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Original Article
A Study to Determine Minimum Effective Dose of Oxytocin Infusion during Caesarean Delivery in Parturients at High Risk of Uterine Atony Abstract
Background: Oxytocin, a commonly used drug to prevent uterine atony after caesarean section, should be administered as dilute rapid infusion rather than as a bolus. This study was conducted to calculate ED90 of oxytocin infusion during caesarean delivery in parturients at high risk of postpartum haemorrhage (PPH). Materials and Methods: One hundred and twenty parturients having one or more risk factors for PPH received a blinded infusion of oxytocin following emergency caesarean delivery. The initial dose of oxytocin infusion was started as 0.4 IU min−1. The dose of oxytocin infusion for the next parturient was based on the response of preceding patient in increments or decrements of 0.1 IU min−1 as per a biased‑coin design up‑down sequential method (UDM). Measurements of non‑invasive blood pressure and heart rate were taken at 2 min intervals from the time of oxytocin infusion. Intraoperative blood loss was noted. Side effects such as tachycardia, hypotension, nausea, vomiting, chest pain, headache and flushing were also recorded. Results: The ED90 of oxytocin infusion was found to be 0.405 IU min−1 (95% confidence interval 0.3864–0.4125) as calculated by Firth’s penalised likelihood estimation using a biased‑coin design UDM. Hypotension was observed for brief period of time in 25.6% of parturients and brief period of tachycardia was observed in 9.4% of parturients. No headache, flushing, chest pain and vomiting were observed in any parturients in our study. The estimated blood loss was within the normal limits. Conclusion: Our study showed that ED90 of oxytocin infusion required to achieve adequate uterine tone (UT) after an emergency caesarean delivery in parturients at high risk of uterine atony was 0.405 IU min−1. The higher doses of oxytocin did not result in further improvement of UT. Therefore, early use of alternative uterotonic therapy is preferable to achieve adequate UT.
Shashikiran, Harsimran Kaur1, Renu Bala, Neha Gupta2 Department of Anaesthesiology and Critical Care, Pandit Bhagwat Dayal Sharma, Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, 1Department of Anaesthesia, CMC, Ludhiana, Punjab, 2Department of Anaesthesia, King George Medical College, Lucknow, Uttar Pradesh, India
Keywords: Caesarean section, oxytocin, postpartum haemorrhage, uterine atony
Introduction Prophylactic oxytocin is commonly administered after delivery of the infant or placenta and has been shown to reduce the incidence of postpartum haemorrhage (PPH) by up to 40%.[1] A slow intravenous (i.v.) bolus dose of 5 IU of oxytocin after delivery of the infant is recommended by the Royal College of Obstetricians and Gynaecologists (UK) during caesarean section.[2] This dose is also widely used across most of Europe and Australia.[3‑5] In UK, the use of an oxytocin bolus was a standard treatment, although the dose varied between 5 and 10 IU.[6] In settings where an oxytocin bolus is used routinely, an additional infusion of oxytocin may be required if haemorrhage occurs. Therefore, some obstetricians prefer to use an additional infusion of oxytocin for high risk cases.[6,7] In the United States, it is recommended to use an oxytocin infusion This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact:
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instead of a bolus dose to prevent adverse effects of bolus oxytocin.[8] Because of short half‑life of oxytocin, its infusion is advantageous in maintaining uterine contractility throughout the surgical procedure and immediate postpartum period.[9] There is paucity of literature regarding minimum effective dose of oxytocin infusion to prevent uterine atony during caesarean delivery in parturients at high risk of PPH; therefore, this study was planned to determine the minimum effective dose of oxytocin infusion during caesarean delivery in parturients at high risk of uterine atony.
Materials and Methods After the approval of Ethics Committee of the hospital, the present prospective randomised study was conducted in our Department of Anaesthesiology and Critical Care. One hundred twenty parturients aged
Address for correspondence: Dr. Renu Bala, Department of Anaesthesiology and Critical Care, Pandit Bhagwat Dayal Sharma, Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India. E‑mail:
[email protected]
Access this article online Website: www.joacc.com DOI: 10.4103/joacc.JOACC_42_16 Quick Response Code:
How to cite this article: Shashikiran, Kaur H, Bala R, Gupta N. A study to determine minimum effective dose of oxytocin infusion during caesarean delivery in parturients at high risk of uterine atony. J Obstet Anaesth Crit Care 2017;7:75-80.
© 2017 Journal of Obstetric Anaesthesia and Critical Care | Published by Wolters Kluwer ‑ Medknow
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between 18 and 35 years, belonging to American Society of Anaesthesiologists (ASA) physical status I and II, having one or more risk factors for PPH due to uterine atony such as pre‑eclampsia, placenta praevia, multiple gestation, history of uterine atony/PPH in previous pregnancy, high parity (>5 previous deliveries) and uterine fibroids, undergoing caesarean delivery under spinal anaesthesia were enrolled in the study. Patients with cardiac disease, haemodynamic instability before commencement of surgery, bleeding disorders and known drug allergy to oxytocin were excluded from the study. All the parturients were examined before surgery and subjected to complete physical as well as systemic examination. Routine investigations such as haemoglobin, bleeding time, clotting time and urine examination were noted in all the patients. The purpose and protocol of study was explained to parturients and informed written consent was obtained. Upon arrival in operating room, usual monitoring including non‑invasive blood pressure (NIBP), ECG and pulse oximetry were established. Intravenous line was secured and sample for baseline haematocrit was drawn. Parturients were preloaded with 10 ml kg−1 of Ringer’s lactate infusion 15 min before spinal anaesthesia. Baseline maternal heart rate (HR) and invasive blood pressure were recorded as an average of three readings. All parturients received spinal anaesthesia in sitting position in L3‑4 space with 25 G Quincke spinal needle with 1.5 ml of 0.5% hyperbaric bupivacaine along with 25 µg of fentanyl. Parturient was laid supine with wedge under the right flank to achieve leftward tilt of 15°. Surgery was commenced after a T4 sensory level to cold perception had been achieved. Following delivery and clamping of the umbilical cord, an infusion of oxytocin was started. The initial dose of oxytocin infusion was started as 0.4 IU min−1 (24 IU of oxytocin in 250 ml normal saline over 1 h). The obstetrician was asked to palpate the uterus, which was not exteriorised and the uterine tone (UT) was assessed according to a five‑point scale (1 = atonic, 2 = partial but inadequate contraction, 3 = adequate contraction, 4 = well contracted and 5 = very well contracted). If the tone was assessed as inadequate (i.e. UT scale 2 or 1) at 2, 3, 6 and 9 min, then a ‘rescue’ bolus of 0.5 units oxytocin was administered. A maximum of two ‘rescue’ doses of oxytocin were permitted during the study period. If UT was assessed as inadequate after two rescue doses of oxytocin, then 3 IU bolus of oxytocin was administered. If UT would still be inadequate, then alternative uterotonic therapy (AUT) was administered [intramuscular (IM) carboprost tromethamine 0.25 mg or rectal misoprostol 800–1000 mg). All parturients continued to receive a maintenance infusion of i.v. oxytocin at 0.04 IU min−1 (2.4 IU in 500 ml normal saline) until discharge from post‑anaesthesia care unit (PACU). The dose of oxytocin infusion for the next parturient was based on the response of preceding patient in increments 76
or decrements of 0.1 IU min−1 as per a biased‑coin design up‑down sequential method (UDM). After spinal anaesthesia, monitoring of vitals was done continuously and recorded every 2 min till the administration of oxytocin. Hypotension was defined as a decrease in mean arterial blood pressure ≥10% of the baseline value, and each episode of hypotension was treated with an i.v. bolus of 3 mg of ephedrine. Tachycardia was defined as an increase in maternal HR ≥20% of the baseline value. The study also included the assessment of UT at 2, 3, 6 and 9 min after starting the oxytocin infusion and the number of rescue doses of oxytocin. Intraoperative blood loss was measured by calculating the weight of blood on surgical swabs. Haematocrit values were measured before surgery and at 30 min after completion of surgery. Side effects associated with oxytocin such as tachycardia, hypotension, nausea, vomiting, chest pain, headache and flushing were noted after administration of oxytocin until discharge from PACU. The primary outcome measure was determination of minimum effective dose of oxytocin infusion. The secondary outcome measure was to assess the side effects associated. The sample size was determined by interim analysis of data of 20 patients and it was found that 100 patients will generate power of more than 85% and alpha error 2
Value 120
24.28±3.3 20-36 70.27±7.73 55-98 56 (46.66%) 37 (30.83%) 27 (22.50%)
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atony was found to be 0.405 IU min−1 [95% confidence interval (CI) 0.3864–0.4125] [Figure 1]. Table 2 shows UT at various time intervals after starting oxytocin. Adequate UT (i.e. UT score ≥3) at 2, 3, 6 and 9 min was observed in 4.2% (5 out of 120), 95% (114 out of 120), 98.3% (118 out of 120) and 100% (120) of parturients, respectively [Table 3]. The parturients who required first and second rescue boluses of oxytocin were 50% (60 out of 120) and 49.2% (59 out of 120) parturients, respectively. Three units of oxytocin were required in 26.7% (32 out of 120) parturients. AUT as IM carboprost was required in 10% (12 out of 120) of parturients, whereas no parturient required rectal misoprost [Table 4]. The variations in HR and blood pressure are shown in Figures 2-5. Hypotension was observed for a brief period of time in 25.6% of parturients that responded to small incremental doses of ephedrine. Brief period of tachycardia was observed in 9.4% of parturients. No side effects such as nausea, flushing, chest pain and vomiting were observed
in any parturient in our study. The estimated blood loss was 865.58 ± 141.05 ml. There was significant decrease Table 2: UT score after starting oxytocin infusion at various time intervals
Time (min) 2 3 6 9
No. of parturients (n) 120 120 120 120
UT score (Mean±SD) 2.04±0.20 2.98±0.28 3.33±0.50 3.63±0.53
Table 3: Number of parturients having adequate UT after starting oxytocin infusion at various time intervals
Time (min) 2 3 6 9
No. of parturients (n) 120 120 120 120
Frequency 5 114 118 120
Percentage 4.2 95 98.3 100
100
Mean heart rate (bpm)
98
97.91
95.7
95.53
96
94.71
94.69 93.76
94
92
90
Figure I: Fitted probabilities of successful responses at the specific oxytocin infusion doses tested using Firth’s bias reduced penalized maximum likelihood logistic regression 95% confidence intervals
4 min 6 min Time
8 min
10 min
115 110.52 110
104.03
Mean bp (mmhg)
105.03 105 Mean heart rate (bpm)
2 min
Figure 2: Heart rate changes at various time intervals after administration of spinal anaesthesia
110
101.74 100.1 100
98.78
95
90
Baseline
Atdb
2 min
4 min
6 min
98.01
96.96
96.14
95.18
94.37
8 min 10 min 15 min 20 min 25 min 30 min Time
Figure 3: Heart rate changes after delivery of baby and administration of oxytocin at various time intervals(at time of delivery of baby –ATDB)
104.49
105
103.89 100.94 99.48
100
97.8
95
90
Baseline
2 min
4 min 6 min Time
8 min
10 min
Figure 4: Variations in mean blood pressure after administration of spinal anaesthesia
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105
Mean blood pressure (mmhg)
101.45 100.23 100.26 100
98.78
98.75
98.18 98.32
98.2
97.23 96.42 95
90
Atdb
2 min 4 min 6 min 8 min 10 min 15 min 20 min 25 min 30 min Time
Figure 5: Variations in mean blood pressure at various time intervals after delivery of baby and administration of oxytocin ( at the time of birth of baby –ATDB)
Table 4: Number of parturients who required rescue boluses of oxytocin (RBO), 3 IU of oxytocin and AUT as IM carboprost and rectal misoprost
Rescue drug RBO I RBO II 3 IU of oxytocin Carboprost (IM) Misoprost (Rectal)
Frequency 60 59 32 12 None
Percentage 50 49.2 26.7 10 None
in post‑operative haematocrit as compared to pre‑operative haematocrit, i.e. 28.60 ± 2.22% (mean ± SD) and 25.04 ± 2.47%, respectively (P
