Vivian Phyo, PharmD Lauren Schmidt, PharmD

PGY2 Internal Medicine Resident PGY2 Critical Care Resident

September 7, 2023
 : Elevated INR
in Cirrhosis
: Cefepime
and Neurotoxicity
: AKI-
Related Myths
 Learning Objectives
1. Recognize the conflicting data behind the
presented pharmacy “myths”.
2. Evaluate the literature presented on each
pharmacy “myth”.
3. Develop a stance on the topic as it applies to
clinical practice.
 Key:

Coagulation Pathway Black – hepatic synthesis

Red – non-hepatic synthesis

Intrinsic Pathway Extrinsic Pathway

XII XIIa VIIa VII

XI XIa vWF Tissue factor

IX IXa VIIIa VIII

X X
Xa
Prothrombin (II) Thrombin (IIa)
Va
V Fibrinogen (I) Fibrin (Ia)
Active Protein C

Protein S XIIIa XIII

Protein C + Thrombomodulin Fibrin clots

vWF: von Willebrand factor Harrison MF. West J Emerg Med. 2018;19(5):863-871
 International Normalized
Ratio (INR)
𝑃𝑎𝑡𝑖𝑒𝑛𝑡 𝑃𝑇
INR = adjusted for ISI
𝐶𝑜𝑛𝑡𝑟𝑜𝑙 𝑃𝑇

Compared to INR in warfarin-anticoagulated controls,

patients in end-stage liver disease:
↓VIIa ↓VII

↑X ↑X
↑Xa
↑Prothrombin (II) ↑Thrombin (IIa)
↓Va
↓V ↓Fibrinogen (I) ↓Fibrin (Ia)
ISI: international sensitivity index
PT: prothrombin time Kujovich JL. Crit Care Clin. 2005;21(3):563-587
 A patient with cirrhosis and hepatocellular
carcinoma is admitted with INR of 2. Your team
decided not to order DVT prophylaxis as patient is
already “auto-anticoagulated.”

How many of you feel comfortable justifying DVT

prophylaxis in this patient?
Rebalance of Hemostasis in Cirrhosis

Bleeding Clotting

↑ anti-
↓ platelets phospholipid
antibodies

platelet function systemic

defects inflammation

↓ coagulant ↓ anticoagulant
factors factors

Harrison MF. West J Emerg Med. 2018;19(5):863-871

 VTE Incidence vs. INR Results
VTE Incidence Among Chronic Liver Disease
Non-DVT,
178 (93.7%)
Class C, 8

DVT, 12
(6.3%)

Class A, 1
Class B, 3
Patients with VTE (n=12)
INR < 1.4 3
1.4 < INR < 1.7 3
1.7 < INR < 2.2 4
INR > 2.2 2
VTE: venous thromboembolism
Dabbagh O, et al. Chest. 2010;137(5):1145-1149
INR: international normalized ratio
 “Auto-anticoagulation”
Barclay SM, et al. Pharmacotherapy 2013.
To determine whether pharmacologic prophylaxis for VTE was associated with a
Purpose decrease in the incidence of VTE or an increased incidence of bleeding in patients
with chronic liver disease
• Retrospective cohort analysis
Design • VTE includes DVT, PE, and PVT
No VTE Prophylaxis VTE Prophylaxis p Value
Primary (n=1189) (n=392)
Outcomes VTE 21 (1.8%) 2 (0.5%) 0.05
Bleed 123 (10.3%) 8 (2.0%) <0.001
Odds Ratio 95% Confidence Interval
Active malignancy 8.76 2.56-29.58
Risk Factors Trauma/surgery 10.29 1.18-89.51
History of VTE 26.48 6.93-101.16
VTE prophylaxis 0.34 0.042-0.88
VTE: venous thromboembolism, DVT: deep vein thrombosis
PE: pulmonary embolism, PVT: portal vein thrombosis
 “Auto-anticoagulation”
VTE Incidence Stratified by Child-Pugh Class VTE Incidence Stratified by INR
3.0% 3.0%

2.5% 2.5%

2.0% 2.0%

Incidence
Incidence

1.5% 1.5%

1.0% 1.0%

0.5% 0.5%

0.0% 0.0%
Child-Pugh A Child-Pugh B Child-Pugh C <1 1.1-1.3 1.4-1.5 > 1.5
INR Quartiles

VTE prophylaxis (n=392)

No VTE prophylaxis (n=1189)

VTE: venous thromboembolism

Barclay SM, et al. Pharmacotherapy. 2013;33(4):375-382
INR: international normalized ratio
 What factors would you take into
consideration to advocate for DVT
prophylaxis in a patient with chronic
liver disease?
Your patient with PMH of end-stage liver disease
is planned for a bedside procedure (i.e.,
paracentesis) but patient has elevated INR of 3.

How many of you would advocate for

periprocedural correction of coagulopathy?
 Bleeding Risk Stratification
Low Risk High Risk
Paracentesis/Thoracentesis Biliary intervention (cholecystostomy or
percutaneous biliary drain)
Drainage catheter exchange Liver biopsy (percutaneous or
transjugular)
PICC line placement Central nervous system procedures
CVC placement/removal TIPS
Diagnostic Endoscopic retrograde
esophagogastroduodenoscopy cholangiopancreatography with
sphincterotomy
Variceal band ligation
*Not an inclusive list. See guidance document for a complete list of bleeding risk stratification of common procedures
High risk = if major bleeding is expected in >1.5% of procedures or if even minor bleeding is likely to result in permanent
organ damage or death

Northup PG, et al. Hepatology. 2021;73(1):366-413

 Bleeding Risk Evidence
Low Bleeding Risk High Bleeding Risk

Paracentesis Endoscopic Liver biopsy

1100 cases in 628 variceal ligation 2740 cases in
patients (EVL) advanced fibrosis
- 513 with cirrhosis 150 patients with or well-
- 292 with INR > 2 cirrhosis compensated
- 598 with - Elevated INR and cirrhosis
Plt < 50,000/μL thrombocytopenia - 0.6% bleeding
were not predictive rate
of post-EVL - No bleeding-
bleeding related deaths

INR: international normalized ratio

Northup PG, et al. Hepatology. 2021;73(1):366-413
CTP: Child-Turcotte-Pugh
 Guideline Comparison

Organization Platelet Count INR Fibrinogen Level

(x 1000/μL) (mg/dL)
American Association for the Study No routine No routine No routine
of Liver Diseases, 2020 preprocedural preprocedural preprocedural
correction correction correction
American Gastroenterological > 50 No correction > 120
Association, 2019
American College of > 50 No correction > 120-150
Gastroenterology, 2020
Society of Interventional Radiology, > 30 < 2.5* > 100
2019
*Correction of INR using vitamin K, not fresh frozen plasma, is recommended by this society

INR: international normalized ratio Northup PG, et al. Hepatology. 2021;73(1):366-413

 Phytonadione
Drug Class Fat soluble vitamin K
MOA Promotes liver synthesis of vitamin K-dependent
clotting factors
Dosing 10 mg per dose oral or IV
Clinical Pearls IV administration limit is 1 mg/minute as it carries
the risk of anaphylaxis

For vitamin-K deficient patients, AGA recommends a dose of

vitamin K 10 mg administered either orally or IV.

Absence of an improvement in INR after a 10 mg dose of vitamin

K indicates that repeated administration is unlikely to have
therapeutic benefit.

IV: intravenous Phytonadione. In: Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc; Updated June 27, 2023. Accessed August 16, 2023
AGA: American Gastroenterological Association O'Leary JG, et al. Gastroenterology. 2019;157(1):34-43.e1
 Chapman AR, et al.
Evaluation of Response to High-Dose Intravenous Vitamin K Administration
To characterize patient factors associated with response to repeated dosing of
Purpose vitamin K for coagulopathy secondary to liver disease

Design Retrospective case-control study at Cleveland Clinic Health System

• With coagulopathy (baseline INR > 1.5)
Patient
• Have received 3 consecutive days of 10 mg IV vitamin K
Characteristics Of 497 total patients, 455 patients (91.5%) had underlying cirrhosis
Primary Outcome Secondary Outcomes
Change in INR over time with 1. Patient factors associated with response to
subsequent vitamin K doses first dose
Outcomes • Responders = INR decrease by 30% or
below 1.5 after first dose
2. Adverse effects of vitamin K

Chapman AR, et al. Ann Pharmacother. 2023;0(0) [published online ahead of print]
 Chapman AR, et al. (cont.)
Cirrhosis

Change in INR 151

+4.06% -16.5% Responder
-27% (33.2%)
2 304 Nonresponder
(66.8%)

1.5
INR

1
Predictors of response to IV vitamin K:
0.5
Low weight

0
Baseline Day 1 Day 2 Day 3 Absence of
Overall (n = 497) Responder (n = 182) Nonresponder (n = 315) cirrhosis

Lower serum
bilirubin

Chapman AR, et al. Ann Pharmacother. 2023;0(0) [published online ahead of print]
 Risk vs Benefit
Phytonadione Fresh frozen plasma
Ingredient Vitamin K All coagulation factors (except platelets)
Onset Oral: 6-10 hours 30-60 minutes
IV: 1-2 hours
Peak Effect Oral: 24-48 hours 2-6 hours
IV: 12-14 hours
Risks Anaphylaxis risk with • Risk of disease transmission
intravenous • Immunologic complications
administration • Transfusion-related acute lung injury
• Transfusion-associated circulatory
overload (TACO)

Phytonadione. In: Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc; Updated June 27, 2023. Accessed August 16, 2023
O'Leary JG, et al. Gastroenterology. 2019;157(1):34-43.e1
Summary

INR values have not been found to predict bleeding risk or VTE
incidence in patients with cirrhosis

Independent risk factors for VTE development in cirrhosis

are similar known risk factors for VTE

First dose of IV vitamin K provides most benefits to reverse

coagulopathy in vitamin K-deficient patients

Most low-bleeding risk procedures can be safely performed

without delay from correcting abnormal INR
In your day-to-day practice,
do you consider cefepime as
a drug with risk for
neurotoxicity?
 Distribution into the CNS
Normally, ~10% of
serum cefepime
crosses the BBB.

In patients with
renal impairment or
decreased protein
binding, up to 45%
of serum cefepime
concentrations can
cross the BBB.
Lexicomp Online ©2022. Wolters Kluwer.
CNS: central nervous system; BBB: blood brain barrier Payne L, et al. Critical Care. 2017.
 Breakdown of Neurologic ADRs
Cefepime’s neurologic ADRs have an overall incidence of <1%

Most Common
Less Common
AMS (92-100%)
Rare
Reduced Non-convulsive
consciousness (47%) seizure (27.7%) Psychosis,
Myoclonus (37-42%) Agitation, delirium, hallucinations (8%)
encephalopathy (11- Convulsive seizure
15%) (11-13%)
Aphasia (11-15%)
Focal deficit (3%)
**Percentages are taken out of patients experiencing neurotoxicity on cefepime, not all patients on cefepime
Khan A, et al. CHEST. 2020.
AMS: altered mental status; ADR: adverse drug reaction
Maan G, et al. J Antimicrob Chemother. 2022.
Risk Factors for Developing
Cefepime-Induced Neurotoxicity

Renal dysfunction

Age ≥ 65 years

Neurological comorbidities

Higher cefepime doses and troughs

Payne L, et al. Critical Care. 2017.

 Neurotoxicity Based on
Cefepime Dose
Khan A, et al. CHEST. 2020.
To determine the effect of cefepime dosage on the development of cefepime-
Purpose associated neurotoxicity (AN) in critically ill adults with renal dysfunction
• Retrospective, observational cohort study
• Subgroup analysis performed to assess moderate vs. severe renal dysfunction
Design Moderate (CrCl 30-60 ml/min) Severe (CrCl 11-29 ml/min)
• High Dose: ≥ 8 g in 48 h • High Dose: ≥ 4 g in 48 h
• Low Dose: <8 g in 48 h • Low Dose: <4 g in 48 h
Primary Outcome Secondary Outcomes
• CAN development stratified by • Hospital mortality
Outcomes cefepime dosage • ICU and hospital LOS
• Time to CAN development & resolution

CrCl: creatinine clearance, LOS: length of stay

 Results
Low Dose High Dose
Outcome OR 95% CI p-value
(n=108) (n=92)
Change in neurological status, No
42 (42) 29 (32) 0.64 0.36-1.15 0.14
(%)
CAN, No. (%) 4 (4) 9 (10) 2.82 0.84-9.48 0.093
Moderate renal insufficiency,
No. (%)
4 (5) 4 (7) 1.42 0.34-5.92 0.72
Severe renal insufficiency, No.
(%)
0 (0) 5 (16) - - 0.064

Hospital LOS, median (IQR), d 12.3 (7.2-24.6) 18.2 (7-32.3) - - 0.04

Time to CAN Development,
3 (1.2-4.3) 4.4 (1.8-5.6) - - 0.33
median (IQR), d
Time to CAN Resolution, median
7 (2.3-9.2) 4 (2.5-9) - - 0.82
(IQR), d

CAN: cefepime-associated neurotoxicity; LOS: length of stay; d: days

 Who receives “high-dose”
cefepime at EH?
CrCl 10-29 CrCl 30-49 CrCl 50-60
ml/min ml/min ml/min
• None • CNS infections • All patients
• All patients • Neutropenic EXCEPT
would be fever weight <120
considered • Patients ≥ 120 kg in urologic
“low-dose” kg in non- indications
urologic
infections

EH: Eskenazi Health; CrCl: creatinine clearance, LOS: length of stay

 At EH, who is at higher risk?

CrCl 10-29 CrCl 30-49 CrCl 50-60

ml/min ml/min ml/min
• None • CNS infections • All patients
• All patients • Neutropenic EXCEPT
would be fever weight <120
considered • Patients ≥ 120 kg in urologic
“low-dose” kg in non- indications
urologic
infections

EH: Eskenazi Health; CrCl: creatinine clearance, LOS: length of stay

 Cefepime Pharmacokinetics
Studies
Citation Finding
Huwyler, et. al. Clin Troughs > 20 mg/L had a 5-fold higher risk for neurotoxicity (OR
Microbiol Infect. 2017. 5.05, 95% CI 1.3-19.8)

Chapuis, et. al. Crit Care. 2/21 ICU patients with neurotoxicity; found to have cefepime
2010. trough of 20-30 mg/L

Lamoth, et. al. Antimicrob Median trough of 28 was associated with neurotoxicity versus 7.2
Agents Chemother. 2010. mg/L in those without neurotoxicity (p<0.0001)

Lau, et. al. J Antimicrob Cefepime trough of 36 mg/L was associated with higher
Chemother. 2020. neurotoxicity risk

Boschung-Pasquier, et. al. No neurotoxicity with cefepime trough <7.7 mg/L

Clin Microbiol Infect. 2020. All patients had neurotoxicity with cefepime troughs ≥ 38.1 mg/L

Maan G, et al. J Antimicrob Chemother. 2022.

 Applications of Cefepime PK
at Eskenazi Health

• May be beneficial in ruling

• Levels are not routinely out neurotoxicity
Do at
drawn weEskenazi
monitor • Beneficial
Should we for monitor
therapeutic
• Cefepime
cefepime troughs are
levels? efficacy in renal
cefepime levels?
difficult to predict insufficiency, altered
kinetics (i.e. burn), obesity

PK: pharmacokinetics
 Alternatives to Cefepime

• Significant concern; incidence <1%

Meropenem • Lowest neurotoxicity concern compared to
cefepime and piperacillin/tazobactam

• Significant concern; incidence <1% except

Piperacillin/ insomnia (7%)
tazobactam • 2nd highest neurotoxicity risk between
cefepime and meropenem

Ciprofloxacin • High risk; BBW for CNS effects

or Levofloxacin • Reserve as last line option

Haddad N, et al. Neurocrit Care. 2022.

BBW: black box warning Lexicomp Online ©2022. Wolters Kluwer.
What factors would you take
into consideration if your
team suspects neurotoxicity
from cefepime?
 Summary

High Doses at EH:

Higher risk groups:
Cefepime has a risk of CNS, neutropenic fever,
renal impairment, high
neurotoxicity. ≥ 120 kg, CrCl 50-60
dose
ml/min

May be beneficial to Alternative options

Neurotoxicity onset at monitor cefepime include meropenem
~ 4 days levels and piperacillin/
tazobactam.
 Intrarenal Effects of ACEI/ARBs

Normal Angiotensin II ACEI/ARBs

Angiotensin II Angiotensin II

ACEI/ARBs

Acute increase in SCr < 30%

ACEI/ARBs: angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers

Bakris GL, Weir MR. Arch Intern Med. 2000;160(5):685-693
 KDIGO Criteria

Serum creatinine (SCr) Urine output

Stage 1 • 1.5-1.9 times from baseline OR • < 0.5 mL/kg/h for 6-12
• > 0.3 mg/dL absolute increase in hours
Stage 2 • > 2.0-2.9 times from baseline • < 0.5 mL/kg/h for > 12
hours
Stage 3 • SCr > 4.0 mg/dL OR • < 0.3 mL/kg/h for > 24
• Initiation of renal replacement therapy OR hours OR
• Patients < 18 years, decrease in eGFR to • Anuria for > 12 hours
< 35 mL/min per 1.73 m2

KDIGO: Kidney Disease Improving Global Outcomes

Khwaja A. Nephron Clin Pract. 2012;120(4):c179-c184.
SCr: serum creatinine, eGFR: estimated glomerular filtration rate
 How many of you would hold
home ACEI/ARBs in the patient
who developed an AKI during
hospital stay?
 Hospital-acquired AKI

Alabdan N, et al. Am J Med Sci 2017.

To evaluate patient characteristics and interventions associated with the
Purpose
development of AKI in patients who continued ACEI/ARBs during hospitalization
• Retrospective chart review
• Inclusion: stable kidney function and had restarted on home ACEI/ARBs within
Design
24 hours
• AKI staging based on SCr and urine output per KDIGO criteria
AKI (n=92) Non-AKI (n=92) p-value
Baseline Mean SCr on admission, mg/dL 1.2 + 0.4 1 + 0.3 < 0.0001
Characteristics CKD 40% 14% < 0.0001
Loop diuretics 52% 36% 0.02

AKI: acute kidney injury, ACEI/ARBs: angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers

KDIGO: Kidney Disease Improving Global Outcomes, SCr: serum creatinine, CKD: chronic kidney disease
 Risk Factors
Mean time to AKI:
Chronic kidney 6 + 4 days
Hypotension
disease
Mean duration of AKI:
6 + 5 days
Surgical Required ICU
procedure admission
62/92 patients (67%)
returned to baseline SCr

Loop diuretics 8/92 patients (9%) required

renal replacement therapy

AKI: acute kidney injury, ACEI/ARBs: angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers

SCr: serum creatinine, CKD: chronic kidney disease
 Mortality Benefits
Zhu X, et al. Front Pharmacol 2022.
To determine whether exposure to ACEI/ARB therapy during AKI reduces mortality
Purpose
in critically ill patients
• Retrospective observational study
Design • Propensity-matched patients with and without ACEI/ARB
• AKI staging based on SCr and urine output per KDIGO criteria
ACEI/ARBs No ACEI/ARBs
Adjusted HR
(n=3179) (n=3179)

Primary ICU mortality 114 275 0.34 (95% CI 0.27-0.42)

Outcomes In-hospital mortality 198 406 0.47 (95% CI 0.39-0.56)
30-day mortality 202 411 0.47 (95% CI 0.40-0.56)
180-day mortality 263 469 0.53 (95% CI 0.45-0.62)
Secondary Hyperkalemia 191 172 1.21 (95% CI 0.96-1.51)
Outcomes Acute kidney disease 637 462 1.81 (95% CI 1.55-2.12)

AKI: acute kidney injury, ACEI/ARBs: angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers

KDIGO: Kidney Disease Improving Global Outcomes, SCr: serum creatinine
Do you consider vancomycin
+ piperacillin/tazobactam as
a cause of AKI?
 Piperacillin/Tazobactam +
Vancomycin Overview
Piperacillin/tazobactam Vancomycin

Reported Increased SCr, increased BUN, AKI,

Nephrotoxicity (5%), AKI
Incidence of nephrotoxicity, interstitial nephritis
(frequency not defined)
AKI (frequency not defined)

• Most likely due to acute tubular necrosis from direct oxidative stress
Mechanism on proximal tubules
of AKI • May also be associated with interstitial nephritis from an
immunologically mediated process

• Vancomycin exposure • Troughs ≥ 15 mg/L

Risk Factors • Age >65, renal impairment, • AUC 650-1300 mg-h/L
critically ill, obesity • Doses ≥ 4 g/day

SCr: serum creatinine; BUN: blood urea nitrogen; AKI: acute kidney injury; AUC: area under curve Lexicomp Online ©2022. Wolters Kluwer.
 Cefepime vs. Piperacillin/
Tazobactam (PTZ)
AKI
VC VPTZ
Severity
RIFLE Criteria:
• VPTZ: 81 (29%) Risk 12 (4.3) 40 (14.3)

RIFLE Criteria
• VC: 31 (11.1%)
• HR 4.0; 95% CI 2.6-6.2; p<0.0001 Injury 8 (2.9) 21 (7.5)

Failure 11 (3.9) 20 (7.2)

AKIN Criteria: Stage 1 20 (7.2) 48 (17.2)

AKIN Criteria
• VPTZ: 89 (32%)
• VC: 39 (14%) Stage 2 8 (2.9) 21 (7.5%)
• HR 3.5; 95% CI 2.3-5.2; p<0.0001
Stage 3 11 (3.9) 20 (7.2)
**No. (%)

VPTZ: vancomycin + piperacillin/tazobactam; VC: vancomycin + cefepime; RIFLE: Risk, Injury,

Failure, Loss of kidney function, End stage renal disease; AKIN: Acute Kidney Injury Network Navalkele B, et. al. Clin Infect Dis. 2017.
 Ceftolozane/Tazobactam
(CTZ) vs. PTZ
AKI VCTZ VPTZ
Incidence of AKI was Severity (n=90) (n=284)
significantly higher in VPTZ Risk 7 (7.7) 20 (7)

RIFLE Criteria
group only when using AKIN
Injury 1 (3.3) 15 (5.3)
criteria.
Failure 3 (3.3) 18 (6.3)

Vancomycin AUCs were Stage 1 7 (7.7) 38 (13.4)

AKIN Criteria
higher in the VPTZ group
Stage 2 1 (1.1) 16 (5.6)
(not a significant finding)
Stage 3 3 (3.3) 16 (5.6)
**No. (%)

VCTZ: vancomycin + ceftolozane/tazobactam Alosaimy S, et. al. Clin Infect Dis. 2023.
 Pseudo-AKI?
Miano T, et al. Intensive Care Med 2022.
• Many studies associate VPTZ with increased AKI risk, but it is unclear
Background
whether this is true AKI or pseudotoxicity based creatinine secretion
• Sub-study of the MESSI project, an ongoing prospective
observational study enrolling ICU patients with severe sepsis or
septic shock
Design
• Compared patients on VPTZ vs. VC
• Multiple kidney function biomarkers (SCr, cystatin C, and BUN) were
considered
Primary Outcomes Secondary Outcomes
• SCr and Cys-C at baseline and • BUN at baseline and at 48-72
Outcomes
at 48-72 hours after hours after antibiotic initiation
antibiotic initiation • KDIGO criteria-defined AKI

MESSI: Molecular Epidemiology of SepsiS in the ICU; Cys-C: cystatin C

 Results

Lower Cys-C in VPTZ group than

Significantly higher mean SCr
Serum VC at Day 2
and higher frequency of SCr Cystatin C
Creatinine
increases ≥ 50% at Day 2 No significant difference in Cys-
C increases ≥ 50%

No significant difference in VPTZ-associated

Dialysis AKIand was not
mean BUN or BUN
BUN increases ≥ associated with higher HD, RRT,
50% at Day 2 or Mortality
mortality rates.

SCr: serum creatinine; Cys-C: Cystatin C; BUN: blood urea nitrogen; HD: hemodialysis; RRT: renal replacement therapy Miano T, et al. Intensive Care Med. 2022.
 What will you take into
consideration if your team
considers vancomycin +
piperacillin/tazobactam as a
cause of AKI?
Summary

Many studies show significantly increased AKI incidence with

the combination of vancomycin + piperacillin/tazobactam

Many studies’ outcomes are heavily driven by mild AKI

Not enough strong data to completely rule out this ADR

Rule out all other causes of AKI before changing antibiotic

therapy if the patient requires broad-spectrum coverage
Season One Recap
Elevated INR in Cirrhosis
• Common VTE risk factors still apply to patients with cirrhosis
• INR does not predict bleeding risk in patients with cirrhosis and most
procedures can be safely performed without correction of abnormal INR

Cefepime and Neurotoxicity

• Neurotoxicity is not as common as some may assume
• Risk factors include high dose / trough and renal dysfunction

AKI-Related Myths
• ACEI/ARBs increases SCr and may induce AKI with/without renal recovery
• Vancomycin + piperacillin/tazobactam increases SCr but did not show
increased incidence of Cys-C-defined AKI, HD, or mortality
 Vivian Phyo, PharmD Lauren Schmidt, PharmD
PGY2 Internal Medicine Resident PGY2 Critical Care Resident
Wintwar.phyo@eskenazihealth.edu Lauren.schmidt@eskenazihealth.edu