Acute Tocolysis in Labour ‘Tocolysis’ – ‘Emergency uterine relaxation’

1. Acute Tocolysis in Labour‘Tocolysis’ – ‘Emergency uterine relaxation’ S.Arulkumaran Professor & Head Division of Obstetrics & Gynaecology St.George’s Hospital Medical School University of London

2. Tocolysis - Indications • Acute fetal distress/ especially with uterine hypertonus • Cord prolapse • Fetal entrapment during delivery - Transverse lie at time of CS – esp. preterm, dorso-inferior, prolonged ROM, advanced labour After coming head of pre-term breech at CS

3. Conversion of category 1 to 2The ‘Category 1’ Caesarean SectionRisk management and intrauterine resuscitation • To reduce the risk to the mother –GA to regional • To improve the condition of the fetus even without uterine hyperstimulation • Problem with getting a busy obstetrician/anaesthetist – 2’nd obstetrician or anaesthetist • Difficulty in getting the second theatre

4. Tocolysis - Indications • External cephalic version • Delivery of second twin – for external cephalic or internal podalic version • Cephalic replacement and CS in shoulder dystocia (Zavanelli manoeuvre) • Retained but separated placenta • Manual replacement of uterine inversion

5. Emergency uterine relaxation • Need for short lived profound relaxation • GA and halogenated agents • GA and it’s potential complications • Halothane – action unpredictable, not the desired effect, reversal unpredictable> PPH, Halothane toxicity • Amyl nitrite – highly volatile, flammable liquid administered by inhalation; action inadequate? • More CS done under regional block – use tocolytics that can be used under regional block

6. Nitroglycerin • Sublingual or Intravenous • Sublingual aerosol spray 400 ug – absorption and action not predictable • Intravenous – More predictable response • Nitroglycerine 5 mg in 1 ml vial – diluted in 100 ml saline – 50 ug/ml – 20 ml syringe • Initial dose 200 ug – repeat at 1-2 min intervals till desired effect • Desired effect in 90 secs – lasts for 1-2 mins – rapid degradation in 1-3 mins • 100 ug doses in third stage – Must correct hypotension/ hypovolaemia before its use

7. Nitroglycerin – ester of nitric acid • Rapidly metabolised by the liver – half life 2 - 2.5 mins • Molecular weight 227 – crosses the placenta – no adverse fetal or neonatal effects • Maternal hypotension – peripheral vasodilatation and reduced venous tone • Vasodilatation reversed by ephedrine • Uterine relaxation reversed by oxytocics • ‘Contraindications’ - hypovolaemia / hypotension

8. Beta adrenergics • Preferred drug for uterine hypertonus/ FHR changes • Discontinue oxytocin infusion/ remove PG (propace) – Variable absorption of PG • Ritodrine 6 mg in 10 ml saline - 2-3 mins • Terbutaline 0.25 mg (1/2 vial) in 5ml saline IV over 5 mins (0.25 mg SC – NICE) • Improves FHR – labour can continue & NVD, even if delivery by CS –baby in better condition • Useful – if delay in getting OT/ Obstetrician/ Anaesthetist

9. Single injection of terbutaline in term labour –1. Effect on fetal pH in cases with prolonged bradycardia 33 – prolonged bradycardia FHR<100bpm > 3 min or < 80 bpm > 2min Stopped oxytocin, nursed on the side, O2 If no recovery by 4 min > terbutaline 0.25 mg IV > scalp pH within 40 min ; if pH <7.24 repeat scalp pH within 40 min If abdominal delivery needed within a short time – 1 to 2 mg propranolol IV after del. Ingemarsson I, Arulkumaran S et al Am J O&G 1985

12. Possible events related to the episode of prolonged bradycardia • Abnormal uterine activity Spontaneous 7; Induced 6; VE 1; IUP 1 • Abruptio placentae 2 • Cord prolapse 2 • Epidural top up 1 • Ominous FHR &/ or meconium 4 • Unknown 9

13. Injection to recovery time, duration of bradycardia & mean scalp pH

14. Delivery by CS – 10 cases

15. Single injection of terbutaline - I. Effect on fetal pH with prolonged bradycardia • Fetal acidosis was more common if the rate was < 80 bpm –particularly if the BLV was <3 for > 4 min • FHR improved in 30 cases: 23 had vaginal delivery – newborns in good condition • Terbutaline is a temporary measure –whilst waiting for FHR to recover – prepare for CS Ingemarsson I, Arulkumaran S, Ratnam SS. Am J O&G. 1985;153:859

16. Prolonged Bradycardia (<80bpm for > 3 min) • 3 – 6 – 9 – 12 – 15 min ‘rule’ – Immediate CS • Exclude abruption, cord prolapse, scar rupture – 3 min – decision • Examine the clinical situation – IUGR, TMS with scanty fluid, IU infection, Post term & oligohydramnios, bleeding – 6min • Check FHR prior to bradycardia – suspicious or abnormal – 6 min • Low risk – No recovery by 9 min > decision for CS > To OT by 12 min > Delivery by 15 min • In OT – Check FHR – if recovered – review clinical situation and decide

17. Do not do a FBS with prolonged bradycardia • Review CTG & clinical situation carefully • Audit cases of immediate CS – compromises the mother – baby’s condition may be improved with tocolysis

23. Single injection of terbutaline in term labor. II. Effect on uterine activity • Compared decrease in uterine activity for 60 min • a) stopped oxytocin (no terbutaline)– uterine activity reduced by 50 % in 45 mins • b) stopped oxytocin and gave bolus dose of terbutaline – ‘reduced’ uterine activity by 75% in 15 min & remained so for 45 mins (mean) • Spontaneous labour 85% reduction in 15 min & took 45 min to recover to 50% of pre-existing uterine activity • Ingemarsson I, Arulkumaran S, Ratnam SS. Am J O&G 1985; 153:865

24. Can terbutaline be used as a nebuliser instead of intravenous injection for inhibition of uterine activity? Group A – 1 mg (4 puffs via an air chamber) Group B – 2 mg (8 puffs via an air chamber) Group C – 0.25 mg IV Uterine activity, maternal & fetal parameters Kurup A, Arulkumaran S, Tay D et.al. Gynecol Obstet invest.1991;32:84

25. Uterine Activity – UAI & Frequency

27. Maternal parameters

28. Can terbutaline be used as a nebuliser instead of IV for inhibition of uterine activity? • Although convenient to use – 1 or 2mg doses did not reduce the uterine activity • 0.25 mg IV significantly reduced the uterine activity • Maternal parameters – significant rise in pulse rate, slight change in BP (50% had palpitations) with IV use • There was no significant alteration in FHR or it’s pattern Kurup A, Arulkumaran S, Tay D et.al. Gynecol Obstet Invest 1991;32:84

29. REVERSAL OF TOCOLYTIC ACTIVITY

30. Oxytocics reverse the tocolytic effect of GTN on the human uterus • GTN reduced the amplitude & frequency in a concentrations specific manner • The concentration for complete inhibition varied from 44 – 705 uM/ml • In the presence of GTN the decreased contractions were reversed to the untreated (GTN) or higher level of uterine activity by oxytocin 20mU/ml; ergometrine 6.15uM & PG F2a 6.15 uM) • Lau LC, Adaikan PG, Arulkumaran S et.al. Br J Obstet & Gynecol.2001;108:164

31. Oxytocics reverse the tocolytic effect of glyceryl trinitrate on the human uterus

32. Acute tocolysis • Useful in obstetric emergencies • Has contraindications – e.g.Severe cardiac disease, Haemorrhage, Hypotension – because of vasodilator effect and tachycardia • Reversal needed in some situations • Further studies needed on drugs that act specifically on the uterus (e.g. Atosiban) – with little cardiovascular side effects

33. Atosiban – TractocileOxytocin antagonist • Atosiban acetate 7.5 mg/ml (£20/=) • Dose – 6.75 mg IV over 1 min – followed by 300 ug/ min IV infusion • 18 mg/ hr over 3 hours • 100 ml saline bag – withdraw 10 ml saline & replace with 10 ml atosiban (7.5mg/ml) – 750 ug/ml • Nausea, vomiting, tachycardia, hypotension, dizziness, hot flushes, hyperglycaemia !!

34. Atosiban(n=361) Beta-agonists(n=372) Clinical safety: maternal I 75 30 25 % Incidence 20 *this single patient case occurred after switch to beta-agonist therapy 15 10 5 * 0 œdema Hyper- kalaemia Hypo- glycaemia ischaemia Dyspnœa Palpitation Chest pain Pulmonary Myocardial Tachycardia

35. Atosibann=361 Beta-agonistsn=372 Clinical safety: maternal II 25 20 15 % Incidence 10 5 0 Tremor Nausea Vomiting Headache Hypotension Hypertension

36. Clinical safety – maternal III

37. Atosiban(n=361) Beta-agonists(n=372) Clinical safety: fetal 30 25 20 % Incidence 15 10 5 0 distress Hypoxia Fetal Asphyxia Fetaldeath Bradycardia Tachycardia

38. Atosiban(n=406) Beta-agonists(n=432) Clinical safety: neonatal 20 18 16 14 12 % Incidence 10 8 6 4 2 0 RDS Apnœa Arrhythmia Bradycardia Hypotension Cerebral haemorrhage

40. THANK YOU

41. Acute tocolysis – Recommended reading • Ingemarsson I, Arulkumaran S, Ratnam SS. Single injection of terbutaline in term labour. I. Effect of fetal pH on cases with prolonged bradycardia. Am J Obstet Gynecol. 1985;153:859-865. • Ingemarsson I, Arulkumaran S, Ratnam SS. Single injection of terbutaline in term labour. II. Effect on uterine activity. Am J Obstet Gynecol. 1985;153:866-891. • Kurup A. Chua S, Arulkumaran S. Terbutaline used as a nebuliser does not cause relaxation of uterine activity. Asia & Oceania J Obstet Gynaecol. 1991; • Lau LC, Adaikan PG, Arulkumaran S, Ng SC. Oxytocics reverse the tocolytic effect of glyceryl trinitrate on the human uterus. Br J Obstet Gynaecol 2001;108:164-168. • Andersson I, Ingemarsson I, Persson CGA. Effects of terbutaline on human uterine motility at term. Acta Obstet Gynecol Scand 1974;53:1-8.

42. Acute tocolysis - Recommended Reading • Desimone CA…..Intravenous nitroglycerin aids manual extraction of a retained placenta. Anaesthesiology 1990;73:787 • Mayer DC …. Antepartum uterine relaxation with nitroglycerin at caesarean delivery. Can J Anaesth 1992;39:166 • Mercier FJ …… Intravenous nitroglycerin to relieve intrapartum fetal distress related to uterine hyperactivity: a prospective observational study. Anesth Analg 1997;84:1117 • Redick LF & Livingston EA. A new preparation of nitroglycerin for uterine relaxation. Int J Obstet Anesth 1995;4:14 • Riley ET …. Intravenous nitroglycerin: A potent uterine relaxant for emergency obstetric procedures. Review of literature and report of three cases. Int J Obstet Anesth 1996;5:264