Best of Pulmonary 2012-2013 Jennifer R. Hucks, MD University of South Carolina School of Medicine
Topics ARDS- Berlin Definition Prone Positioning For ARDS Lung Protective Ventilation In Patients Without ARDS Steroids For COPD Exacerbations Gabapentin For Chronic Cough
ARDS- The Berlin Definition
JAMA, June 20, 2012 Vol 307, No. 23
ARDS- Berlin 1994 AECC Definition for ARDS is widely used. Acute onset of hypoxemia (PaO2/FIO2 < 200) with bilateral infiltrates on frontal chest radiograph, with no evidence of left atrial hypertension. Also described ALI Issues with 1994 AECC Definition What is acute? CXR findings not always reliable No standardization for PaO2/FIO2 to take into account different ventilator settings Difficulty taking into account heart failure
ARDS- Berlin 2012 Berlin Definition For ARDS Underlying Definition Same acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue [with] hypoxemia and bilateral radiographic opacities, associated with increased venous admixture, increased physiological dead space, and decreased lung compliance. First attempt to link an international consensus panel with an empirical evaluation Decided not to include other clinical variables important in ARDS Static compliance Radiographic severity PEEP > 10 Corrected expired volume >10L/min
ARDS- Berlin Some Differences Acute Onset= within 7 days of some event Sepsis, pneumonia, worsening symptoms noted by patient Bilateral Opacities Consistent with pulmonary edema Not explained by effusions, lobar collapse, nodules CXR or CT Must use minimum PEEP cut offs for PaO2/FIO2 Some Heart Failure Ok Respiratory failure not fully explained by cardiac failure or fluid overload Can use ECHO, don t have to use PAWP
ARDS- Berlin Is it Better? Better Prognostication? Very small superior predictive validity for mortality compared to previous definition When applied to cohort of 4400 patients from previous RCTs More Simple To Put Into Clinical Practice? ALI no longer exists Better defines parameters Will cloud future research with new definitions Not likely to alter morbidity and mortality
ARDS- Prone
Prone Positioning What we know Proning improves oxygenation in ARDS Cumbersome for nursing and staff What we don t know Does proning improve outcomes? RCT have shown improved oxygenation and decreased vent induced lung injury but no improved outcomes Meta-analyses have shown improved survival Who should be proned and how long?
Prone Positioning Question: Does early application of proning affect outcome for severe ARDS? Methods: 27 European ICUs with >5 years experience with proning 466 patients with severe ARDS randomized to prone at least 16 hours No blinding Few differences in groups Prone had more NMB Control sicker? More vasopressors, increased SOFA scores, increased need for dialysis Primary end point Mortality Day 28 Secondary end points 90 day mortality, rate and time to successful extubation, ICU LOS, complications, NIVV, tracheotomy rate, days free from organ dysfunction, ventilator settings, ABG, respiratory mechanics
Prone Positioning Decreased 28 day mortality Prone-position 16% (38/327 deaths) vs 33% supine (75/229 deaths) 17% ARR Similar findings for 90 day mortality No increased adverse events But all centers were comfortable proning patients Benefit persisting when adjusting for differences between the groups So why haven t studies shown similar benefits in past? Death due to other complications Not enough time proned Not early enough
Prone Positioning Consider in all patients with severe ARDS. Encourage health care systems to develop policies and procedures for safe, effective proning. Await similar studies in the US.
Not ARDS
JAMA, October 24/31, 2012 Vol 308, No. 16
Lung Protective Ventilation- Not ARDS What we know LPV accepted for acute lung injury based on ARDSnet What we don t know Would lower tidal volumes protect against acute lung injury in at risk patients? Is higher PEEP safe in patients without ARDS? Are lower tidal volumes safe for all patient populations?
Lung Protective Ventilation- Not ARDS Meta-analysis testing higher vs lower tidal volumes in patients without ALI at time of intubation 20 studies (RCT and observational) with over 2000 patients in variety of clinical scenarios MICU, SICU, NICU, OR 2 groups based on Vt LPV group 6.5 cc/kg IBW vs 10.6 cc/kg IBW Conventional SHORT mechanical ventilation times- both < 7 hours Primary Endpoint Development of lung injury Secondary Endpoints Mortality Atelectasis and pulmonary infection ICU and hospital LOS Time to extubations Respiratory measures
Lung Protective Ventilation- Not ARDS Development of ARDS 4.2% (47/1113 patients) LPV vs 12.7% (138/1090 patients) Conventional group Decrease of all measured outcomes with LPV group No increase in atelectasis or pneumonia with lower Vt Considerations Small, heterogenous meta analysis, short times on vent Most data came from observational studies Most of patients were not in MICU While there is no proof that higher Vt increases risk of complications, likely not all patients will benefit or tolerate Awake ICU patients may need to generate higher Vt May use more sedation to get patients to tolerate lower Vt Hard to control Vt on all vent modes
Lung Protective Ventilation- Not ARDS Need large RCT to evaluate optimal Vt in patients without acute lung injury Should consider LPV for patients without ALI who don t have contraindications
COPD
JAMA, June 5, 2013 Vol 309, No. 21
COPD- REDUCE Trial What we know AECOPD is a BIG deal Corticosteroids aid in treatment of AECOPD Corticosteroids have side effects What we don t know Optimal dose and duration for corticosteroid therapy 2011 GOLD: A dose of 30-40mg prednisolone per day for 10-14 days is recommended (Evidence D) although there are insufficient data to provide firm conclusions concerning the optimal duration of corticosteroid therapy of acute exacerbations of COPD.
COPD- REDUCE Trial Hypothesis: Shorter course (5 days) glucocorticoid therapy for AECOPD is noninferior to conventional (14 days) therapy Methods: 314 severe COPD (FEV1: 31%) presenting to ED for AECOPD at 5 Swiss centers All patients received 40 mg methylprednisolone but no further IV steroids Broad-spectrum antibiotic for 7 days Nebulized bronchodilators as needed, ICS/LABA twice daily along with Tiotropium daily. Randomized to 40 mg Prednisone 5 days (9 days placebo) vs 14 days Primary endpoint Time to next AECOPD (respiratory deterioration requiring a direct health care interaction) over 6 months Secondary endpoints Mortality, change in FEV1, cumulative glucocorticoid dose, clinical performance
COPD- REDUCE Trial Similar numbers reached primary end point Conventional group with 57/155 patients (37%) vs 56/156 patients (36%) in treatment group Did not alter time to next AECOPD Conventional group with 29 days to next AECOPD vs 44 days for treatment group No difference in many secondary endpoints Lung function (FEV1), mortality, need for mechanical ventilation, dyspnea, quality of life scores Treatment group Left the hospital one day sooner (median 8 vs. 9 day hospital stay, p=0.04) Took only about 1/3 the total steroid dose as the long-course treatment group (200 mg vs. 560 mg) Conventional group Did not have more hyperglycemia or adverse effects noted from glucocorticoids
COPD- REDUCE Trial First study showing noninferiority of shorter courses of systemic glucocorticoids during AECOPD
Chronic Cough
Lancet 2012; 380: 1583-1589
Chronic Cough- Gabapentin What we know One of most frustrating diagnosis for patients and MDs alike Despite known common causes, patients rarely respond to treatments GERD, asthma, UACS, ACE inhibitor Anti-tussives not effective, narcotics not ideal
Chronic Cough- Gabapentin Hypothesis: Neuromodulators may be effective on the CNS factors that amplify cough reflex in response to stimuli Patients have hypersensitive cough reflex Patients with neuropathic pain have hypersensitive response to neural stimuli Methods: 62 non-smokers from a single clinic in Australia 2008-2010 8 weeks cough, failed empiric therapy for usual etiologies Randomized to Gabapentin 600 TID vs Placebo x 10 weeks Patients titrated themselves Primary endpoint Change in cough related quality of life after 8 weeks Secondary endpoints Cough frequency, cough severity, urge-to-cough score, laryngeal dysfunction score
Chronic Cough- Gabapentin Gabapentin with greater improvement in LCQ cough score 74% (20/27) vs placebo 46% (12/26) Significant improvement in Cough severity Cough frequency Although only measured 1 hour vs ambulatory monitoring Effect went away off treatment
Chronic Cough- Gabapentin First RCT to evaluate Gabapentin in chronic cough Several case series before Well tolerated in study? More patients with AE and many of these were CNS effects Limitations Small, single site Was Gabapentin able to be masked? Would need long term use. Is this safe?
Thank You- Jennifer R. Hucks, MD University of South Carolina SOM Division of Pulmonary, Critical Care and Sleep Medicine jennifer.hucks@uscmed.sc.edu