Download Pharmacologic Therapy in Heart Disease

Pharmacologic Therapy in Heart
Disease
Rafael Mena MD
December 3rd 2010
Cardiac Medications of Interest in
NICU
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Inotropes and vasopressors
Prostaglandins
Antihypertensives
Diuretics context CHF
MAP
• Cardiac Output X SVR
Inotropes and Vasopressors
• Epinephrine
• Milrinone
• Hydrocortisone
Hypotension
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Difficult to define and measure
MAP and Gestational age
Consensus end organ damage not beneficial
? Treatment decreases mortality and adverse
long-term outcomes
Current definitions of hypotension do not
predict abnormal HUS findings in preemies
• Measured Hypotension 84 infants <30wks via
UAC’s in first 72 hours
• 3 definitions of hypotension
• HUS lesions were not predicted by any of the
definitions or MAP variability
• Blood pressure management alone might not
prevent injury
Limperopouloset al Pediatrics November 2007
Early systemic hypotension and vasopressors in
LBW: Impact Neurodevelopment
• Prospective study evaluating effect on
neurodevelopment with inotropes in LBWI
• 130 infants. Half treated with Epinephrine and
Dopamine. The rest control group
• Outcome measures: Cranial US and
neurodevelopment at 2 years
• No differences between groups in
neurodevelopment and developmental delay
• Inotropes seem be safe
Pellicer et al, Pediatrics May 2009
Epinephrine and others
Courtesy Beth Ann Johnson
G proteins
Epinephrine vs. Dopamine in LBWI
• Prospective RCT in 60 newborns <1500g.
Dopamine dose 2-10ug/kg. Epinephrine 0.1 to
0.5 ug/kg
• Similar effectiveness in raising BP
• Epinephrine more hyperglycemia and increase
lactate (Beta stimulation not hypoperfusion)
• No difference PDA,BPD,NEC,ROP
• Epinephrine could be used first line
Valverde et al, Pediatrics May 2006
Previous studies
• Have reported a decrease in cardiac
performance with dopamine
• Higher doses,>10 ug/kg might lead to increase
in SVR and leading to myocardial depression
• Different Dopamine studies prefer 2-10 ug/kg
dose in preterm infants with impaired CV
function
Milrinone
• Inhibitor of phosphodiesterase III (cardiac and
vascular tissues)
• In cardiac muscle,  CAMP, potentiates
Calcium delivery (Inotrope)
• Vascular smooth muscle, CAMP produces
relaxation( decrease SVR)
Afterload Reducer
• LV afterload reduction due to decrease in total
peripheral resistance and a resulting increase
in CO
• Decreases PVR resulting in biventricular
afterload reduction
Side effects
• Hypotension
• Thrombocytopenia
• Arrythmias
Efficacy and safety of milrinone in preventing
LCOS in infants and children after corrective
surgery for CHD
• PRIMACORP study
• Prophylactic Intravenous Use of Milrinone
After Cardiac Operation in Pediatrics
• Circulation 2003
PRIMACORP study
• Evaluate the safety and efficacy of
prophylactic Milrinone in pediatric patients at
high risk of developing LOCS
• Multicenter(31), randomized, double blind,
placebo controlled
Results
Hoffman et al, Circulation 2003
PRIMACORP study
• The results show a 64% relative risk reduction
in the development of LOCS with the
prophylactic use of high dose milrinone
• High dose milrinone: 75 ug/kg bolus, followed
by a 0.75 ug/kg/min infusion for 35 hrs
Milrinone improves oxygenation in
newborns with severe PPHN
• Many neonates with severe PPHN are poor
responders to NO
• 9 full term infants with severe PPHN, OI>20,
failure of INO therapy, ECHO confirmation
received Milrinone median 70 hrs
• OI marked better especially first 24 hrs
• No systemic hypotension
Mcnamara et al, Journal of Critical Care 2006
Hydrocortisone
• Preemies can have a transient adrenal
insufficiency
• Improves cardiovascular stability
• Dexamethasone impairs neurodevelopment,
does hydrocortisone?
RCT of a stress dose of Hydrocortisone for
refractory hypotension in premature infants
• Assess effectiveness of a hydrocortisone stress
dose in infants with refractory hypotension
• Prospective RCT of 48 infants with
hypotension
• 24 had Dopamine + Hydrocortisone
• 24 had Dopamine + placebo
• Stress dose hydrocortisone dose 1mg/kg every
8 hrs 5 days
Ng et al, Pediatrics 2006
Hydrocortisone for refractory
hypotension works
• Hydrocortisone group weaned vasopressor
support faster
• 2 in HC group vs. 11 infants in placebo group
required an additional vasopressor
• Preferable than Dexamethasone, but caution
• Prostaglandins
When Prostaglandins are not enough: Lesions likely
to require urgent intervention after delivery
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HLH with intact atrial septum
TGA with restrictive ASD
TAPVR with obstruction
TOF with absent pulmonary valve
Hypoplastic Left
Heart with intact
atrial septum
1) Hypoplastic ascending
aorta and aortic arch
2) Hypoplastic Left Ventricle
3) Large PDA supplying the
only source of blood flow
to the body
4) ASD allowing blood return
from the lungs to reach
single ventricle
Transposition Great
Arteries with
restrictive ASD
1) Aorta arising from the
RV(poor Oxygenated
blood body)
2) Pulmonary artery
arising from LV(well
oxygenated blood back
to lungs)
Total Anomalous Pulmonary Venous Return with
Obstruction
Supracardiac
Blood return to SVC
Infracardiac
Blood Return to Hepatic Veins, then
IVC. Most common type to be
Obstructed
Tetralogy of Fallot
with absent
Pulmonary Valve
1) Severely dilated main
and branch pulmonary
arteries causing external
bronchial compression
Examples of ductal dependent lesions
• Left sided lesions
-Coarctation of Aorta
-Critical Aortic Stenosis
• Right sided lesions
- Tricuspid/Pulmonary Atresia
• TGA
Neoreview Question
• You are reviewing the records of a 5-month-old African American female
infant in the neonatal intensive care unit. She was delivered at 36 weeks'
gestation with an antenatal diagnosis of truncus arteriosus and
interrupted aortic arch. Postnatal echocardiography confirmed the
antenatal findings and revealed ductus-dependent coronary circulation.
The infant has been receiving alprostadil infusion since birth and is
awaiting heart transplantation. She was also diagnosed to have Di
George syndrome with hypoparathyroidism and immunodeficiency, and
is receiving calcitriol, calcium glubionate, and bactrim prophylaxis. She is
receiving decongestive therapy with furosemide and aldactone. She is
also receiving metoclopramide for gastroesophageal reflux. The resident
physician reports firm swelling of both forearms without any tenderness,
erythema, fluctuation, or signs of inflammation. Complete blood count
measurement taken the same day shows normal findings for age. You
request radiography of the forearms.
Describe Figure
Hyperostosis
• Long treatment(>40 days)
• Clavicle is most frequent site
• No long term problems with bone growth
once stopped
Other complications
• Fever
• Hypotension
• Apnea
• Drugs for neonatal hypertension
Sounds familiar?
• An ex 24 wk now 37 wks old is on full feeds
and ready to go home. You are rounding and
the nurse brings to your attention that his
systolic pressures have been >110 for the past
3 days. Work up including renal labs and US,
urine Ca to creatinine ratio is normal. What
are your therapeutic choices?
Systemic hypertension in VLBW infants
with BPD
• Purpose: determine if systemic HTN occurred
in VLBW with BPD
• 73 patients in their cohort , which 41 had BPD
and 12% of them had HTN
• The hypertensive infants all had BPD and
longer hospital stay
• Infants with severe BPD risk of hypertension
Alagappan et al, Am J Perinatol 1998
Age specific percentiles of blood pressure
measurement (n=13,000 infants)
Age in months
Systolic BP’s 95%
Systolic BP’s 50%
1
108
85
2
108
85
3
110
90
4
110
90
Report of the Second Task Force of Blood Pressure Control in Children
Important tests in Neonatal
Hypertension
• Renal panel
• Calcium
• Renal US with Doppler
Useful Oral Agents
Drug
Class
Dose
Comments
Captopril
ACE inhbitor
From 0.01mg/kg up Common
to 6mg/kg
Monitor K and
creatinine
Amlodipine
Channel blocker
From 0.1 to 0.6
mg/kg
Being used more
often
Hydrochlorothiazide
Thiazide
20-40mg/kg/day
Monitor
electrolytes
Flynn, Pediatric Nephrology 2000
Mechanism of Action
Drug
Mechanism of Action
Ace Inhibitors
Blocks angiotensin converting enzyme,
thus decrease in Angiotensin 2 leading
to vasodilation and less salt retention
Calcium Channel Blockers
Relaxation of vascular smooth muscle
Thiazide diuretics
Inhibits Na in the distal tubule,
natriuresis
• Diuretics in context of Heart Failure
Recent UC case
3 wk old former 37 weeker with Trisomy 21
with known AV canal. Initially taking almost
80% PO. As weeks progressed, she got more
tachypneic, was barely taking PO and had
hepatomegaly on physical exam. Started on
Lasix, Aldactone and afterwards in Captopril.
Diuretics
• Lasix works in loop of Henle and is has strong
Natriuresis
• Aldactone weak diuretic and potassium
sparing
• Alleviate pulmonary edema and
overcirculation seen in heart failure
Spironolactone therapy in infants with
CHF secondary to CHD
• Studied the efficacy of spironolactone on
heart failure in 21 patients under 1 year
• All received Digoxin and Chlorothiazide
• 10 without vs. 11 with Aldactone
• Improved hepatomegaly and reduction in
weight
• Addition of Aldactone can improve symptoms
in heart failure patients
Hobbins, Archive of Disease in Childhood 1981
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• Thanks
References
1)
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5)
Pellicer et al,Early systemic hypotension and vasopressor support
in LBWI: Impact on Neurodevelopment, Pediatrics 2009 123:1369
Limperoupoulos et al, Current definitions of hypotension do not
predict abnormal cranial US finding in preterm infants, Pediatrics
Nov 2007;120, 966-977
Valverde et al, Dopamine vs. Epinephrine for cardiovascular
support in LBWI: Analysis of systemics effect and neonatal clinical
outcomes, Pediatrics 2007;117, 1213-1222
Hoffman et al, Efficacy and Safety of Milrinone in preventing low
cardiac output syndrome in infants and children after corrective
surgery for congenital heart disease, Circulation 2003;107:9961002
Mcnamara et al, Milrinone improves oxygenation in neonates with
severe persistent pulmonary hypertension of the newborn,
Journal of Critical Care 2006;21:217-223
5) Ng et al, A double blind Randomized controlled study of a
dose of Hydrocortisone for Rescue treatment of refractory
hypotension in preterm infants, Pediatrics:110, February
2006
6) Alagappan et al, Systemic hypertension in VLBW with BPD:
incidence and risk factors. Am J Perinatol Jan 1998;15(1)
3-8
7) Flynn, Neonatal Hypertension : Diagnosis and
Management, Pediatric Nephrology 2000 14:332-341
8) Hobbins et al, Spironolactone therapy in infants with
congestive heart failure secondary to congenital heart
disease, Archives of Disease in Childhood, 1981, 56:934-938