Acute Tocolysis in Labour

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Acute Tocolysis in LabourTocolysis
Emergency uterine relaxation

• S.Arulkumaran
• Professor Head
• Division of Obstetrics Gynaecology
• St.Georges Hospital Medical School
• University of London

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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

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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/anaesthet
  ist 2nd obstetrician or anaesthetist
• Difficulty in getting the second theatre

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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

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Emergency uterine relaxation

• Need for short lived profound relaxation
• GA and halogenated agents
• GA and its potential complications
• Halothane action unpredictable, not the desired
  effect, reversal unpredictablegt 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

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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

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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

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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

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Single injection of terbutaline in term labour
1. Effect on fetal pH in cases with prolonged
bradycardia

• 33 prolonged bradycardia FHRlt100bpm gt 3 min or
  lt 80 bpm gt 2min
• Stopped oxytocin, nursed on the side, O2
• If no recovery by 4 min gt terbutaline 0.25 mg IV
  gt scalp pH within 40 min if pH lt7.24 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 OG 1985

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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

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Injection to recovery time, duration of
bradycardia mean scalp pH
Lag time FHR lt100 gtIV terbut Injection to recovery time gt100 Duration lt100 bpm scalp pH
2-3 min 4-6 min 14 12 23 4 - 19 7.32
7-9 min 10-14 min 2 0 1 0 7.29 4 7.22




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Delivery by CS 10 cases
Complications Duration of FHR lt80 Bradycardia to birth Cord arterial pH
FHR ominous AT 8 20 7.10
PolyhydramnioARMgtabruptio 10 25 6.98
FHR ominous -30m after adm 13 25 7.04
Cord prolapse 8 24 7.22
Cord prolapse 6 19 7.12
Abruptio? 4 30 7.19

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Single injection of terbutaline - I. Effect on
fetal pH with prolonged bradycardia

• Fetal acidosis was more common if the rate was lt
  80 bpm particularly if the BLV was lt3 for gt 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
  OG. 1985153859

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Prolonged Bradycardia (lt80bpm for gt 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 gt decision for CS
  gt To OT by 12 min gt Delivery by 15 min
• In OT Check FHR if recovered review
  clinical situation and decide

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• Do not do a FBS with prolonged bradycardia
• Review CTG clinical situation carefully
• Audit cases of immediate CS compromises the
  mother babys condition may be improved with
  tocolysis

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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 OG
  1985 153865

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• 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.19913284

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Uterine Activity UAI Frequency
-30 gt0 mins 0gt15 mins 15gt30 mins 30-45 mins 45-60 mins 60-75 mins
Gp A UAI Freq 1275 5.8 1270 5.3 1282 5.7 1712 5.9 1728 6.0 1567 5.9
Gp B UAI Freq 1120 4.8 1002 4.0 1002 4.0 1084 3.9 1015 4.0 1273 4.4
Gp C UAI Freq 1526 5.9 279 0.9 480 3.3 658 4.3 669 3.6 750 4.3
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Maternal parameters
Mins -30 gt0 0gt 15 15gt30 30gt45 45gt60 60gt75
A Sys Dias Pulse 120 78 81 116 78 82 116 79 82 117 79 83 117 79 84 114 78 81
B Sys Dias Pulse 115 79 81 117 80 80 119 80 80 119 80 81 117 80 80 118 79 81
C Sys Dias Pulse 119 76 84 112 72 109 122 73 100 121 75 94 121 77 94 120 77 94
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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
  its pattern
• Kurup A, Arulkumaran S, Tay D et.al. Gynecol
  Obstet Invest 19913284

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REVERSAL OF TOCOLYTIC ACTIVITY
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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.2001108164

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Oxytocics reverse the tocolytic effect of
glyceryl trinitrate on the human uterus
Oxyt 20 mU/ml GTN uM 44 88 176 705 Controls 2649 2543 1765 2656 GTN 1057 826 400 288 GTNOxy 7031 5985 4665 3959

Ergometri6.15 uM 88 176 2199 1763 364 146 2257 1439

PG F2a 6.15 uM 176 352 1512 1972 697 729 2245 1790

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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

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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 !!

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Clinical safety maternal I
75
30
25
Incidence
20
15
this single patient case occurred after switch
to beta-agonist therapy
10
5

0
œdema
Hyper-
kalaemia
Hypo-
glycaemia
ischaemia
Dyspnœa
Palpitation
Chest pain
Pulmonary
Myocardial
Tachycardia
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Clinical safety maternal II
25
20
15
Incidence
10
5
0
Tremor
Nausea
Vomiting
Headache
Hypotension
Hypertension
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Clinical safety maternal III
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Clinical safety fetal
30
25
20
Incidence
15
10
5
0
distress
Hypoxia
Fetal
Asphyxia
Fetal death
Bradycardia
Tachycardia
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Clinical safety neonatal
20
18
16
14
12
Incidence
10
8
6
4
2
0
RDS
Apnœa
Arrhythmia
Bradycardia
Hypotension
Cerebral
haemorrhage
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THANK YOU
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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.
  1985153859-865.
• Ingemarsson I, Arulkumaran S, Ratnam SS. Single
  injection of terbutaline in term labour. II.
  Effect on uterine activity. Am J Obstet Gynecol.
  1985153866-891.
• 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 2001108164-168.
• Andersson I, Ingemarsson I, Persson CGA. Effects
  of terbutaline on human uterine motility at term.
  Acta Obstet Gynecol Scand 1974531-8.

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Acute tocolysis - Recommended Reading

• Desimone CA..Intravenous nitroglycerin aids
  manual extraction of a retained placenta.
  Anaesthesiology 199073787
• Mayer DC . Antepartum uterine relaxation with
  nitroglycerin at caesarean delivery. Can J
  Anaesth 199239166
• Mercier FJ Intravenous nitroglycerin to
  relieve intrapartum fetal distress related to
  uterine hyperactivity a prospective
  observational study. Anesth Analg 1997841117
• Redick LF Livingston EA. A new preparation of
  nitroglycerin for uterine relaxation. Int J
  Obstet Anesth 1995414
• Riley ET . Intravenous nitroglycerin A potent
  uterine relaxant for emergency obstetric
  procedures. Review of literature and report of
  three cases. Int J Obstet Anesth 19965264