A Pulmonary Puzzle:

Patient Case of Acute

Respiratory Distress
Syndrome
Delaney Straw, PharmD
Trauma Neuro ICU Final Presentation
Objectives

1) Identify appropriate criteria for diagnosis and tp

pathophysiology of acute respiratory distress syndrome

2) Describe the therapeutic management and supportive

care for acute respiratory distress syndrome

3) Assess patient factors that may contribute to the

treatment approach
Abbreviations
ARDS Acute Respiratory Distress Syndrome

CHF Congestive Heart Failure

PaO2 Partial Pressure of Arterial Oxygen

FiO2 Fraction of Inspired Oxygen

VTE Venous Thromboembolism

PEEP Positive End Expiratory Pressure

BiPAP Bilevel Positive Airway Pressure

TV Tidal Volume

RR Respiratory Rate

HAP/VAP Hospital/Ventilator Associated Pneumonia

Meet Patient AR

- 66 year old male admitted on 1/3 to the neuro ICU

- Complaints of fatigue, lack of appetite, and shortness of breath

- Past medical history: Non-small cell lung cancer with brain

metastases, coronary artery disease, hypertension,
hyperlipidemia

- Recent hospitalization 12/27-12/29 for sepsis with covid

- Treated with 3 days of remdesivir
Home Medications

Valsartan 40 mg daily Atorvastatin 20 mg daily

Metoprolol succinate 25 mg Aspirin 81 mg daily
daily
Ferrous fumarate 325 mg daily Dexamethasone 4mg with
chemo
Ondansetron 8 mg PRN Prochlorperazine 10 mg PRN

Pembrolizumab Carboplatin Pemetrexed

Initial Exam

Temp: 100.5 degrees F

Weight: 90.2 kg

Heart Rate: 125 bpm

Oxygen therapy: 4 L
Respiratory rate: 30 bpm nasal cannula
Oxygen saturation: 92%

Blood pressure: 150/70 mmHg

Patient Workup

WBC 1.2
Na 128
PO4 2.7 Hgb 7.3
K 2.6
Mg 1.7 Hct 22.1
Cl 92
Alk Phos 76 Plt 36
CO2 23
Albumin 3.6
Glucose 120
AST 95 pH PaO2 PaCO2 Base deficit
BUN 28
ALT 56 7.43 27 33 3
SCr 1.1
Billi 1.4
Ca 8.1
QTc 465
Patient Workup

WBC 1.2
Na 128
PO4 2.7 Hgb 7.3
K 2.6
Mg 1.7 Hct 22.1
Cl 92
Alk Phos 76 Plt 36
CO2 23
Albumin 3.6
Glucose 120
AST 95 pH PaO2 PaCO2 Base deficit
BUN 28
ALT 56 7.43 27 33 3
SCr 1.1
Billi 1.4
Ca 8.1
QTc 465
Patient Workup

WBC 1.2
Na 128
PO4 2.7 Hgb 7.3
K 2.6
Mg 1.7 Hct 22.1
Cl 92
Alk Phos 76 Plt 36
CO2 23
Albumin 3.6
Glucose 120
AST 95 pH PaO2 PaCO2 Base deficit
BUN 28
ALT 56 7.43 27 33 3
SCr 1.1
Billi 1.4
Ca 8.1
QTc 465
Imaging

Day 1 (1/3) Day 9 (1/11) Day 10 (1/12) Day 14 (1/16)

Chest X-ray: Chest X-ray: Chest CT: Chest X-ray:

Patchy Multifocal No acute Mild patchy
airspace airspace pulmonary atelectasis and
opacities in opacities embolism, infiltrates,
bilateral lung worse from lower lobe noted
bases (left previous bilateral emphysema in
greater than consolidations right upper
right) with scarring chest
Infectious Workup

MRSA and Covid Rapid Nasal Swab (-)

Viral Panel: (-) except for COVID (+)

Blood cultures: No growth

Respiratory culture: > 100,000 Stenotrophomonas

maltophilia
Acute Respiratory Distress Syndrome
 Acute Respiratory Distress Syndrome (ARDS)

- Rapidly progressive respiratory disorder

- 16.1% of all ventilated patients are expected to develop an acute
lung injury or ARDS
- Highly associated with mortality in 34-55% of patients

Dyspnea, tachypnea,
Respiratory failure
hypoxemia

https://www.aafp.org/pubs/afp/issues/2012/0215/p352.html#:~:text=Acute%20respiratory%20di
Pathophysiology

Direct or indirect injury

Release of inflammatory
mediators

Increased vascular
permeability
Cleveland Clinic. ARDS. 2023 Dec 7. .
Pathophysiology

Direct or indirect injury

Pulmonary edema, loss of

surfactant, and hyaline membrane
Releaseformation
of inflammatory
mediators

Long term fibrosis

Increased vascular
permeability
Cleveland Clinic. ARDS. 2023 Dec 7. .
Causes

Infectious pneumonia Burns and smoke inhalation

Severe trauma Medications

Non-pulmonary sepsis Pancreatitis

Major thoracic surgery Transfusion related lung injury

Fujishima S. J Intensive Care. 2023 Mar 10;11(1):10.

Causes

Infectious pneumonia Burns and smoke inhalation

Severe trauma Medications

Non-pulmonary Sepsis Pancreatitis

Major thoracic surgery Transfusion related lung injury

Fujishima S. J Intensive Care. 2023 Mar 10;11(1):10.

Diagnosis

Berlin Definition:

Timing Within 1 week of injury or worsening

Chest Imaging Bilateral opacities
Edema Causes Not fully explained by cardiac or fluid status
Oxygenation
Mild PaO2/FiO2: 201-300 with PEEP
Moderate PaO2/FiO2: 101-200 with PEEP ≥ 5
Severe PaO2/FiO2: ≤ 100 with PEEP ≥ 5

Fujishima S. J Intensive Care. 2023 Mar 10;11(1):10.

General Management of ARDS

Ventilator management

Adequate pain and

Supportive Care
sedation

Neuromuscular
Steroids
blockers

Fujishima S. J Intensive Care. 2023 Mar 10;11(1):10.

General Management of ARDS

Ventilator management

Adequate pain and

Supportive Care
sedation
Identify and treat offending cause

Neuromuscular
Steroids
blockers

Fujishima S. J Intensive Care. 2023 Mar 10;11(1):10.

Ventilation Management

- Protective therapy for the lungs

- Focus on minimizing ventilator induced lung injury

- Low TV of 6 mL/kg
- Prevent hyperinflation and barotrauma
- Higher PEEP values of 12 cm H2O
- Limit atelectasis
- In ARDS higher values showed mortality benefit
- RR ≤ 35
- Oxygen saturation of 88 - 95%

Fujishima S. J Intensive Care. 2023 Mar 10;11(1):10.

Pain and Sedation Management

Ketamine
- Opioids are 1st line for
Precedex, Adjunctive analgesia
propofol, +/- agents - If appropriate, minimal
midazolam sedation and interaction to
reduce delirium is
Sedatives recommended
Fentanyl or
- Awakening and breathing
dilaudid trials
- Sedation target should be
Opioid reassessed at least twice daily
pushes or
infusion
Chanques G, et al. Intensive Care Med. 2020 Dec;46(12):2342-2356.
Sedation Spectrum

Sedation Goal Agents

RASS
Light 0 to -1 Precedex

Moderate -2 to -3 Propofol

Deep -4 to -5 Midazolam

Chanques G, et al. Intensive Care Med. 2020 Dec;46(12):2342-2356.

Use of Neuromuscular Blockers

- Reversible smooth muscle paralysis of lung tissues and the

diaphragm
- Improves compliance with ventilator, improves gas exchange,
reduces barotrauma, and has anti-inflammatory effects

- Recommended in patients with severe ARDS:

- Refractory hypoxemia
- Patient-ventilator dyssynchrony
- High risk of barotrauma

- Contradictory evidence for use

Bourenne J, et al. Annals of Translational Medicine 2017 July 25;5(14).

Neuromuscular Blockers

Cisatracurium 0.1- 0.2 mg/kg → 1-3

mcg/kg/min

Rocuronium 0.6 to 1 mg/kg → 3- 8

mcg/kg/minute

Vecuronium 0.08 to 0.1 mg/kg → 0.8-1.7

mcg/kg/minute

Always ensure patients are

adequately sedated prior to
initiation!

Bourenne J, et al. Annals of Translational Medicine 2017 July 25;5(14).

Lexicomp. Wolters Kluwer. 2024.
Use of Systemic Steroids

- Indicated in moderate to severe ARDS with an underlying

inflammatory process or early ARDS (within 14 days of onset)
resistant to standard therapy
- Some evidence that this improves mortality

Methylprednisolone 1 mg/kg/day x 14 days → taper for 28 days

Dexamethasone 20 mg daily x 5 days → 10 mg daily x 5 days

Banavasi H, et al. Am J Med Sci. 2021 Jul; 362(1): 13–23.

Lexicomp. Wolters Kluwer. 2024.
Prone Positioning

-Supine position → increase dorsal pressure with

the weight of the heart and visceral tissue
- Naturally the fluid and edema is
increased in the dorsal alveoli
- Prone positioning reduces the difference between
dorsal and ventral pressures → balance of
ventilation
- Improves pulmonary circulation and gas
exchange
Recommended proning 12-16
hours a day for benefit
Banavasi H, et al. Am J Med Sci. 2021 Jul; 362(1): 13–23.
Chemotherapy Cause of ARDS
Chemo Regimens

- Chemotherapy agents in NSCLC → drug induced

pulmonary toxicity

- Pathogenesis:
1) Cytotoxicity: reactive oxygen species and cytokines that
directly injure pneumocytes and the endothelium
2) Immune-mediated injury: hypersensitivity reaction to the
chemotherapy
3) Opportunistic infections: immunosuppression

Dhamija E, et al. Indian J Radiol Imaging. 2020 Jan-Mar; 30(1): 20–26.

Pulmonary drug toxicity
Interstitial Accumulation of fluid, cells, and Bleomycin, methotrexate, taxanes,
infiltrates protein in the parenchyma platins, rituximab, everolimus

Diffuse alveolar Injury to type-2 pneumocytes and Bleomycin, carmustine,

damage endothelial cells in the alveoli cyclophosphamide

Pulmonary Damage to the alveolar capillaries Cyclophosphamide, cytarabin,

hemorrhage platins, bevacizumab

Capillary leak Increase in vascular permeability Gemcitabine, immune mediated

syndromes leading to interstitial edema therapies

Pulmonary Airspace consolidations resulting Methotrexate and bleomycin

infections from a bacterial or viral cause

Immune-mediat Proinflammatory state of the lungs Methotrexate

ed lung injury
Dhamija E, et al. Indian J Radiol Imaging. 2020 Jan-Mar; 30(1): 20–26.
Types of Pulmonary Damage from Chemo

Interstitial Infiltrates Pulmonary Infections

Diffuse Alveolar
Damage
Dhamija E, et al. Indian J Radiol Imaging. 2020 Jan-Mar; 30(1): 20–26.
Non-Small Cell Lung Cancer Treatment

Platinum
Pembrolizumab Pemetrexed
therapy

Given every 21 days for 4 cycles

Stevenson MM, et al. Medscape. 2023 Nov 29.

Pembrolizumab

- Monoclonal antibody that acts as an immune checkpoint inhibitor

- Promotes killing of tumor cells by inhibiting programmed
death receptor on T cells

- Adverse effects: cardiovascular toxicity, hypertension, colitis,

pneumonitis, rash, nephrotoxicity, hepatotoxicity
- Pneumonitis: 2-11% of patients
- Pneumonia: at least 2% of patients
- Pulmonary hemorrhage: seen in 1 patient case report

Micromedex. Merative. 2024

Carboplatin

- Alkylating agent and platinum analog

- Inhibits DNA replication in cancer cells

- Adverse effects: myelosupression, mucositis, N/V, neurotoxicity,

alopecia, infertility, secondary malignancies
- Pulmonary toxicity usually only associated in combination
with other agents

Micromedex. Merative. 2024

Pemetrexed

- Antimetabolite
- Inhibit the formation of nucleotides and therefore DNA

- Adverse effects: myelosuppression, mucositis, hepatotoxicity,

nephrotoxicity
- Several case studies have shown rare occurrence of
pemetrexed induced pneumonitis
- Dyspnea is highly reported with this medication: 21-39%
of patients

Micromedex. Merative. 2024

Treatment of Pneumonia
Stenotrophomonas maltophilia
- Non-fermenting gram-negative bacillus
- Highly resistant organism
Sulfamethoxazole - trimethoprim
400/80mg IV or PO
Sulfamethoxazole - trimethoprim
For HAP or VAP:
- 8-12 mg/kg/day divided in 2
to 3 doses based on
Respiratory fluoroquinolones trimethoprim (max: 960
mg/day)
- Bacterial folic acid synthesis
inhibitor
Eravacycline/ tigecycline or cefiderocol - Hyperkalemia/hepatotoxicity
Chanques G, et al. Intensive Care Med. 2020 Dec;46(12):2342-2356.
Patient AR’s Treatment
Respiratory Support Course

Increasing nasal Intubated with an

cannula endotracheal tube
requirements with high ventilator
2L→5L requirements

Transition to
BiPAP
Respiratory Support Course

Increasing nasal Intubated with an

cannula endotracheal tube
requirements with high ventilator
2L→5L requirements

Ventilator settings:
- TV: 450 mL (5 mL/kg)
- PEEP: 10-12 cm H2O
Transition to - RR: 26 bpm
BiPAP - FiO2: 100%
Pain and Sedation Management

Fentanyl: 50-125 mcg/hr RASS: 0 to -1

Propofol: 5-40 mcg/kg/min

Hydromorphone: 0.5-1.5 mg/hr RASS: -4

Midazolam: 6 - 10 mg/hr

BIS: 40 to 60
Rocuronium: 4 mcg/kg/min
Supportive Care

Steroids → methylprednisolone 60 mg IV Q12H

VTE prophylaxis → enoxaparin 40 mg subcutaneous daily

Stress ulcer prophylaxis → omeprazole 40 mg gastric daily

Electrolyte repletion and home medications

Plan with Patient AR - Infection Timeline

Cefepime x 7 days

Isavuconazonium Bactrim x 2
Remdesivir x 5 days
x 3 days days

Vancomycin x 5 days

Steroid x 10 days

Zinc supplementation
Conclusions

- Recognizing cause is key to diagnosis and treatment of ARDS

- A very patient specific treatment plan is necessary to weigh

benefit and hard in each individual
- Controversial treatment strategies that may not always be
effective
 Questions?

Delaney Straw, PharmD

Trauma Neuro ICU Final Presentation