ACP Update in Hospital Medicine November 6, 2015

Transcription

1 ACP Update in Hospital Medicine November 6, 2015 Charles Pizanis, MD Director, 4 West Medical Unit Hospitalist Patrick Rendon, MD FACP Associate Program Director Hospitalist

2 Disclosures Employment with UNM Hospital No disclosures to report

3 Audience Composition

4 Roadmap Methods of article selection Case-based review Full review Quick takes

5 Inclusion Criteria Articles from October Relevance Practice changing Practical

6 Sources UNMH Journal Club ACP Journal Club The Hospitalist In the Literature Annals Internal Medicine Review UpToDate What s New NEJM Journal Watch Other Updates in HM

7 Developing themes Sepsis Venous Thromboembolism (VTE) GI topics Community Acquired Pneumonia (CAP)

8 REVERSE DISCLOSURE

9 Case You are contacted for an admission in the ED. The patient is a 72-year-old woman with severe sepsis presumed secondary to acute pyelonephritis. The ED has obtained blood and urine cultures, started CTX, and given 2000 ml of normal saline (30 ml/kg body weight). Lactate upon presentation was 4.2. Current blood pressure is 110/60 and other organ perfusion markers are normal.

10 Given the patient s severe sepsis, you decide to: A)Continue current antibiotics, recheck a lactate, and reassess volume status B)Get ready to line her up with CVC for CVP and ScvO2 and arterial line for MAP monitoring C)Decide that she s probably okay for cipro and close PCP follow up D)Severe sepsis??? Rrrrut rrrro!!!

11

12

13 Early Goal Directed Therapy E. Rivers et al. randomized adult patients presenting to the Emergency Department with severe sepsis and septic shock to protocolbased resuscitation or usual care Absolute risk reduction in-hospital mortality 16%, NNT = 6

14

15

16

17 ProMISE, ProCESS, ARISE Trials Question: Is EGDT superior to usual care for patients presenting to ED with severe sepsis and septic shock? Study design: prospective, randomized, parallel group trials; protocolized EGDT vs usual care Outcomes: mortality outcomes (28-day, 90-day mortality), costs, LS

18 ProMISE ARISE Rivers Usual EGDT Usual EGDT Usual EGDT 28-day mortality In-hospital mortality : p = 0.05 : p = < 0.05

19 ProMISE ARISE Rivers Usual EGDT Usual EGDT Usual EGDT 28-day mortality 24.50% 24.80% 15.90% 14.80% 49.20% 33.30% In-hospital mortality : p = 0.05 : p = < 0.05

20 ProMISE ARISE Rivers Usual EGDT Usual EGDT Usual EGDT 28-day mortality 24.50% 24.80% 15.90% 14.80% 49.20% 33.30% In-hospital mortality 24.60% 25.60% 15.70% 14.50% 46.50% 30.50% : p = 0.05 : p = < 0.05 Similar lack of superiority of EGDT in ProCESS trial early 2014

21 Is EGDT Dead? Usual care in 2001 is not usual care in 2014/2015 Metrics for antibiotics, IVF, vasopressor administration in usual care groups similar to EGDT group in Rivers trial Principles of early antibiotics, IVF resuscitation, vasopressor support part of usual care

22 Is EGDT Dead? Usual care patients in Rivers trial with were sicker and died more APACHE II at entry = 20.4 (ProMISE: 18, ARISE: 15.3) Lactate at entry = 6.9 (ProMISE: 5.1, ARISE: 4.2) 28-day mortality = 49.2% (ProMISE: 24.5%, ARISE: 15.9%) In-hospital mortality = 30.5% (ProCESS: 18.9%, ProMISE: 24.6%, ARISE: 15.7%)

23 Are We Really Comparing the Same Intervention Here? Rivers et al. implemented a unique practice setting Treatment in special 9-bed unit in ED Harmonized trials much of care in ICU Harmonized trails enrolled later in ED course Rivers trial enrollment up presentation to ED Pre-enrollment care included many important elements likely effecting outcome

24 Bottom Line Consider forgoing titrating resuscitative efforts to protocolized CVP, ScvO2 given our current care for patients with severe sepsis and septic shock presenting through the ED

25

26 2012 International Guideline for Management of Severe Sepsis and Septic Shock 3-hour bundle Measure lactate level Obtain blood cultures prior to antibiotics Administer broad spectrum antibiotics Administer 30ml/kg crystalloid for hypotension or lactate 4mmol/L 6-hour bundle Vasopressors for hypotension not responding to fluids to MAP 65 mm Hg If persistent hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/l (36 mg/dl): Measure central venous pressure (CVP) target goal 8 mm Hg Measure central venous oxygen saturation (ScvO2) target goal 70% Re-measure lactate if initial lactate was elevated

27 2015 Updated Recommendation 3-hour bundle SAME! 6-hour bundle Apply vasopressors to maintain MAP 65 mmhg Re-measure lactate if initial lactate elevated In the event of persistent hypotension after IVF or if initial lactate 4mmol/L, re-assess volume status and tissue perfusion and document findings Either Repeat focused exam (after initial fluid resuscitation) including vital signs, cardiopulmonary, capillary refill, pulse, and skin findings Or Two of the Following Measure CVP Measure ScvO2 Bedside cardiovascular ultrasound Dynamic assessment with passive leg raise or fluid challenge

28 Given the patient s severe sepsis, you decide to: A)Continue current antibiotics, recheck a lactate, and reassess volume status B)Get ready to line her up with CVC for CVP and ScvO2 and arterial line for MAP monitoring C)Decide that she s probably okay for cipro and close PCP follow up D)Severe sepsis??? Rrrrut rrrro!!!

29 Case You ve stabilized your 72-year-old woman with pyelo. It s time for breakfast and you can finally take a breather. A nurse pages you with an new isolated WBC elevation on a 84-year-old male patient recently admitted with AKI. All other vitals and labs have been normal.

30 Regarding the new leukocytosis, you decide: A) Not to worry about it because the patient does not have SIRS B) To explain it away, saying he must have taken some steroids somewhere, somehow C) To consider the patient could be experiencing sepsis since not everyone with infection and organ dysfunction manifests with SIRS D) Mmmmm, jelly donut

31

32 Study Design Question: How accurate is the cut off of 2 or greater SIRS criteria in the definition of sepsis? Study design: Retrospective study of sepsis database in Australia and New Zealand Analyzed number of SIRS criteria in patients with diagnostic codes for infection and organ failure within 24 hours of ICU admission Outcomes: % patients with SIRS +/- infection and organ failure, mortality based on # SIRS criteria

33 12.1% patients with infection and organ failure had <2 SIRS criteria Characteristics of SIRS-negative severe sepsis: increasing age, male sex, surgical admission

34 Odds ratio for each additional criterion, 1.13 (95% CI, 1.11 to 1.15; P<0.001)

35 Regarding the new leukocytosis, you decide: A) Not to worry about it because the patient does not have SIRS B) To explain it away, saying he must have taken some steroids somewhere, somehow C) To consider the patient could be experiencing sepsis since not everyone with infection and organ dysfunction manifests with SIRS D) Mmmmm, jelly donut

36 Bottom Line Consider sepsis even if fewer than 2 SIRS criteria, particularly in elderly, males, and those with surgical admission Recognize higher risk of mortality with increasing number of SIRS criteria

37 Case (continued) You figured a jelly donut was in order (while considering sepsis in this patient). While paying for it the cafeteria, the same nurse calls you again saying the same patient has now screened positive for SIRS and wants to know if you want to grab a lactate. You say okay but secretly wonder to yourself, What s the deal with all these SIRS screens these days?

38 Quick Take

39 The Study Setting: University of Pennsylvania Health System Objective: to describe development, implementation, and impact of an early warning and response system for sepsis Study design: pre- and post-implementation analysis looking at a variety of sepsis-related care measures, mortality, dispositions

40

41

42 Bottom Line Sepsis alert systems can lead to earlier delivery of sepsis-related care

43 Just another day in the office

44 I saw My you student working just so hard asked on about the Update recent for Hospital literature Medicine on bridging this week patients and I thought with A. Fib you d for know certain procedures. the answer Can to a you student s look into question this?

45

46 Ok, not really, but what I did do

47

48

49 The Study Question: in patients with A. Fib, is heparin bridging needed during interruption of warfarin therapy before and after an operation or other invasive procedure? Study design: Randomized, double-blind, placebo-controlled, non-inferiority trial

50 The Study Patients with chronic A. Fib/Flutter Mean CHADS2 of 2.3, with 38.3% at score of 3 or more Outcomes: Follow-up: 30 days after the procedure Primary outcomes: arterial thromboembolism and major bleeding

51 Bridging occurred from 3 days before the procedure until 24 hours before the procedure and then for 5-10 days after the procedure Warfarin was stopped 5 days before the procedure and then resumed within 24h after the procedure

52

53 Bottom Line Consider forgoing bridging anticoagulation for patients with A. Fib undergoing elective procedures Note the increased risk of major bleeding when using a bridging strategy

54 Quick Take

55 The Study Background: 2 prior studies showed no significant difference in screening for cancer with occult VTE Objective: assess the efficacy of a screening strategy for occult cancer for a first-time unprovoked VTE Multicenter, open-label RCT Primary outcome: Confirmed cancer that was missed by the screening strategy and detected by the end of the 1-year follow-up period

56 The Groups Limited Screening -History -Physical -CBC -Electrolytes -LFTs -CXR -Sex-specific screening Limited Screening + +

57

58 Bottom Line For patients with first unprovoked VTE, remember that performing CT abdomen studies beyond routine cancer screening does not provide a clinically significant benefit

59 Case You re coming in the morning to start your day. Your colleague signs out a patient admitted overnight with alcoholic hepatitis (discriminate function = 48). The patient has no signs of bleeding or infection. Renal function is normal. Your colleague has started him on prednisolone and consulted nutrition for optimization of his nutritional status.

60 Given the patient s severe alcoholic hepatitis, you: A) Stop the prednisolone and start pentoxifylline given its definite superiority B) Continue the current regimen and continue to work with patient on goals of care discussions C) Stop all medications and tell the patient there is nothing we can do to help D) Groan, wondering, Haven t we figured out this prednisolone vs. pentoxifylline thing out yet?

61

62 STOP-AH Trial Question: What is the optimal treatment for severe alcoholic hepatitis? Prednisolone? Pentoxifylline? Study design: multicenter, randomized, double-blind trial with a 2-by-2 factorial design Exclusion: acute renal failure, active GI bleed, sepsis, need for vasopressors Outcomes: mortality at 28 days, composite outcome mortality at 90 days + liver transplant, mortality at 1 year + liver transplant

63 Results Prednisolone Odds ratio (95% CI), p value Pentoxifylline Odds ratio (95% CI), p value 28-day mortality 90-day mortality or liver transplant 1-year mortality or liver transplant

64 Results Prednisolone Odds ratio (95% CI), p value Pentoxifylline Odds ratio (95% CI), p value 28-day mortality 0.72 ( ), NS 1.07 ( ), NS 90-day mortality or liver transplant 1-year mortality or liver transplant

65 Results Prednisolone Odds ratio (95% CI), p value Pentoxifylline Odds ratio (95% CI), p value 28-day mortality 0.72 ( ), NS 1.07 ( ), NS 90-day mortality or liver transplant 1-year mortality or liver transplant 1.02 ( ), NS 0.97 ( ), NS

66 Results Prednisolone Odds ratio (95% CI), p value Pentoxifylline Odds ratio (95% CI), p value 28-day mortality 0.72 ( ), NS 1.07 ( ), NS 90-day mortality or liver transplant 1-year mortality or liver transplant 1.02 ( ), NS 0.97 ( ), NS 1.01 ( ), NS 0.99 ( ), NS In prednisolone groups, significantly more infections (13% vs. 7%) and lung infections (7% vs 3%)

67 28-day Mortality Multivariate analysis: INR, age, WBC, urea, creatinine, bilirubin, hepatic encephalopathy Odds Ratio (95% CI) P value Prednisolone vs. no prednisolone Pentoxifylline vs. no pentoxifylline

68 28-day Mortality Multivariate analysis: INR, age, WBC, urea, creatinine, bilirubin, hepatic encephalopathy Odds Ratio (95% CI) P value Prednisolone vs. no prednisolone 0.61 ( ) 0.02 Pentoxifylline vs. no pentoxifylline

69 28-day Mortality Multivariate analysis: INR, age, WBC, urea, creatinine, bilirubin, hepatic encephalopathy Odds Ratio (95% CI) P value Prednisolone vs. no prednisolone Pentoxifylline vs. no pentoxifylline 0.61 ( ) ( ) NS Some benefit in prednisolone when controlling for above factors

70 Given the patient s severe alcoholic hepatitis, do you: A) Stop the prednisolone and start pentoxifylline given its definite superiority B) Continue the current regimen and continue to work with patient on goals of care discussions C) Stop all medications and tell the patient there is nothing we can do to help D) Groan, wondering, Haven t we figured out this prednisolone vs. pentoxifylline thing out yet?

71 Bottom Line Increasingly bleak picture for severe alcoholic hepatitis and currently available agents unlikely to provide much benefit

72 Case (continued) The patient starts to bleed. He is taken to EGD and a gastric ulcer with visible vessel is identified. After endoscopic intervention, you decide to keep a PPI drip going for 72 hours. The pharmacist calls you and says, PPI drips, um, yeah we don t do that any more.

73 Quick Take

74 The Study Background: current guidelines recommend an intravenous bolus dose of PPI followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers Objective: compare risk of rebleeding with intermittent dosing PPI to bolus plus continued infusion PPI in high-risk bleeding ulcers Study design: systematic review and meta-analysis of RCTs; main outcome recurrent bleeding within 7 days

75 Intermittent dosing noninferior to bolus plus continued infusion PPI (risk ratio = 0.72, 1-sided 95% CI upper boundary 0.97)

76 Bottom Line Consider ordering intermittent dosing PPI instead of PPI drip in patients with high-risk ulcers

77 Case (continued) You successfully stabilize the patient and his alcoholic hepatitis resolves! You discharge him home after a stern talking-to about alcohol cessation. After a couple of weeks, you see the patient back on the medicine census re-admitted with alcohol withdrawal. You respond sadly, question your motivational interviewing skills, and wonder if there is anything you could have done to prevent the patient s relapse.

78

79 Quick Take

80 The Study Background: readmission rates are now tied with reimbursements. CMS only adjusts for patients age, sex, discharge diagnosis, and diagnoses present in claims during the 12 months prior to admission Objective: to assess the extent to which a comprehensive set of patient characteristics accounts for differences in hospital readmission rates

81 The Study Study design: retrospective analysis of Medicare readmissions from Patient characteristics from the Health and Retirement Survey assessed for risk for readmission Associations between patient characteristics and hospitals to which they were readmitted evaluated

82 Results After standard CMS adjustments, 22 patient characteristics significantly predicted readmission risk Examples: inability to perform ADLs/IADLs, decreased mobility, smoking, lower education status, lower income, Medicaid, self-rated health Hospitals in highest quartile for readmissions were more likely to have patients with 16 of these characteristics

83 Bottom Line It ain t just the physician s fault! Many risk factors for readmission are related to patient characteristics

84 Case A 69 year-old previously healthy man is admitted to the hospital with acute onset of fever, cough, and pleuritic chest discomfort. CXR shows a right lower lobe infiltrate. This is the 8 th admission today for community pneumonia. You think to yourself out of all these patients, I wonder what the most likely bug could be?

85 Which of the following is the most likely cause of this patient s pneumonia? A. Influenza virus B. Rhinovirus C. Strep pneumoniae D. Human metapneumovirus E. No clue. Let me google it.

86 THEN NOW

87 Quick Take

88 The Study Objective: To determine estimates of pathogen incidence of radiographically confirmed pneumonia Active population-based surveillance for CAP requiring hospitalization in patients 18 years old or older via analysis of blood, urine, and respiratory specimen Exclusion: recent hospitalization or severe immunosuppression

89

90 Which of the following is the most likely cause of this patient s pneumonia? A. Influenza virus B. Rhinovirus C. Strep pneumoniae D. Human metapneumovirus E. No clue. Let me google it.

91 Bottom Line(s) No pathogen was detected in the majority of patients Respiratory viruses detected more often than bacteria The incidence of CAP requiring hospitalization was highest among older adults

92 Case Upon taking additional history you note that this patient (69 M) has had symptoms for 5 days prior to his presentation. You cleverly deduce that this is more likely to be a bacterial infection.

93 Which of the following would be the most appropriate regimen for this patient? A. Beta-lactam antibiotic only B. Beta-lactam antibiotic + macrolide C. Fluoroquinolone monotherapy D. That s a tough one. I ll just sit here patiently until you give me the answer

94

95 The Study Purpose: To compare empiric treatment strategies with: Beta-lactam monotherapy (656) vs Beta-lactam/macrolide combination therapy (739) vs Fluoroquinolone monotherapy (888) Deviations in treatment allowed for medical reasons Study design: Cluster-randomized, crossover non-inferiority study with strategies rotated in 4-month periods Primary outcome: 90 day mortality

96 Results

97 Sometimes all you need is an arrow or 2

98 Results Strategy Mortality Beta-lactam 59 patients (9%) Beta-lactam + macrolide 82 patients (11.1%) Fluoroquinolone 78 patients (8.8%) **No statistically significant difference in mortality between groups

99 Which of the following would be the most appropriate regimen for this patient? A. Beta-lactam antibiotic monotherapy B. Beta-lactam antibiotic + macrolide C. Fluoroquinolone monotherapy D. I m tired already. I ll just sit here patiently until you give me the answer

100 Bottom Line For patients on the wards, remember that betalactam monotherapy is non-inferior to beta-lactam/macrolide combination or fluoroquinolone monotherapy *Study allowed for deviations for medical reasons

101 Case Unfortunately your patient becomes progressively ill to the point where he is having difficulty with breathing. You are called to the bedside. His vitals are: T 38.1, BP 120/80 (baseline), P 100, RR 25, O2S 86% RA. Mental status is intact. You wonder about next steps...

102 To improve the patient s mortality should you next A) Get an ABG and place NIPPV (BIPAP) B) Intubate now C) Place large bilateral nasal prongs (optiflow) D) Get an ABG and place a Non- Rebreather E) If you really want to improve the patient s mortality, transfer care to a more skilled hospitalist

103

104 The Study Question: In patients with acute hypoxemic, nonhypercapneic respiratory failure, should NIPPV should be used vs alternative? Alternative - High-flow O2 Multicenter (France, Belgium), open-label RCT 310 patients: RR >25, PaO2/FiO2 <300 mmhg, PaCO2 <45mmHg, no chronic respiratory failure Primary outcome: patients requiring intubation at 28 days Secondary: all-cause mortality in the ICU at 90 days and number of ventilator-free days at day 28

105 Exclusion Criteria Asthma exacerbation Acute on chronic respiratory failure Cardiogenic pulmonary edema Severe neutropenia Hemodynamic instability Vasopressor use Reduced consciousness Contraindication to NIPPV Urgent intubation DNI order

106

107 CAP was main cause of respiratory failure (64%) For those that were intubated there was no difference between groups

108

109 To improve the patient s mortality should you next A. Get an ABG and place NIPPV (BIPAP) on the patient B. Intubate now C. Place large bilateral nasal prongs (optiflow) D. Get an ABG and place a non-rebreather E. My neighbor here has it right, call on them

110 Bottom Line In patients with non-hypercapneic acute hypoxemic respiratory failure, consider treatment with high-flow oxygen (optiflow) before non-invasive ventilation

111 Case Your patient ends up avoiding intubation. Given this close call for you, you can t help but wonder if you could have done anything differently to avoid the patient becoming more ill. You wonder would steroids have worked?

112 Would steroids have worked? A. No, there is no benefit whatsoever to adding steroids B. Yes, but I m not sure about IV vs PO C. No, it will increase the patient s mortality D. Yes, definitely, throw em some steroids. It s what we do when things are inflamed

113 JAMA

114 The Study Question: In patients with CAP, can the treatment failure and associated excessive inflammatory response be avoided via use of steroids? Study design: Multicenter, randomized, doubleblind, placebo-controlled trial Patients with severe CAP + high inflammatory response (CRP >150 mg/l at admission)

115 2 Groups Methylprednisolone 0.5 mg/kg was given for 5 days starting within 36 hours of hospitalization

116 The Study Primary outcome: treatment failure Early: Clinical deterioration (shock), need for intubation, death within 72 hours of treatment Late: Radiographic progression, development of shock, death between 72 and 120 hours after starting treatment Secondary: in-hospital mortality

117 Radiographic progression is an independent surrogate marker for mortality No difference for in-hospital mortality, need larger numbers

118 Quick take

119 The Study Objective: Assessed whether short-term steroid (50 mg prednisone for 7 days) treatment reduces time to clinical stability in patients admitted to hospital for CAP Primary outcome: time to clinical stability defined as days until stable vital signs for at least 24h

120 1) Reduction in time to clinical stability (1.4 days) 2) Reduced LoS (1 day) 3) Reduction in duration of IV antibiotics (1 day)

121 Bottom Line(s) For patients with severe CAP and high initial inflammatory response, consider steroids within 36 hours of admission

122 In Summary Start Heeding SIRS screens Recognizing >2 SIRS is not a hard and fast rule for infection and organ dysfunction Having goals of care discussions early with patients with severe alcoholic hepatitis Stop Bridging anticoagulation for patients with atrial fibrillation undergoing elective surgery Absolutely adhering to EGDT (CVP, ScvO2 monitoring) for patients with severe sepsis/septic shock Ordering CT a/p for cancer screening after idiopathic, first-time VTE PPI drips for patients with upper GI bleed Consider Initiating optiflow over non-rebreather/nippv in patients with purely acute hypoxemic respiratory failure Beta-lactam monotherapy in admitted patients with CAP Using steroids for patients with admitted patients with CAP

123 ICD 10

124 ICD 10 Overview 68,000 billing codes under the new ICD- 10 system Early 2015: CMS and AMA Announced Efforts to Help Providers Get Ready for ICD - 10 We thought our guide to the top ICD 10 codes would be more useful

125 2-3 MCQs on ICD 10

126

127

128 Questions? S10.87XA: Other superficial bite of other specified part of neck, initial encounter

129 Thank You!!!

130 References 1. Rivers E, Nguyen B, Havstad S, et al. Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. New Engl J Med 2001; 345: Mouncey PR, Osborn TM, Power GS, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med 2015; 372: Kaukonen KM, Bailey M, Pilcher D, et al. Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis. N Engl J Med 2015; 372: The Arise Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371: Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: Crit Care Med. 2013;41(2): Surviving Sepsis Campaign: Updated Bundles in Response to New Evidence. Date accessed 1 November Umsheid CA, Betesh J, VanZanderbergen C, et al. Development, implementation, and impact of an automated early warning and response system for sepsis. J Hosp Med. 2015;10(1): doi: /jhm Epub 2014 Sep Thursz MR, Richardson P, Michael Allison M, et al. Prednisolone or Pentoxifylline for Alcoholic Hepatitis. N Engl J Med 2015; 372: Sachar H, Vaidya K, Laine L.Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014;174(11): Douketis, James et. al. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation.. N. Engl J Med Carrier, Mark et al. Screening for Occult Cancer in Unprovoked VTE.. N. Engl J Med Vol. 373; No Frat, Jean-Pierre et. al. High flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N. Engl J Med. 2015; 372. No Blum, Claudine Angela et. al. Adjunct prednisone therapy for patients with CAP: a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet Vol. 385; apr Torres, Antoni, et. al. Effect of corticosteroids on Treatment Failure Among Hospitalized Patients with severe CAP and High Inflammatory Response. JAMA Postma, Douwe et. al. Antibiotic Treatment Strategies for CAP in Adults.. N. Engl J Med Jain, S et. al. CAP Requiring Hospitalization among US Adults. N. Engl J Med. 2015