THE BEST I HAVE READ THIS YEAR (IN PULMONARY AND CRITICAL CARE)

Transcription

1 23 March 2018 Boca Raton, Florida THE BEST I HAVE READ THIS YEAR (IN PULMONARY AND Johnson.margaret2@mayo.edu No disclosures or off label uses CRITICAL CARE) Margaret M. Johnson, MD Chair, Division of Pulmonary Medicine Mayo Clinic Florida

2 E-CIGARETTES-GOOD FOR SMOKING CESSATION? Kalkhoran S. Lancet Respiratory Medicine, , Volume 4, Issue 2, Pages

3 E-CIGARETTES-GOOD FOR SMOKING CESSATION? Two prior meta-analysis suggested a possible benefit OR of quitting if using e-cigarettes 2.29 ( ) McRobbie H. Cochrane Database Syst Rev % cessation rate at 6 months Rahman MA PLoS One 2015 Meta-analysis of 38 studies Examined quite rates at different times points and varying duration Kalkhoran S. Lancet Respiratory Medicine, , Volume 4, Issue 2, Pages

4 E-CIGARETTES-GOOD FOR SMOKING CESSATION? Kalkhoran S. Lancet Respiratory Medicine, , Volume 4, Issue 2, Pages

5 E-CIGARETTES-GOOD FOR SMOKING CESSATION? Favors E-cigarettes Kalkhoran S. Lancet Respiratory Medicine, , Volume 4, Issue 2, Pages

6 E-CIGARETTES-GOOD FOR SMOKING CESSATION? Did not support use of e-cigarettes to achieve smoking cessation 28% lower chance of cessation with use No identified subgroup who showed benefit Kalkhoran S. Lancet Respiratory Medicine, , Volume 4, Issue 2, Pages

7 WHAT DO I TELL PATIENTS No recognized benefit of e-cigarette use Avoid if not a current smoker For current smokers: Encourage abstinence at every opportunity Explore all potential avenues to facilitate smoking cessation If your patient is using e-cigarettes Discuss potential risks and health concerns Emphasize that effects of long-term use are uncertain Kalkhoran S. Lancet Respiratory Medicine, , Volume 4, Issue 2, Pages

8 STEROIDS FOR COUGH FROM COMMON COLD RCT, nonasthmatic patients 401 patients Prednisolone 40 mg/daily Placebo Outcome Cough duration and severity Hay AD. JAMA 2017; Aug

9 STEROIDS FOR COUGH FROM COMMON COLD Hay AD. JAMA 2017; Aug

10 DOES PROPHYLAXIS REDUCE VTE AFTER ARTHROSCOPIC KNEE SURGERY OR CASTING 2 Trials Arthroscopy ( n= 1543) Casting (n=1519) LMWH * 8 days v. placebo Outcome VTE within 3 months No difference Arthroscopy (0.7% v. 0.4%) Casting (1.4% v. 1.8%) Van Adrichem RA N Eng J Med 2017; 376(6):

11 DOES PROPHYLAXIS REDUCE VTE AFTER ARTHROSCOPIC KNEE SURGERY OR CASTING VTE incidence if low This does not affect TKA prophylaxis Prophylax (Grade 1B) LMWH over other agents (Grade 2C/2B) IPC while hospitalized (Grade 2C) Extend to 35 days (Grade 2B) CHEST Guidelines Beneficial to specified patients? Van Adrichem RA N Eng J Med 2017; 376(6):

12 HOW LONG IS ENOUGH: PROLONGED PROPHYLAXIS Risk for recurrent VTE increases once anticoagulation stopped However Indefinite anticoagulation associated with increased risk Could prolonged treatment at prophylactic dose balance risk/benefit Weitz JI. New Eng J Med 2017; 376(13): 1211

13 HOW LONG IS ENOUGH: PROLONGED PROPHYLAXIS 3365 patients who had completed 6-12 months treatment of anticoagulation Randomized to: Rivaroxaban 20 mg Rivaroxaban 10 mg ASA 100 mg Endpoint Symptomatic recurrent VTE Bleeding One Year Treatment dose 15 mg BD * 21 days, then 20 mg daily Weitz JI. New Eng J Med 2017; 376(13): 1211

14 HOW LONG IS ENOUGH: PROLONGED PROPHYLAXIS Recurrent VTE Rivaroxaban 20 mg 1.5% Rivaroxaban 10 mg 1.2% ASA 4.4% Similar bleeding Major/Nonmajor Rivaroxaban 20 mg 0.5%/2.7% Rivaroxaban 10 mg 0.4%/2.0% ASA 1.8%/0.3% Weitz JI. New Eng J Med 2017; 376(13): 1211

15 HOW LONG IS ENOUGH: PROLONGED PROPHYLAXIS Excluded those with active cancer Evidence still suggests use of LMWH for this population Lead to FDA approval for Rivaroxaban10 mg Prior WARFASA trial showed ASA superior to placebo with recurrent VTE 5.5% Practice change? Probably for those with limited reserve Weitz JI. New Eng J Med 2017; 376(13): 1211

16 CAN ASTHMA EXACERBATION BE HALTED WITH INCREASING INHALED STEROIDS McKeever, T. New Eng J Med 2018; 378:10, 902

17 CAN ASTHMA EXACERBATION BE HALTED WITH INCREASING INHALED STEROIDS Extension of asthma action plan Measures of control Increased use of reliever Poor sleep due to asthma Peak flow < 80% Intervention Quadruple ICS dose Begin oral steroids McKeever, T. New Eng J Med 2018; 378:10, 902

18 CAN ASTHMA EXACERBATION BE HALTED WITH INCREASING INHALED STEROIDS Study population (n =1022) Age 56 2/3 female 60% never smoker Endpoints Exacerbations needing oral steroids Hospitalizations, side effects McKeever, T. New Eng J Med 2018; 378:10, 902

19 CAN ASTHMA EXACERBATION BE HALTED WITH INCREASING INHALED STEROIDS Caveats: Mostly recruited in primary care (validity) Fewer hospitalizations (3 v. 18) Open label study inherently biased Clinical relevance (may) increase in light of chronicity of disease What is gain? Similar trial in pediatric patients negative McKeever, T. New Eng J Med 2018; 378:10, 902

20 ASSOCIATION BETWEEN LONG ACTING BRONCHODILATORS AND CARDIOVASCULAR EFFECTS Nested case-control trial in Taiwan N = 284,220 National Health Insurance Database LAMA/LABA naïve patients Followed for average 2.0 years Any cardiac event Inpatient or ED JAMA Int Med 2018; 78(2):

21 ASSOCIATION BETWEEN LONG ACTING BRONCHODILATORS AND CARDIOVASCULAR EFFECTS Average age 71, 71% male 37,700 cases v. 146,000 controls Approximately 50% RR with both classes within 30 days of initiation LABA 1.50 (CI , p <.001) LAMA 1.51 (CI , p <.001) Risk not associated with either baseline cardiovascular risk profile nor exacerbations JAMA Int Med 2018; 78(2):

22 ASSOCIATION BETWEEN LONG ACTING BRONCHODILATORS AND CARDIOVASCULAR EFFECTS Absolute risk 1% Correlation doesn t equate with causality Most studies leading to approval of long acting bronchodilators excluded patients with CVD and pharmaceutical funded The interplay of COPD and cardiovascular disease is incompletely understood JAMA Int Med 2018; 78(2):

23 TIOTROPIUM IN EARLY STAGE COPD 2 yrs of daily tiotropium v. placebo in 841 patients with mild (45%) or moderate (55%) COPD N = 841 Endpoint Change in pre and post bronchodilator FEV1 Rate of decline in FEV1 Zhou Y. New Eng J Med 2017; 377:

24 TIOTROPIUM IN EARLY STAGE COPD FEV1 favored tiotropium throughout the trial ml Rate of decline Pre-BD 38 v. 53 cc (NS) D 15 Post-BD 29 v. 51 cc (p = 0.006) D 22 cc Zhou Y. New Eng J Med 2017; 377:

25 TIOTROPIUM IN EARLY STAGE COPD Significant financial impact (14 M in US with COPD) Do the statistically meaningful changes merit adoption cc difference Annual rate of decline difference Pre-BD 15 cc (NS) Post-BD 22 cc ( p = 0.006) Funded, in part, by BI Zhou Y. New Eng J Med 2017; 377:

26 EGDT FOR SEPTIC SHOCK: A PATIENT LEVEL META-ANALYSIS EGDT-Early Goal Directed Therapy Fluid resuscitation, measuring lactate, central access Recommended by Surviving Sepsis guidelines following a small single center trial showed benefit The PRISM Investigators NEJM 2017:376; 23:2223

27 EGDT FOR SEPTIC SHOCK: A PATIENT LEVEL META-ANALYSIS 3723 patients at 138 hospitals in 7 countries No difference in 90 day mortality EGDT associated with higher cost, more ICU resources and cardiovascular support Subgroup analysis failed to identify any markers of mortality benefit The PRISM Investigators NEJM 2017:376; 23:2223

28 EGDT FOR SEPTIC SHOCK: A PATIENT LEVEL META-ANALYSIS The PRISM Investigators NEJM 2017:376; 23:2223

29 EGDT FOR SEPTIC SHOCK: A PATIENT LEVEL META-ANALYSIS The PRISM Investigators NEJM 2017:376; 23:2223

30 AND YET. CMS Payments still linked to completion of ALL components of sepsis bundle Includes IVF 30 cc/kg

31 COULD IT REALLY BE THIS SIMPLE? VITAMIN C, THIAMINE, HYDROCORTISONE FOR SEPTIC SHOCK Before and after analysis The cocktail: Vitamin C 1.5 gr IV q 6 hrs Hydrocortisone 50 mg IV q 6 hrs Thiamine 200 mg IV q 12 hrs Marik PE. Chest 2017 (6):

32 COULD IT REALLY BE THIS SIMPLE? VITAMIN C, THIAMINE, HYDROCORTISONE FOR SEPTIC SHOCK Outcomes Mortality Treatment 8.5% (4/47) Control 40.4% (19/47) Vasopressor use (hrs) Treatment 18.3 hrs Control 54.9 hrs Marik PE. Chest 2017 (6):

33 COULD IT REALLY BE THIS SIMPLE? VITAMIN C, THIAMINE, HYDROCORTISONE FOR SEPTIC SHOCK Predicted mortality by APCHE IV Marik PE. Chest 2017 (6):

34 COULD IT REALLY BE THIS SIMPLE? VITAMIN C, THIAMINE, HYDROCORTISONE FOR SEPTIC SHOCK Caveats 94 patients Before and after not RCT Downside Probably limited?? Marik PE. Chest 2017 (6):

35 Rozencwaig S. Crit Care. 2016; 20: 392

36 Rozencwaig S. Crit Care. 2016; 20: 392

37 Rozencwaig S. Crit Care. 2016; 20: 392

38 Rozencwaig S. Crit Care. 2016; 20: 392

39 Rozencwaig S. Crit Care. 2016; 20: 39

40 LESSONS LEARNED AND PRACTICES CHANGES Can t strongly recommend e-cigarettes for smoking cessation Chicken soup remains gold standard for treating a cold No identified benefit of VTE prophylaxis after casting or knee arthroscopy Prolonged low dose prophylaxis after VTE treatment (probably) worthwhile Self management of asthma with increased ICS may be appropriate Keep cardiovascular disease in mind and educate patients with initiation of long acting bronchodilators

41 LESSONS LEARNED AND PRACTICES CHANGES Sepsis management still needs personalization And, CMS needs to catch up with the literature Vitamin C/Thiamine/steroids Still on the fence ECMO is a viable alternative for patients with severe ARDS Have arrangements for implementation or transfer before needed

42 I JUST COULDN T RESIST. Tsuwaga Y, JAMA Internal Medicine, (2):