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Uterotonics and Tocolytics in Medical
DisordersHow Safe are They?
Nuzhat Aziz
Hyderabad, INDIAwww.fernandezhospital.com
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Tocolytics are drugs used to stop Uterine contractions
Uterotonics to INDUCE / INCREASE uterine contractions
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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
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Why do Obstetricians use these?
Tocolytics For in utero resuscitation For external cephalic version Difficult delivery
Uterotonics Miscarriage
To improve fetal survival
Important - maternal survival
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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
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Smooth Muscles
We want to either relax or contract the uterine muscle
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Smooth Muscles Other parts of the body
We get GI disturbances
Affects heart contractility
Bronchial muscles
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Smooth Muscles Other parts of the body
Pulmonary arteries / veins Pulmonary vascular resistanceSystemic circulation Systemic vascular resistanceCoronary arteries Angina, IschemiaBrain Vasospasm, strokes
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What is the recommended drug?
Beta-mimetics Ritodrine IsoxsuprineTerbutaline
Magnesium sulphateCalcium channel blockers NifedipineProstaglandin inhibitors IndomethacinOxytocin receptor antagonist Atosiban
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Very Important to Remember
Tocolytic treatment for the management of preterm labour: a systematic review. Tan et al. Singapore Med J 2006; 47(5) : 364
They are of benefit only for short time tocolysis
No LONG Term
Therapy
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Why are we worried about using them in
Medical Disorders ?
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Beta-mimetics DrugsTerbutaline
Hemodynamic Changes
Heart RateMyocardial O2 demand
Vascular Resistance
Myocardial Fatigue
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Beta-mimeticsContraindications
Cardiac disease Hyperthyroidism Chorioamnionitis Maternal tachycardia Sepsis
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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
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Beta-mimeticsContraindications
Cardiac disease Hyperthyroidism Chorioamnionitis Maternal tachycardia Sepsis Poorly controlled
diabetes
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Pulmonary Edema, Maternal DeathsBeta-mimetics
Incidence of pulmonary edema – 4% Non cardiogenic Multiple tocolytics Fluid overload Multifactorial
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Predisposing Risk Factors for Pulmonary Edema
Heart disease Pregnancy induced HTN Chorio-amnionitis Sepsis, Infections
Betamimetics + Corticosteroids + IV fluids
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Terbutaline Not for prolonged treatment / No Oral use
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Oral Nifedipine
Effective smooth muscle dilator Lesser maternal effects Better tocolytic Contraindicated in
Cardiac disease, aortic stenosis Hypotension
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Sublingual Nifedipine
Increased adverse effects Systemic vasodilation
Early, profound Delayed response on heart Angina, Reflex tachycardia Increased MORTALITY
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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
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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
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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
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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
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Uterotonics and
Medical Disorders
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Uterotonics
1. Oxytocin 2. Prostaglandins
Misoprostol (Cytotec) 15-methyl Prostaglandin F2!
3. Ergot Alkaloids Methylergonovine (Methergine)
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Uterine Contraction causesAuto-transfusion
Uterine Blood into
Systemic Circulation
Cardiac Output15% in I stage50% in II stage
Uterotonicseffect
smooth musclefunction
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Uterotonics have an important role in prevention
and management of PPH
Medical Diseases and Uterotonic Agents
Cardiac Disease Pre-eclampsia
Asthma Vascular diseases
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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
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Hemodynamic changesOXYTOCIN
Dose dependent 3 units - 5 units – 10 units One bolus Vs 2 bolus
Increases heart rateDecreases contractility
Decreases SVR significantly
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Changes with 5 U Oxytocin
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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
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OxytocinTake home message
IV infusion or IM use preferred IV bolus at cesarean section:
3 or 5 IU IV infusion:
Dose dependent effects - TITRATE
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Prostaglandins
Endogenous prostaglandins in labour
Peak at placenta delivery
Action by increasing calcium
Prostaglandins E : Misoprostol
F classes : Carboprost tromethamine
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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
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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
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Methyl ergometrine
Potent uterotonic drug Increases BP Intense vasospasm : angina, strokes Exaggerated response: pre eclampsia IV cause more hemodynamic changes.
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Medical Disorders and Uterotonics
How can we make the safe?
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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 ?
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CARPREG ScorePrior cardiac events 1 Heart failure, TIA, stroke before pregnancy
Prior arrhythmia 1NYHA III or IV or cyanosis 1Valvular and outflow tract obstruction 1 Aortic v area < 1.5 cm2, mitral v area < 2 cm2, Lt vent outflow tract peak gradient > 30 mm
Myocardial dysfunction 1 LVEF < 40%, Cardiomyopathy
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CARPREG ScorePrior cardiac events 1 Heart failure, TIA, stroke before pregnancy
Prior arrhythmia 1NYHA III or IV or cyanosis 1Valvular and outflow tract obstruction 1 Aortic v area < 1.5 cm2, mitral v area < 2 cm2, Lt vent outflow tract peak gradient > 30 mm
Myocardial dysfunction 1 LVEF < 40%, Cardiomyopathy
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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 DiseaseUse a syringe pump
20 units in 20 cc syringe5 U per hour for 4 hours
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Cardiac diseaseSevere Valvular Heart Disease
without PAH
Life threatening hemorrhage
PGF2α : watching for its effects
Methyl ergometrine
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Cardiac diseaseDecreased Ejection Fraction
PPCM, Cardiomyopathy Oxytocin may cause sudden hypotension
IV infusion Being prepared to tackle a crisis Second drug of choice - Misoprostol
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Cardiac diseaseIncreased Pulmonary HTN
Primary / secondary Avoid PGF2 alpha
Intense pulmonary vascular constriction Increases PAH Shunt reversal
Methyl Ergometrine : before PGF2 alpha
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Asthma
Prostaglandin F class
Bronchospasm
Pulm vasoconstriction
History Vs acute episode
Tackle bronchospasm
Oxytocin
Carboprost
Methergine
123
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Moderate to High Risk LesionsNYHA III or IV
Invasive hemodynamic monitoringAneasthetist / intensivist / cardiologist
Know the effectsBe prepared to tackle the effects
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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
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Uterotonics are life saving
drugsPart of PPH protocol
Relative contraindications
ABC of resuscitation
Bimanual compression
Uterotonics
Compression sutures
Tamponade
Hysterectomy
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ConclusionsTocolytics : 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
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ConclusionsUterotonics : Life Saving Drugs
IV bolus Oxytocin : not to be given Tertiary care centre : multidisciplinary Carboprost increases PAH Oxytocin and cardiomyopathy Medical disorders : relative contraindications