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Critical Care M&M Conference
Acute Respiratory Distress Syndrome
Justin Goralnik PGY3
Nilsa Jiminez PGY2
Department of Medicine
Hartford Hospital
H&P
• 54 year old male with PMH large B cell lymphoma
on maintenance Rituxan presented to ED with
worsening SOB, cough and sputum production
after being recently treated for pneumonia. Two
days prior to presentation the patient’s wife was
notified by DPH that the patient is positive for
Pertussi. On arrival to ED on 3/18 patient was
found to be hypoxic with sats in the 80s at RA.
Placed on NRB and started on treatment
including Azithromycin, Vanco and Cefepime.
Past Medical History
• PMH
– Non Hodgkin Lymphoma
– CLL with Richter
transformation to Large
B cell
– Atrial Fibrillation 2010
– Diabetes Mellitus
– Obesity
– CVA x2 2012 with
residual right sided
weakness and dysarthria
• PSH
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Mediastinoscopy
Radiation to the chest
Lymph node resection
Hickam placement
• Medications
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Rituxan q2months
Prednisone
Atorvastatin
Baclofen
Albuterol
Plavix
Gabapentin
Duloxetine
Metoprolol
Levothyroxine
Pantoprazole
Valsartan
Tessalon Pearls
Lamictal
• Allergies
– NKDA
• Social History
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Former smoker
No ETOH abuse
No h/o IVDU
Married
Police officer
Physical Exam
• VS: Afebrile, BP 96/56, HR 84, RR 22, Sat 96% on 40% VM
• General: AAOx3, NAD
• HEENT: PERRLA, left pupilary reflex slightly decreased but
baseline. Moist oral mucosa.
• Neck: supple, no bruits
• Lungs: Wheezing and ronchii at the bases
• Heart: RRR, no m/r/g, S1/S2 normal
• Abdomen: BS presents, NT/ ND
• Extremities: Right calf larger than the left and
erythematous. Non tender to palpation.
• Neuro: No focal deficit.
Admission Labs
12.2
12.6
37.7
134
138
102
19
4.6
25
1.2
11
Influenza PCR- negative
HIV –negative
Bordatella Pertussi (nasopharyngeal) – negative
LFT wnl
CK and Trop wnl
Igg- 149
IgM – 7
IgA - 23
166
Admission Imaging
• Chest X-ray- significant progression of
reticulonodular changes with focal opacity in
right upper lobe and left lower lobe.
• CT chest- worsening pulmonary nodule and
patchy opacities in RUL and RLL with
additional area of consolidations, bilateral
hilar and mediastinal lymphadenopathy
Hospital Course
• Day 1- Started on Vanco, Cefepime and
Azithromycin. ID on board. Also, started on
Solumedrol.
• Day 2 – Hem Onc consulted and patient started
on IVIg
• Day 3- worsening respiratory status. No changes
to treatment at the time.
• Day 4 – Mental status changes overnight. CT head
did not show acute changes. Neurology
consulted. AMS likely 2/2 infectious process.
Hospital Course
• Day 6: Worsening respiratory status. Patient now on
80% High flow.
– Repeat CTA showed significant worsening of groundglass
and nodular opacities. Started on Bactrim for possible PCP.
– CTA Unconclussive for PE. LE doppler positive for DVT in
the SFV. Started on Heparin gtt.
– Cardiology also consulted for Afib management.
• Day 7: Given clinical deterioration patient was
electively intubated for bronchoscopy which was
performed same day in the ICU. Post-Intubation ABG
7.43/46/126.
• Day 8: BAL positive for RSV.
Day #9
• 12:00am – Patient with persistent hypoxemia despite
vent trials including APRV, AVC and APC.
• 1:00am- Oxygen saturation remained in the low 80s
despite keeping FIO2 at 100% and trying different
PEEP 8-20. ABG 7.39/42/58 on AC with PEEP 20, FIO2
70%. At this time to bag mask was made with some
improvement of O2 Sats.
• 2:00am – Oxygenation continued to be difficult but
better saturation on abg. ABG 7.36/41/64 on 100%
bagging. A prone bed was requested at that time but
team was notified that it would take 3 hours to get
the bed.
Day #9
• 2:30 am – Manual ventilation was continued. Paralytics
were considered however not done because patient
was on steroids. Not used due to potential side effects.
• 3:00 am- Ordered for Ribavirin inhaler was placed but
this medication was not available at the time in
Connecticut.
• 3:30 am- Dr. Gluck consulted for ECMO evaluation.
• 6:00 am- Patient was ruled out for ECMO due to overall
poor prognosis and significant comorbidities.
• 6:30 am- Discussion with family. Family decided to reintubate patient and not to escalate care.
Day #9
• 10:00am – Life choice contacted and patient
ruled out for donation.
• 4:00pm- Family requested to make patient
CMO. Patient was extubated.
• 5:00pm – Patient pronounced dead by
provider.
Acute Respiratory Distress Syndrome
Agenda
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Introduction
Criteria
Etiology
Management
Prognosis
Future Considerations
Introduction to ARDS
• Acute hypoxic respiratory failure of BOTH lungs
• First described in 1960’s, military clinicians in the Vietnam
War called it “shock lung”
• Rubenfeld et al. (NEJM 2005) showed age-adjusted incidence
as follows:
– 16 per 100,000 person-years in P:F < 300
– 64 per 100,000 person-years in P:F < 200
• Incidence increased from 16 per 100k to 306 per 100k in pts
75-84 years of age
• Extrapolation suggests approx 190,000 cases annually in US
Agenda
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Introduction
Criteria
Etiology
Management
Complications & Prognosis
Future Considerations
The Diagnosis ARDS
• Berlin Criteria (2012)
• Replaced American-European Consensus Conference’s
definition (1994)
– Onset of respiratory symptoms within 1 week of insult
Berlin
Definition
vs.
AECC
– Bilateral opacities on CXR or CT, which cannot be explained
•The term “acute lung injury” has been eliminated
by pleural effusions, nodules, or lobar collapse
•Pulmonary capillary wedge pressure was removed
– Cardiogenic
edema
MUST
be ruled out
•Minimal
ventilator settings
were
added
– Moderate-to-severe oxygen impairment MUST be present
on ventilator with (at least) PEEP of 5
• Mild: 200 < PaO2/FiO2 < 300
• Moderate: 100 < PaO2/FiO2 < 200
• Severe: PaO2/FiO2 < 100
Acute Respiratory Distress Syndrome, The ARDS Definition Task Force, AMA.
2012;307(23):2526-2533
Agenda
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Introduction
Criteria
Etiology
Management
Complications & Prognosis
Future Considerations
Predisposing Factors
Sepsis
•Most common
causeInjury
of ARDS
Indirect
Lung
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Direct Lung Injury
•Risk is more than DOUBLED in patients with chronic alcohol abuse
Sepsis
•Prospective cohort study in 2003:
• Pneumonia
•220 Trauma
patients with septic shock
Major
Aspiration
•70% with chronic EtOH abuse vs. 31% in •
non-alcoholics
Multiple
Blood is decreased levels of glutathione in epithelial lung
•Proposed mechanism
• Pulmonary
lining, predisposing to oxidative lung injury
Transfusions
Contusion
Pancreatitis
Pneumonia
• Toxic Inhalation
Cardiopulmonary
•CAP most common cause occurring outside hospital
Bypass
• Near-Drowning
Drug
Overdose
Aspiration
• Reperfusion Injury
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•Study shows 1/3 patients with recognized aspiration of gastric contents
• Drug-Induced
•Tracheo-esophageal fistula
Agenda
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Introduction
Criteria
Etiology
Management
Complications & Prognosis
Future Considerations
Management of ARDS
1. SUPPORTIVE CARE
2. TREATMENT of HYPOXEMIA
Supportive Care
• Some patients with ARDS die from respiratory failure alone, BUT the
majority succumb to the 1⁰ cause of ARDS or 2⁰ complications
Sedation
•Improves tolerance of ventilator & decreases O2 consumption
•Swinamer et al. (1998) demonstrated the use of morphine reduced resting
and total energy expenditure by 6% and 8.6%, respectively
Design
•Multicenter, Double-Blinded, Placebo-Controlled
2006-2008 in France
•N= 340
• Cisatracurium (n=178) Bottom Line
• Placebo (N=162) Paralysis with cisatracurium for
•1⁰ outcome = mortality before
discharge
or 90-days
48 hours
in early severe
ARDS
improves 90-day survival and
Interventions
increases ventilator-free days
•Sedated to a Ramsay sedation of 6 (no response to glabellar tap)
•Cisatracurium 15mg IV x 1, followed by 37.5mg/hr x 48 hours
•Ventilators at low-volume and goal SpO2 88-92% or PaO2 55-80mmHg
Results
•1⁰ (Mortality): 31.6% vs. 40.7% (RR 0.68, CI 0.48-0.98, p=0.04)
•Ventilator-free days: 10.6% vs. 8.5% (days 1-28), 53.1% vs. 44.6% (days 1-90)
Supportive Care Cont’d
Hemodynamic Monitoring
•Wheeler et al. (NEJM 2006): central venous catheter (CVC) with pulmonary
artery catheter (PAC) in HD monitoring
•No difference in mortality, lung function, ventilator-free days, or ICU-free days
•Rates of hypotension, dialysis, and vasopressor use were the same
•PAC group had 2x rate of catheter-related complications, primarily arrhythmias
Nutrition
•ARDS patients are severely catabolic
•Offset stress, oxidative injury, improve immunity
•Enteral feeding preferred
•Avoid over-feeding
Nosocomial Pneumonia
•Major complication in ARDS
•Increases morbidity and prolongs mechanical ventilation
•Delclaux et al. (Am J Respir Crit Care Med 1997): 60% of pts with severe ARDS
Fluid Management Strategy?
Design
•Multi-center, RCT in North America (2000-2005)
Bottom Line
•N=1000
• Conservative (N=503):Conservative
CVP < 4 fluid strategy
• Liberal (N=497): CVP improves
10-14 lung function and
•1⁰ outcome: all-cause mortality
60-days,
dialysis
60-days
reduces
ventilator
days,atbut
does not impact mortality
Results
•All-cause mortality: 25.5% vs. 28.4%
•Dialysis: 10% vs. 14%
(2⁰ outcome of ventilator-free days: 14.6% vs. 12.1%)
Management of ARDS
1. SUPPORTIVE CARE
2. TREATMENT of HYPOXEMIA
Improving Oxygenation
1.
2.
3.
4.
High FiO2
Decrease O2 consumption
Manipulations in mechanical ventilation
Increase O2 delivery
Design
•Multi-center, RCT, in 27 ICU’s across Europe (2008-2011)
•N=466
•Supine (N=229)
•Prone (N=237)
•1⁰ outcome: all-cause mortality at 28-days
PROSEVA Study
Inclusion Criteria
•P:F < 150
•FiO2 > 60%
•PEEP > 5 cm H20
•Vt 6mL/kg
Interventions
•Turned to prone for > 16 hours/day
•Repeated daily for > 28 days
Results
•1⁰ (28-day mortality): 16.0% vs. 32.8% [HR 0.39, CI 0.25-0.63, p<0.001]
Mechanical Ventilation Strategies
Design
•Multi-center, RCT in 10 university-affiliated ARDSNet centers (1996-1999)
•N=861
•LTVV (N=432): 6ml/kg PBW + PP < 30cmH2O
•Traditional (N=429): 12ml/kg PBW + PP < 50cmH2O
•1⁰ outcome: 180-day mortality
ARDSNet Study
Interventions
•LTTV: starting at 6ml/kg, Vt titrated to maintain PP < 30cmH2O
(minimal 4ml/kg)
•TVV: same protocol, only PP kept < 50cmH2O
Results
•1⁰ (180-day mortality): 31% vs. 39.8% [HR 0.78, p=0.007]
•Ventilator-free days: 12 vs. 10
•Breathing w/o assistance by day 28: 65.7% vs. 55.0%
Criticisms of ARDSNet
• Auto-PEEP
– To maintain adequate minute ventilation with LTVV, higher RR must be
employed
– Time available for expiration is reduced
– Subgroup analysis debunked this theory by demonstrating negligible
auto-PEEP levels
• Sedation
– Patient-ventilator asynchrony more likely to occur when Vt < 7ml/kg
– Breath-stacking as a result can deliver higher Vt, thus undermining the
benefits of LTVV
MV Strategies Cont’d
Open Lung Ventilation
•Combines LTVV + (least amount) PEEP to maximize alveolar recruitment
• LTVV mitigates alveolar over-distension
• PEEP minimizes cyclic atelectasis
• Permissive hypercapnea
• Two separate studies showed ICU mortality benefit with OLV, however there
were several limitations
High PEEP
•Aim is to open collapsed alveoli, thus decreasing alveolar over-distention
•This is achieved because each subsequent breath is shared by more open alveoli
•Clinical relevance of high PEEP is unclear
•A universally accepted method for applying high PEEP not established
•Harms (potential): barotrauma, reduced CO
Recruitment Maneuvers
•Brief application of high positive airway pressure, upwards to 35-40cmH2O
•Data is unclear; studies have failed to show mortality benefit
•May benefit pts who’ve been temporarily disconnected from vent
Airway Pressure Release Ventilation
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Phigh delivered for long durations (Thigh)
Plow for short duration (Tlow)
Transition from high to low deflates lungs and expels CO2
Vt depends on driving pressure (Phigh – Plow) and compliance
Not universally accepted, but commonly used in ARDS
Varpula et al. (2004) failed to show significant clinical difference between
APRV and SIMV plus PSV in ARDS patients
Novel Therapies
Recombinant Surfactant Protein C
Antioxidants – Eicosapentaenoic acid (EPA) & Gamma-linolenic
acid (GLA)
Inhaled Vasodilators – NO, Prostacyclins
Anti-Inflammatory Agents - Glucocorticoids
Agenda
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Introduction
Criteria
Etiology
Management
Complications & Prognosis
Future Considerations
Morbidity & Mortality
• Rubenfeld et al. (NEJM 2005) estimated 26%-58% mortality
• Underlying cause most commonly kills the patient
• Erickson et al. (Critical Care Med 2009) demonstrated a fall in
mortality from 1996-2005
Morbidity Among Survivors
•Cognitive
•Psychiatric
•Physical Disabilities
•Diminished Lung Function
The End.