. Status epilepticus:
a. Labs, history as above
b. Imaging
i. Non-contrast head CT (can defer if able to obtain MRI quickly)
ii. MRI with contrast seizure protocol
c. Consider LP: obtain opening pressure, culture and smear, protein, glucose, cell count
and differential (tubes 1 & 4), save extra for additional studies
d. Long-term EEG monitoring
Management
1. All seizures:
a. Monitor airway patency and oxygenation/ventilation. Consider intubation if:
i. Patient unable to maintain airway or oxygenation/ventilation with supportive
measures, OR
ii. Persistent convulsive seizure activity despite first and second-line AEDs below
b. Vitals sign monitoring: start telemetry, HR, pulse ox, temperature, BP (cycle Q15min
initially, then Q4H if stable)
c. Ensure at least 2 peripheral IVs
d. Obtain FSBG, correct if < 50 and empirically administer 100 mg IV thiamine prior to
dextrose (especially for patients with unknown medical history)
e. Workup as above, correct any toxic or metabolic abnormalities and fever if present
f. For ongoing seizure activity: within 5 minutes, do not delay for diagnostics
i. First-line AED:
1. Give home acute seizure plan if known
2. If no known seizure plan: give lorazepam 2-4 mg IV once. If no effect in 5 minutes
consult neurology and repeat lorazepam 2-4 mg IV if respiratory status will
tolerate
3. If no IV options available give midazolam 10mg IM or diazepam 20mg PR

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ii. If persistent seizure activity despite above, proceed to “Status epilepticus
management” section
g. Maintenance AED therapy:
i. First seizure: discuss with neurology, AED may not be indicated for provoked
seizure or single unprovoked seizure with normal imaging and normal EEG
ii. Self-limited typical seizure with clear provoking factor: address trigger, resume home
AEDs and follow-up levels as above
iii. Atypical seizure or self-limited typical seizure without clear provoking factor: Discuss
with patient’s outpatient neurologist if changes need to be made to AEDs. If unable
to contact outpatient neurologist, consult neurology.
iv. Drug Interactions:
1. A helpful resource of medication interactions specific to COVID-19 patients can be
found here.
2. AEDs are notorious for interacting with other medications (Johannessen, Curr
Neuropharmacol, 2010). A few specific considerations:
a. Phenytoin, Carbamazepine, Phenobarb: reduce levels of warfarin, doxycycline,
metronidazole, some antivirals (indinavir), haldol, valproic acid
b. Valproic acid increases levels of carbapenem antibiotics
c. Macrolide antibiotics alter carbamazepine levels, rifampin alters lamotrigine
levels, isoniazid alters phenytoin and valproic acid levels
AED characteristics
AED PO:IV Goal Considerations Side Effects
Level
Levetiracetam 1:1 No goal, Renally cleared, Psychiatric sx (irritability,
(Keppra) level to adjust dosing per anxiety, depression,
check renal function. sedation, psychosis).
adherence
Valproic acid 1:1 50-100 Avoid in patients Teratogenic. Abnormal
(Depakote) mcg/mL with hepatic LFTs, weight gain, N/V,
(>1h post dysfunction or encephalopathy ( NH3),
load) thrombocytopenia. pancreatitis,
Check carefully thrombocytopenia. Good
for drug for mood disorders.
interactions.
Phenytoin 1:1 10-20 Avoid in patients Teratogenic. Gingival

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Phenytoin 1:1 10-20 Avoid in patients Teratogenic. Gingival
(Dilantin), mcg/mL, with hepatic hypertrophy, hair growth,
Fosphenytoin correct for dysfunction or rash, AMS, diplopia,
alb, (2h cardiac ataxia, slurred speech,
post load) dysfunction / hypotension / arrhythmia
arrhythmias. (if run faster than
Check carefully 50mg/min; Fosphenytoin is
for drug less cardiotoxic).
interactions.
Lamotrigine 1:1 1-13 mg/L Requires slow Rash, SJS, nausea,
(Lamictal) uptitration. somnolence, dizziness,
ataxia. Good in mood
disorders.
Topiramate Only N/A Weak carbonic Weight loss, fatigue,
(Topamax) PO anhydrase teratogenic.
inhibitor, avoid in Nephrolithiasis, cognitive,
renal dysfunction. anxiety, anorexia, tremor
Lacosamide 1:1 N/A Avoid in patients Headache, diplopia,
(Vimpat) with cardiac dizziness, nausea,
dysfunction or hypotension. Obtain EKG
arrhythmias after load, and watch for
(especially AV PR prolongation.
block).
Carbamazepine Only 4-12 Check carefully SIADH, N/V/D, rash,
(Tegretol) PO mcg/mL for drug pruritis, fatigue, blurred
interactions. vision, diplopia, lethargy.
h. Order seizure precautions during hospitalization

i. Discharge instructions:
i. Do not drive for 6 months following a seizure / episode of loss of consciousness per
Massachusetts law. Further information can be found at
https://www.epilepsy.com/driving-laws/2008746.
ii. Do not climb on ladders, work at heights (eg on a roof) or operate heavy machinery
for 6 months.
iii. Only take a bath or go swimming if others are around and can help you (eg leave
the bathroom door unlocked).

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a. Treat acute seizure as above including ABCs, VS, first line AED, and consult
neurology
b. Start second-line AED if no response to benzodiazepines within 5-10 min
c. Start third-line AED if no response to second-line AED within 20-30 min
i. Intubate patient, discuss with neurology if neurosciences ICU transfer is appropriate
Status Epilepticus Management

Drug Dose
First line AED
Lorazepam 0.1 mg/kg (up to 4 mg/dose); repeat once in 5-10 min (max total dose 8
mg)
Diazepam 0.15 mg/kg IV (up to 10 mg/dose); repeat every 3-5 min (max total
dose 10 mg)
Midazolam 0.2 mg/kg IM (up to 10 mg/dose)
Second Line AED
Levetiracetam 60 mg/kg IV (max 4.5g), over 15 min (Best side effect and drug
interaction profile, renally cleared so load on the lower side in AKI)
Valproic acid 40 mg/kg IV (max 3g), no faster than 200 mg/min (Avoid in liver failure
or if using liver metabolized drugs - enzyme inhibitor)
Fosphenytoin/ 20 mg phenytoin equivalents/kg (max 1500 mgPE)
Phenytoin If using phenytoin, no faster than 50 mg/min (Avoid in myocarditis, or
other cardiac pathology. Can cause arrhythmia and hypotension. Liver
enzyme inducer.)
Lacosamide 200-400 mg IV over 1 hour (Avoid in myocarditis or other conduction

disease. Causes PR prolongation.)
Third Line AED
Propofol 1-2 mg/kg loading dose; 20-83 mcg/kg/min infusion
Monitor for propofol infusion syndrome if > 67mcg/kg/min for > 48 hrs
(EKG, creatine kinase, triglycerides, amylase, lipase, troponin, liver
function tests, urine myoglobin)

Midazolam 0.2 mg/kg loading dose; 0.05-2 mg/kg/h infusion

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Pentobarbital 5-15 mg/kg loading dose; 0.5-5 mg/kg/h infusion
Ketamine 0.5-4.5 mg/kg loading dose; 0-5 mg/kg/h infusion
Lidocaine 100 mg IV; may repeat in 30 min
Altered Mental Status

Incidence
1. SARS-CoV-2: In a series of 214 hospitalized patients, 7.5% had impaired

consciousness, including confusion and delirium. Median time to onset was 8 days
after admission (Mao, JAMA Neurology, 2020).
a. More common in severe cases (14.8%) compared to non-severe cases (2.4%)
2. MERS-CoV: In a series of 70 patients, 25.7% developed confusion (Saad, Int J Infect
Dis, 2014).
3. Altered mental status (AMS) is common in a diverse array of illness
4. Delirium, characterized by waxing and waning arousal and impaired attention, is
common in ill patients of advanced age and with multiple comorbidities.
a. Prior studies have shown that 83.3% of ICU patients develop delirium. Delirium was
present in 39.5% of easily arousable patients and persisted in 10.4% of patients at
discharge (Ely, JAMA, 2011).
Workup
1. Initial evaluation:
a. Note that agitated delirium should be considered aerosol generating, providers
should don appropriate PPE
b. Ddx includes: metabolic derangements, infection, medication effect / toxins, primary
CNS dysfunction, delirium (due to an underlying systemic cause and/or hospital-
acquired)
c. Particular considerations for COVID-19 patients:
i. Metabolic derangements:
1. Hypoxemia or hypercarbia due to respiratory failure

2. Renal or hepatic dysfunction that may present with COVID-19
3. Nutritional deficiencies (eg thiamine) in patients with poor nutritional status

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3. Nutritional deficiencies (eg thiamine) in patients with poor nutritional status
ii. Infection:
1. In addition to SARS-CoV-2 infection, consider other concurrent or hospital-acquired
infections (eg HAP, CAUTI, CLABSI)
iii. Medication effects:
1. Sedation required for prolonged intubation
2. Antibiotics used for empiric pneumonia or sepsis treatment, especially
cephalosporins and quinolones (Bhattacharyya, Neurology, 2016)
iv. Primary CNS dysfunction:
1. 2.8%-5.0% risk of stroke in COVID-19 patients (Mao, JAMA Neurology, 2020; Li,
Preprint in Lancet, 2020)
2. Reports of COVID-19-associated seizure, acute necrotizing encephalopathy, and
meningoencephalitis (Mao, JAMA Neurology, 2020; Poyiadji, Radiology, 2020;
Moriguchi, Int J Inf Dis, 2020)
Evaluation Considerations
ABCs and vitals - Consider intubation if unable to protect
EKG airway due to AMS
- SpO2 - hypoxemia may contribute
- RR - if low, consider hypercarbia
- BP - hypotension / hypertension can
contribute
- HR and EKG - hypoperfusion due to
arrythmia
Neurologic exam - Level of arousal, attention (eg days of week
backwards), command following, evaluate
for focal weakness
- Check for asterixis, myoclonus
Basic diagnostic evaluation - FSBG

- CBC with diff, BMP, LFTs
- UA, UCx, BCx
- Lactate
- Ammonia
- VBG or ABG

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- VBG or ABG
- B12
- treponemal Ab
- TSH w reflex fT4
- CXR
- Bladder scan
- Consider COVID-19 PCR
- Consider AM cortisol if hyperkalemia and/or
hyponatremia
- Consider ESR, CRP, urine/serum tox
Symptom review - Pain

- Constipation
- Urinary retention
- Sleep-wake cycle disturbance
Review for common medication - Benzodiazepines
classes that can contribute to AMS - Opiates
(subset listed here)
- Antibiotics (eg cephalosporins, quinolones)
- Anti-cholinergic medications (eg
diphenhydramine, hydroxyzine, meclizine,
amitriptyline)
- Muscle relaxants (eg tizanidine,
cyclobenzaprine, baclofen)
2. Neurologic evaluation:
a. If above evaluation is unrevealing, or if abnormalities are corrected and mental status
remains altered, recommend neurology consultation to discuss:
i. Imaging:
1. MRI with contrast once patient off COVID-19 precautions
2. If concerned for an acute neurologic etiology and MRI unable to be performed
quickly, perform non-contrast head CT.
ii. Routine EEG
1. Defer until patient off COVID-19 precautions unless likely to change short-term
management
iii. Lumbar puncture (especially if fever without clear source, meningeal signs, or focal

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iii. Lumbar puncture (especially if fever without clear source, meningeal signs, or focal
neurologic findings not explained by above studies)
1. Opening pressure, culture and smear, protein, glucose, cell count and differential
(tubes 1 & 4), save extra for additional studies
Management
1. Treat specific causes as discovered in workup.

2. Minimize or discontinue medications that may be contributing to AMS.
3. If evidence of primary CNS dysfunction on imaging, EEG, or LP, discuss management
with neurology.
4. Treat for delirium as discussed in the palliative care section.
Management for patients with pre-existing neurologic

conditions
CHAPTER 12
Gastroenterology
Section Editor: Emilie Mitten, MD
Contributors: Kunal Jajoo MD, Bina Choi MD

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Fecal Viral Shedding and Transmission
1. Pathophysiology:
a. SARS-CoV-2 infects host cells by binding to the host receptor, ACE2. ACE2 is
expressed in enterocytes of the ileum and colon (Qi et al, Biochem and Biophys Res.
Com., 2020).
i. To date, biopsy data is limited. There is one report of positive immunofluorescent
staining for the viral nucleocapsid protein in luminal biopsies from a patient with
severe COVID-19 (Xiao et al, Gastroenterology, 2020).
i
ii. Similarities are seen with SARS.
2. Incidence:
a. About 50-55% of hospitalized patients have detectable levels of SARS-CoV-2 RNA in
the stool (Young et al, JAMA, 2020; Xiao et al, Gastroenterology, 2020; Wu et al,
Lancet, 2020).
b. There is now a report of successful culture of the COVID-19 virus from a single stool
specimen (WHO, Scientific Brief, 2020).
3. Correlation with symptoms:
a. Viral shedding in the stool does not correlate with gastrointestinal symptoms or
diarrhea (Amirian, Preprints, 2020; Zhang et al, J Med Virol, 2020; Amirian, Preprints,
2020; Young et al, JAMA, 2020).
i
i.
b. The duration of viral shedding in the respiratory tract is similar in those with and
i
without viral shedding in the stool (Wu et al, Lancet Gastroenterol Hepatol, 2020).
i. Neither the presence of viral shedding in stool or the duration of such shedding
appears to be correlated with the severity of pulmonary disease (Zhang et al, J Med
Virol, 2020).
c. Indices of inflammation are similar in those with and without viral shedding in the stool
(Ling et al, Chin Med J, 2020).
4. Duration:
a. Viral shedding in stool takes roughly 2-4 weeks to clear (Wu et al, Lancet, 2020).
i. Persistent shedding is seen in patients who have clinically recovered from illness
(Amirian, Preprints, 2020; Ling et al, Chin Med J, 2020).
ii. Shedding in the stool is prolonged in patients taking glucocorticoids.

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ii. Shedding in the stool is prolonged in patients taking glucocorticoids.
i
1.
iii. Shedding in the stool lags behind shedding in the respiratory tract and oropharynx,
in terms of both onset and clearance (Wu et al, Lancet, 2020; Ling et al, Chin Med J,
2020; Xiao et al, Gastroenterology, 2020; Zhang et al, Emerg Microbes Infect,
2020).
5. Transmission:
a. The infectivity of RNA-positive stool remains unclear.
b. Until proven otherwise, stool should be assumed to be infectious.
i. Healthcare workers should use appropriate PPE while handling feces and disposing
of material contaminated by feces (Amirian, Preprints, 2020).
ii. Frequent and extensive cleaning of bathrooms is important.
c. Both upper and lower endoscopy are considered aerosolizing procedures.
i. Obtain GI / Hepatology consultation to determine timing of endoscopic procedures.
ii. Society recommendations for the timing of endoscopic procedures and protection
during endoscopy can be found here:
1. The Joint GI Society “Clinical Insights” for Gastroenterologists during the COVID-
19 pandemic can be found here: Joint GI Society Message, March 23, 2020.
2. The European Society of Gastroenterology and Endoscopy Nurses and Associates
“Position Statement” on endoscopy during the COVID-19 pandemic can be found
here: ESGE / ESGENA, Position Statement on Endoscopy, March 18, 2020.
6. Testing recommendations:
a. We recommend against the addition of stool testing to nasopharyngeal testing for the
purpose of diagnosing COVID-19, as respiratory samples are often positive prior to
stool samples (Wu et al, Lancet Gastroenterol Hepatol, 2020).
b. We do not currently test fecal samples for clearance, though this may change in the
future, as stool samples often remain positive after respiratory samples have cleared
(Wu et al, Lancet Gastroenterol Hepatol, 2020).
7. Fecal Microbiota Transplant:
a. If the patient has C. Difficile, the FDA has put the clinical use of fecal microbiota
transplantation (FMT) on hold until there are proper donor screening protocols in
place for COVID-19 (FDA Safety Alert).

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Luminal disease
Overview
1. Incidence:
a. The incidence of gastrointestinal symptoms is variable across studies, from <5% to
50%. (Huang et al, The Lancet, 2020; Zhou et al, Gastroenterology, 2020; Wang et al,
JAMA, 2020; Luo et al, Clin. Gastro, 2020; Pan et al, The Am. J. Gastroenterol,
2020).
i. This variability may be due to differences in study populations, biases in patient or
provider reporting, and/or differences in definitions. In particular, the incidence of
gastrointestinal symptoms varies based on whether or not anorexia is included as
such a symptom. i
b. Of those with GI symptoms, typical complaints include:
i. Anorexia (seen in 78-98% of those with gastrointestinal symptoms)
ii. Diarrhea (seen in 34-37% of those with gastrointestinal symptoms)
1. High volume or clinically severe diarrhea is not common
iii. Nausea (seen in 73% of those with gastrointestinal symptoms)
iv. Vomiting (seen in <5-65% of those with gastrointestinal symptoms)
v. Abdominal pain (seen in <5-25% of those with gastrointestinal symptoms)
vi. Sources: (Luo et al, Clinical Gastroenterology and Hepatology, 2020; Pan et al, The
Am. J. Gastroenterol, 2020)
c. Very few patients have gastrointestinal symptoms as the only manifestation of
infection throughout their course of illness (Pan et al, The Am. J. Gastroenterol, 2020;
Hosoda, Infect Control Hosp Epidemiol, 2020). i
2. Clinical course:
a. Gastrointestinal symptoms commonly precede respiratory symptoms by 1-2 days
(Wang et al, JAMA, 2020; Amirian, Preprints, 2020; Pan et al, The Am. J.
Gastroenterol, 2020).
b. GI symptoms are associated with an increased likelihood of having elevated
aminotransferase levels, but not associated with duration of admission, days in
intensive care, or mortality (Pan et al, The Am. J. Gastroenterol, 2020).
3. Pathophysiology:
a. Several potential mechanisms include:

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i. Direct damage to the intestinal mucosa via viral infection (see Viral Shedding)
i
ii. Indirect alterations in mucosal immunity via the “gut-lung axis”.
iii. Adverse medication effects i or secondary infections, especially if symptoms arise
later in the course of disease.
Workup
1. COVID-19 testing is not recommended for patients presenting with mild GI symptoms
in the absence of other COVID-19 symptoms.
a. Patients should be educated that gastrointestinal symptoms may precede the onset of
respiratory symptoms and be given strict return precautions.
2. In patients with suspected or known COVID-19 disease, always remember to consider
non-COVID-19 etiologies for gastrointestinal symptoms
a. Workup will depend on the nature and severity of the symptoms:
i. Basic laboratories are included in the workup described in chapter 2.
ii. More extensive laboratory evaluation (such as lipase, amylase, lactate, Clostridium
difficile testing) and more extensive imaging (such as CT abdomen / pelvis,
abdominal US, or pelvic US) may be indicated.
1. Do not miss critical conditions for concerns about transport to imaging.
iii. Surgical and/or gastroenterology consultation may be indicated.
Management
1. The gastrointestinal manifestations of COVID-19 (such as diarrhea, loose stool,

nausea, vomiting, abdominal pain) are generally mild and transient
a. Treat symptomatically
b. If symptoms are not mild and transient, consider alternative etiologies, including drug
side effects and secondary infections
Liver disease
Overview
1. Incidence:

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a. About 15-50% of patients with COVID-19 have abnormal liver function tests (LFTs)
(Zhang et al, Lancet Gastroenterol Hepatol, 2020; Xu et al, Liver International, 2020;
Fan et al, MedRxiv, 2020).
i. The variability in the incidence may be due to differences in disease severity,
multiple etiologies hepatic injury (such as direct viral injury, indirect inflammatory
injury, drug-induced injury), as well as non-hepatic sources of elevated
transaminases.
2. Pattern and severity of liver injury:
a. The pattern of injury is predominately hepatocellular. Elevations in the following are
seen:
i. AST and ALT are seen in 18-78% and 18-28% of patients, respectively.
ii. Total bilirubin is seen in 5-6% of patients.
iii. Alkaline phosphatase is rare (seen in <4% of patients).
iv. GGT is seen in 18-54% of patients.
v. LDH is seen in 35-98% of patients.
vi. CK is seen in 5% of patients.
vii. Prothrombin time is seen in 2% of patients.
viii. Low levels of albumin are very common and seen in 98.5% of patients.
ix. Sources: (Shi et al, Lancet Infect Dis, 2020; Guan et al, NEJM, 2020; Huang et al,
Lancet, 2020; Xu et al, Liver International, 2020; Zhou et al, Lancet, 2020; Wu et al,
JAMA Intern Med, 2020; Fan et al, MedRxiv, 2020; Wang et al, JAMA, 2020; Zhang
et al, Lancet Gastroenterol and Hepatol, 2020)
b. Liver injury is often mild, even in patients with severe disease, and is self- resolving
(Guan et al, NEJM 2020; Huang et al, Lancet, 2020; Xu et al, Liver International,
2020; Zhou et al, Lancet, 2020; Wu et al, JAMA Intern Med, 2020, Bangash, Lancet
Gastroenterol Hepatol, 2020; Shi et al, Lancet Infect Dis, 2020) i
c. Acute liver failure has not been reported (Ong et al, BMJ, 2020), even in those who
are severely ill (Bangash, Lancet Gastroenterol Hepatol, 2020; Chen et al, The
Lancet, 2020) and those with chronic liver disease (Xu et al, Liver International,
2020).
3. Prognostic associations:
a. Abnormal LFTs are more common in patients with symptomatic disease vs pre-
symptomatic disease. i
b. Abnormal LFTs are more common in patients with clinically severe disease vs non-
severe disease (Zhang et al, Lancet Gastroenterol Hepatol, 2020; Guan et al, NEJM,

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severe disease (Zhang et al, Lancet Gastroenterol Hepatol, 2020; Guan et al, NEJM,
2020; Huang et al, Lancet, 2020; Cai, MedRxiv, 2020) are associated with markers of
systemic inflammation (such as higher fever, higher CRP levels, higher procalcitonin
i
level, and lower lymphocyte counts) (Fan et al, MedRxiv, 2020).
c. Some studies have shown no difference in the incidence of abnormal LFTs between
critically ill survivors and non-survivors (Yang et al, Lancet Respir Med, 2020), while
others have found higher incidence of abnormal LFTs among non-survivors (Xu et al,
Liver International, 2020). i i
4. Pathophysiology:
a. Non-hepatic causes of elevated ALT and AST:
i. May reflect strain on skeletal muscles or myocardium. Elevated LDH, CK,
myoglobin, and troponin are seen, especially in more severe disease. And elevated
aminotransferase levels due to myositis has been seen in other viral respiratory
illnesses, including influenza (Bangash et al, Lancet Gastroenterol Hepatol, 2020;
Fan et al, MedRxiv, 2020).
b. Indirect injury from inflammation:
i. Immune-mediated hepatic inflammation and cytokine storm may cause elevated
aminotransferases (Bangash et al, Lancet Gastroenterol Hepatol, 2020; Zhang et al,
i
Lancet Gastroenterol Hepatol, 2020; Fan et al, MedRxiv, 2020)
c. Direct injury from a virus-induced cytopathic effect (i.e. viral hepatitis)
i. ACE2 is expressed in cholangiocytes (and in hepatocytes, to a lesser extent) (Chai
et al, BioRxiv, 2020), and in SARS, viral cytopathic effect appeared to play a role
(liver biopsies from patients with SARS showed detectable SARS-CoV-1 RNA)
(Chau et al, Hepatology, 2004; Ding, J Pathol, 2004; Xu et al, Liver International,
2020).
ii. However, there are also a number of arguments that suggest direct liver injury is
unlikely. i
d. Hepatotoxic drugs
i. Drug-induced liver injury does not explain the mild LFT abnormalities seen on
presentation with COVID-19, but initiation of drugs (such as antibiotics, antivirals,
and steroids) for the treatment of COVID-19 likely contributes to abnormalities
arising later. (Bangash et al, Lancet Gastroenterol Hepatol, 2020; Xu et al, Liver
International, 2020; Fan et al, MedRxiv, 2020).
e. Critical illness
i. Ischemic hepatitis (“shock liver”); hypoxic hepatitis; and hepatic congestion (which
can be seen when high levels of PEEP or excessive volume overload leads to

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can be seen when high levels of PEEP or excessive volume overload leads to
elevated right atrial pressures and impaired venous return) (Bangash et al, Lancet
Gastroenterol Hepatol, 2020).
Workup
1. Obtain liver biochemistries (AST, ALT, ALKP, total and direct bilirubin, albumin, and total
protein, INR. See Diagnostics for full lab chart):
a. For all patients on admission
i. Also recommend LDH, CK, and troponin to assess non-hepatic sources
i
ii. If abnormal, consider serologic testing for hepatitis B and C
b. Daily:
i. If initial LFTs are abnormal
ii. If the patient is in the ICU
i
iii. If they are on hepatotoxic medications
i
c. Every other day in other inpatients
2. Imaging:
a. Parsimony is advised in ordering abdominal ultrasound. Order for bedside whenever
possible to avoid transport.
b. Advanced imaging (such as MRI/MRCP) should be ordered in conjunction with GI
consultation to avoid unnecessary testing.
Management
1. Review medications carefully for offending agents

i. Discontinue where possible
ii. If the patient is on an investigational or off-label therapeutic, discuss with ID and
pharmacy
2. Consult GI / hepatology if:
a. Hepatitis B or C positive
i
b. Concern for significant underlying liver disease.
c. If LFT abnormalities are severe or significantly worsening, especially if concern for
acute liver failure (defined as severe acute liver injury with encephalopathy and an

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acute liver failure (defined as severe acute liver injury with encephalopathy and an
INR of ≥1.5)
3. Liver injury is most often mild and self-resolving
a. No specific therapy is typically needed
b. For patients with severe liver injury the risk / benefit of N-acetyl-cysteine (NAC)
should be discussed with GI / hepatology, as it involves a significant volume load,
which could worsen respiratory status.
CHAPTER 13
Oncology
Section Editor: Katherine H. Walker MD MSc
Contributors: Martha Wadleigh MD, Marlise R. Luskin MD MSCE, Amy C. Bessnow MD

MPH
General Management
1. Data:
a. Based on early descriptive studies from China, patients with cancer - particularly
those on active treatment for cancer - appear to have a worse prognosis. This
includes higher prevalence, higher risk of severe disease, and higher risk of death
from COVID-19 in patients with cancer compared to those without. (WHO-China Joint
Mission on COVID-19, Yu et al, JAMA Oncology 2020, anecdotal reports)
2. Oncology Consultation/Coverage:
a. For established DFCI patients, oncology consultation and guidance is provided by
each patient’s primary oncologist (or coverage).

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each patient’s primary oncologist (or coverage).
b. Contact primary oncologist via page, not the general pager or fellow on call, to
establish the best means of ongoing communication.
3. Prognosis:
a. Many patients have a reasonable or even good oncologic prognosis with current
therapies. Do not assume an oncologic prognosis, even with metastatic disease:
involve the primary oncologist.
4. Meds:
a. Check in Epic medications tab and in “Research: Active” tab to include experimental
medications. Contact the primary oncologist with questions.
5. Workup:
a. Additional labs to standard workup:
i. Weekly glucan/galactomannan in neutropenic/transplant patients.
ii. Specific patient populations may require additional monitoring (such as CMV, EBV
monitoring in transplant patients – ask primary oncologist).
6. Exam:
a. Examine catheters (port, CVC, others) daily.
b. Avoid rectal exams and any per-rectum therapies in neutropenic patients, but
examine the perirectal area if symptoms or persistent fevers.
c. In patients with heme malignancy or SCT: findings are more subtle or absent in
neutropenic and immune suppressed patients.
7. Pain management:
a. Patients with cancer-related pain may have high opiate needs at baseline. Opiates
should not be stopped but type may need to be adjusted in the setting of respiratory
failure, renal injury, or liver injury.
i. Consider Pain / Palliative Care consult
8. Goals of Care:
a. Involve primary oncologist whenever possible (recognizing that in critical/emergent
situations, this may not be possible).
9. Anticoagulation:
a. Patients with solid tumors are at very high risk of thrombosis but at lower risk of
infection than most heme malignancy patients.
b. Thrombosis prophylaxis for all unless contraindicated

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b. Thrombosis prophylaxis for all unless contraindicated
i. Hold pharmacologic prophylaxis if platelet count < 30K, use pneumoboots
ii. Both COVID-19 infection and malignancy increase thrombotic risk, particularly with
solid tumors.
iii. See “Thrombotic Disease” section within “Thrombotic and Coagulation
Manifestations” chapter for guidelines on both prophylactic and therapeutic
anticoagulation.
10. Transfusions:
a. The BWH blood bank reviews orders and releases appropriate products (i.e.,
irradiated, leukoreduced, etc).
b. See “Blood Products” section for transfusion thresholds of all patients - of note, the
recommended RBC transfusion threshold for all patients, including oncology patients,
is Hgb 7, Hct 21.
Patient DVT ppx Transfusion Thresholds
Transfuse 1 unit at a time
RBC Platelets Cryo FFP
No bleeding, LMWH daily or Hgb < 7 n/a Fibrinogen INR
Plts > 30k SC UFH TID If ACS,** < 100 >
Hgb > 10 10
No bleeding, but Heparin gtt Plts <
patient requires PTT goal depends 30k
anticoagulation on indication
Plts < 30k Hold 10k
pharmacologic
Mild Bleeding, Continue Plts < INR
Rigors, pharmacologic 20k >3
or Minor Procedures ppx in most
(a-lines, CVCs) patients
SCDs* if not using
pharmacologic
Serious Bleeding# or + SCDs* Transfuse Plts < INR
Major Procedure Hold for active 50k or >
(includes LP) pharmacologic if bleeding higher 1.5
able
c. * SCDs = sequential compression devices = “pneumoboots”

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c. * SCDs = sequential compression devices = “pneumoboots”
d. ** ACS = Acute Coronary Syndrome
e. # Massive bleeding is not included here. In these cases, the massive transfusion
protocol must be activated by the attending, given blood product shortages.
Febrile Neutropenia
1. Definition:
a. ANC < 500 cells/mm3 AND T ≥ 101F or T ≥ 100.5 for 1hr
2. Workup:
a. Blood cultures from peripheral (ideally two sets), and each lumen of central line (label
clearly); UA/sed with urine culture (UA may not be as informative with neutropenia);
glucan and galactomannan (if not checked recently), sputum if able; CXR
i. Continue DAILY blood cultures while febrile.
ii. Monitor serum galactomannan and 1-3-beta glucan once weekly.
iii. Any positive glucan or galactomannan prompts ID consult.
3. Initial Empiric Antibiotics:
a. Cover GNRs in all patients: Ceftazidime 2g Q8h or Cefepime 2g Q8h
i. Alternatives: Piperacillin-tazobactam (2nd line, high dose 4.5g Q6h) or meropenem
(3rd line, 1g Q8h).
b. GPCs: add Vancomycin if hemodynamically unstable, or if MRSA pneumonia or
catheter-associated infection is suspected. Check dosing with pharmacy if able.
4. Removal of lines:
a. Catheter removal should be discussed if associated infection is suspected - involve
primary oncologist and/or ID team to weigh risks and benefits, given that not all lines
require removal.
5. Persistent Neutropenic Fever:
a. If fever persists x3 days despite antibiotics
i. Add Micafungin 100mg IV daily
ii. Consideration of further imaging even if the patient appears stable (discuss with
oncology / ID).
6. Anti-infective course:

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6. Anti-infective course:
a. Anti-Infectives should be continued until the patient has met all of these criteria:
i. clinically improved, and
ii. has been afebrile for 48h, and
iii. has been non-neutropenic for 48h.
Immune Checkpoint Inhibitors

1. Overview
a. Immune Checkpoint Inhibitors (ICIs) are not immunosuppressive when used alone,
but the steroid dosages used to treat immune toxicities are often immunosuppressive.
b. Most common ICIs are CTLA-4 inhibitor (ipilimumab) and PD-1/PD-L1 inhibitors
(pembrolizumab, nivolumab, durvalumab, atezolizumab and avelumab).
2. Immune toxicity
a. If patient develops organ dysfunction, it may be due to immune toxicity
i. Consult the service team of the involved organ system and inform primary
oncologist.
b. Common immune toxicities include pneumonitis / respiratory failure (may be difficult
to distinguish between COVID19 disease or may be aggravated by COVID19
infection), colitis, endocrine dysfunction (thyroid, pituitary / hypothalamic, adrenal),
nephritis. Less common hepatitis, meningitis, dermatitis.
i. Check TSH, ACTH, cortisol if hypotension or concern for endocrine dysfunction.
ii. Check T-spot, HIV, HBV, HCV serologies if immune toxicity is suspected, in case
additional immunosuppression (particularly TNF-alpha blockade) is required.
c. Immune toxicities are usually treated with high dose steroids
i. risks and benefits must be weighed immediately with primary oncologist and ID
consult teams if immune toxicity is suspected concurrent with COVID19 infection.
d. BWH/DFCI iTox guidelines can be found here (Partners login required)
CHAPTER 14
Intubation and Anesthesiology

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Intubation and Anesthesiology
Section Editor: Kevin Olsen MD
Contributors: Josh Finkel MD, Alissa Sodickson MD, Suzanne Klainer MD, Caroline Gross
MD
Intubation Personal Protective Equipment, Materials,

and Set Up
PPE for All Floor/ICU/ED intubations
1. Treat all floor/ ICU/ ED intubations as a presumed COVID positive patient

2. Intubating with the necessary PPE is often unfamiliar/difficult to many providers -
consider practicing via simulation (APSF Considerations for Airway Manipulation,
3/20/2020)
i
3. Our current recommendation includes:
a. Disposable hair bouffant or cap
b. eye protection (face shield only vs face shield AND protective eyewear)
c. either N95 or PAPR (N95 + hood for neck protection)
d. fluid resistant gowns (blue impermeable)
e. double gloves
f. leg protection (boot covers) to below the knee
PPE for Perioperative Anesthesia Intubations
1. Unknown Status/Not Suspected(i.e. outpatient laparoscopic appendectomy):

a. If possible, screen patients for: fever, sore throat, cough, runny nose or nasal
congestion, loss of sense of smell, muscle aches, shortness of breath.

i. If patient has none of the above symptoms: Proceed with the procedure using
i
Standard Precautions.

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i
Standard Precautions.
ii. If the patient has any of these symptoms or cannot provide a history: Defer the
procedure until symptoms resolve and consider COVID-19 testing
iii. If procedure cannot be deferred, proceed as above for COVID-19 confirmed/
suspected case
2. If the patient is undergoing airway surgery: (e.g., transsphenoidal, tracheoplasty,
stenting, etc.)
a. Screen for COVID-19 24-48 hours prior to the scheduled procedure:
i. If positive COVID-19 and case can be delayed, defer for 14 days then retest for
COVID-19 according to Infection Control
ii. If positive COVID-19 and case cannot be delayed, follow procedures for COVID-19
confirmed or suspected cases
iii. If negative, ask again about symptoms the day of surgery and if the patient remains
asymptomatic, proceed with Standard Precautions.
Intubation Materials
1. Airway boxes (nasopharyngeal airways, oral airway, syringes, needles, LMA’s, blue
“bougie” stylet, extra ETT’s 6.0-8.0)
2. Medication boxes(paralytics, phenylephrine, ephedrine, epinephrine, lidocaine,
labetalol, esmolol, propofol/etomidate, midazolam)
3. Dedicated video laryngoscope.
4. With the exception of the video laryngoscope, DO NOT take these boxes into the room
- only remove what you may need and discard materials taken into the room after
intubation even if not used
Ventilator Circuit Configuration for Viral Filtration
1. Anesthesia Machine set up:

a. Place HME filter between patient and in-line EtCO2 monitoring(APSF Anesthesia
Machine Protection) then place a HEPA filter closest to the anesthesia machine on
the expiratory limb as shown below
b. May also consider adding another HEPA filter closest to the patient before HME filter if
your facilities HME filters are not VFE > 99.99% rated

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2. ICU Ventilator set up:
a. Place HEPA filter between patient and EtCO2 monitor to avoid contaminating sample
line(mandatory)
b. If available, place HEPA filter on expiratory limb closest to the ventilator (preferred)
c. If EtCO2 monitor utilizes infrared measurement(i.e. Does not actually pull sample gas
into machine) then may utilize single HEPA filter either between ETT and Y-piece or at
expiratory limb closest to ventilator
Use of Anesthesia Machine for Prolonged ICU Ventilation
1. In the event of shortage of ICU ventilators, anesthesia machines may be used for
prolonged ICU ventilation(ASA/ASPF Ventilator Guidance)
2. A quick reference sheet and hotline to set up and monitor a repurposed anesthesia
machine are provided(ASA/APSF Quick Setup Instructions)(1-800-224-1001)
3. Draeger and GE have provided specific guidance for their anesthesia machines(GE
Guidance)(Draeger Guidance)
Intubation in Emergency Department, ICU, or Floor

Preparation

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Preparation
1. Rapid Sequence Induction(RSI) should be performed by the most experienced airway

provider using a video laryngoscope(SCCM COVID19 Guidelines)(APSF
Considerations for Airway Manipulation, 3/20/2020)
2. Limit providers in room to 3: 1 airway team member(s), respiratory therapist, and
registered nurse
a. Assign roles and airway plan (who will “hold/do” what)
3. Perform a “pre-induction” checklist prior to starting:
a. Suction available
b. Audible pulse oximetry
c. NIBP cycling
d. Ventilator setup and ready with quantitative EtCO2 monitor in-line and ready (avoid
color change device if possible)
e. Free-flowing IV access
f. Post-intubation sedation ready
g. HEPA filter in-line
h. Medications ready
i. Non-rebreather, flow “OFF” until ready to preoxygenate
j. If no ventilator is available, ambu bag post intubation with HEPA filter, +/- CO2
detector. Flows turned down during circuit changes
4. Ensure patients are in negative pressure rooms for all intubations/extubations(SCCM
COVID19 Guidelines). i
Procedure
1. Don appropriate PPE via “read/do” checklist, gather supplies and review airway plan
2. Preoxygenate the patient: maintain preoxygenation technique until neuromuscular
blockade has set in
a. Option 1: 3-5 minutes of tidal breathing 1.0 FiO2 on non-rebreather at 15L/min flow
b. Option 2: facemask attached to AMBUbag with HEPA filter (2 hand technique to
maintain seal)
c. Option 3: if patient already on BiPAP then maintain BiPAP with tight seal until ready to
intubate(turn “OFF” BiPAP flow prior to removing mask)
3. Intubate the patient with an RSI technique/video laryngoscopy

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3. Intubate the patient with an RSI technique/video laryngoscopy
a. use awake intubation only when absolutely necessary as deemed by attending
anesthesiologist
4. If mask ventilation becomes necessary:
a. use 2-hand technique with oral airway to create tight seal
b. use AMBUbag with HEPA filter in-line with high frequency/low tidal volume
c. do not remove mask for 2nd attempt intubation until end exhalation
5. After successful intubation:
a. Inflate cuff
b. connect patient directly to ventilator with HEPA filter with EtCO2 gas sampling line
post-filter or use an infrared CO2 analyzer with no gas sampling
c. confirm via quantitative in-line EtCO2 (gold standard > 3 breaths), bilateral chest rise,
“fogging” of ETT, cuff palpation and possibly increasing SpO2
d. avoid listening bilaterally for risk of contamination(touching ears with
stethoscope/hands)
e. secure ETT per hospital policy
6. Clean the laryngoscope:
a. Remove soiled gloves and replace with clean gloves
b. Clean the video laryngoscope and allow it to dry - 3 minutes if PURPLE Sani-
Cloth(Sani-Cloth Technical Sheet).
c. Push video laryngoscope out of room with clean gloves on
7. Follow “read/do” instructions for doffing of PPE per hospital protocol
Intubation in Operating Room (COVID positive or

suspected)
Preparation
1. If possible, intubate the patient via dedicated airway teams in a negative pressure room
in the ER or ICU in anticipation of surgical intervention. This allows for a closed circuit
during transport and minimizes transmission

2. Ensure OR is set to be on negative pressure

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a. hang signage to prevent unnecessary entry
3. 3-person team is the preferred method:
a. Intubator - most senior provider, will manipulate airway only
b. “Clean anesthesia provider” will manipulate anesthesia machine, administer
medications, chart, and read checklists
c. Circulating RN as assistant to intubator
4. Perform routine anesthesia machine check and pre-induction checklist:
a. consider removing all medications you may need for entire case to minimize omnicell
contamination/movement in and out of room
5. Gather supplies:
a. Place ETT, airway adjuncts, temperature probe, OG tube, eye protection, bite block
and tape in a basin and hand to circulating RN positioned at side of bed
6. Position equipment:
a. video laryngoscope plugged in and working within reach
b. trash cans open and near table
Procedure
1. Personal Protective Equipment:

a. don appropriate PPE via “read/do” checklist prior to entering OR
2. Transition patient to OR oxygen delivery
a. Move patient to OR table
b. If patient has supplemental O2 (i.e. nasal cannula) then continue until ready to pre-
oxygenate with anesthesia machine. Ensure flow of supplemental O2 is turned “OFF”
before manipulating device
c. The “clean anesthesia provider” ensures APL at “zero” and all flows “OFF”2, remove
patient facemask and immediately use 2-hand technique to place circuit face mask on
patient
3. Preoxygenate:
a. Turn O2 flow to 2L/min and allow patient to preoxygenate for 3-5 minutes at tidal
breathing to minimize facemask leak that may occur with vital capacity breathing
Intubate:

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4. Intubate:
a. “Clean anesthesia provider” will push RSI medications once preoxygenation is
complete.
b. Avoid hand ventilation if possible. If hand ventilation needed, intubating provider to
maintain 2-hand mask and “clean anesthesia provider” will touch bag/APL valve
c. “Clean anesthesia provider” turns off gas flows
d. Intubating provider disconnects facemask and place next to patient’s head, and uses
video laryngoscopy to intubate patient
5. After successful intubation
a. Circulating RN pulls stylet, intubating anesthesia provider occludes end of ETT with
finger, circulating RN inflates cuff, and then connects circuit
b. “Clean anesthesia provider” turns on gas flows and ventilator and confirms
EtCO2(gold standard > 3 breaths with consistent waveform and value)
c. intubator monitors for bilateral chest rise and “fogging” of ETT
i. avoid listening to breath sounds as can cause contamination of providers
d. Circulating RN will take control of ETT while the intubating provider tapes
e. Intubator will place OG tube, temperature probe, eye protection and bite block
f. “Clean anesthesia provider” will start appropriate anesthetic i.e. inhaled volatile vs
TIVA and chart as needed
6. Clean equipment:
a. Intubating provider and circulating RN will change top gloves with and then clean
video laryngoscope/any other equipment that may have been contaminated
7. Allow 18 minutes to facilitate 99% aerosolized virus removal(assumes ACH of
15/hr) from time of intubation then allow other OR personnel(i.e. Surgeons/scrub tech)
into the OR with proper PPE
Transporting from the OR to the ICU
1. Place HEPA filter between patient and Y-piece to prevent viral contamination of circuit
2. Maintain patient in a negative pressure environment with PPE including N95 or PAPR
prior to transitioning to transport ventilator
3. Clamp ETT, remove from anesthesia circuit and then place onto transport ventilator.=
4. Unclamp the tube and confirm ventilation. If EtCO2 monitoring is used for transport,
ensure it is POST HEPA filter(EtCO2 closer to ventilator)

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ensure it is POST HEPA filter(EtCO2 closer to ventilator)
Extubation
Perioperative/OR Extubations
1. Don clean gloves on top of baseline PPE

2. Confirm patient will tolerate extubation:
a. <0.4 FiO2
b. chemical paralysis reversed
c. maintaining adequate minute ventilation and tidal volumes with minimal support (i.e.
PSV 5/5)
d. hemodynamically stable
e. airway reflexes intact
3. “Clean anesthesia provider” places patient on 1.0 FiO2, “Extubator” loosen tape
securing ETT, suction mouth, remove OG tube, eye protection and temperature probe
4. “Extubator” places a nasal cannula in the patient’s nares with oxygen flow “OFF”
5. Consider placing a plastic drape on top of patient to prevent exposure to any coughing
that may occur(i.e. Clear plastic head piece from Bair hugger)
6. “Clean anesthesia provider” turns all gas flows to “OFF” and “extubator” extubates the
i
patient.
7. Circulating RN will remove plastic drape and ETT as one item and discard while
“extubator” will immediately place anesthesia facemask over patient with good seal and
connect circuit, “clean anesthesia provider” will increase gas flows to confirm that the
patient is ventilating appropriately
8. Once the patient is confirmed to be supporting their own oxygenation/ventilation - the
“clean anesthesia provider” will turn “OFF” gas flows. i
9. “Extubator” will remove the anesthesia face mask and immediately place surgical face
mask down from forehead to cover the patient’s mouth/nares
10. “Clean anesthesia provider” will turn on supplemental nasal cannula O2 to appropriate
L/min flow
11. All providers will sanitize/change gloves while maintaining base layer PPE. Do not
allow anyone into the room for at least 18 minutes after extubation to facilitate
99% of aerosolized virus removal by negative pressure room (assumes ACH of
15/hr)

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15/hr)
ICU Extubation
1. Don appropriate PPE via “read/do” checklist

2. Only respiratory therapist and/or airway provider(anesthesiologist/intensivist) should be
in the room
3. Confirm patient will tolerate extubation (See “vent weaning” section of respiratory
chapter)
4. Place patient on 1.0 FiO2 and ensure non-rebreather mask ready with flow “OFF”
5. Place “chuck” or towel on patient chest and ensure yankauer suction on ready readily
available
6. Respiratory therapist to cut tape holding ETT, turn vent flows to “OFF” and extubate
patient
7. Immediately discard of ETT and chuck or towel and immediately place non-rebreather,
then turn oxygen flow to 10-15L/min
8. Ensure patient is oxygenating and ventilating
9. All providers will sanitize/change gloves while maintaining base layer PPE. Do not
allow anyone into the room for at least 47 minutes after extubation to facilitate
99% of aerosolized virus removal by negative pressure room(assumes ACH of
6/hr)
CHAPTER 15
Palliative Care
Section Editor: Richard Leiter MD MA

Contributors: Janet Abrahm MD, Samantha Gelfand MD, Mihir Kamdar MD, Stephanie
Kiser MD MPH, Andrew Lawton MD, Barbara Reville DNP ANP-BC ACHPN, Kate Sciacca
MSN NP, Jaclyn Shameklis MD, Lorie Smith MD, Jane deLima Thomas MD, Mark Zhang

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MSN NP, Jaclyn Shameklis MD, Lorie Smith MD, Jane deLima Thomas MD, Mark Zhang
DO MMSc
Please see also Pallicovid.app for one-page guides, pocket cards, nursing resources, and
related information.
Anxiety related to Dyspnea or at End of Life

1. For general anxiety, please see the Anxiety section of Psychiatry.
2. Non-pharmacologic:
a. Counseling (Spiritual, Psychocological, SW), Reiki
3. Pharmacologic
a. Benzodiazepines (if patient is not delirious; can use in either intubated or non-
intubated pts)
i. Lorazepam (longer half-life) 0.5-2 mg PO/SL q4-6h PRN; 0.5-2 mg IV q2h PRN
ii. Midazolam (shorter half-life) 0.2-0.5 mg IV slowly q 15 min PRN or 0.1-0.3 mg/hr IV
infusion
b. SSRI/SNRI: Continue home dose if possible. If NPO, replace with prn benzodiazepine
Dyspnea & Acute Pain

Non-opioid management
1. Non-Pharmacologic for Dyspnea:

a. Positioning: sitting patient up in bed, if possible. See also Anxiety above.
2. Pharmacologic:
a. Please see “Therapeutics” for discussion about NSAID use vs acetaminophen. No
recommendation is made at this time
b. Ativan (as above) can be used to ease the anxiety associated with dyspnea, but
would avoid in patients who have had a previous paradoxical reaction (i.e. worsened
agitation).
c. Opioids can be used for both dyspnea and acute pain (see below)

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Opioid management
1. General principles:
a. Additional information, including algorithm for opioid-induced respiratory depression is
available at: DFCI Pink Book
b. ALWAYS use PRN boluses to address acute, uncontrolled symptoms. PRN bolus
dosing should be 10-20% of the 24-hour opioid dose
2. For opioid naive patients:
Renal function
Normal Abnormal (GFR<50)
COPD No - Morphine 5-10mg PO q3h PRN (use - Hydromorphone 1-2mg
the 20mg/ml concentrate) PO q3h PRN
- Morphine 2-4mg IV q2h PRN - Hydromorphone
0.1-0.2mg IV q2h PRN
Yes - Morphine 2-5mg PO q4h PRN (use the - Hydromorphone 2-4mg
20 mg/ml concentrate) PO q4h PRN
- Morphine 1-2 mg IV q2h PRN - Hydromorphone
0.2-0.4mg IV q2h PRN
c. If patient is not well managed with the above, add opioid infusion:
i. Consider drip If > 3 bolus doses in 8 hours
ii. Calculate initial dose with total mg used/8 hours
1. e.g. 1+2+2+2= 7 mg; begin drip at 7mg/8 hr = 1 mg/h
2. Depending on symptoms and goals of care, consider reducing hourly rate by 30-
50%. If patient is at end of life, would use 100% of hourly rate.
iii. Continue PRN dosing at current dose (if effective) or titrate as per above.
3. For Opioid tolerant patients:
a. If able to take PO:
i. Continue current long-acting doses if renal and hepatic function tolerate
ii. Continue current oral PRN dose if effective q4h prn

1. If ineffective, increase dose by 50% and order range of up to 3 x basal dose

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a. e.g. 5 mg PO MS q3h prn; increase to 7.5 mg; 7.5-22 mg PO q3h PRN
b. If unable to take PO, severe or rapidly escalating symptoms:
i. Convert as-needed PO doses to IV pushes as needed
1. Use the IV Conversion chart (see chart below, or DFCI Pink Book)
2. Decrease PRN dose by for incomplete cross-tolerance when switching between
opioid classes
a. e.g. to convert 20 mg of oxycodone to IV hydromorphone: 20 mg oxy = 1.5 mg IV
hydromorphone; 1.5 mg x =1 mg IV
ii. Convert PO long-acting/ sustained release opioids to an infusion:
1. Calculate 24-hour dose of PO sustained release (SR) morphine
a. Divide by 3 for the total 24h mg IV (Morphine PO/IV = 3:1)
2. Divide the 24h mg IV total by 24h for the hourly drip rate (mg)
a. e.g. 30 mg SR PO morphine q8 hr= 90 mg PO in 24 h; 90 mg /3 = 30 mg IV dose;
30 mg / 24 h~ 1 mg/hr IV morphine infusion
3. Continue PRN dosing. PRN dose should be 100-200% of opioid drip rate
a. e.g. 1 mg/hr IV morphine infusion; PRN dose is 1-2 mg IV q2h
Abbreviated Opioid Equianalgesic Table (for complete table and an example

conversion see DFCI Pink Book)
Opioid Equianalgesic Doses

Drug PO/PR (mg) Subcut/IV (mg)
Morphine 30 10
Oxycodone 20 n/a
Hydromorphone 7.5 1.5
Fentanyl n/a 0.1 (100 mcg)
(See table below for transdermal conversions)
Nausea and Vomiting

1. Match treatment to etiology of nausea:

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1. Match treatment to etiology of nausea:
a. Chemoreceptor Trigger Zone (blood brain barrier breakdown)
i. haloperidol, metoclopramide, ondansetron, olanzapine, aprepitant
b. Gastrointestinal:
i. ondansetron, metoclopramide, dexamethasone (if malignant obstruction)
c. CNS cortical centers:
i. lorazepam for anticipatory nausea, dexamethasone (tumor burden causing ICP)
d. Vestibular:
i. meclizine, scopolamine, diphenhydramine
2. Additional information can be found at the DFCI Green Book. See page 11 for more
dosing recommendations:
a. Ondansetron 8-24mg/day IV/PO (max single dose 16mg) *causes constipation*
b. Haloperidol 0.5-2 mg IV/PO q 4-8 hours *EPS unlikely at these low doses*
c. Metoclopramide 10-40 mg IV/PO TID-QID *pro-motility*
d. Olanzapine 2.5-10 mg PO/dissolvable daily *off label, effective for concurrent anxiety,
will not exacerbate constipation*
e. Prochlorperazine 10 mg PO TID-QID (max 40 mg/day) 25 mg PR BID *very sedating,
overlaps with haloperidol, metoclopramide, perphenazine*
f. Meclizine 25-50 mg PO daily
Constipation
1. If able to take oral agents, start:
a. Senna 2 tabs PO qhs, can increase up to 2 tabs PO TID if needed
b. Polyethylene Glycol 17gm packet PO QD-BID prn
c. Avoid Docusate given lack of data demonstrating benefit
2. If unable to take oral agents, suggest Bisacodyl suppository PR daily prn signs of
abdominal discomfort/distention likely due to constipation.
3. For more information, see DFCI Pink Book
Care of The Imminently Dying Patient

General principles

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General principles
1. Signs and symptoms of imminent death

a. Somnolence
b. Warmth, and later cooling and mottling of extremities
c. Change in respiratory pattern, intermittent apnea, Cheyne-Stokes pattern
d. Gurgling sounds from oropharynx (often more distressing to family than patient)
2. Symptom management
a. Should follow the guidelines provided in sections above
b. Intensive Comfort Measures Guidelines (BWH Policy 5.5.5) (Partners login required)
3. Communication
a. See common questions from families
Intensive Palliative Care Unit
1. The Palliative Care Service has opened the COVID-19 Intensive Palliative Care Unit
(COVID-IPCU) and suspended the usual oncology IPCU service. The COVID-IPCU is
intended as a unit for end of life care during the COVID pandemic. The Palliative Care
Team aims to leverage the interdisciplinary expertise of the IPCU team and Palliative
Medicine clinicians to provide symptom management andpsychosocial support quickly
and effectively for patients likely to die from COVID-19, whether or not they have
cancer.
2. The admission criteria to the COVID IPCU are as follows:
a. COVID-19+ or pending results
b. Experiencing organ failure such that the patient would be expected to die without life
sustaining treatments and an estimated prognosis of less than a week
c. Patient/family assenting to comfort-focused care
d. Code Status is “DNR/DNI/LLST (Comfort)” or “DNR/DNI” with no escalation of care to
the ICU
e. Communication with the COVID-IPCU team is required prior to transfer; page “IPCU”
in the Partners Paging Directory
Visitors
1. Visitor guidance is changing. These are the current public guidelines. Please check
with your unit to see up to date guidance on visitor policies for patients nearing end of

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with your unit to see up to date guidance on visitor policies for patients nearing end of
life.
2. If the visitor has been exposed to a COVID-19 confirmed or COVID-19 presumed
positive person in the past 14 days, the visitor cannot enter the hospital even with the
end-of-life exception
3. The visitor needs to wear a surgical mask. They will also need a gown and gloves if
within 6 feet of the patient
Compassionate Extubation
1. For Brigham and Women’s suggested protocol, please see this handbook page.
(Partner’s login required)
2. See also Von Gunten and Weissman, Palliative Care Fast Fact #33, Ventilator
Withdrawal Protocol
3. For staff and visitor safety, we do not recommend physical extubation, but rather
patient should be weaned down to PSV 0/0 with FiO2 0.21 to maintain a closed circuit
Palliative Sedation
1. See Salacz and Weissman, Palliative Care Fast Fact #106, Controlled Sedation for
Refractory Suffering
2. BWH Palliative Sedation in the non-ICU Setting Policy (BWH Policy 1.4.13 (Partners
login required)
Terminal Delirium
1. For general delirium, please see Delirium section in Psychiatry

2. Diagnosis: CAM method
a. Use the Confusion Assessment Method (CAM)
b. CAM is positive if (1) AND (2) and EITHER (3) or (4) are present
i. Acute often fluctuating change in mental status (vs dementia)
ii. Difficulty focusing attention
iii. Disorganized thinking (rambling, illogical flow of ideas)

iv. Altered level of consciousness (too sedated or too hyperactive)

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3. Treatment:
a. Non-pharmacologic:
i. Daytime lights, nighttime dark. Frequent reorientation. Reverse contributing medical
conditions as able.
ii. Consult Psychiatry; for terminal delirium, consult Palliative Care
b. Pharmacologic
i. Additional information available at: Guidelines for Acute Hospital Acquired Delirium
(Partners login required)
ii. Alter existing medications and treat comorbid symptoms.
iii. QTc prolonging agents <65 yo or DNR/I +LLST Comfort Measures
1. Haloperidol, Mild agitation:0.5-1.0 mg IV or 1 to 2 mg PO q6h and 1-2 mg q2h
PRN.; Moderate agitation: 2-4 mg IV; Severe agitation: 4-10 mg Maximum dose:
20 mg / 24 hours
2. If refractory, olanzapine, 2.5 to 5 mg (PO, SL, or IV) q12 hr and 2.5 mg q4h PRN;
Maximum dose: 30mg / 24 hours
iv. QTc prolonging agents ≥ 65 yo or frail
1. Haloperidol, Mild agitation 0.25 -0.5 mg IV or 1 to 2 mg PO q6h and 1 mg q2h
PRN; Moderate agitation: 1-2 mg IV; Severe agitation: 2 mg IV Maximum dose: 20
mg / 24 hours
v. Non-QTc prolonging agents
1. Aripiprazole (Abilify), 5 mg PO daily; maximum dose 30 mg daily
2. Valproic Acid 125-250mg IV q8h PRN.
Excessive Salivary Secretions at the End of Life
1. For secretions with significant mucous, evaluate benefit/burden of repositioning and

deep suctioning
2. Communicate with families to expect sounds:
a. Reassure them that although the “rattling” sound is distressing to hear, the patient is
not experiencing difficulty breathing or having to clear phlegm from his or her throat.
The rattling sound comes from the movement of air over secretions pooled in the
throat and airways.
3. Pharmacologic management (not to be used with secretions with significant mucous)

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a. Glycopyrrolate 0.2 – 0.4mg IV q2hrs prn secretions, rattling sound
b. Hyoscyamine 0.125-0.25mg PO q4hrs prn secretions, rattling sound
c. Scopolamine 1.5mg TD q72hrs if patient not awake and no apparent delirium or
history of delirium. NB The patch will take ~ 12 hours to take effect
d. Avoid using > 2 of these at the same time; if more than one is required, monitor for
development of anticholinergic crisis
Communication Skills
1. Skills for COVID-19 Scenarios
i. The BWH Division of Palliative Medicine has created brief videos outlining common
communication tasks in COVID-19 across settings
1. ICU Conversation #1: Sharing concern illness may get worse
2. ICU Conversation #2: Discussing Illness getting worse/GOC
3. ICU Conversation #3: Talking about Dying
4. Hospital Medicine #1: GOC & Code Status (goals c/w intubation)
5. Hospital Medicine #2: GOC & Code Status (goals not c/w intubation)
6. ED #1: GOC & Code Status (goals not c/w intubation)
ii. Experts at VitalTalk have created a COVID-19 Communication Guide. See also:
Suggested Language for COVID-19 scenarios
2. Important Skills for All Conversations
a. Respond to emotion with empathy
i. Key Skill: NURSE Statements (Back et al. CA Cancer J Clin 2005)
1. Name, Understand, Respect, Support, Explore
2. NURSE Skills for Responding to Emotion
b. Assess Understanding & Delivering Information
i. Key Skill: ASK-TELL-ASK (Back et al. CA Cancer J Clin 2005)
ii. For COVID, it is important to make patients and families aware that patients with
significant comorbid illnesses or who have poor baseline functional or health status
may decompensate rapidly and have very high mortality due to COVID-19.
c. Discussing Goals of Care

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i. Key Skill: REMAP mnemonic (Childers et al. J Oncol Pract 2017)
1. Reframe, Expect Emotion, Map Values, Align, Propose Plan
2. The REMAP Framework
d. Managing Uncertainty
i. Key Skill: Pairing hope and worry (Jackson et al, JPM 2013)
1. “I hope you will improve AND I am also worried because your oxygen level is
getting worse.”
Documenting Important Conversations
1. The Advance Care Planning (ACP) Module in Epic is the single BEST place to
document serious illness conversations for patients with COVID-19 and their families.
Where to find and how to use the ACP Module in Epic.
2. In conscious patients, review or sign Health Care Proxy form.
CHAPTER 16
Surgery
CHAPTER 17
Obstetrics
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Obstetrics
Section Editors: Khady Diouf MD, Sarah Rae Easter MD
Contributors: Daniela Carusi MD MSc, Katherine E. Economy MD MPH, Kate Gregory RN

PhD, Stephanie Guseh MD, Sarah Lassey MD, Julianna Schantz-Dunn MD, Sigal Yawetz
MD, Hope Yu MD
Health care providers are encouraged to enroll females exposed to COVID-19 during
pregnancy in the PRIORITY registry (Pregnancy CoRonavIrus Outcomes RegIsTrY)
Information for pregnant patients about COVID-19 in 7 different languages can be found
online via Pregistry here.
Clinical Presentation and Clinical Course of COVID-19

in Pregnancy
Clinical Presentation
1. Like non-pregnant patients, the most common presenting symptoms are fever and
cough (Zaigham, Acta Obstet Gynecol Scand, 2020; Wu et al, JAMA 2020, Liu et al,
AJR 2020)
a. About 85% will have mild disease, 10% severe disease and 5% critical disease
(Breslin et al, Am J Obstet Gynecol MFM, 2020)
b. A cohort of 118 pregnant women from China revealed 92% had mild disease, 7%
severe disease, and 1% critical disease. Rates of severe disease were reported to be
16% among all people in China (Chen, NEJM, 2020)
c. Comorbidities, such as obesity, diabetes, asthma, hypertension may make pregnant
women more susceptible to effects of COVID-19 (ACOG COVID –19 FAQs for
Obstetrician Gynecologists).
2. Diagnostic Considerations: This clinical presentation mirrors other diseases in
pregnancy.
a. If a patient is presenting with COVID-like symptoms, particularly a fever, a high
clinical suspicion for alternative or comorbid processes such as chorioamnionitis

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clinical suspicion for alternative or comorbid processes such as chorioamnionitis
or influenza is needed.
i. Laboratory derangements may overlap with other obstetric diagnoses (e.g.
transaminitis and pulmonary findings can confound a diagnosis of preeclampsia or
HELLP syndrome.
b. If a patient develops new signs / symptoms during hospitalization or labor, COVID-19
needs to be considered regardless of a priori risk of other common infectious
processes (such as epidural fever or chorioamnionitis).
i. In a study from two New York hospitals with universal testing 10 of 14 patients who
were asymptomatic at admission became symptomatic during hospitalization with
fever as the primary complaint (Breslin et al, Am J Obstet Gynecol MFM, 2020).
3. Asymptomatic Infection: Patients may present early in their infectious course prior to
symptoms, or may have asymptomatic viral carriage.
a. In a series of 43 COVID-19 infected pregnant women in New York, 32.6% of them
presented WITHOUT symptoms. Of these, 46.2% developed symptoms within 7 days
after the positive test (Breslin et al, Am J Obstet Gynecol MFM, 2020).
b. A recent series of 215 pregnant patients from New York demonstrated a 13.7% rate of
positive testing for SARS-CoV-2 amongst asymptomatic women.
i. Twenty-nine of the 33 patients who were positive for the virus were asymptomatic
(Sutton et al, NEJM, 2020).
ii. Asymptomatic women tested on labor and delivery had positive results for SARS-
CoV-2 at a rate <5%.
Maternal and Obstetric Outcomes
1. Experience with COVID in pregnancy is limited. Data to date is based in case-series

and not controlled. The background comorbidities in the population, local testing
policies, and obstetric care practices may limit generalizability to our population.
2. In pregnant women with viral pneumonias due to non-COVID viruses such as influenza,
pregnant women demonstrate increased susceptibility to infection and higher rates of
mortality (Callaghan et al, Obstet Gynecol, 2015) However, thus far, COVID-19 (SARS-
CoV-2) appears to have less severe maternal pregnancy outcomes than SARS-CoV-1
or MERS (Schwartz et al, Viruses, 2020).
a. There are approximately 100 cases of SARS from 2002-2003 in pregnancy reported
in the literature. There was a strong association with severe manifestations of disease
in pregnant compared to nonpregnant individuals (Lam et al, BJOG, 2004).

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in pregnant compared to nonpregnant individuals (Lam et al, BJOG, 2004).
b. Only 11 pregnancy-associated cases of MERS were reported from the 2012 outbreak,
with a 91% rate of severe maternal morbidity (compared to a background severe
maternal morbidity rate of 2-3%) (Schwartz et al, Viruses, 2020).
3. While the data is limited, COVID-19 appears to have somewhat less of a severe
presentation than SARS or MERS, but is associated with variable rates of maternal and
obstetric complications:
a. In a systematic review of 18 articles reporting on 108 pregnancies affected by COVID-
19 infection:
i. 3 women were admitted to the ICU
ii. 1 experienced a neonatal demise
iii. 1 experienced an intrauterine fetal demise (Zaigham et al, Acta Obstet Gynecol
Scand, 2020).
b. In a systematic review of 6 reports of COVID-19 affecting 41 patients reported from
China, (Dimascio et al, Am J Obstet Gynecol MFM, 2020).
i. Findings out of 41 pregnancies with deliveries:
1. Preterm delivery less than 37 weeks gestation: 41%
i
2. Preterm birth less than 34 weeks gestation: 15%
3. Perinatal death: 7%
4. Preeclampsia: 13.6%
i
5. Cesarean delivery: 91%
c. Two New York hospitals published outcomes of 43 patients followed for a two week
time period. (Breslin et al, Am J Obstet Gynecol MFM, 2020). i
i. Findings out of 43 pregnancies, 18 deliveries:
1. Preterm labor: 5% (1/18)
2. Labor induction: 50% (9/18, mix of indications)
3. Cesarean delivery: 44% (background cesarean rate not stated)
4. No reports of preeclampsia, pregnancy loss or perinatal death
Fetal and Neonatal Outcomes
1. The fetal course for COVID-19 is not fully elucidated, but other maternal respiratory
illnesses and pyrexial infections are associated with worse fetal outcomes:
a. Complications of other respiratory viral illnesses include preterm labor, premature

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a. Complications of other respiratory viral illnesses include preterm labor, premature
rupture of membranes, intrauterine growth restriction, intrauterine fetal demise,
neonatal death (Schwartz et al, Viruses, 2020).
i. Increased rates of intrauterine growth restriction and intrauterine fetal demise have
yet to be reported for COVID-19. However, these outcomes are biologically plausible
in the setting of maternal inflammation, hypoxia, and pro-thrombotic state and
warrant consideration in antenatal care.
b. Fever in early pregnancy may be associated with an increased rate of birth defects,
with neural tube defects being the most commonly described (Moretti et al,
Epidemiology, 2005)
c. Fever during labor may also be associated with neonatal risk, though distinguishing
adverse outcomes due to noninfectious inflammation and intrauterine infection is
challenging (Petrova et al, Obstet Gynecol, 2001)
2. Vertical Transmission: Definitive evidence that SARS-CoV-2 crosses the placenta and
infects the fetus is lacking; however, a few cases of possible in utero infection have
been reported.
a. Three of 33 infants born to mothers with COVID-19, developed early-onset infection.
Amniotic fluid, cord blood, and breast milk, were negative for SARS-CoV-2 in these
cases. Clinical symptoms from these infants infected with COVID-19 were mild and
outcomes were favorable (Zeng et al, JAMA Pediatrics, 2020).
b. In a US cohort of 18 infants tested for COVID-19 via SARS-Cov2-19 PCR
nasoparyngeal swab all infants ultimately tested negative (Breslin et al, Am J Obstet
Gynecol MFM, 2020).
c. Reports of possible vertical transmission include a positive IgM in a neonate of a
COVID-19 + mother at 2 hours of life without other exposure. The early time period of
detection coupled with knowledge that IgM does not cross the placenta has called into
question the possibility of vertical transmission in this case (Dong et al, JAMA, 2020).
Screening and Testing of Pregnant Women

1. Identifying pregnant women with SARS-CoV-2 infection has several goals:
a. To tailor frequency and location of prenatal care for identified COVID-19 positive
women and COVID people under investigation (PUI)
i. Whether or not an obstetric patient is seen for an in-person evaluation and the
location of this evaluation should be based on a review of symptoms informing
clinical suspicion for severe disease (Poon et al, Int Journal Obstet Gynaecol, 2020)

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clinical suspicion for severe disease (Poon et al, Int Journal Obstet Gynaecol, 2020)
ii. At BWH pregnant patients with respiratory symptoms in the absence of obstetric
complaints are first evaluated in the Emergency Department with fetal and obstetric
evaluation for those with viable pregnancies facilitated by an obstetrics consult.
b. To decrease risk of transmission to other patients, healthcare personnel, and family
living in the same space
c. To plan for labor and delivery care
d. To plan for mother-infant separation strategies, if necessary
2. Symptom Screening
a. Symptom screening should be conducted over the phone before patient presents for
care and again upon arrival at the facility of care
b. All obstetric patients with symptoms should be considered COVID PUI and laboratory
testing should be performed
3. Laboratory Testing:
a. World Health Organization guidelines recommend laboratory testing (qRT-PCR) for all
suspected cases (i.e. symptomatic patients). Due to testing capacity issues, the
Centers for Disease Control (CDC) recommends testing at provider’s discretion.
Testing criteria vary by institution.
b. Current BWH testing criteria can be found here and include universal testing for
patients being admitted to Labor and Delivery or those with a planned admission for
scheduled induction of labor or cesarean delivery within the next 48 hours.
c. Support persons of patients testing positive for SARS-CoV-2 should also be tested
Prenatal Care in the Setting of COVID-19

1. Different models of prenatal care have been proposed to minimize exposures to
patients (with and without COVID-19) and providers by decreasing frequency of in-
person visits and ultrasounds. (SMFM Ultrasound Practice Suggestions).
a. Selection depends on the resources available and provider discretion based on
medical complexity
2. BWH suggestions modify ACOG recommendations based on the needs of our high-risk
patient population. (Boelig et al, Am J Obstet Gynecol MFM, 2020).
a. Low Risk Patients: Low risk patients include patients without intermediate or high-
risk obstetrical criteria. They should be asymptomatic (no pain or bleeding), without
risk factors for ectopic pregnancy, and with low-risk aneuploidy screening.

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risk factors for ectopic pregnancy, and with low-risk aneuploidy screening.
i. Dating scan with nuchal translucency at 11-13 weeks gestation coordinated with first
OB visit
ii. Fetal survey at 19-20 weeks (favor 20 weeks with increasing BMI) coordinated with
return OB visit
iii. For patients with a placenta previa or low-lying placenta on second trimester
ultrasound repeat ultrasound for placental location at 32 weeks in the absence of
bleeding.
b. Intermediate Risk Patients: Hypertension not on medication, gestational diabetes or
pregestational diabetes not on medication, advanced maternal age > 40 years old,
BMI > 35, uncomplicated dichorionic diamniotic twin pregnancies, history of
intrauterine growth restriction (IUGR) or preeclampsia in a prior pregnancy.
i. Similar approach to first and second trimester screening as low risk patients.
ii. Ultrasound for estimated fetal weight at 30-32 weeks for those with a history of
IUGR or preeclampsia in prior pregnancy. Repeat ultrasound every 6 weeks.
Identification of IUGR places patient in high risk category.
iii. Dichorionic Twins: Ultrasound every 4 weeks for fetal growth beginning at 28 weeks.
iv. Diet-Controlled Pregestational Diabetes or Gestational Diabetes: Third trimester
ultrasound for assessment of fetal weight at discretion of MD
v. Fetal Anomalies: Growth surveillance tailored to fetal anomaly with more frequent
surveillance in the face of hydrops, polyhydramnios, or concern for genetic
syndrome.
vi. Short Cervix > 2.5 cm: Monitor cervical length every 2 weeks until 25 weeks if
cervical length remains stable.
c. High Risk Patients: Hypertension on medications, preeclampsia, gestational
hypertension, pregestational or gestational diabetes on medications, IUGR in the
current pregnancy, monochorionic twins and higher-order multiples, maternal renal
disease, other complex maternal or fetal comorbidities.
i. Similar approach to first and second trimester screening as low risk patients.
ii. Hypertension or Diabetes: Growth ultrasound every 6 weeks with weekly nonstress
tests (NSTs) for interval fetal testing.
iii. Monochorionic Twins: Ultrasounds every 2 weeks to monitor for evidence of twin-to-
twin transfusion syndrome.
iv. IUGR: Weekly NSTs with biophysical profile (BPP) and umbilical artery Doppler
every 4 weeks in place of NST. Increase NSTs to twice weekly in the setting of
abnormal Dopplers.

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abnormal Dopplers.
v. Short Cervix < 2.5 cm before 25 Weeks: Weekly ultrasound for cervical length at the
discretion of the OB care provider until 25 weeks. A final cervical length ultrasound
can be considered after cerclage placement.
Prenatal Care for Patients with known COVID-19
1. Given the theoretic concerns for adverse fetal outcomes, we recommend increased
fetal surveillance for women with symptomatic COVID-19 infection
a. Third trimester growth ultrasound surveillance at 28 weeks or time of diagnosis
repeated every 3-4 weeks.
b. Weekly fetal testing with nonstress test beginning at 32 weeks until delivery.
c. Performance of biophysical profile in lieu of nonstress test at times of growth
surveillance ultrasounds.
2. To help conserve PPE and limit unnecessary precautions discontinuing
isolation/infection precautions in patients with previously confirmed COVID-19
according to institutional policy is of paramount importance.
Labor and Delivery

Inpatient Antepartum Care for COVID-19 Positive and PUI
1. Admission and Care Protocols:

a. Patients known to be positive prior to arrival should be escorted by a member of the
clinical staff from the main hospital entrance directly to a negative pressure room.
They must wear an N-95 mask. In their rooms they may remove the mask in place of
a surgical mask.
b. Visitors will be limited to a single support person for all women admitted to Labor and
Delivery. This support person should be the same individual for the duration of the
hospitalization, and should remain in the room for the duration of the admission.
Support persons are not allowed in the Labor and Delivery Triage area (an outpatient
facility), the inpatient Antepartum floors, or in the operating room during cesarean
delivery.
c. Patients must identify a health care proxy and/or an advance directive on admission.
d. Teams should designate one or two providers who will principally be involved in direct
(in-person) patient care to minimize staff exposure
i. Providers are encouraged to reduce the frequency of in-person assessment if

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i. Providers are encouraged to reduce the frequency of in-person assessment if
clinically appropriate through use of ipad, telephone, headsets or other remote
technologies
e. PPE should be selected, donned and doffed per hospital policy (see here).
i. The CDC does not categorize a vaginal delivery as an aerosolizing procedure;
therefore droplet and contact precautions are deemed adequate (CDC FAQ)
ii. The Society for Maternal Fetal Medicine (SMFM) believes it is reasonable to
consider N95 mask use for providers with significant and prolonged exposure given
several variables unique to childbirth such as length of patient contact, repeated and
prolonged exhalations, and substantial exposure to body fluids (SMFM and SOAP
Labor and Delivery Considerations)
2. Antenatal Corticosteroids and Tocolysis:
a. The impact of exposure to corticosteroids on COVID-19 infection is uncertain (see
systemic corticosteroids). How this applies to a short course of antenatal
corticosteroids is not known. (SMFM and SOAP Labor and Delivery Considerations)
b. BWH recommends following the guidance from the American College of Obstetricians
and Gynecologists (ACOG) (ACOG FAQs for COVID):
i. Given well-established benefit to neonates, use of antenatal betamethasone
between 24+0 and 33+6 weeks of gestation in patients at high risk of preterm birth
within seven days, and suspected or confirmed COVID-19 disease.
ii. Do not offer late preterm steroids for women between 34 0/7 weeks and 36 6/7
weeks of gestation
iii. These recommendations must be tailored to specific clinical circumstances,
weighing the individualized risks and benefits to both neonates and mothers
c. If antenatal corticosteroids are administered, tocolysis can be administered until
completion.
d. Magnesium Sulfate: Magnesium is routinely used for both fetal neuroprotection or
preeclampsia/seizure prophylaxis, but carries some risks in the setting of COVID-19
infection:
i. Benefits of therapy should be weighed against potential risks of maternal respiratory
depression
1. Respiratory depression typically occurs at levels of 10-13 mg/dL and will be
preceded by loss of deep tendon reflexes often occurring at levels of 7-10 mg/dL.
2. A single 4-gram bolus of magnesium sulfate without subsequent infusion may
serve as an alternative to usual dosing in the setting of mild respiratory distress.
ii. If renal function is impaired, dose should be adjusted accordingly

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ii. If renal function is impaired, dose should be adjusted accordingly
Intrapartum Care for COVID-19 Positive and PUI
1. Internal Monitors (Fetal Scalp Electrodes, Intrauterine Pressure Catheters):

a. Limited data thus far do not suggest maternal-to-fetal transmission of SARS-CoV2 is
likely to occur
b. The use of this technology may provide more reliable monitoring limiting healthcare
provider exposure for readjustment of monitors
2. Amniotomy:
a. Limited data do not suggest maternal-to-fetal transmission
b. Amniotomy may still be utilized for labor management as clinically indicated (SMFM
and SOAP Labor and Delivery Considerations)
3. Labor Analgesia:
a. Consider early epidural analgesia for labor to mitigate risks associated with general
anesthesia in the setting of an emergent cesarean
b. Avoid nitrous oxide due to risk of aerosolized infectious droplets
c. Birthing pools will not be offered
4. Mode of Delivery:
a. Mode and timing of delivery should be individualized based on clinical status of the
patient, gestational age, fetal condition. While COVID-19 itself is not an indication for
delivery, elective delivery at 39 weeks can be considered given the uncertain impact
of COVID-19 infection on fetal outcomes.
b. Vaginal delivery is not contraindicated.
c. Operative Delivery: Data on perinatal transmission at this time does not preclude the
use of forceps or vacuum. An operative vaginal delivery may be considered to shorten
the second stage since active pushing while wearing a surgical mask may be difficult
for the patient
d. Cesarean Delivery:
i. Cesarean delivery should be performed in an operating room with negative pressure
if the woman is suspected or confirmed to have COVID-19
ii. While regional and general anesthesia are both options, regional is preferable both
for maternal benefit and prevention of exposure to staff given the aerosolizing nature
of intubation.

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of intubation.
5. Cord Clamping: Do not delay cord clamping. There is insufficient evidence regarding
whether delayed cord clamping increases the risk of infection to the newborn via direct
contact (Poon et al, Int Journal Obstet Gynaecol, 2020)
6. Post Delivery: Placental tissue, miscarried embryos/fetuses should be treated as
infectious tissues and disposed of appropriately. Routine pathologic examination should
be encouraged and if possible, testing of these tissues for SARS-CoV-2 by qRT-PCR
should be undertaken.
Postpartum Care for COVID-19 Positive and PUI
1. Postpartum patients with COVID-19 should be evaluated for stability prior to transfer.
This does not need to be an in person evaluation, but rather a “huddle” with the L&D
nurse charged with giving passoff and the OB care provider. The patient’s disease state
should be categorized and high-risk comorbidities identified:
a. Asymptomatic for COVID-19 Symptoms
b. Mild Disease: Symptomatic (excluding shortness of breath) but afebrile with normal
stable vital signs.
c. Moderate Disease: Subjective shortness of breath, heart rate > 100 but < 120, fever >
100.4 despite anti-pyretics, respiratory rate > 20 but <30, O2 < 95% without need for
supplemental O2 (targeting O2 >92%), lab abnormalities (leukopenia, transaminitis),
or infiltrates on chest x-ray
d. Severe Disease: Heart Rate > 120, respiratory rate > 30, O2 < 95% on room air or
requiring supplemental oxygen to maintain O2 > 92%, or oliguria (<30 cc/hr for two
hours).
2. Postpartum Monitoring:
a. Asymptomatic: Routine care unless comorbid risk factors for decompensation (i.e.
preeclampsia, pulmonary disease other than mild intermittent asthma,
immunosuppressed)
b. Mild Disease: Recommend Q4H vital signs and strict I&Os for first 24 hours for
vaginal delivery and 48 hours for c-section.
c. Moderate Disease: Transfer to postpartum with continuous pulse oximetry monitoring
for the first 24 hours or until improvement in presentation to mild disease (whichever
takes longer). Plan for lab monitoring and additional imaging should be explicitly
stated on transfer.
d. Severe Disease: Features of severe disease or other clinical concern based on
evaluation of the obstetric care provider remain on labor and delivery. If oxygen

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evaluation of the obstetric care provider remain on labor and delivery. If oxygen
requirement is decreasing or stable after 24 hours consider transfer to postpartum
with continuous O2 monitoring.
3. Discharge and Follow Up: Patients with a history of mild disease should have a 1 week
telehealth visit coordinated prior to discharge with their obstetric care provider. Patients
with a history of moderate or severe disease should have a phone call from a
healthcare provider (RN, CNM, PA, NP, MD) 48 hours after discharge and a 1 week
dedicated telehealth visit coordinated after discharge. Patients with moderate to severe
disease should also be offered VNA services for vital sign monitoring and
anticoagulation teaching when indicated.
Breastfeeding
1. Human milk helps provide protection to newborn infants against many illnesses during
early life and is the best source of nutrition for most infants. A limited number of studies
suggest that SARS CoV-2, the virus that causes COVID-19, is not detectable in the
human milk of mothers with COVID-19 (Chen et al, Lancet, 2020).
a. The CDC, WHO, and AAP suggest that the benefits of breastfeeding in the setting of
COVID-19 appear to outweigh the potential risks of viral transmission from mother to
infant.
2. The following are recommended strategies for the breastfeeding mother-infant dyad
with COVID-19:
a. Mothers are encouraged to practice excellent hand hygiene and pump their breasts
following birth to initiate lactogenesis.
i. A dedicated breast pump should be made available to each woman during the
postpartum hospitalization.
ii. Breast pumps and components should be thoroughly cleaned in between pumping
sessions using standard policies that must include cleaning the pump with
disinfectant wipes and washing pump attachments with hot soapy water.
b. Infants should be fed pumped milk by a healthy caregiver during the hospitalization
and until the mother is recovered from her COVID-19 illness.
i. Recovery from COVID-19 illness is defined as at least 72 hours since resolution of
symptoms of COVID and at least 7 days from when her illness began.
c. Mothers who wish to breastfeed directly are encouraged to practice excellent hand
hygiene and wear a surgical mask during breastfeeding.

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Pregnant Patients Presenting with COVID-19
Mild Disease
1. For patients with no known comorbidities or respiratory symptoms (Poon et al, Int
Journal Obstet Gynaecol, 2020)
a. Ensure patient comes in for COVID-19 testing, concurrent testing for influenza/ RSV,
and vital sign check
i. If patient has normal vital signs, no difficulty breathing or shortness of breath, no
clinical indication for imaging or treatment, and is able to follow up with care then the
patient can be managed at home (ACOG and SMFM, Outpatient Assessment and
Management)
ii. If any of these is not the case the patient should be referred to the Emergency
Department for evaluation (see “moderate” disease below). For patients with
symptoms and with medical comorbidities (e.g., hypertension, diabetes, asthma,
HIV) a lower threshold should be used.
b. Treatment for mild disease is symptomatic.
i. Use pregnancy-approved medications such as acetaminophen and cough
suppressants.
ii. There is currently no antiviral treatment recommended for mild cases of COVID-19 ·
iii. Fever may be associated with an increased rate of birth defects, especially neural
tube defects, so we recommend the use of acetaminophen for pregnant women with
a temperature ≥ 100.40F
iv. Maintain adequate hydration
c. Patient should self-isolate in the home (e.g., separate bedroom, appropriate
caregivers available at home, access to food and other necessities)
d. A reliable system should be implemented for healthcare providers to check-in on
symptoms with a phone call 48 hours after evaluation and a telehealth visit 7-10 days
after initial evaluation.
e. Patients should be instructed to return to care if they develop:
i. Worsening dyspnea at rest or with ambulation
ii. Inability to tolerate oral hydration

iii. Hemoptysis
iv. Chest pain/pressure

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iv. Chest pain/pressure
v. Dizziness
vi. Obstetric complaints
Moderate or Severe Disease
1. Decision to admit:
a. Pregnant women, due to both younger age and physiologic adaptation, have a
remarkable ability to compensate for medical illness in a way that masks its severity
until their hemodynamic reserves are suddenly exhausted. Classically, they will
appear quite well until they rapidly deteriorate.
b. Any pregnant patient with respiratory symptoms should be observed or admitted as
an inpatient for a 48-hour period. Suggested criteria for observation or admission
include:
i. SpO2 < 95% on room air. Please obtain ambulatory saturations as well.
ii. Respiratory rate > 30
iii. Maternal tachycardia > 110 not improved with fluids
iv. Blood pressure abnormalities;
1. Hypotension with systolic blood pressure < 90 or diastolic blood pressure < 50
(unless baseline blood pressure below these criteria based on review of prenatal
record)
2. Hypertension defined by systolic blood pressure > 140 or diastolic blood pressure
> 90 on two separate measurements at reasonably spaced intervals in the
absence of chronic hypertension
v. Persistent fever > 101°F despite antipyretic
vi. Lab abnormalities including transaminitis, elevated creatinine, or new
thrombocytopenia < 150K
vii. Headache not resolved by medications without other explanation (given risk for
preeclampsia)
viii. Unexplained abdominal pain
ix. Category 2 fetal heart rate tracing despite adequate maternal resuscitation
x. Obstetric complaints (includes the presence of contractions, leakage of fluid, vaginal
bleeding, or decreased fetal movement)

1. Patients with even mild disease may warrant admission for obstetric indications
independent of severity

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independent of severity
xi. The presence of maternal or fetal comorbidities
1. Maternal examples include asthma or pulmonary disease, HIV infection, or
hypertension including preeclampsia.
2. Fetal examples include intrauterine growth restriction, monochorionic twin
pregnancy, or other markers of placental insufficiency.
2. If admitting, the appropriate admission location (i.e. medical ward, labor and delivery, or
intensive care unit) should be made in conjunction with the obstetric care team.
3. Inpatient diagnosis and management:
a. Management is the same as for the nonpregnant patient with rare exceptions.
b. Routine pharmacologic DVT prophylaxis is warranted
c. Suggested diagnostic and therapeutic orders for pregnant patients can be found here.
i. Most medications are safe in pregnancy and breastfeeding. NSAIDs,
fluoroquinolones, and doxycycline should be avoided if possible. Medication
guidelines specific to COVID in pregnancy can be found below.
4. Indications for ICU transfer:
a. A low threshold for evaluation is encouraged and suggested criteria include:
i. Increased work of breathing
ii. Increasing tachypnea
iii. Hypoxia requiring 6L nasal cannula
iv. PCO2 > 40 or pH < 7.35
v. Hypotension or oliguria despite adequate fluids
vi. Chest pain, worsening tachycardia, or arrhythmia other than sinus tachycardia
vii. Altered mental status
5. Discharge considerations: Discharge planning for patients admitted with manifestations
of COVID-19 mirrors that of the general population with a few notable additions:
a. Arrange for follow up with her obstetric care provider within the first 48 hours and then
within a week to assess for evolution of symptoms and consider repeat testing for
removal from precautions.
b. Ensure the patient has the requisite resources to access the hospital system prior to
discharge (i.e. transportation, access to emergency services in a language spoken by

the patient, clear instructions to re-engage accessible to the patient based on her
level of health literacy).

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level of health literacy).
Critical Illness
1. Modifications from the standard of care should be to support the physiology of

pregnancy and optimize maternal (and therefore fetal) hemodynamics.
a. Care should be undertaken as a part of a collaborative multidisciplinary team
including the ICU team, the obstetrics team, and consultants in the location that
makes the most sense based on the patient’s anticipated clinical needs. For patients
with active obstetric issues that outweigh their critical care needs the possibility of
providing some components of critical care on labor and delivery (such as
vasopressor support or hemodynamic monitoring) should be considered due to the
close proximity to the operating room.
b. Pathways for communication with obstetrics and contingencies for notification should
be clearly outlined and readily available to the primary team.
2. Hallmark physiologic changes of pregnancy include:
a. Increased cardiac output (heart rate and stroke volume)
b. Decreased systemic vascular resistance
c. Increased minute ventilation (driven by respiratory rate)
d. Physiologic compensated respiratory alkalosis
e. Increased GFR and volume of distribution
f. Expanded plasma volume
g. Alterations in clotting cascade to promote coagulation
3. The majority of management of the critically-ill pregnant patient is unchanged from that
of the general population
a. These are quick tips for intensivists caring for critically ill obstetric patients.
b. Intubation should be considered early given increased airway edema and aspiration
risk in pregnancy as well as limited functional residual capacity.
c. Ventilation should target the respiratory alkalosis of pregnancy maintaining a pCO2 <
45 and a pH > 7.35.
i. Permissive hypercapnea may be acceptable but inability to maintain these targets
alongside other standards of care for lung-protective ventilation should prompt a
discussion with the obstetric care team.

ii. Depending on the gestational age and clinical status this may prompt more liberal
parameters, additional fetal monitoring, or consideration of delivery.

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parameters, additional fetal monitoring, or consideration of delivery.
d. Prone positioning in pregnancy has been reported and should be considered for
standard indications (Dennis et al, BMC Pregnancy Childbirth, 2018). Early discussion
of the feasibility of this strategy and gestational-age dependent patient positioning
considerations should take place with the obstetric team.
4. Fetal outcomes vary according to gestational age. The obstetrics team should share
anticipated outcomes at a given gestational age with the critical care team to inform
their clinical decision-making and management.
a. Antenatal Corticosteroids: Antenatal corticosteroids are typically given as
betamethasone 12 mg IM Q24 hours for two doses which is the equivalent of 60 mg
methylprednisolone. Importantly, methylprednisolone and prednisone are metabolized
by the placenta making the administration of betamethasone or dexamethasone
necessary to impact fetal lung maturity.
b. Magnesium: Theoretic respiratory depression is less concerning in an intubated
patient population. The additional benefit of magnesium for seizure prophylaxis in
addition to medications used for sedation is uncertain.
c. Tocolysis: Tocolysis is not contraindicated in critical illness but should be
individualized based on maternal status, gestational age, and risk of progression of
preterm labor. The fetal risks of slowing spontaneous preterm labor in a critically ill
patient with the potential for comorbid intrauterine infection as well as the maternal
side effects of the individual agents should be balanced with the gestational-age
dependent fetal benefit.
i. Data associating NSAIDs to adverse outcomes in COVID-19 infection is inconsistent
but warrants caution in those with limited clinical reserve.
ii. Immediate-release nifedipine is a potent systemic and pulmonary vasodilator which
can worsen hypotension or VQ mismatch. Nifedipine is contraindicated for women
with cardiac manifestations of the disease.
d. Rates of spontaneous preterm birth in the critically-ill population are high.
i. Unexplained maternal tachycardia, hypertension, increasing sedation requirements,
and tachypnea should prompt a call to the obstetric care team for evaluation for
possible preterm labor.
ii. Contraindications to labor (i.e. placenta previa, nonvertex presentation, prior uterine
surgery) should be noted and incorporated into the checklist outlining considerations
for vaginal delivery.
e. A plan for fetal monitoring should be clearly communicated and facilitated by
members of the obstetric team.
i. For critically-ill patients twice daily nonstress tests should be considered both to

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i. For critically-ill patients twice daily nonstress tests should be considered both to
monitor fetal status and assess maternal hemodynamics.
ii. Any change in clinical status should prompt consideration of fetal assessment
balancing gestational age,
f. Neonatology should be notified of any pregnant patient admitted to the hospital at or
beyond 22 weeks to offer a consultation when appropriate and for situational
awareness.
5. Delivery planning is an essential part of every admission
a. A vaginal delivery kit, cesarean delivery kit, and neonatal warmer and resuscitation kit
should be at the bedside in anticipation of spontaneous delivery or maternal cardiac
arrest for all patients.
b. A discussion of the pathway for emergent delivery for fetal indications (STAT c-
section) including the location of delivery, transport process, and involved personnel
should take place and account for gestational age and maternal stability.
i. The BWH-specific protocol should be displayed in a visible location and members of
the care team should be familiar with its use.
c. Delivery may become necessary in select circumstances where oxygenation or
ventilation are thought to be impaired by pregnancy.
i. Anticipate the autotransfusion after delivery as blood returns from the uterus into the
circulation. Diuresis, PEEP optimization, and judicious use of alveolar recruitment
maneuvers may be needed.
ii. Vaginal delivery is the preferred mode of delivery for patients in the absence of
contraindication to labor. The decision for vaginal versus cesarean delivery in the
critically-ill patient should be individualized taking into account parity, gestational
age, monitoring needs, and a priori likelihood of a successful vaginal birth.
d. Maternal cardiac arrest at or beyond 20 weeks, or when the uterus is at the level of
the umbilicus, includes specific modifications to account for the impact of the gravid
uterus (Jeejeebhoy et al, Circulation, 2015).
i. Provide immediate left uterine displacement by either pushing or pulling the uterus
off the IVC.
1. This is a dedicated role for a member of the code team.
ii. Ensure the IV used for code medications is above the level of the diaphragm to
ensure no interference with return to circulation

iii. Remove and detach all fetal monitor.
iv. Prepare to begin a resuscitative hysterotomy (i.e. cesarean delivery) by 4 minutes

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iv. Prepare to begin a resuscitative hysterotomy (i.e. cesarean delivery) by 4 minutes
without return of spontaneous circulation (ROSC) with goal for delivery of the fetus
by 5 minutes in an attempt to restore ROSC
Therapeutics in Pregnancy
Antipyretics
1. Acetaminophen:
a. Acetaminophen is the preferred antipyretic for COVID-19. It is also the preferred
antipyretic for influenza in pregnancy (ACOG Guidance on the Assessment and
Treatment of Pregnant Women with Suspected or Confirmed Influenza; SMFM, Am J
Obstet Gynecol, 2017).
b. While some epidemiologic studies raised the possibility of an association between in
utero acetaminophen exposure and the risk of ADHD in later life (Masarwa R et al,
Am J Epidemiol, 2018), data review by the US FDA and the Society for Maternal Fetal
Medicine found these data to be inconclusive (FDA safety communication, US FDA,
2015; SMFM Am J Obstet Gynecol, 2017).
c. The recommended dose of acetaminophen for pregnant women is the same as the
recommended dose in adults: up to 1,000 mg in a single dose, not-to-exceed 3,000
mg in a 24-hour period.
2. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
a. For review of NSAID use in COVID-19 in adults, please refer to the therapeutics
chapter
b. NSAIDs are generally avoided as first line agents for management of fever or pain in
pregnancy due to inconclusive data regarding first trimester risk, and risk of
premature closure of the ductus arteriosus in later pregnancy.
3. Aspirin
a. Low-dose aspirin is used in pregnancy for several indications, most commonly in
preventing preeclampsia (ACOG Guidance on Low-Dose Aspirin Use During
Pregnancy) We support continued use of low-dose aspirin after discussion with
maternal-fetal-medicine and other relevant consultative services (e.g. cardiology)
b. We recommend against using moderate or high dose aspirin as an antipyretic
Experimental Antiviral Agents for COVID-19 in Pregnancy
1. Treatment for COVID-19 is evolving rapidly. The BWH infectious diseases COVID-19
treatment guidelines (Partners login required), Infectious Diseases, and Maternal Fetal

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treatment guidelines (Partners login required), Infectious Diseases, and Maternal Fetal
Medicine consultations take precedence over the information provided in the sections
below. For all the agents below please refer to the therapeutics chapter
2. Hydroxychloroquine
a. HCQ Use in Pregnancy
i. HCQ crosses the placenta
ii. HCQ is considered safe to continue for the management of rheumatologic diseases,
such as systemic lupus erythematosus (SLE), in pregnancy
iii. Several studies of women in whom HCQ therapy was continued in pregnancy
revealed no adverse fetal outcomes (Parke, J Rheumatol, 1996; Clowse et al,
Arthritis Rheum, 2006, Costedoat-Chalumeau, Arthritis Rheum, 2003)
b. HCQ Use in Lactation
i. HCQ levels in breastmilk are low and it’s considered safe to use in lactating
mothers.
c. Evidence for HCQ for COVID-19 in Pregnancy
i. HCQ is an investigational agent for the treatment of COVID-19 and has not yet been
demonstrated to be effective. i
d. Recommendations
i. In consultation with the Infectious Diseases and Maternal Fetal Medicine consult
services, HCQ may be used for the treatment of inpatient pregnant and lactating
women who:
1. are not candidates for clinical trials
2. have indicators of moderate to severe disease, or other risk factors for progression
ii. We do not routinely recommend the use of azithromycin with HCQ for the indication
of COVID-19 (therapeutics chapter)
iii. Per our treatment guidelines, dosing of HCQ for pregnant inpatients is the same as
for non-pregnant adults:
1. Hydroxychloroquine 400 mg PO every 12 hours on the first day, followed by 200
mg every 12 hours for 4 additional days (5-day total course)
2. May extend up to 10 days depending on clinical response
3. The half-life of HCQ is over 7 days, so a 5-day treatment course should still yield
therapeutic HCQ levels past day 10 (Yao et al, Clin Infect Dis, 2020)
3. Remdesivir

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a. Remdesivir is an investigational agent. Pregnancy is an exclusion for participation in
trials NCT04292730 and NCT04292899. It is available for pregnant women with
confirmed COVID-19 infection and severe manifestation of the disease through an
individual compassionate emergency use access program offered by Gilead
Sciences.
i. The Infectious Diseases and Maternal Fetal Medicine consult services should be
involved in all decisions to apply for compassionate use.
1. Application and contact information can be found in our treatment guidelines
(partners login required).
2. Providers outside the BWH may fill a Gilead online application
b. Remdesivir in Pregnancy
i. Remdesivir has not yet been studied in pregnant women. A few pregnant women
with Ebola virus infection have received remdesivir through clinical trials (Mulangu S
et al, NEJM, 2019)
4. Immunomodulators
a. Anti-IL6 Agents (Tocilizumab, Siltuximab, Sarilumab)
i. For an overview of current available data, recommendations, and available clinical
trials for anti-IL-6 agents please consult the therapeutics chapter
1. We do not recommend the routine use of anti-IL-6 agents in COVID-19 or in
pregnancy unless part of a clinical trial
b. Tocilizumab in Pregnancy
i. Tocilizumab crosses the placenta
ii. Post-marketing data analysis of pregnancy outcomes in 288 evaluable women out of
399 who were exposed to tocilizumab shortly before or during pregnancy revealed
no substantial increase in adverse pregnancy outcomes. However, this series is too
small and diverse to demonstrate the safety of this agent in pregnancy
(Hoeltzenbein M et al. Semin Arthritis Rheum, 2016)
iii. Outcome data during pregnancy are limited
1. Tocilizumab may only be considered for use in pregnant women who have severe
or critical COVID-19 AND suspicion of cytokine activation syndrome with elevated
IL-6 levels in conjunction with Infectious Diseases consultation
5. Systemic Corticosteroids
a. For an overview of current available data and recommendations for the use of
corticosteroids in adults with COVID-19 please consult the therapeutics chapter

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corticosteroids in adults with COVID-19 please consult the therapeutics chapter
b. We do not recommend the routine use of systemic corticosteroids for COVID-19
except as part of a clinical trial or if treating another indication
c. There are no data to inform on the risks and benefits of the use of steroids for fetal
maturation in women with suspected or confirmed COVID-19 (see above)
6. Systemic Antibiotics
a. Information on treatment of bacterial infections that may be associated with COVID-
19 can be found in the therapeutics chapter
b. There is no sufficient supporting evidence to recommend the use azithromycin in
combination with hydroxychloroquine for the indication of COVID-19 treatment
i. Concomitant treatment of community-acquired bacterial pneumonia, if suspected,
and typical coverage is desired, should be considered with an infectious diseases
consultation, after weighing cardiac risks and benefits
c. Suspected or confirmed COVID-19 should not delay treatment with antibiotics that
would usually be given for a non-COVID-19 indication (for example treatment of
bacteriuria, or evaluation or treatment of fever with prolonged rupture of membranes
or postpartum fever)
CHAPTER 18
Ethics
Section Editor: William Feldman MD
Contributors: Aimee Miliken PhD RN HEC
Overview
1. Further details about the BWH and Partners HealthCare model will be linked here when

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1. Further details about the BWH and Partners HealthCare model will be linked here when
available.
2. Below are general considerations and references about resource allocation in the
setting of scarcity. For a comprehensive framework for resource allocation, please see
the model developed Douglas White and colleagues at the University of Pittsburgh.
Triage
Crisis Standards of Care
1. A “crisis standard of care” is a set of principles to help guide triage when there are
insufficient resources (including ICU beds, ventilators, dialysis machines, etc.) to meet
medical needs (Institute of Medicine 2012).
2. It is triggered by “a substantial change in usual healthcare operations and the level of
care it is possible to deliver, which is made necessary by a pervasive (e.g. pandemic
influenza) or catastrophic (e.g. earthquake, hurricane) disaster” (Institute of Medicine
2012)
a. It must be formally declared by regional/state authorities and hospital leadership.
b. It typically involves contingencies for different stages of a crisis
3. It allows transparency. Transparency in decision making, particularly when resources
are scarce and cannot be allocated to all who are in need, is essential (Biddison et al.
2014)
Stages of crisis

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(Christian et al. 2014)
Triage principles
1. The goal of triage is to maximize population benefit while treating individuals fairly.
a. This is different from the usual goal in medicine of promoting the wellbeing of
individuals.
2. The most widely endorsed strategies are to maximize lives saved or life-years saved:
a. Lives saved (no explicit preference given based on age)
b. Life-years saved (some explicit preference given to younger patients all else being
equal)
3. Several other strategies have been proposed to allocate scarce resources, but have
been criticized for failing to maximize benefit (NY State Task Force 2015). These
include:
a. first-come first served
b. lottery
c. preferential allocation (e.g. for healthcare workers)

4. Consensus statement policies (Biddison et al. 2014) suggest no ethical difference
between withholding and withdrawing care.

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between withholding and withdrawing care.
Structure of triage teams
1. Consensus guidelines suggest that all decisions about triage are made by a Triage
Officer, not the bedside clinicians caring for patients (Christian 2014).
2. The Triage Officer should be a physician with critical care training.
3. Decisions about triage should be made based on protocols established by the hospital.
These protocols should be evidence based and nondiscriminatory (Gostin & Hanfling
2009)
4. Bedside clinicians, patients, and families should have mechanisms for appealing triage
decisions.
5. An oversight committee should be established to review decisions made by Triage
Officers to ensure consistent application of the triage protocol and to adjudicate
appeals.
Duties of Health Care Workers

1. Regardless of scarcity, clinicians have a duty to care for all patients—including by
providing compassionate comfort-oriented to those who will benefit from it.
a. The duty to care requires that clinicians accept a reasonable level of risk in the
provision of care, founded in the principles of fidelity, respect for persons, and non-
abandonment.
b. There is a corollary obligation of organizations to ensure risk is minimized to clinicians
as much as possible through, for example, the provision of personal protective
equipment (Veterans Health Administration 2010).
CHAPTER 19
Psychiatry
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Psychiatry
Section Editor: Adrienne Taylor, MD
Contributors: Adrienne Taylor, MD Sara Vasudeva, MD
Psychiatry Consultation
1. Clinical scenarios that should prompt psychiatry consultation:
a. Suicidal ideation or risk of self harm
b. Agitation in the setting of delirium or neurocognitive disorder
c. New onset psychosis or assistance with management of antipsychotics
d. Assistance with management of mood symptoms
e. Severe alcohol or opioid withdrawal
f. Assistance with management of psychotropic medications in the setting of other QTc
prolonging agents (i.e. hydroxychloroquine and azithromycin)
g. Transfer of patient from psychiatric facility for COVID rule out
2. Pro-active psychiatry consultation on select COVID units:
a. Brigham Medical Psychiatry Service is offering consultation by fellows to COVID ICU
units with goal to:
i. Provide a designated psychiatrist to a assist with clinical care and
ii. Provide support to individual medical team members to discuss
emotional/psychological responses to difficult cases.
b. These consults are virtual, via telephone with either the patient directly or the primary
team
c. These services will be available roughly 9am-3pm Monday - Friday, with some
exceptions. This team is also the psychiatry consult service for the rest of the hospital.
If a COVID provider is interested in consulting the psychiatry service, please place an

order in Epic and contact the Psychiatry service.

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General Management of Anxiety/PTSD
1. Preliminary data from China found that 96.2% of patients hospitalized for COVID-19
reported significant PTSD symptoms prior to discharge from the hospital (Bo et al,
Psychol Med, 2020)
2. For management of anxiety related to dyspnea and at the end of life, please refer to the
Palliative Care section.
3. Non-pharmacologic
a. Feelings of uncertainty and fear can fuel anxiety
i. Important to first acknowledge and normalize distress reactions
ii. Correct misinformation. Provide accurate information (regarding patient’s current
medical condition and next steps, regarding hospital protocols and measures being
taken for safety)
iii. Encourage limiting media exposure
b. Counseling (Spiritual, Psychocological, SW)
c. Reiki
d. Strategies for reducing distress
i. Restful sleep, eating regular meals, exercising
ii. Talking to loved ones (via telephone or video chat)
iii. Diaphragmatic breathing
iv. Muscle relaxation
4. Pharmacologic
a. Continue home psychotropic medication regimen if possible
b. For patient with evidence of delirium
i. Quetiapine 12.5-25mg TID PRN
c. For patient without evidence of delirium
i. Quetiapine 12.5-25mg TID PRN
ii. Lorazepam 0.5-2 mg PO/SL TID PRN; 0.5-2 mg IV TID PRN
d. For patient with risk of respiratory depression or history of respiratory illness

i. Buspirone 5-15mg PO TID

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Affective Disorders
Depression
1. Symptoms: Dysphoric mood, withdrawn, difficulty concentrating, disrupted sleep,

decreased appetite, fatigue, tearfulness, worthlessness, hopelessness, helplessness
2. Non-Pharmacologic
a. Physical distancing can worsen depression given increase in isolation.
i. Using safe communication channels between patients and families such as
smartphone communication should be encouraged to decrease isolation
b. Feelings of guilt and stigma surrounding COVID positivity may also increase
symptoms of depression
i. Bring focus to what the patient and family can control going forward and that the
appropriate steps to ensure safety are being taken
3. Pharmacologic
b. SSRI: Sertraline 50mg daily. If tolerated, can uptitration of 50mg every 5-7 days to
target symptoms. Max dose 200mg daily.
c. Depression with sleep disruption and low appetite: mirtazapine 7.5mg qhs. Can
uptitrate to 30mg qhs as tolerated.
d. Consider consulting Psychiatry if depressive symptoms persist after non-
pharmacologic interventions have been attempted or patient reports suicidal ideation
Bipolar Disorder
1. Symptoms of Mania/Hypomania: sleeping very little BUT feeling extremely energetic,

racing thoughts, rapid speech, flight of ideas, elevated or irritable mood, grandiose
beliefs, highly distractible, impulsivity/recklessness. Psychotic symptoms can be
present in severe cases (delusions/hallucinations).
2. Pharmacologic

b. Consider consulting Psychiatry if patient appears to have decompensated hypomania
or mania that is affecting ability to engage in patient care

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or mania that is affecting ability to engage in patient care
General Delirium
Incidence
1. Disorders of consciousness were significantly more common in patients who died from
complications of COVID-19 (22%) than in those who survived (1%). Chen et al, BMJ,
2020
2. From anecdotal clinical experience across the US, COVID-19 patients seem to be
experiencing very high rates of delirium with associated symptoms including agitation,
aggressive behaviors, and disinhibition
Diagnosis
1. Use the Confusion Assessment Method (CAM)

a. CAM is positive if (1) AND (2) and EITHER (3) or (4) are present
b. Acute often fluctuating change in mental status (vs dementia)
c. Difficulty focusing attention
d. Disorganized thinking (rambling, illogical flow of ideas)
e. Altered level of consciousness (too sedated or too hyperactive)
Management
2. Non-pharmacologic:
a. Daytime lights, nighttime dark. Frequent reorientation. Reverse contributing medical
conditions as able.
b. Consult Psychiatry; for terminal delirium, consult Palliative Care (and see
recommendations here)
c. Additional information available at: Guidelines for Acute Hospital Acquired Delirium
(Partners login required)
3. Pharmacologic
a. Avoid deliriogenic medications (anticholinergics, benzodiazepines, opioids) as

possible
b. Treat comorbid symptoms and underlying medical illness

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b. Treat comorbid symptoms and underlying medical illness
c. For agitation/aggression
i. Antipsychotics
1. Haloperidol: Mild agitation:0.5-1.0 mg IV or 1 to 2 mg PO q6h and 1-2 mg q2h
PRN.; Moderate agitation: 2-4 mg IV; Severe agitation: 4-10 mg Maximum dose:
20 mg / 24 hours
2. If refractory, olanzapine (Zyprexa), 2.5 to 5 mg (PO, SL, or IV) q12 hr and 2.5 mg
q4h PRN; Maximum dose: 30mg / 24 hours. **do not combine with parenteral
benzodiazepines due to increased risk of respiratory depression**
3. If haloperidol/olanzapine not effective or contraindicated, could try:
a. Quetiapine (Seroquel) 12.5-50 mg qHS
b. aripiprazole (Abilify) 5 mg PO daily; maximum dose 30 mg daily
ii. Alpha 2 agonists - helpful for patients for vent weaning; also good option if
prolonged QTc (Link for further information)
1. dexmedetomidine (Precedex) IV - easily titratability given short half-life
2. Consider use of clonidine 0.1 mg BID (can uptitrate) - available as a transdermal
patch as well.
iii. Mood Stabilizers
1. Valproic Acid (good option if prolonged QTc): Start at 125-250mg IV q8h TID,
however, COVID patients are seeming to need escalations in doses (up to anti-
manic dosing of 15-25 mg/kg) in combination with antipsychotics (i.e. haloperidol or
olanzapine as above).
iv. Others
1. For regulation of sleep/wake cycle: Mirtazapine (Remeron): 7.5 mg (can uptitrate,
but it is more sedating at lower doses)
d. Considerations for Geriatrics Patients
i. High risk for delirium given no-visitors policy, disorienting effect of PPE use by staff,
difficulty hearing/identifying caregivers through masks
ii. Avoid deliriogenic medications such as anticholinergics and benzodiazepines (See
here for a comprehensive list, Beers Criteria)
iii. If acutely agitated, not redirectable by non-pharmacologic means, trial 12.5 mg
trazodone x 1 prn, repeat dose x 30 min if no effect

iv. Use of antipsychotics (e.g. haloperidol, olanzapine, quetiapine) as last resort only,
and only if QTc is < 500

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and only if QTc is < 500
Assessment of Capacity
General Capacity Assessment
1. Capacity is an essential component of consent and deals with the process of decision-
making. The evaluation of capacity is decision-specific and time-specific and involves a
need to balance autonomy and beneficence. A capacity assessment can be completed
by any physician. There are four decision-making abilities that patient require to be
able to demonstrate capacity
a. Ability to understand relevant information
i. Patient must be able to comprehend basic information about the current condition,
potential options, and risks/benefits associated with these options
b. Ability to appreciate the situation and its consequences
i. This is the ability to recognize how the above information pertains to one’s own
situation
c. Ability to reason
i. Ask patient to describe how they reached their decision and what factors influenced
this.
d. Ability to communicate and express a consistent choice
Patients Refusing Recommended Medical Intervention
1. Considerations
a. Assess urgency of intervention and consequences of refusal
i. Embedded in a capacity assessment is a risk assessment
ii. The clinician needs to distinguish between tolerable risks and intolerable risks. Only
intolerable risks require assessment of capacity. Intolerable risks might include
behavior that is new and unprecedented (not consistent with past behavior) and
behavior that is causing significant harm.
b. Assess differential for refusal (i.e. delirium, anxiety, agitation, volitional, psychosocial
stressors)
c. Patients who refuse testing or airborne precautions will likely require a full capacity

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c. Patients who refuse testing or airborne precautions will likely require a full capacity
assessment. Given that symptomatic patients seem to have increased frequency of
transmission to others, patients will likely have a higher threshold to demonstrate
capacity in this setting.
2. If patient lacks capacity, have low threshold for use of medications for agitation and/or
restraints
Patients Requesting to Leave Against Medical Advice (AMA)
1. Identify psychosocial stressors and address as able

2. Patients who request to leave AMA will likely require a full capacity assessment. Given
that symptomatic patients seem to have increased frequency of transmission to others,
patients will likely have a higher threshold to demonstrate capacity in this setting.
3. If patient is found to have capacity to leave AMA but poses significant infection risk to
others, call legal and/or risk and consider involvement of security. Likely Boston Public
Health Commission (BPHC)/Department of Public Health (DPH) will need to be alerted.
a. At this time DPH has not invoked their authority to forcibly quarantine such patients
4. For patients with unstable housing, DPH may be able to assist with shelter
recommendations or placement.
5. If patient lacks capacity, have low threshold for use of medications for agitation and/or
restraints
Addictions Psychiatry
Alcohol Use Disorder
1. High risks of relapse and escalation of alcohol use during this time due to isolation and
increased stress
2. Withdrawal
a. Severe - Likely still needs inpatient management
b. Mild or Moderate
i. For unsupervised withdrawal, consideration of anticonvulsant medications such as
gabapentin, topiramate or carbamazepine (SAMHSA Guidelines) - advantage is
lower abuse potential
ii. Could also consider short duration of benzodiazepines for taper

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Opioid Withdrawal
DEA Guidelines during COVID-19 (Link)
1. Decision tree for prescribing controlled substances during COVID-19 (Link)

a. Buprenorphine
i. Practitioners who prescribe buprenorphine are now able to prescribe buprenorphine
to new patients with opioid use for maintenance treatment or detoxification treatment
following an evaluation via telephone voice calls, without first performing an in-
person or telemedicine evaluation, if deemed clinically appropriate and safe
Psychological Effects of Quarantine

1. The following is adapted from Brooks et al, Lancet, 2020
2. Stressors during quarantine include:
a. Frustration and boredom from isolation, loss of one’s usual routine, and limited social
and physical contact with others
b. Inadequate supplies and access to regular medical care
c. Insufficient information
d. Longer duration of quarantine (i.e. 10 days or longer) as well as extension of
quarantine length
e. Fears about becoming infected and/or infecting others which can manifest as
increased attention to and worry about one’s health and physical symptoms
3. Stressors following quarantine include:
a. Financial loss (i.e. absence from work, healthcare costs, and other unanticipated
financial burdens) leading to socioeconomic distress
b. Stigmatization and rejection from family, neighbors, co-workers or friends
c. Resuming one’s “normal” routine
4. Promoting Psychological Well-being during quarantine
a. Provide clear, understandable, and practical communication about the nature of

disease, reason for quarantine and treatment, and other essential information.
Information will often need to be repeated and developmentally/culturally appropriate.

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Information will often need to be repeated and developmentally/culturally appropriate.
b. Facilitate communication with loved ones when possible with use of technology
(e.g. phone and video calls, social media) when available
c. Keep quarantine as short as possible and restrict to what is scientifically
appropriate
Psychological First Aid and Supporting Well-Being

General Measures for Patients and Providers
1. The following is adapted from WHO, Banerjee, Asian J Psychiatr, 2020

2. Safety/Basic Needs
a. Offer immediate assistance by looking for ways to make them feel safe and
comfortable (blankets, water, somewhere to sit, etc).
3. Good Communication
a. Being calm and showing understanding can help people in distress feel more safe
and secure, understood, respected and cared for appropriately
b. Important not to pressure anyone to tell you what they’ve been through
c. Allow for sharing silence - remember, some people are may not feel comfortable
sharing, speaking, or asking for help
d. Validate feelings and thoughts - allow them to talk as little or as much as they want
to. Try not to push too hard to get them to talk about what happened or how they are
feeling
e. Avoid temptation to judge the rightness or wrongness of their reactions
4. How to Help People Feel Calm
a. Keep your tone of voice calm and soft
b. Make eye contact
c. Remind them you are there to help, remind them that they are safe, if it is true
d. If feeling disconnected from their surroundings, it may help to make contact with the
environment and themselves
i. Place and feel feet on the floor
ii. Tap fingers or hands on lap
iii. Notice some non-distressing things in the environment, such as things you can see,
hear, or feel.
iv. Focus on breathing, and to breathe slowly

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iv. Focus on breathing, and to breathe slowly
5. Education
a. All reactions and emotions are “normal”
b. Common stress responses include confusion, insomnia, panic attacks, health-anxiety,
fear of illness, increase in substance use, irritability, guilt, shaken religious faith, loss
of confidence in self or others, shock, grief, physical symptoms (GI distress,
headaches, pain) and feelings of hopelessness or helplessness
6. Coping
a. Encouraging health-promoting behaviors
i. Get enough rest
ii. Maintain routines
iii. Eat as regularly as possible and drink water
iv. Talk with family and friends (via phone or video)
v. Discuss problems with someone you trust
vi. Do activities that help you relax (walk, sing, pray)
vii. Do physical exercise
viii. Find safe ways to help others in the crisis and get involved in community activities
b. Minimizing negative coping activities
i. Drugs, smoking, or drinking alcohol
ii. Sleeping all day
iii. Working all the time without any rest or relaxation
iv. Isolating yourself from friends and loved ones
v. Neglecting basic personal hygiene
vi. Being violent
c. Support Problem-Solving (re: pets, transportation, updating family)
7. Connect individuals with support systems
a. See therapy resources below
b. Facilitate spiritual practices
c. Help families to provide support and care for loved ones who are hospitalized as
possible (including virtually).
8. Emotional Re-Adjustment (after the crisis)
a. Best helped by:

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i. Acceptance of the event and the losses
ii. Identification, labeling, and expression of emotions
iii. Regaining a sense of control and mastery over our lives
Supporting Family Members of COVID Hospitalized Patients
1. The following is adapted from the Center for the Study of Traumatic Stress
2. Managing Uncertainty and Elevated Distress
a. Encourage health-promoting behaviors for family members at home
b. Remind family that their loved one is receiving the necessary care to support their
recovery and that the majority of hospitalized individuals are successfully treated and
are able to return home
c. Recommend obtaining ready access to the patient’s medical, legal, and financial
documents during hospitalization should the need arise in his/her absence
d. Set expectations for frequency of updates
3. Staying Connected During Family Separations
a. Remind family members that physical separation from loved ones is necessary to
keep everyone safe and healthy and that keeping family members away from the
hospital also allows healthcare teams to more effectively focus on caring for patients
b. Create opportunities to communicate safely with the hospitalized family member via
text, telephone, email, or video chat
c. Encourage important conversations if health status deteriorates and prior to need for
intubation
i. To understand last wishes
ii. To provide opportunities to say goodbye
4. Stigmatization from Others
a. People are understandably concerned about the virus spreading to themselves and
their loved ones
b. Confirm with your health care provider when your loved one and other family
members are no longer at risk of spreading the virus
i. After all family members are cleared by healthcare providers, share this information
with friends, family, and community members so they understand that the family is
not at risk of spreading the virus
5. Discussing Coronavirus with Children (Link)

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5. Discussing Coronavirus with Children (Link)
Supportive Resources
Immediate Assistance
1. Disaster Distress Helpline (SAMHSA)

Call 1-800-985-5990 or text TalkWithUs to 66746
2. National Suicide Prevention Lifeline (Link)
Call 800-273-8255 or Chat with Lifeline
3. Crisis Textline (Link)
Text TALK to 741741
4. Veterans Crisis Line (VA)
Call 800-273-8255 or text 838255
Therapy Resources (for patients and/or providers)
1. Therapy Matcher: free telephone referral service that connects to licensed clinical
social workers. Phone: 617-720-2828 or email info@therapymatcher.org - provide
name/phone number and a social worker will call back to learn about needs and
recommend several potential therapists (based on requested location, gender,
insurance)
2. William James Interface Referral Service: Free telephone referral service that connects
to licensed clinicians. Note: Only serves participating communities. Phone: 888-244-
6843.
3. Psychology Today: online directory of therapists
Helpful Tools
1. Headspace (meditation/mindfulness app)

a. available via iOS, Android or desktop, offers sets of guided meditations aimed at
tackling problems related to anxiety, sleeplessness and relationships. For the rest of
2020, Headspace is offering a free subscription to all providers with NPI numbers
2. 10% Happier (Free Coronavirus Sanity Guide)

a. A stress/meditation/relaxation and sleep app free to all healthcare providers with code
HEALTHCARE

Página 195 de 196
HEALTHCARE
3. The Evermind app
a. available via iOS and Android, can help you build resilience and handle stress using
cognitive behavioral therapy techniques. In the app, you can access guided programs
on improving sleep, disconnecting, challenging negative thought patterns and more.
4. The Care Online: iCBT program
a. available via iOS, Android or desktop, is an online self-directed cognitive behavioral
therapy course offered to patients with anxiety or low-to-moderate levels of
depression to help them self-manage symptoms of these conditions.
5. Calm (free meditation/mindfulness app)
6. Down Dog Yoga & Exercise Apps (HIIT, Barre, 7 Minute)
a. Free for anyone with a .edu address and healthcare workers until July 1
7. For more resources: MGH Guide to Mental Health Resources
1.
Please send suggestions and questions: covidprotocols@bwh.harvard.edu

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All Chapters - COVID-19 Protocols

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CHAPTER 1

Clinical Course, Prognosis, and

Section Editors: Benjamin S. Parker MD MBA, Katherine H. Walker MD MSc

Updated: April 19, 2020

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Disease course and progression

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Death or hospital discharge

1. Cause of death (Ruan et al, Intensive Care Med, 2020):

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1. Initially recognized in December 2019 by Chinese authorities in the setting of cases of

real-time phylogenetic tracking of the viral genome can be found at NextStrain

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1. Transmission of SARS-CoV-2 is incompletely understood, and new data continue to

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1. Equity focuses on eliminating avoidable, unfair or remediable differences among

a. Upholding equity in health allows prioritization of fair opportunities for everyone to

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Demographics of COVID-19 Patients

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1. Skilled nursing facilities (SNF):

Addressing Health Equity at the Hospital Level

1. Collect transparent data:

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ED & Inpatient Floor

Section Editor: Katherine H. Walker MD MSc

Updated: April 20, 2020

Personal Protective Equipment and Infection Control

1. Location-specific PPE guidance: There are location-specific differences (e.g.,

a. Easy to read “grid” summarizing PPE here (Partners login required)

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ICU Strict isolation manual

1. Step-by-step protocols for working in COVID-19 precaution patient rooms (e.g.,

Epic Note and Lab Templates

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f. Last set of COVID labs (LASTCOVID)

Laboratory studies and EKGs

On admission CBC with differential

Extended Respiratory Viral Panel - only if would

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1. Findings: Please see this excellent resource from Radiopedia.

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Respiratory Escalation Pathways and Intubation

1. Nasal Cannula, oxymizer, venturi mask:

For Persons Under Investigation (PUI) or with confirmed COVID-19

1. Goals of oxygen therapy:

b. Maintain stable work of breathing

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Considerations for Geriatric Patients

nursing home resident, page geriatrics tele-consult pager (Pager #38251)

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Early Advance Care Planning

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1. RN wears standard PPE

1. RN wears standard PPE

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