Update in Hospital Medicine2019-2020

Brad Sharpe, MD SFHM

Year in Review 2020

Year in Review

• Updated literature • March 2019 – March 2020

Process:• CME collaborative review of journals

• Including ACP J. Club, J. Watch, etc.

• Independent analysis of article quality

Year in Review

Year in Review 2020

Chose articles based on 3 criteria:

1) Change your practice2) Modify your practice3) Confirm your practice

• Hope to not use the words:• Student’s t-test, meta-regression, Mantel-Haenszel

statistical method, etc.• Focus on breadth, not depth

Year in Review

Year in Review 2020

• Major reviews/short takes• Case-based format• Multiple choice questions• Promote retention

Year in Review

Syllabus/Bookkeeping

• No conflicts of interest• Final presentation

available by email:

sharpeb@medicine.ucsf.edu

Update in Hospital Medicine

Fluids in SepsisQuestion: In critically-ill medical patients with sepsis,

how do balanced crystalloids compare to normal saline?

Design: Secondary analysis of a large RCT; critically-ill patients admitted to the ICUAnalyzed patients admitted with sepsis

Update in Hospital MedicineBrown RM, et al. AJRCCM.2019;200(12):1487-1495.

• Randomized to “balanced crystalloids” vs. normal saline• Otherwise standard of care

Fluids in Sepsis

Brown RM, et al. AJRCCM.2019;200(12):1487-1495.

Outcome Balanced NS p30-day In-hospital Mortality

Major Kidney Event

• 1,641 patients in total (10.4%)• Pulmonary, urinary, abdominal sources• 35% on pressors, 40% intubated• Total fluid given equivalent

Fluids in Sepsis

Brown RM, et al. AJRCCM.2019;200(12):1487-1495.

Outcome Balanced NS p30-day In-hospital Mortality 26.3% 31.2% <0.05

Major Kidney Event 35.4% 40.1% <0.05

• 1,641 patients in total (10.4%)• Pulmonary, urinary, abdominal sources• 35% on pressors, 40% intubated• Total fluid given equivalent

• More ventilator-free days, more vasopressor-free days, & less RRT

Update in Hospital Medicine

Fluids in SepsisQuestion: In patients with sepsis, how do balanced

crystalloids compare to normal saline?Design: Secondary analysis of a large RCT; critically-ill

patients admitted to the ICU Analyzed patients admitted with sepsis

Conclusion: Balanced fluids with lower mortality, less adverse kidney events; less ventilator, pressors, renal replacement

Comments:Subgroup analysis? Otherwise RCTBalanced fluids probably better than NSIn sepsis, use LR or Plasmalyte

Update in Hospital MedicineBrown RM, et al. AJRCCM.2019;200(12):1487-1495.

Short take: Nutrition in the Hospital

• In a randomized controlled trial of patients at “nutritional risk” (high NRS scores), 2088 patients were randomized to:• Individualized nutrition support

• ≥ 75% of caloric and protein needs• Micronutrients• Use enteral or parenteral nutrition if needed

• No dietary consultation

Update in Hospital MedicineScheutz P, et al. Lancet. 2019;393:2312.

Short take: Nutrition in the Hospital

• Improved quality of life at 30 days• No impact on length of stay• No adverse side effects

Update in Hospital MedicineScheutz P, et al. Lancet. 2019;393:2312.

Outcome Nutrition No pAdverse Outcome (30d) 23% 27% 0.02

Mortality (30d) 7% 10% 0.01

Short take: PPI and Drug Resistance

• Systematic-review and meta-analysis• A total of 26 observational studies including

29,382 patients

• Acid suppression was associated with:• Increased MDRO (OR=1.74, 95%CI 1.40-2.16)

• Increased risk for resistant GNR and VRE• PPI = bad.

Update in Hospital MedicineWillems RP, et al. JAMA Intern Med.2020;180(4):561-571.

Update in Hospital Medicine

Question: What is the impact of “intensifying” antihypertensive regimens at discharge?

Design: Retrospective cohort study; VA database Intensification vs. no change

Increasing Blood Pressure Medications

Anderson TS, et al. JAMA Intern Med.2019;Aug 19 epub.

• Admitted for pneumonia, UTI, or VTE• Intensification: new medication or increase ≥ 20%• Propensity matched to control for confounders

Increasing Blood Pressure Medications

Anderson TS, et al. JAMA Intern Med. 2019;Aug 19 epub.

Outcome Intensified Not pReadmission (30d) 21.4% 17.7% <0.05

Serious Adverse Events(ED, hospitalization) 4.5% 3.1% <0.05

CV Events (30d) 3.6% 2.2% <0.05

CV Events (1yr) 13.8% 11.9% NS

• A total of 14,915 enrolled• Total of 2074 (14%) had intensification• Propensity matched with 2074

• No difference in follow-up blood pressure• Same for controlled vs. uncontrolled HTN

Update in Hospital Medicine

Question: What is the impact of “intensifying” antihypertensive regimens at discharge?

Design: Retrospective cohort study; VA database Intensification vs. none, propensity matched

Conclusion: Intensification leads to readmissions & serious adverse events; no change in CV outcomes at 1 year; no change in BP

Comments:Retrospective study, confounders?Intensification likely leads to harm; Acute hypertension common in the hospital – treatment can cause harm; Generally avoid adjusting HTN regimens

Increasing Blood Pressure Medications

Anderson TS, et al. JAMA Intern Med.2019;Aug 19 epub.

Short take: Afib and Stable CAD

Methods:• Multi-center, open-label RCT• Diagnosis of afib and stable CAD

• PCI or MI > 1 year prior• Randomized to:

• Rivaroxaban• Rivaroxaban + aspirin (or P2Y12 inhibitor)

Update in Hospital MedicineYasuda S, et al. NEJM. 2019;381:1103.

Short take: Afib and Stable CAD

Results:

• For most patients with afib and stable CAD, go with monotherapy with a DOAC

Update in Hospital MedicineYasuda S, et al. NEJM. 2019;381:1103.

Outcome RivaroxabanRivaroxaban

+ ASA pCV Event or Death 4.14% 5.75% <0.01

Major Bleeding 1.62% 2.76% 0.01

Case SummaryConsider

1. In patients with sepsis, using balanced fluids over normal saline

2. Consulting nutrition in patients at nutritional risk.

3. PPIs may increase the risk for acquiring drug-resistant organisms.

4. Not increasing BP meds in the hospital.5. In patients with afib and stable CAD on a

DOAC, stop the aspirin.

Antipsychotics for DeliriumQuestion: What are the benefits and harms of using

antipsychotics to treat inpatient delirium?Design: Systematic review, 26 trials (16 RCTs, 10 obs)

5607 hospitalized patients with delirium.

Nikooie, R et al. Ann Intern Med. 2019;171:485-95

Studies assessed:• Haloperidol vs placebo• 2nd-generation antipsychotics vs placebo• Haloperidol vs 2nd-generation antipsychotics

Antipsychotics for DeliriumKey Findings:• No difference vs. placebo: (low-mod evidence)

• Sedation status• Length of stay• Delirium duration* • Mortality**

*Meta-analysis of 4 RCTs with 0.2d increase**1 RCT of haloperidol with increased mortality

Nikooie, R et al. Ann Intern Med. 2019;171:485-95

Antipsychotics for DeliriumKey Findings:Insufficient/inconsistent evidence:

• Cognitive function• Delirium severity• Inappropriate continuation

Increased QTc for several agents

No difference in neurologic adverse events

Nikooie, R et al. Ann Intern Med. 2019;171:485-95

Antipsychotics for DeliriumQuestion: What are the benefits and harms of using

antipsychotics to treat inpatient delirium? Design: Systematic review, 26 trials (16 RCTs, 10 obs)

5607 hospitalized patients with delirium Conclusion: No difference in outcomes vs. placebo,

No impact on sedation or mortality;Comments: Heterogeneity, generalizability?

No good evidence supporting anti-psychotics to treat deliriumMaximize non-pharmacologic means; use only for safety

Nikooie, R et al. Ann Intern Med. 2019;171:485-95

Short Take: Early De-escalation of Antibiotics

• Retrospective cohort study of 808 patients ≥18 years old with Enterobacteriaceae bacteremia

• Excluded patients with known CDI, hospitalized < 48h

Seddon MM, et al. Clin Infect Dis. 2019;69(3):414-20

Duration of APBL Incidence of CDI

Short Take: Early De-escalation of Antibiotics

• Retrospective cohort study of 808 patients ≥18 years old with Enterobacteriaceae bacteremia

• Excluded patients with known CDI, hospitalized < 48h

• C diff risk may increase with more days of broad-spectrum antibiotics

Seddon MM, et al. Clin Infect Dis. 2019;69(3):414-20

Duration of APBL Incidence of CDI≤48h 1.8%>48h 7.0%

Year in Review

Gram Negative Rod BacteremiaQuestion: What is the optimal duration of therapy for

gram-negative rod bacteremia?Design: Randomized, multi-center, open-label trial;

7 vs. 14 days of antibiotics for GNR bacteremia

Yahav D, et al. Clin Infect Dis 2019 Sep;69(7):1091-1098.

• Hemodynamically stable, afebrile x 48 hours• Source control

Update in Hospital Medicine

Results

Update in Hospital MedicineUpdate in Hospital MedicineUpdate in Hospital MedicineYahav D, et al. Clin Infect Dis 2019 Sep;69(7):1091-1098

• Total of 604 patients• Main sources: urinary (68%), abdominal (12%)• Mainly Enterobacteriaceae (E. coli 63%)

Outcome 7 Days 14 days p90 Day Mortality 11.8% 10.7% 0.7

Readmissions (90d) 38.9% 42.6% 0.3New Infection (90d) 22.9% 22.8% 0.9

• No difference in side effects• Return to baseline shorter in 7 day group

Year in Review

Gram Negative Rod BacteremiaQuestion: What is the optimal duration of therapy for

gram-negative rod bacteremia?Design: Randomized, multi-center, open-label trial;

7 vs. 14 days of antibioticsConclusion: In GNR bacteremia, 7 days noninferior to 14

days of antibiotics; no diff. in mortality or adverse events; return to baseline faster

Comments: Open-label; mostly EnterobacteriaceaeWell-done study; most can be treated with 7 days (source control)Can switch to orals & discharge when stable

Yahav D, et al. Clin Infect Dis 2019 Sep;69(7):1091-1098.

Case SummaryConsider

1. Avoiding routine use of antipsychotics to manage inpatient delirium

2. In stable patients with GNR bacteremia, de-escalating antibiotics by 48 hours

3. Treating patients with Enterobacteriaceaebacteremia with 7 days of antibiotics.

Case SummaryConsider

1. In patients with sepsis, using balanced fluids over normal saline

2. Consulting nutrition in patients at nutritional risk.

3. PPIs may increase the risk for acquiring drug-resistant organisms.

4. Not increasing BP meds in the hospital.5. In patients with afib and stable CAD on a

DOAC, stop the aspirin.

Update in Hospital Medicine2019-2020

Brad Sharpe, MD SFHM