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Pharmacologic Therapy in Heart Disease

Pharmacologic Therapy in Heart Disease

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Pharmacologic Therapy in Heart Disease

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  1. Pharmacologic Therapy in Heart Disease Rafael Mena MD December 3rd 2010

  2. Cardiac Medications of Interest in NICU • Inotropes and vasopressors • Prostaglandins • Antihypertensives • Diuretics context CHF

  3. MAP • Cardiac Output X SVR

  4. Inotropes and Vasopressors • Epinephrine • Milrinone • Hydrocortisone

  5. Hypotension • Difficult to define and measure • MAP and Gestational age • Consensus end organ damage not beneficial • ? Treatment decreases mortality and adverse long-term outcomes

  6. 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

  7. 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

  8. Epinephrine and others Courtesy Beth Ann Johnson

  9. G proteins

  10. 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

  11. 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

  12. 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)

  13. 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

  14. Side effects • Hypotension • Thrombocytopenia • Arrythmias

  15. 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

  16. 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

  17. Results Hoffman et al, Circulation 2003

  18. 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

  19. 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

  20. Hydrocortisone • Preemies can have a transient adrenal insufficiency • Improves cardiovascular stability • Dexamethasone impairs neurodevelopment, does hydrocortisone?

  21. 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

  22. 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

  23. Prostaglandins

  24. When Prostaglandins are not enough: Lesions likely to require urgent intervention after delivery • HLH with intact atrial septum • TGA with restrictive ASD • TAPVR with obstruction • TOF with absent pulmonary valve

  25. Hypoplastic Left Heart with intact atrial septum Hypoplastic ascending aorta and aortic arch Hypoplastic Left Ventricle Large PDA supplying the only source of blood flow to the body ASD allowing blood return from the lungs to reach single ventricle

  26. Transposition Great Arteries with restrictive ASD Aorta arising from the RV(poor Oxygenated blood body) Pulmonary artery arising from LV(well oxygenated blood back to lungs)

  27. Total Anomalous Pulmonary Venous Return with Obstruction Supracardiac Infracardiac Blood return to SVC Blood Return to Hepatic Veins, then IVC. Most common type to be Obstructed

  28. Tetralogy of Fallot with absent Pulmonary Valve 1) Severely dilated main and branch pulmonary arteries causing external bronchial compression

  29. Examples of ductal dependent lesions • Left sided lesions -Coarctation of Aorta -Critical Aortic Stenosis • Right sided lesions • Tricuspid/Pulmonary Atresia • TGA

  30. 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 truncusarteriosus 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.

  31. Describe Figure

  32. Hyperostosis • Long treatment(>40 days) • Clavicle is most frequent site • No long term problems with bone growth once stopped

  33. Other complications • Fever • Hypotension • Apnea

  34. Drugs for neonatal hypertension

  35. 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?

  36. 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

  37. Age specific percentiles of blood pressure measurement (n=13,000 infants) Report of the Second Task Force of Blood Pressure Control in Children

  38. Important tests in Neonatal Hypertension • Renal panel • Calcium • Renal US with Doppler

  39. Useful Oral Agents Flynn, Pediatric Nephrology 2000

  40. Mechanism of Action

  41. Diuretics in context of Heart Failure

  42. 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.

  43. 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

  44. 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

  45. ????????????????? • Thanks

  46. References • 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;107:996-1002 • Mcnamara et al, Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn, Journal of Critical Care 2006;21:217-223

  47. 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