Transcript Mythbusters

CICU Pharmacotherapy
Myth-Busters
Jaclyn Sawyer, PharmD
Clinical Pharmacy Specialist,
Cardiology
Division of Pharmacy
Cincinnati Children's Hospital
Medical Center
David Nelson, MD, PhD
Medical Director,
Cardiovascular Intensive Care Unit
Division of Cardiology
Cincinnati Children's Hospital
Medical Center
MYTHS
• CALCIUM INFUSIONS ARE NOT AN EFFECTIVE
INOTROPE
• INTRAVENOUS POTASSIUM REPLACEMENT IS
MORE EFFECTIVE THAN ENTERAL
POTASSIUM REPLACEMENT
• ECONOMIC MYTHS – OLDER DRUGS ARE
CHEAPER – COST REALITY CHECK
MYTH:
CALCIUM INFUSIONS ARE NOT AN
EFFECTIVE INOTROPE
Cardiomyocyte Calcium Concentration
Contractility and Relaxation
• Mature mammalian myocytes =>
Sarcoplasmic reticulum
• Sarcoplasmic reticulum is
immature in neonatal
hearts
Na/Ca Exchanger
– Structurally and functionally
under-developed
Neonatal Hearts Demonstrate
Markedly Increased Ca+2
Sensitivity
L-type Ca Channel
Calcium Chloride
• Unique inotrope
– Improves myocardial function with minimal
change in heart rate minimizing myocardial
oxygen demand => Improved cardiac output in
patients with myocardial dysfunction with no
increase in heart rate
• Small incidence of non-cardiac side effects
• Ongoing studies
– Prospective
– Safety
Calcium Chloride Infusions, Used as an Inotrope,
Improve the Hemodynamics of Critically Ill
Children
• Calcium Chloride
– Retrospective – CaCl for hemodynamic instability
• 2.5-15 mg/kg/hr
– May 2011-May 2012
– Efficacy at 2hrs and 6hrs
•
•
•
•
•
•
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Heart Rate
Blood Pressure
Systemic arterial O2 and mixed venous O2 – AVO2 difference
NIRS
Lactate
Urine Output
Other inotropes
– Safety
Averin K. CCHMC data awaiting publication
Calcium Chloride Infusions Improve
Cardiac Output: Baseline Characteristics
Table 1.
Characteristics
Total Population
(N = 116)
Newborn (0-30
days)
(N = 65)
Infant (1-6
months)
(N = 21)
Children (>6
months)
(N = 30)
0.87 ± 2.67
68 (59%)
5.93 ± 6.75
0.02 ± 0.02
36 (55%)
2.98 ± 0.76
0.26 ± 0.11
17 (81%)
4.57 ± 0.84
3.15 ± 4.58
15 (50%)
13.28 ± 10.1
67.25 (IQR 37.33,
130.44)
70.10 (IQR
44.93, 138.98)
71.40 (IQR
54.88, 177.37)
52.82 (IQR 27.68,
83.35)
8 (7%)
88 (76%)
20 (17%)
6
76
17
1
10
2
1
2
1
Ionized Calcium Level at
Initiation (mmol/L)
1.22 (IQR 1.09, 1.30)
1.17 (IQR 1.03,
1.30)
1.27 (IQR 1.22,
1.35)
1.23 (IQR 1.12,
1.26)
Ionized Calcium Level at
Initiation (mmol/L)
<1
1-1.45
>1.45
16 (16%)
79 (80%)
4 (4%)
12 (21%)
45 (79%)
0
2 (12%)
13 (76%)
2 (12%)
2 (8%)
21 (84%)
2 (8%)
Inotropes at Baseline
None
1 Inotropes
2 Inotropes
3 Inotropes
16 (14%)
51 (44%)
36 (31%)
13 (11%)
14 (22%)
30 (46%)
16 (25%)
5 (8%)
1 (5%)
10 (48%)
6 (29%)
4 (19%)
1 (3%)
11 (37%)
14 (47%)
4 (13%)
Demographics
Age (y)
Male
Weight (kg)
Calcium Infusion Duration
(hours)
Duration of calcium infusion
<24 hours
1-7 days
>7 days
Averin K. CCHMC data awaiting publication
LCO etiology:
• Nonsurgical: 46%
• Surgical: 53%
(CHD)
Calcium Chloride – HD Response
Heart Rate
SBP
DBP
MAP
AV Difference
Lactate
NIRS
8
64% to 69%
P<0.001
69 to 77
P<0.001
6
4
Change from Baseline
2
0
2 hours
6 hours
3.4 to 2.5
P<0.0001
-2
-4
Not significant
-6
-8
33% to 26%
P<0.001
-10
UOP increased by 29% in 8hr period after Ca initiation
Averin K. CCHMC data awaiting publication
Calcium Chloride Infusions Improve
Cardiac Output: Results
• Baseline iCa does not change effect to Ca
infusion
• HD improvements did not correlate with
higher iCa
• All age groups had improvements CO
measures
– Neonates most robust
• Single and Bi – ventricular groups both had
improvements in CO
• Surgical and non-surgical groups both had
improvements in CO
Averin K. CCHMC data awaiting publication
Calcium Infusion Considerations
• Calcium Chloride vs Calcium Gluconate
– calcium gluconate: 4.65 mEq Ca++/gram
– calcium chloride: 13.6 mEq Ca++/gram
• Safety monitoring
– Pancreatic enzymes
– Nephrolithiasis and nephrocalcinosis
• Compatibility considerations
– TPN
MYTH:
INTRAVENOUS POTASSIUM
REPLACEMENT IS MORE EFFECTIVE
THAN ENTERAL POTASSIUM
REPLACEMENT
Institute for Safe Medication Practices
classifies Intravenous Potassium as a
“High-alert” medication
ISMP - IV Potassium classified as
“high alert medication”
• Inappropriate administration can lead to
serious adverse events such as cardiac
arrest or death
• 1980s-1990s - Concentrated KCl products
removed from patient care areas
• Commercially mixed solutions used when at
all possible
• Other safety measures
– Standard concentrations
– Double checks, infusion pump guardrails, storage
precautions
•
•
Texas Children’s Hospital
Practice change: Enteral potassium supplementation preferred over IV
unless severe GI disease (NEC, surgical abdomen)
• IV:
1 mEq/kg/dose (max 40mEq/dose); 0.3mEq/mL over 1 hr
• Enteral: 1 mEq/kg/dose (max 40mEq/dose) oral or NG;
2.67mEq/mL with SW eq vol for flush
• Definitions:
– Hypokalemia: <3.5 mmol/L
– Hyperkalemia: >5.5 mmol/L
Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5
Enteral Potassium Supplementation
Patient Demographics
IV Potassium
(n=15)
Enteral Potassium
(n=25)
Intravenous and
Enteral Potassium
(n=36)
7.8 (0.1-108.2)
6.1 (0.1-72)
2.4 (0.1-143.5)
7.6 ± 4.6
7.2 ± 4.2
5.5 ± 4.7
Surgery prior to KCl (%)
14 (93.3%)
25 (100%)
36 (100%)
Mechanical Support (%)
1 (6.7%)
0 (0%)
5 (13.8%)
Urine Output (mL/kg/day)
3.9 ±1.5
3.1 ± 1.7
3.9 ± 1.2
Inotropic medication (%)
11 (78.6%)
21 (84%)
34 (94.4%)
Vasopressin (%)
4 (26.7%)
2 (7.4%)
17 (47.2%)
Diarrhea (%)
1 (6.7%)
1 (3.7%)
5 (13.8%)
Age in Months
(median and range)
Weight (kg)
• Treatment Bias
− Preference of IV in patients on vasopressin
Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5
Enteral Potassium Supplementation
Change in Serum Potassium Concentrations
Intravenous
Enteral Bolus
Bolus
Intravenous (n=15)
0.89 ± 65
−
Enteral (n=25)
−
0.65 ± 0.33
IV and Enteral (n=36)
0.85 ± 0.39
0.72 ± 0.36
Totals (n=76)
0.86 ± 0.48
0.69 ± 0.34
• Treatment Bias’
− Preference of IV in patients on vasopressin
− Preference of IV in patients with lower potassium levels
Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5
Enteral Potassium Supplementation
• Enteral and intravenous potassium
supplementation are equivalent
• Other advantages beyond safety
–
–
–
–
Reduced fluid administration
Cost $
Decreased resource utilization
Decrease frequency of IV line access
• Too small to assess safety
– No difference in potassium related ADE
Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5
Enteral Potassium Supplementation
• Enteral and intravenous potassium
supplementation are essentially equivalent
• Other advantages beyond safety
– Reduced fluid administration
• Example: 3 Kg infant, K Replacement 1mEq/Kg
– Central IV Potassium: 15 mL
» 0.2 mEq/mL (CCHMC standard concentration)
– Peripheral IV Potassium: 75 mL
» 0.04 mEq/mL (CCHMC standard concentration)
– Enteral Potassium: 1.1 mL
» 2.67mEq/mL
Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5
Enteral Potassium Supplementation
• Enteral and intravenous potassium
supplementation are essentially equivalent
• Other advantages beyond safety
–
–
–
–
Reduced fluid administration
Cost $
Decreased resource utilization
Decrease frequency of IV line access
• Too small to assess safety
– No difference in potassium related ADE
Moffett B. et al. Ped Crit Care Med 2011 Vol 12, No 5
MYTH:
ECONOMIC MYTHS - OLDER DRUGS
COST LESS MONEY
$ COST REALITY CHECK $
Older drugs cost less?
Diuretics
FDA
Approval
Dosage Form
Dose
Cost/dose for 10kg
patient (AWP)
Furosemide (Lasix)
1966
PO – tablet
1 mg/kg
$0.07
1987
PO – solution
1 mg/kg
$0.17
1982
IV
1 mg/kg
$1.64
Chlorothiazide (Diuril) – Initial FDA approval
1973
PO – tablet
10-15 mg/kg
$0.28-0.42
1962
PO – solution
10-15 mg/kg
$0.53-0.79
1958
IV
2-5 mg/kg
$14.30-35.72
1967
PO – tablet
1 mg/kg
$6.45
1967
IV
1 mg/kg
$601.61
Ethacrynic Acid (Edecrin)
Cost Reality Check
ACE Inhibitors
Captopril
Enalapril
Lisinopril
Dosage Form
Dose
Cost for 5kg
patient x 30 DAYs
(AWP)
PO – tablet
0.5mg/kg/dose TID
$27.90
PO – compound*
0.5mg/kg/dose TID
$47.90*
PO – tablet
0.1mg/kg/dose BID
$10.50
PO – Epaned
suspension
0.1mg/kg/dose BID
$68.40
PO - tablet
0.1mg/kg/dose Qday
$1.49
PO - compound*
0.1mg/kg/dose Qday
$21.49*
*Includes average compounding fee: $20
Cost Reality Check
Dexmedetomidine vs. Midazolam
Dose
Cost for 10kg
patient (AWP)
X 24 hrs
Midazolam
(Versed)
0.1 mg/kg/hr
$6.77
Dexmedetomidine
(Precedex)
0.5 mcg/kg/hr $39.99
Cost Reality Check
• The Affordable Care Act and Accountable
Care Organizations
Reduce expenditures and preserve or
improve the quality of care
Summary – Myths-Busted!?
• Calcium chloride infusions are effective in
improving hemodynamics in patients with
LCOS, with a low incidence of non-cardiac
side effects and a trend towards a decrease
in heart rate
• Efficacy of enteral potassium is equivalent to
that of intravenous potassium for potassium
replacement in pediatric patients in the CICU
• Due to the Affordable Care Act, costs of
medications will become much more relevant
to clinicians and Health Care Administrators
Thank you!
Are there other Pharmacy-related
myths to bust at your institution?
Jaclyn Sawyer, PharmD
Clinical Pharmacy Specialist,
Cardiology
Division of Pharmacy
Cincinnati Children's Hospital
Medical Center
David Nelson, MD, PhD
Medical Director,
Cardiovascular Intensive Care Unit
Division of Cardiology
Cincinnati Children's Hospital
Medical Center
FINAL MYTH:
PHYSICIANS AND NURSE PRACTITIONERS
HAVE ADEQUATE TRAINING IN
PHARMACOLOGY AND DO NOT NEED
CLINICAL PHARMACISTS (PHARM.D.) TO
PROVIDE OPTIMAL CARE.