Justin Goralnik PGY3 Nilsa Jiminez PGY2 Department of Medicine Hartford Hospital
Jan 06, 2018
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