1. Uterotonics and Tocolytics in Medical Disorders How Safe are They?
Nuzhat Aziz
Hyderabad, INDIA

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

3. Why do we use them? Tocolytics Uterotonics
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
Pulmonary arteries / veins
Pulmonary vascular resistance
Systemic circulation
Systemic vascular resistance
Coronary arteries
Angina, Ischemia
Brain
Vasospasm, strokes

9. What is the recommended drug?
Beta-mimetics
Ritodrine
Isoxsuprine
Terbutaline
Magnesium sulphate
Calcium channel blockers
Nifedipine
Prostaglandin inhibitors
Indomethacin
Oxytocin receptor antagonist
Atosiban

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 Drugs Terbutaline Hemodynamic Changes
Myocardial Fatigue
Heart Rate
Myocardial O2 demand
Vascular Resistance

13. Beta-mimetics Contraindications
Cardiac disease
Hyperthyroidism
Chorioamnionitis
Maternal tachycardia
Sepsis

14. Beta-mimetics Drugs Lactic Acidosis
Glycogenolysis ↑
hyperglycemia
Lactic acid production ↑
→ metabolic acidosis
Hypokalemia
b2-Adrenergic Agents—Epinephrine, Ritodrine, Terbutaline, Salbumatol,
and Dobutamine
b-Agonists cause lactic acidosis in several ways. First, b2-adrenergic–mediated stimulation
of muscle and hepatic phosphorylase and inhibition of glycogen synthetase stimulates
glycolysis and, thereby, an increase in pyruvate production.116 In skeletal
muscle, b-agonists stimulate Na1-K1-ATPase via upregulation of cyclic AMP.117 This
increases generation of ADP and then phosphofructokinase, which accelerates glycolysis.
118 Then, the b-agonists inhibit PDH, which leads to decreased oxidation of pyruvate
to acetyl CoA and, thereby, increased reduction of the pyruvate to lactate.119
Lactic Acidosis: Recognition, Kinetics, and Associated Prognosis.
Crit Care Clin 26 (2010) 255–283

15. Beta-mimetics Contraindications
Cardiac disease
Hyperthyroidism
Chorioamnionitis
Maternal tachycardia
Sepsis
Poorly controlled diabetes

16. Pulmonary Edema, Maternal Deaths Beta-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. Terbutaline Not 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. All contraindications have to be
How Safe are they?
Absolute
  Acute vaginal bleeding   Fetal distress   Lethal fetal anomaly   Chorioamnionitis   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 3. Ergot Alkaloids
Misoprostol (Cytotec)
15-methyl Prostaglandin F2!
3. Ergot Alkaloids
Methylergonovine (Methergine)

28. Uterine Contraction causes Auto-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
Medical Diseases and Uterotonic Agents
Cardiac Disease
Pre-eclampsia
Asthma
Vascular diseases

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

31. Hemodynamic changes OXYTOCIN
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. Oxytocin Take 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 : Carboprost tromethamine

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 Uterotonics How 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 Prior cardiac events 1 Prior arrhythmia
Heart failure, TIA, stroke before pregnancy
Prior arrhythmia
NYHA III or IV or cyanosis
Valvular and outflow tract obstruction
Aortic v area < 1.5 cm2, mitral v area < 2 cm2,
Lt vent outflow tract peak gradient > 30 mm
Myocardial dysfunction
LVEF < 40%, Cardiomyopathy

42. CARPREG Score Prior cardiac events 1 Prior arrhythmia
Heart failure, TIA, stroke before pregnancy
Prior arrhythmia
NYHA III or IV or cyanosis
Valvular and outflow tract obstruction
Aortic v area < 1.5 cm2, mitral v area < 2 cm2,
Lt vent outflow tract peak gradient > 30 mm
Myocardial dysfunction
LVEF < 40%, Cardiomyopathy

43. Cardiac disease Severe Valvular Heart Disease
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
Prophylaxis
Oxytocin – IM or infusion only
Misoprostol as a second line
Restrict IV fluids

44. Cardiac disease Severe Valvular Heart Disease without PAH
Life threatening hemorrhage
PGF2α : watching for its effects
Methyl ergometrine

45. Cardiac disease Decreased Ejection Fraction
PPCM, Cardiomyopathy
Oxytocin may cause sudden hypotension
IV infusion
Being prepared to tackle a crisis
Second drug of choice - Misoprostol
IM better , or IV infusion but NEVER IV bolus. Be prepared to tackle severe hypotension. Second drug of choice would be then Prostaglandins

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

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

48. Moderate to High Risk Lesions NYHA III or IV Invasive hemodynamic monitoring Aneasthetist / intensivist / cardiologist Know the effects Be prepared to tackle the effects

49. Cardiac Disease Order 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
Uterotonics are life saving drugs
Bimanual compression
Uterotonics
Part of PPH protocol Relative contraindications
Tamponade
Compression sutures
Hysterectomy

51. Conclusions Tocolytics : Making them Safer
Isoxsuprine / Ritodrine : Not to be used
Terbutaline for rapid action : not available
Do not use multiple drugs
Do not give in CARDIAC disease / infection

52. Conclusions Uterotonics : Life Saving Drugs
IV bolus Oxytocin : not to be given
Tertiary care centre : multidisciplinary
Carboprost increases PAH
Oxytocin and cardiomyopathy
Medical disorders : relative contraindications