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Uterotonics and Tocolytics in Medical Disorders How Safe are They?. Nuzhat Aziz. Hyderabad, INDIA www.fernandezhospital.com. Tocolytics are drugs used to stop Uterine contractions. Uterotonics to INDUCE / INCREASE uterine contractions. Why do we use them?. Tocolytics - PowerPoint PPT Presentation
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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 rateDecreases 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 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
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
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
123
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
drugsPart 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