Justin Goralnik PGY3Nilsa Jiminez PGY2

Department of MedicineHartford 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– Mediastinoscopy– Radiation to the chest– Lymph node resection– Hickam placement

• Medications– Rituxan q2months– Prednisone– Atorvastatin– Baclofen– Albuterol– Plavix– Gabapentin– Duloxetine– Metoprolol– Levothyroxine– Pantoprazole– Valsartan– Tessalon Pearls– Lamictal

• Allergies– NKDA

• Social History – 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

37.713412.6

138

4.6

102

25

19

1.2166

11

Influenza PCR- negativeHIV –negativeBordatella Pertussi (nasopharyngeal) – negativeLFT wnlCK and Trop wnlIgg- 149IgM – 7IgA - 23

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 re-

intubate 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.

• Introduction• Criteria• Etiology• Management• Prognosis• Future Considerations

• 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

• Introduction• Criteria• Etiology• Management• Complications & Prognosis• Future Considerations

• Berlin Criteria (2012)• Replaced American-European Consensus Conference’s

definition (1994)– Onset of respiratory symptoms within 1 week of insult– Bilateral opacities on CXR or CT, which cannot be

explained by pleural effusions, nodules, or lobar collapse– Cardiogenic edema MUST be ruled out– 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

Berlin Definition vs. AECC•The term “acute lung injury” has been eliminated•Pulmonary capillary wedge pressure was removed•Minimal ventilator settings were added

• Introduction• Criteria• Etiology• Management• Complications & Prognosis• Future Considerations

Indirect Lung Injury• Sepsis• Major Trauma• Multiple Blood

Transfusions• Pancreatitis• Cardiopulmonary

Bypass• Drug Overdose• Drug-Induced

Direct Lung Injury• Pneumonia• Aspiration• Pulmonary

Contusion• Toxic Inhalation• Near-Drowning• Reperfusion Injury

Sepsis•Most common cause of ARDS•Risk is more than DOUBLED in patients with chronic alcohol abuse•Prospective cohort study in 2003:

•220 patients with septic shock•70% with chronic EtOH abuse vs. 31% in non-alcoholics

•Proposed mechanism is decreased levels of glutathione in epithelial lung lining, predisposing to oxidative lung injury

Pneumonia•CAP most common cause occurring outside hospital

Aspiration•Study shows 1/3 patients with recognized aspiration of gastric contents•Tracheo-esophageal fistula

• Introduction• Criteria• Etiology• Management• Complications & Prognosis• Future Considerations

1. SUPPORTIVE CARE

2. TREATMENT of HYPOXEMIA

• 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-Controlled2006-2008 in France•N= 340

• Cisatracurium (n=178)• Placebo (N=162)

•1 outcome = mortality before discharge or 90-days⁰Interventions•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•1 (Mortality): ⁰ 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)

Bottom Line

Paralysis with cisatracurium for 48 hours in early severe ARDS improves 90-day survival and increases ventilator-free days

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

Design•Multi-center, RCT in North America (2000-2005)•N=1000

• Conservative (N=503): CVP < 4• Liberal (N=497): CVP 10-14

•1 outcome: all-cause mortality 60-days, dialysis at 60-days⁰

Results•All-cause mortality: 25.5% vs. 28.4%•Dialysis: 10% vs. 14%(2 outcome of ventilator-free days: 14.6% vs. 12.1%) ⁰

Bottom Line

Conservative fluid strategy improves lung function and reduces ventilator days, but does not impact mortality

1. SUPPORTIVE CARE

2. TREATMENT of HYPOXEMIA

1. High FiO2

2. Decrease O2 consumption3. Manipulations in mechanical ventilation4. Increase O2 delivery

Design•Multi-center, RCT, in 27 ICU’s across Europe (2008-2011)•N=466•Supine (N=229)•Prone (N=237)•1 outcome: all-cause mortality at 28-days⁰

Interventions•Turned to prone for > 16 hours/day•Repeated daily for > 28 days

Results•1 (28-day mortality): ⁰ 16.0% vs. 32.8% [HR 0.39, CI 0.25-0.63, p<0.001]

Inclusion Criteria•P:F < 150•FiO2 > 60%•PEEP > 5 cm H20•Vt 6mL/kg

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•1 outcome: 180-day mortality⁰

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%

Interventions•LTTV: starting at 6ml/kg, Vt titrated to maintain PP < 30cmH2O (minimal 4ml/kg)•TVV: same protocol, only PP kept < 50cmH2O

• 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

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

• 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

Recombinant Surfactant Protein C

Antioxidants – Eicosapentaenoic acid (EPA) & Gamma-linolenic acid (GLA)

Inhaled Vasodilators – NO, Prostacyclins

Anti-Inflammatory Agents - Glucocorticoids

• Introduction• Criteria• Etiology• Management• Complications & Prognosis• Future Considerations

• 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