Uterotonics and Tocolytics in Medical Disorders How Safe are They?

1. Uterotonics and Tocolytics in Medical DisordersHow Safe are They? Nuzhat Aziz Hyderabad, INDIA www.fernandezhospital.com

2. Tocolyticsare drugs used to stop Uterine contractions Uterotonics to INDUCE / INCREASE uterine contractions

3. Why do we use them? • Tocolytics • Stop preterm labour for 48 hours • For Corticosteroid effect, in-utero transfer • In utero resuscitation, ECV • Uterotonics • Induction of uterine contractions • Augmentation of labour • To prevent / treat PPH

4. Why do Obstetricians use these? • Tocolytics • For in utero resuscitation • For external cephalic version • Difficult delivery To improve fetal survival • Uterotonics • Miscarriage Important - maternal survival

5. Why should we have this session? • Medical disorders complicating pregnancy • Altered hemodynamics • May not withstand changes • Effects of smooth muscle • Bronchospasm • Patient safety measure • Effects of uterotonics / tocolytics

6. Smooth Muscles We want to either relax or contract the uterine muscle

7. Smooth Muscles Other parts of the body We get GI disturbances Affects heart contractility Bronchial muscles

8. Smooth Muscles Other parts of the body

9. What is the recommended drug?

10. Very Important to Remember They are of benefit only for short time tocolysis No LONG Term Therapy Tocolytic treatment for the management of preterm labour: a systematic review. Tan et al. Singapore Med J 2006; 47(5) : 364

11. Why are we worried about using them in Medical Disorders ?

12. Beta-mimetics DrugsTerbutalineHemodynamic Changes Myocardial Fatigue Myocardial O2 demand Heart Rate Vascular Resistance

13. Beta-mimeticsContraindications • Cardiac disease • Hyperthyroidism • Chorioamnionitis • Maternal tachycardia • Sepsis

14. Beta-mimetics DrugsLactic Acidosis • Glycogenolysis ↑ • hyperglycemia • Lactic acid production ↑ • → metabolic acidosis • Hypokalemia Lactic Acidosis: Recognition, Kinetics, and Associated Prognosis. Crit Care Clin 26 (2010) 255–283

15. Beta-mimeticsContraindications • Cardiac disease • Hyperthyroidism • Chorioamnionitis • Maternal tachycardia • Sepsis • Poorly controlled diabetes

16. Pulmonary Edema, Maternal DeathsBeta-mimetics • Incidence of pulmonary edema – 4% • Non cardiogenic • Multiple tocolytics • Fluid overload • Multifactorial

17. Predisposing Risk Factors for Pulmonary Edema • Heart disease • Pregnancy induced HTN • Chorio-amnionitis • Sepsis, Infections Betamimetics + Corticosteroids + IV fluids

18. TerbutalineNot for prolonged treatment / No Oral use

19. Oral Nifedipine • Effective smooth muscle dilator • Lesser maternal effects • Better tocolytic • Contraindicated in • Cardiac disease, aortic stenosis • Hypotension

20. Sublingual Nifedipine • Increased adverse effects • Systemic vasodilation • Early, profound • Delayed response on heart • Angina, Reflex tachycardia • Increased MORTALITY

21. Indomethacin • Before 32 weeks • Loading Dose: 50 mg • Maintenance 25 mg 4th hourly for 48 hours • Contraindications: • Maternal Hepatic or renal disease • Acid peptic disease • Oligohydramnios

22. Basic Rules for use of Tocolytics • They are used for short time – 48 hours • Calcium channel blockers preferred • Indomethacin before 32 weeks • Do not give: • Cardiac disease, hypotension, critically ill mother • Fetal distress, chorioamnionitis, abruption

23. Avoid Complications • Do not give tocolytics if • Maternal tachycardia - > 120 bpm • Cardiac disease, infection • Be careful with IV fluid infusion • Do not use multiple drugs • WATCH OUT for pulmonary edema

24. How Safe are they? • Absolute •   Acute vaginal bleeding  Fetal distress   Lethal fetal anomalyChorioamnionitis  Preeclampsia or eclampsia  Sepsis  DIC • Relative •   Chronic hypertension  Cardiopulmonary disease  Stable placenta previa  Cervical dilation >5 cm  Placental abruption All contraindications have to be honoured

26. Uterotonics and Medical Disorders

27. Uterotonics • 1. Oxytocin • 2. Prostaglandins • Misoprostol (Cytotec) • 15-methyl Prostaglandin F2! • 3. Ergot Alkaloids • Methylergonovine(Methergine)

28. Uterine Contraction causesAuto-transfusion Uterotonics effect smooth muscle function Uterine Blood into Systemic Circulation Cardiac Output 15% in I stage 50% in II stage

29. Uterotonics have an important role in prevention and management of PPH

30. Oxytocin • Prophylaxis & treatment of atonic PPH • IM : 10 units as prophylaxis • At Cesarean : 3 - 5 units IV bolus • Hemodynamic changes • IV bolus > IV infusion > IM dose

31. Hemodynamic changesOXYTOCIN • Dose dependent • 3 units - 5 units – 10 units • One bolus Vs 2 bolus Increases heart rate Decreases contractility Decreases SVR significantly

32. Changes with 5 U Oxytocin

33. Oxytocin • Hypotension • Chest pain • ECG changes Svanström. Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section. Br J Anaesth 100:683–689

34. OxytocinTake home message • IV infusion or IM use preferred • IV bolus at cesarean section: • 3 or 5 IU • IV infusion: • Dose dependent effects - TITRATE

35. Prostaglandins • Endogenous prostaglandins in labour • Peak at placenta delivery • Action by increasing calcium • Prostaglandins E : Misoprostol • F classes : Carboprosttromethamine

36. Misoprostol in Cardiac Disease • Misoprostol PGE1 • Best uterotonic to use in postpartum period • 800 microgram, per rectal / oral • Antepartum period • Dinoprostone PGE2 • Lesser incidence of hyperstimulation

37. PGF 2 alpha, Carboprost • For PPH • Dose : 250 mcg IM • Maximum of 8 doses at 15 min interval • Can be given intramyometrial • Increases pulmonary vascular resistance • Contraindicated in PAH, Asthma

38. Methyl ergometrine • Potent uterotonic drug • Increases BP • Intense vasospasm : angina, strokes • Exaggerated response: pre eclampsia • IV cause more hemodynamic changes.

39. Medical Disorders and UterotonicsHow can we make the safe?

40. Cardiac Disease and Uterotonics • Ask yourself • Is there PAH? • Will this patient tolerate increased HR? • Can she tolerate fall in cardiac contractility ? • Does she have a tight valvular lesion ? • Can she tolerate fall in systemic vascular resistance ?

41. CARPREG Score

42. CARPREG Score

43. Cardiac diseaseSevere Valvular Heart Disease • Prophylaxis • Oxytocin – IM or infusion only • Misoprostol as a second line • Restrict IV fluids 20 units in 500 ml at 125 ml/hour (4 hours) Cardiac Disease Use a syringe pump 20 units in 20 cc syringe 5 U per hour for 4 hours

44. Cardiac diseaseSevere Valvular Heart Diseasewithout PAH • Life threatening hemorrhage • PGF2α : watching for its effects • Methyl ergometrine

45. Cardiac diseaseDecreased Ejection Fraction • PPCM, Cardiomyopathy • Oxytocin may cause sudden hypotension • IV infusion • Being prepared to tackle a crisis • Second drug of choice - Misoprostol

46. Cardiac diseaseIncreased Pulmonary HTN • Primary / secondary • Avoid PGF2 alpha • Intense pulmonary vascular constriction • Increases PAH • Shunt reversal • Methyl Ergometrine : before PGF2 alpha

47. Asthma 1 • Prostaglandin F class • Bronchospasm • Pulm vasoconstriction • History Vs acute episode • Tackle bronchospasm Oxytocin 2 Methergine 3 Carboprost

48. Moderate to High Risk LesionsNYHA III or IVInvasive hemodynamic monitoringAneasthetist / intensivist / cardiologistKnow the effectsBe prepared to tackle the effects

49. Cardiac DiseaseOrder of use • Oxytocin • 20 units infusion • Titrate to effect • Misoprostol • 800 µg rectal / oral Life threatening PPH • PGF2α • Do not use in PAH, shunts • Methergine • Do not use in CAD, PE, aneurysms

50. Uterotonics are life saving drugs ABC of resuscitation Bimanual compression Part of PPH protocol Relative contraindications Uterotonics Tamponade Compression sutures Hysterectomy