Uterotonics and Tocolytics in Medical

DisordersHow Safe are They?

Nuzhat Aziz

Hyderabad, INDIAwww.fernandezhospital.com

Tocolytics are drugs used to stop Uterine contractions

Uterotonics to INDUCE / INCREASE uterine contractions

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

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

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

Smooth Muscles

We want to either relax or contract the uterine muscle

Smooth Muscles Other parts of the body

We get GI disturbances

Affects heart contractility

Bronchial muscles

Smooth Muscles Other parts of the body

Pulmonary arteries / veins Pulmonary vascular resistanceSystemic circulation Systemic vascular resistanceCoronary arteries Angina, IschemiaBrain Vasospasm, strokes

What is the recommended drug?

Beta-mimetics Ritodrine IsoxsuprineTerbutaline

Magnesium sulphateCalcium channel blockers NifedipineProstaglandin inhibitors IndomethacinOxytocin receptor antagonist Atosiban

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

Why are we worried about using them in

Medical Disorders ?

Beta-mimetics DrugsTerbutaline

Hemodynamic Changes

Heart RateMyocardial O2 demand

Vascular Resistance

Myocardial Fatigue

Beta-mimeticsContraindications

Cardiac disease Hyperthyroidism Chorioamnionitis Maternal tachycardia Sepsis

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

Beta-mimeticsContraindications

Cardiac disease Hyperthyroidism Chorioamnionitis Maternal tachycardia Sepsis Poorly controlled

diabetes

Pulmonary Edema, Maternal DeathsBeta-mimetics

Incidence of pulmonary edema – 4% Non cardiogenic Multiple tocolytics Fluid overload Multifactorial

Predisposing Risk Factors for Pulmonary Edema

Heart disease Pregnancy induced HTN Chorio-amnionitis Sepsis, Infections

Betamimetics + Corticosteroids + IV fluids

Terbutaline Not for prolonged treatment / No Oral use

Oral Nifedipine

Effective smooth muscle dilator Lesser maternal effects Better tocolytic Contraindicated in

Cardiac disease, aortic stenosis Hypotension

Sublingual Nifedipine

Increased adverse effects Systemic vasodilation

Early, profound Delayed response on heart Angina, Reflex tachycardia Increased MORTALITY

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

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

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

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

Uterotonics and

Medical Disorders

Uterotonics

1. Oxytocin 2. Prostaglandins

Misoprostol (Cytotec) 15-methyl Prostaglandin F2!

3. Ergot Alkaloids Methylergonovine (Methergine)

Uterine Contraction causesAuto-transfusion

Uterine Blood into

Systemic Circulation

Cardiac Output15% in I stage50% in II stage

Uterotonicseffect

smooth musclefunction

Uterotonics have an important role in prevention

and management of PPH

Medical Diseases and Uterotonic Agents

Cardiac Disease Pre-eclampsia

Asthma Vascular diseases

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

Hemodynamic changesOXYTOCIN

Dose dependent 3 units - 5 units – 10 units One bolus Vs 2 bolus

Increases heart rate

Decreases contractility

Decreases SVR significantly

Changes with 5 U Oxytocin

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

OxytocinTake home message

IV infusion or IM use preferred IV bolus at cesarean section:

3 or 5 IU IV infusion:

Dose dependent effects - TITRATE

Prostaglandins

Endogenous prostaglandins in labour

Peak at placenta delivery

Action by increasing calcium

Prostaglandins E : Misoprostol

F classes : Carboprost tromethamine

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

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

Methyl ergometrine

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

Medical Disorders and Uterotonics

How can we make the safe?

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 ?

CARPREG Score

Prior 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

CARPREG Score

Prior 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

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

Cardiac diseaseSevere Valvular Heart Disease

without PAH

Life threatening hemorrhage

PGF2α : watching for its effects

Methyl ergometrine

Cardiac diseaseDecreased Ejection Fraction

PPCM, Cardiomyopathy Oxytocin may cause sudden hypotension

IV infusion Being prepared to tackle a crisis Second drug of choice - Misoprostol

Cardiac diseaseIncreased Pulmonary HTN

Primary / secondary Avoid PGF2 alpha

Intense pulmonary vascular constriction Increases PAH Shunt reversal

Methyl Ergometrine : before PGF2 alpha

Asthma

Prostaglandin F class

Bronchospasm

Pulm vasoconstriction

History Vs acute episode

Tackle bronchospasm

Oxytocin

Carboprost

Methergine

1

2

3

Moderate to High Risk LesionsNYHA III or IV

Invasive hemodynamic monitoringAneasthetist / intensivist / cardiologist

Know the effectsBe prepared to tackle the effects

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

Uterotonics are life saving

drugs

Part of PPH protocol

Relative contraindications

ABC of resuscitation

Bimanual compression

Uterotonics

Compression sutures

Tamponade

Hysterectomy

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

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