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Notes


Respiration
ARDS Network tidal volume trial: treatment group had lower PaO2/FiO2 than control (156 vs 178) but improves mortality. 
High PEEP is similar to low PEEP ladders according to ARDSNet, Canadian LOVS trial, and European ExPress trial. 
Stress-index: volume AC, square-wave form and low flow rate, monitor pressure during the flat portion of the flow curve. Stress index < 1 = rounded upward = more PEEP. Stress index > 1 = scooped upward = less PEEP. 
PV curve on the ventilator is a dynamic PV curve at flow rates > 6L/min. It does not tell you the optimal PEEP because this is a static variable; the lower inflection point is useless. The upper inflection point is helpful because if it exists, indicates hyperinflation. The deflation curve is also dynamic therefore does not fully reflect hysteresis and is confounded by airway resistance, and ventilator tubing.
Total lung capacity is a trans-pulmonary pressure of 30cm H2O. Tidal volume best reflects trans-pulmonary pressure whereas plateau pressure does not. People playing wind instruments generate >100cm H2O in their airways but their transpulmonary pressure is normal. 

Time constant is compliance of respiratory system / resistance of respiratory system or (Pplat - PEEP) x (Ppeak/Flow (ml/s)). One time constant is time required to deflate 67%, two time constants 90%, three time constants 95%, four time constants 99%. 

5 types of breaths delivered by the ventilator
    Volume control: time triggered, flow-limited, volume cycled 
    Volume assist: flow or pressure triggered, flow-limited, volume cycled
    Pressure control: time triggered, pressure-limited, time cycled
    Pressure assist: flow or pressure triggered, pressure-limited, time cycled
    Pressure support: flow or pressure triggered, pressure-limited, flow cycled

Conventional Modes
Volume AC: VC and VA 
Pressure AC: PC and PA *patients can actively draw in breaths during inspiratory pressure resulting in greater transpulmonary pressure and greater tidal volume, making this strategy less lung protective
Volume- SIMV: VC and VC plus/minus PS *prolongs weaning in various RCTs
Pressure Support: ventilator delivers a pressure limited breath which it turns off when inspiratory flow rate falls to 25% of initial flow *patients often have to provide expiratory work to end the breath. This is especially exhausting for COPD patients and the threshold has to be turned well above 50%. 

Feedback controls
PRVC delivers pressure controlled/assisted breaths but the machine makes continual small adjustments on pressure limits to achieve a goal volume. 
Adaptive support ventilation delivers volume controlled/assisted breaths but the machine adjusts the flow (hence volume) and respiratory rate to minimize ventilator work. *Tends to choose higher TV 6cc/kg in low lung compliance states
Proportional assist ventilation measures the flow and airway pressure generated from patient initiated breaths and delivers a breath at a custom pressure and flow rate to match the patient's effort. If effort drops, support drops; if effort increases, support increases. It can only deliver assisted breaths and cannot guarantee a minimum tidal volume. 
Neurally adjusted ventilator assist uses diaphragm contraction on EMG as the trigger variable. 

Unconventional Modes
APRV is inverse pressure control IRV with longer Thigh. Plow is 0 and relies on autoPEEP to prevent derecruitment
HFOV is pressure AC at 150-900/min or 2.5-16Hz. Gas exchange is not convective but coaxial flow, taylor dispersion, pendeluft mixing, and molecular diffusion. Ventilation = f x pressure amplitude^2. 

Dyssynchrony 
Ineffective triggering - decreased airway pressure but no breath delivery due to autoPEEP or high threshold
Double-triggering - high respiratory demand with short inspiratory time resulting in early termination of breath and a second breath closely following the first
Flow starvation - scooped out pressure waveform with negative inspiratory deflections due to long inspiratory times

Liberation
Best strategy is one that doesn't wean. SBT should be 30-120min (equally effective) and Tpiece equally effective as PS. Cough velocity > 1L/s. Suctioning <2h. Cuff leak > 110cc (contentious). 
Kress trial showed daily sedation vacations reduced mechanical ventilation days by 2d and ICU time by 3.5d without increasing risk of self-extubation. 
ABC trial in Lancet 2008 showed patients awakened for SBT did self-extubate more but no difference in re-intubation rate. 

ARDS
Initial p/f ratios not related to mortality. ARDSNET improved outcomes but worsened gas exchange and compliance for the first 3 days. 
Immune nutrition (arginine, glutamine nucleotides, omega 3 fatty acids) reduced infections in 2001 JAMA article. Then three positive RCTs in favor of immune nutrition. However, ARDS NET OMEGA trial CCM 2009 which is larger than all three trials was stopped for futility. 
ARDSNET showed pneumothorax was neither related to end inspiratory nor end expiratory pressures but rather to tidal volume. 
Low TV with ECCO2R did not show benefit on mortality. 
Even with Plat < 30, lower TV conferred mortality benefit. Lower TV in healthy lungs decreased risk to ALI. 

ALVEOLI NEJM 2004, LOVS JAMA 2008, and EXPRESS JAMA 2008 compared high versus low PEEP and were negative for high PEEP in terms of survival. Meta-analysis seems to suggest high PEEP reduces mortality in lower PF ratio patients but results in more complications in PF 200-300. 

A 2010 meta-analysis from 6 studies supported HFOV. But a more recent NEJM article suggested harm. 

ECMO was supported by the CESAR trial but there was methodological flaws. 

FACCT NEJM 2006 showed that "dry lungs" was not associated with increased shock and no renal failure but two day faster liberation from ventilator.

Papazian in NEJM 2011 showed 24h of paralysis had a mortality benefit 3 weeks later. 

Plateau pressure - end-inspiratory esophageal pressure = transpulmonary pressure. Some centers raise plateau pressure threshold to patient's BMI.

In 60-75% of patients with ARDS, prone positioning improves the PF ratio. 2001 study by Slutsky showed no effect on mortality proning 7h/d for 10d except in most severe ARDS. PROSEVA trial in 2013 showed benefit proning patients 16h/d for up to 28d improved mortality for PF<150.

iNO improves CO2 elimination by reducing deadspace. 20ppm is the maximal dose because it poses little benefit compared to 80ppm and has a lower risk for methemoglobinemia. In 75% of ARDS patients receiving iNO will see modest improvement if PF to an average of 16. There may be increased renal replacement therapies when in iNO.

Continuous rotational therapy rotating patients 40deg in each direction has been shown by the bedmakers to benefit ARDS patients.

NIPPV
Biggest problem is flow cycling which is amplified by mask leaks or bronchopleural fistuals. Flows never slow down so the breath is prolonged. Variable flow rates or modes with inspiratory time selection help obviate this problem.
Strongest literature for NIPPV is in COPD where failure on SBT can still succeed on NIPPV. NIPPV has had disappointing results in asthma.
Improvements in PaCO2 and pH within 30min of NIPPV predicts success.
C3PO trial demonstrated improved outcomes of CPAP on heart failure. 

Aerosolized beta agonists are more effective than IV. MDI with spacer is equally effective compared to nebs. Nebs delivers several fold higher doses than MDI so its efficiency is lower but allows patients to breath at tidal volume rather than FC to TLC and holding for 10s as is the case with MDI. Aerosols are retarded by the endotracheal tubes. 6-10 puffs of MDI should be given in line to achieve the same effect.

Heliox 40% He and 60% O2 utilized for hypoxemic patients.

PE
38% of angio positive PE had normal ABGs
50-60% of pulmonary vasculature occluded before pulmonary hypertension in patients with no underlying PAH

DFA and EIA is not sensitive for RSV but RT-PCR has high sensitivity. Ribavirin and IVIG may be helpful.
25% of influenza develop pneumonia. 5 retrospective studies with methodological flaws favored no steroids in influenza.

PNA
Blastomycosis: persistent pneumonia unresponsive to antibiotics. Blasto with penchant for CNS, skin, bones, dogs, Chicago disease. Blasto is asymptomatic in 50% and is treated with itraconazole and amphotericin.
Histo is asymptomatic in 95%.
Coccidioiomycosis causes CAP like picture in Arizona/California.
Sporothricosis affects skin in immunocompetent patients. Pulmonary sporotrichosis causes upper lobe disease.

TB can present as GPR in blood. TST and IGRA cannot distinguish between active and latent disease. They are only 70% sensitive in active TB. AFB is gold standard. 50-80% of active TB have positive smears.
    + NAA and + smear : very predictive of + TB
    + NAA and - smear : presume TB if NAA x 2 is positive
    - NAA and + smear : likely false negative NAA due to sputum inhibitors
    - NAA and - smear : ???

TB treatment is isoniazid, rifampicin, pyrazinamide, ethambutol (IRPE). MDR-TB is resistant to at least IR.
Legionella pneumonophilla requires non-routine media. Only serotype 1/16 (70%) is detected by urinary antigen test. Enigmatic pneumonias, compromised hosts, during out break, failed  treatment with beta-lactam, travel history within 2w, and nosocomial PNA of unknown etiology. Antigenuria is 60-95% sensitive and highly specific. Azithro, levoflox, moxiflox are therapies.

Anthrax is a GNR causing cutaneous, GI, or inhalational disease in humans around herbivores. Cutaneous anthrax has 20-30% death rate starting as papules that progress to deep ulcers then eschars with regional lymphadenopathy. Huge fluid requirement and resistant shock. GI anthrax has a 50-100% mortality with severe inflammation and gut necrosis. Inhalation anthrax can incubate for up to 1 month. The bacteria is transported to lymph nodes where toxins are produced leading to hemorrhage, lymphedema, shock, and death. Hemorrhagic mediastinitis and pleural effusions are the most common manifestations with CXR showing wide mediastinum. Meningeal hemorrhage is also common. Mortality is 90% if treated and 100% if not treated. There is no risk of person to person transmission. Treatment is vaccine, Ig, cipro/doxy plus rifampin, chloramphenicol, clinda, pen, amp, vanc, imi, clarithro.

Yersinia pestis. Mortality rate 15%. GNcoccobacilli with safety pin appearance. Presents as bubo or petechial if it progresses. Must be cultured specifically. Differential is staph, strep, glandular tularemia, cat scratch disease. Pneumonic plague is person to person  transmission with 70% mortality. Differential is anthrax, tularemia, melidoidosis, CAP, flu, hantavirus, hemorrhagic leptospirosis. Septicemic plague differential is meningococcus, RMSF, TTP. Treatment is streptomycin, gentamicin or doxy, cipro, chloramphenicol. Health care workers require post-exposure prophy with doxy, cipro, chloramphenicol, TMP.

DAH
Differential includes HF, MS, PVOD, ANCA+ vasculitis, catastrophic APLS, goodpasteur's syndrome, inhaled cocaine, negative pressure pulmonary hemorrhage.
Smoking crack also produces melanoptysis.
Goodpasteur's syndrome can be precipitated by smoke, influenza, hydrocarbon exposure. It is treated with plasmapheresis, cyclophosphamide, and steroids.

Tropical pulmonary eosinophilia - peripheral eosinophilia, negative stool O&P, elevated IgE, negative ABPA. Results from sensitization to W. bancrofti, Brugia malayi, Brugia timori. + Antifilaria antibodies with prominent evening symptoms. Treatment is with diethylcarbamazepine.

Air embolism: place patient in L lateral decub and trendelenburg to trap air in the R atrium.

Lemierre's syndrome: fuosbacteria necrophorum - pharyngitis, liver abscesses, iliac crest inflammation, lung abscess, suppurative arthritis, jaundice; tx with prolonged clindamycin, incision, and anticoagulation.
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