Comparison of low-rate oxytocin infusion versus bolus oxytocin for initiating uterine contraction during Cesarean delivery: A randomized, controlled, non-inferiority trial

Comparison of low-rate oxytocin infusion versus bolus oxytocin for initiating uterine contraction during Cesarean delivery: A randomized, controlled, non-inferiority trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of low-rate oxytocin infusion versus bolus oxytocin for initiating uterine contraction during Cesarean delivery: A randomized, controlled, non-inferiority trial Monsicha Somjit, Wichuda Pongsri, Cattleya Kasemsiri, Darunee Sripadungkul, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5402053/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : Administration of oxytocin is the standard for preventing and treating postpartum hemorrhage. This study aims to evaluate the efficacy of low-rate oxytocin infusion compared to a 5 IU intravenous oxytocin bolus, specifically assessing its impact on uterine contractions at 3 minutes and comparing associated side effects. Material and Methods: This randomized, controlled, non-inferiority trial was conducted at Srinagarind Hospital, Khon Kaen University, between October 2022 and August 2023. A total of 160 pregnant women undergoing cesarean section under spinal anesthesia were randomized into two groups: low-rate oxytocin infusion (Group L) and oxytocin bolus (Group B), with 80 participants in each group. The primary objective was to assess adequate uterine contraction at 3 minutes post-oxytocin administration. Secondary outcomes included uterine tone (measured on a 0–10 linear analog scale) at 3 minutes, the total amount of uterotonic drugs used, additional obstetric procedures required and adverse effects. Results: Adequate uterine contraction at 3 minutes was achieved in a total of 120 patients. Group L had a significantly lower rate of adequate uterine contraction compared to Group B, with 47 (58.75%) in Group L versus 73 (91.25%) in Group B (RR 0.64; 95% CI 0.53 to 0.78). The mean uterine tone at 3 minutes was lower in Group L than in Group B (4.68 ± 1.35 vs. 6.01 ± 1.78, respectively; P < 0.001). The incidence of hypotension was also lower in Group L than in Group B (11.25% vs. 26.25%, RR 0.43; 95% CI 0.21 to 0.88). Conclusions: Low-rate oxytocin infusion was found to be inferior to a 5 IU oxytocin bolus in achieving adequate uterine contraction during cesarean delivery. Higher doses of oxytocin were associated with an increased risk of hypotension. Further studies are warranted to identify the optimal oxytocin regimen that achieves effective uterine contraction while minimizing the need for additional uterotonic agents and reducing adverse effects. Low-rate oxytocin infusion Uterine contraction Cesarean delivery Hypotension Figures Figure 1 Introduction Inadequate uterine contractions during childbirth are a primary cause of postpartum hemorrhage (PPH), which can result in maternal mortality. The World Health Organization (WHO) recommends administering oxytocin, a uterotonic agent, at a dosage of 10 IU as the standard for preventing and treating PPH due to inadequate uterine contractions ( 1 ). However, the Royal College of Obstetricians and Gynecologists (RCOG) in the United Kingdom suggests reducing the oxytocin dosage to 5 IU ( 2 ). Both 5 IU and 10 IU doses of oxytocin have been associated with significant side effects, particularly hypotension ( 3 , 4 ). Additionally, studies have reported higher mortality rates in patients receiving higher doses of oxytocin ( 5 ). Previous studies have compared the administration of intravenous oxytocin as a bolus followed by continuous infusion with continuous infusion alone, showing no significant differences in uterine contractions between the two methods ( 6 ). Studies examining low-rate oxytocin infusion have also demonstrated that uterine contraction outcomes are comparable to those with high-rate infusion ( 7 ). Thus, avoiding immediate intravenous bolus administration before continuous infusion may reduce the risk of oxytocin-related side effects while effectively initiating and sustaining uterine contractions. Currently, oxytocin administration practices, including dosage and regimens for preventing and managing inadequate uterine contractions during cesarean sections, vary among hospitals. At Srinagarind Hospital, there is no standardized protocol for oxytocin administration in cesarean deliveries, despite a general trend towards reducing oxytocin doses in alignment with RCOG recommendations. In clinical practice, the standard 5 IU intravenous bolus of oxytocin is still commonly used, though it can result in adverse side effects. This study aims to evaluate the efficacy of low-rate oxytocin infusion as a standalone intervention compared to the standard 5 IU intravenous bolus, assessing its impact on uterine contractions within the first 3 minutes and comparing associated side effects. Materials and Methods Setting and Participants This study was designed as a randomized, controlled, non-inferiority trial. The protocol was approved by the Khon Kaen University Ethics Committee in Human Research, following the Declaration of Helsinki, the ICH Good Clinical Practice guidelines (HE651289), and registered with the Thai Clinical Trials Registry on November 12, 2022 (TCTR20221113003). The study was conducted at Srinagarind Hospital, Khon Kaen University, between October 2022 and August 2023. Written informed consent was obtained from all pregnant women scheduled for cesarean sections who agreed to participate. Eligibility Criteria Pregnant women aged 18–40 years, with a gestational age of 37–42 weeks and classified as ASA physical status class II, undergoing cesarean section under spinal anesthesia, were eligible for enrollment. Exclusion criteria included a history of prior uterine surgery (excluding prior cesarean section) and conditions associated with a higher risk of inadequate uterine contractions, such as estimated fetal weight > 4000 grams, twin pregnancies, chorioamnionitis, polyhydramnios (amniotic fluid index > 25 cm), or a history of uterine fibroids during pregnancy. Patients at elevated risk for PPH, including those with a low-lying placenta, prior history of PPH, coagulopathy, thrombocytopenia, and pre-eclampsia, were also excluded. Participants who experienced failed spinal anesthesia were withdrawn from the study. Randomization and Allocation Participants were randomly assigned to groups using sealed opaque envelopes prepared in advance with a computer-generated sequence. Baseline characteristics and anesthesia details were documented for analysis. Qualified anesthesia personnel performed the spinal anesthesia, positioning each patient in either a left lateral or sitting position. A spinal needle (No. 25 or No. 27) was used to administer 0.5% heavy Marcaine (10–15 mg) combined with morphine (0.2 mg), followed by left uterine displacement after the spinal injection. Upon delivery of the infant, the investigational drug was administered immediately (slow push over 15 seconds) according to the randomized group, followed by an intravenous infusion rate of 125 ml/h. The investigational drug was prepared by a non-research anesthesia staff member who was not involved in data collection. The two groups received the following preparations: Low-rate oxytocin infusion group (Intervention Group) : Normal Saline Solution (NSS) in a 5 ml syringe was prepared for intravenous bolus. Additionally, a low-rate oxytocin infusion was prepared using Lactated Ringer’s Solution (LRS) 1,000 ml + oxytocin 20 IU for intravenous infusion. Oxytocin bolus group (Control Group) : Oxytocin 5 IU was prepared in a 5 ml syringe for intravenous bolus, along with Lactated Ringer’s Solution (LRS) 1,000 ml for intravenous infusion. At 3 minutes post-delivery, a blinded obstetrician assessed uterine contraction adequacy, categorizing it as either “adequate” or “inadequate.” Uterine tone was evaluated on a linear analog scale (LAS) from 0 to 10, where 0 represents absent uterine tone and 10 indicates optimal tone. Uterine tone, blood pressure, heart rate, and adverse events were recorded at 0, 3, 6, 9, and 15 minutes, with standard monitoring every 5 minutes until the surgery was completed. If inadequate uterine tone was observed, or if the obstetrician required additional medication to stimulate uterine contractions, uterotonic drugs were administered per the anesthesiologists’ rescue protocol. In the oxytocin bolus group, the first rescue agent was 5 IU oxytocin. In the low-rate infusion group, oxytocin 5 IU, repeatable up to two times, was administered intravenously over 15 seconds. Subsequent rescue agents in both groups included methylergonovine maleate (0.2 mg, intravenous), misoprostol (800 µg, rectal suppository), and sulprostone (500 µg, intravenous drip over 30 minutes). Any observed side effects were managed according to established standards and guidelines under the anesthesiologist’s supervision. Primary and Secondary Objectives The primary objective of this study was to assess adequate uterine contraction at 3 minutes following oxytocin administration. Secondary objectives included evaluating uterine tone on a linear analog scale (0–10) at 3 minutes, as well as the total amount of uterotonic drugs used, additional obstetric interventions (e.g., uterine artery ligation, B-Lynch procedure, hysterectomy), mild adverse effects of oxytocin (e.g., nausea, vomiting, flushing, tachycardia), and severe adverse effects (e.g., hypotension, chest pain, ECG changes). Statistical Analysis A rigorous methodology was applied to evaluate whether low-rate oxytocin infusion was non-inferior to the intravenous 5 IU oxytocin bolus in achieving adequate uterine contraction during cesarean delivery. Power analysis was based on a previous study, where the rate of adequate uterine contraction was reported as 84.6%. To detect a 15% difference in uterine contraction rates between groups (non-inferiority margin = 0.15) with a 5% significance level and a power of 90%, a sample size of 72 patients per group was calculated. To account for a 5% dropout rate, 80 patients per group were recruited. Categorical data were analyzed using Fisher’s exact test or the Chi-square test, with results presented as numbers and percentages. Continuous data were analyzed using the independent sample T-test, and findings were reported as Mean ± SD. Additionally, relative risk (RR) with a 95% confidence interval (CI) was calculated for relevant outcomes. Analyses were conducted using STATA 10 statistical software. Results From the initial pool of 181 registered participants, 160 participants were ultimately enrolled in the study and randomized into two groups: the low-rate oxytocin infusion group (Group L) and the bolus oxytocin group (Group B), with 80 participants in each group (Figure 1). Baseline characteristics were similar between the two groups are presented in Table 1. Table 1 Baseline characteristics Characteristics L group (n = 80) B group (n = 80) Mean age, years 32.06 (4.83) 31.79 (4.64) Age > 35 25 (31.25) 21 (26.25) Mean Body Mass Index, kg/m2 28.04 (4.13) 28.56 (3.74) Nulliparous, n (%) 20 (25) 20 (25) Mean gestational age, week 38.09 (0.81) 38.26 (0.88) Indication of cesarean section, n (%) Previous Cesarean section 55 (68.75) 49 (61.25) Cephalopelvic disproportion 13 (16.25) 13 (16.25) Fetal condition 4 ( 5 ) 6 (7.5) Other 8 ( 10 ) 12 (15) Anesthetic level, n (%) T4 39 (48.75) 34 (42.5) T5 7 (8.75) 5 (6.25) T6 34 (42.5) 41 (51.25) Preoperative baseline Mean arterial pressure (mmHg) 83.96 (9.71) 82.31 (11.20) Mean heart rate (beat/mins) 88.96 (11.89) 87.89 (14.42) Intravenous fluid preload (mL) 923.13 (232.34) 922.31 (222.60) Hematocrit (%) 43.24 (51.97) 35.19 (4.81) Birth weight, g 3140.88 (356.71) 3151.53 (327.12) Primary Outcome Adequate uterine contraction at 3 minutes post-oxytocin administration was achieved in a total of 120 participants. A significant difference was observed between the two groups, with 47 participants (58.75%) in the low-rate oxytocin group achieving adequate uterine contraction, compared to 73 participants (91.25%) in the bolus oxytocin group (RR = 0.64; 95% CI 0.53 to 0.78). Secondary Outcomes Secondary outcomes are presented in Table 2 . The mean uterine tone at 3 minutes, categorized on a scale from poor to strong, showed a statistically significant difference between groups. Group L exhibited a lower mean uterine tone (4.68 ± 1.35) compared to Group B (6.01 ± 1.78) (P-value = 0.000). Table 2 Primary and secondary outcome Outcomes All (N = 160) L group (n = 80) B group (n = 80) RR (95%CI) Adequate uterine contraction at 3 minutes, n (%) 120 (75) 47 (58.75) 73 (91.25) 0.64 (0.53, 0.78) Uterine tone at 3 minutes, n (%) Poor (0–5) Moderate ( 6 – 8 ) Strong ( 9 – 10 ) 87 (54.37) 67 (41.88) 6 (3.75) 59 (73.75) 21 (26.25) 0 28 (35) 46 (57.5) 6 (7.5) 2.11 (1.52, 2.92) 0.45 (0.30, 0.69) NA Additional uterotonic agents, n (%) Oxytocin Methylergonovine maleate Misoprostol Sulprostone Estimate blood loss ≥ 500 ml 91 (56.88) 24 (15) 1 (0.63) 0 1 (0.63) 59 (73.75) 13 (16.25) 1 (1.25) 0 1 (1.25) 32 (40) 11 (13.75) 0 0 0 1.84 (1.37, 2.49) 1.18 (0.56, 2.48) NA 0 NA Apgar score at 1, 5 min < 7 0 0 0 0 Data are presented as number (percentage). Low-rate oxytocin is the reference group. RR, relative risk; CI, confidence interval The low-rate oxytocin group required significantly more additional oxytocin than the bolus oxytocin group (73.75% in Group L vs. 40% in Group B; RR = 1.84, 95% CI 1.37 to 2.49). Group L also received a higher proportion of methylergonovine maleate compared to Group B, though this difference was not statistically significant (16.25% vs. 13.75%; RR = 1.18, 95% CI 0.56 to 2.48). One participant in Group L experienced blood loss exceeding 500 ml and subsequently received additional sulprostone. Neonatal Outcomes Neonatal outcomes were favorable in both groups, with all Apgar scores exceeding 7, and no cases requiring neonatal resuscitation or NICU admission. Adverse Effects Mild adverse effects, including nausea, vomiting, flushing, and tachycardia, were minimal and not statistically significant between groups (Table 3 ). However, a statistically significant difference was noted in the incidence of severe adverse effects, particularly hypotension. Group L had a lower incidence of hypotension (11.25%) compared to Group B (26.25%), with a relative risk of 0.43 (95% CI 0.21 to 0.88). No cases of chest pain or ECG changes were reported in either group. Table 3 Oxytocin- related adverse effects outcomes Adverse effects All (N = 160) L group (n = 80) B group (n = 80) RR (95%CI) Mild adverse effects, n (%) Nausea/Vomiting Flushing Tachycardia 5 (3.13) 5 (3.13) 10 (6.25) 1 (1.25) 0 2 (2.50) 4 (5.0) 5 (6.25) 8 (10.00) 0.50 (0.05, 5.40) NA 0.25 (0.05, 1.14) Severe adverse effects, n (%) Hypotension Chest pain ECG change 30 (18.75) 0 0 9 (11.25) 0 0 21 (26.25) 0 0 0.43 (0.21, 0.88) 0 0 Data are presented as number (percentage). RR, relative risk; CI, confidence interval; ECG, electrocardiographic. Discussion This double-blind, randomized study demonstrated that low-rate oxytocin infusion was less effective than an intravenous 5 IU oxytocin bolus for initiating adequate uterine contractions during cesarean delivery. The reduced effectiveness observed with the 0.04 IU/min infusion rate in the low-rate group likely stems from its lower initial dose, which may delay achieving adequate plasma levels of oxytocin necessary for effective uterine contractions. Consequently, the low-rate group required a greater use of additional uterotonic agents to achieve comparable outcomes. Importantly, both groups experienced a low incidence of postpartum hemorrhage (PPH). Our findings contrast with Duffield et al.’s study ( 8 ), which compared oxytocin infusion rates of 2.5 IU/h and 15 IU/h following a 1 IU bolus. In their study, approximately 73% of participants in the low-rate group achieved adequate contractions, whereas our study observed only 58%. This discrepancy may be attributed to protocol differences, as the Duffield study administered a 1 IU bolus for rescue, while we used a 5 IU bolus. Additionally, the Duffield study reported a higher PPH rate, potentially due to the lower bolus dosage in their rescue protocol. Similarly, Qian et al. ( 9 ) examined oxytocin infusion rates ranging from 0 to 8 IU/h after a 1 IU bolus, with adequate uterine tone rates varying from 48–92% across groups. Our study observed lower adequate tone rates in the low-rate group, which may be due to differences in administration protocols. Specifically, initiating an infusion without a bolus may delay reaching effective therapeutic levels of oxytocin. The definition of postpartum hemorrhage (PPH) classifies blood loss exceeding 500 ml as minor and over 1000 ml as major or severe. Prior studies ( 10 ) comparing oxytocin infusion rates of 2.5 IU/h and 5 IU/h reported no significant difference in PPH incidence, aligning with our findings. This suggests that low-rate oxytocin infusion does not increase PPH risk. Oxytocin is associated with dose-dependent cardiovascular effects, including hypotension, tachycardia, and, in rare cases, myocardial infarction. Our study focused on the impact of oxytocin administration on blood pressure, finding that the low-rate infusion group (2.5 IU/h) experienced significantly less hypotension than the 5 IU bolus group at 3 minutes. This result aligns with Sartain et al. ( 3 ), who observed a higher incidence of hypotension with a 5 IU bolus compared to lower doses. Similarly, Butwick et al. ( 11 ) reported greater hypotension incidence with 5 IU doses compared to lower doses (0.5–5 IU). This finding underscores the dose- and rate-dependent nature of oxytocin’s hypotensive effect. Other oxytocin-related side effects, such as flushing and nausea, were infrequent in both groups, consistent with our study. One limitation of our study is the lack of an objective, clinically validated method for assessing uterine tone, necessitating subjective evaluation. We sought to minimize variability by using experienced obstetricians for tone assessments. Conclusion This study found that low-rate oxytocin infusion at 2.5 IU/h was less effective than a 5 IU oxytocin bolus in initiating adequate uterine contractions during cesarean delivery, leading to a higher requirement for additional uterotonic drugs in the low-rate group. Hypotension was associated with the higher dose and faster rate of oxytocin administration. No significant differences were observed in other oxytocin-related adverse events between the two groups. After establishing adequate uterine tone, estimated blood loss (EBL) did not differ between groups. We recommend further research to identify an optimal oxytocin infusion regimen that achieves effective uterine contractions, maintains uterine contractility, minimizes the need for additional uterotonic drugs, and reduces oxytocin-related adverse events. Clinical Implications What is already known on this topic? Current evidence indicates that a 5 IU intravenous oxytocin bolus is effective for initiating adequate uterine contractions during cesarean deliveries. However, a standardized protocol for oxytocin administration during cesarean sections remains lacking, resulting in dosage and regimen variability across hospitals. What does this study add? This study suggests that low-rate oxytocin infusion is less effective for initiating adequate uterine contractions during cesarean delivery compared to a 5 IU bolus, indicating that bolus administration may be preferable for achieving prompt uterine contraction. Declarations Ethics approval and consent to participate The study has been reviewed and approved by the Khon Kaen University Ethics Committee for Human Research based on the Declaration of Helsinki and the ICH Good Clinical Practice Guidelines ( HE651289 ) , and registered with the Thai Clinical Trials Registry on November 12, 2022 (TCTR20221113003). Written informed consent was obtained from all pregnant women scheduled for cesarean sections who agreed to participate. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Funding The authors received no specific funding for this review. Author Contribution Conceptualization: MS, WP, KK; Methodology:MS, WP, CK, KK; Resources: MS, WP, CK, KK; Data collection: MS, WP, CK, DS, MS, NB, KK; Formal analysis: MS, WP, KK; Data Curation: MS, KK; Writing - Original Draft: MS, WP, CK; Writing - Review & Editing: MS, WP, CK, KK; Supervision: KK. Acknowledgements We would like to thank the patients for their participation and the staff at Srinagarind Hospital for their assistance. Availability of data and materials The data used to support the findings of this study are available from the corresponding author upon request. References World Health Organization. WHO recommendation on routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth [Internet]. Geneva: World Health Organization. 2020 [cited 2022 May 13]. https://apps.who.int/iris/handle/10665/336308 Wedisinghe L, Macleod M, Murphy DJ. Use of oxytocin to prevent haemorrhage at caesarean section–a survey of practice in the United Kingdom. Eur J Obstet Gynecol Reprod Biol. 2008;137(1):27–30. Sartain JB, Barry JJ, Howat PW, McCormack DI, Bryant M. Intravenous oxytocin bolus of 2 units is superior to 5 units during elective Caesarean section. Br J Anaesth. 2008;101(6):822–6. Langesaeter E, Rosseland LA, Stubhaug A. Haemodynamic effects of repeated doses of oxytocin during Caesarean delivery in healthy parturients. Br J Anaesth. 2009;103(2):260–2. Thomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing Caesarean section. Br J Anaesth. 2007;98(1):116–9. King KJ, Douglas MJ, Unger W, Wong A, King RAR. Five unit bolus oxytocin at cesarean delivery in women at risk of atony: a randomized, double-blind, controlled trial. Anesth Analg. 2010;111(6):1460–6. Somjit M, Surojananon J, Kongwattanakul K, Kasemsiri C, Sirisom M, Prawannoa K, et al. Comparison of Low Dose versus High Dose of Oxytocin for Initiating Uterine Contraction During Cesarean Delivery: A Randomized, Controlled, Non-Inferiority Trial. Int J Womens Health. 2020;12:667–73. Duffield A, McKenzie C, Carvalho B, Ramachandran B, Yin V, El-Sayed YY, et al. Effect of a High-Rate Versus a Low-Rate Oxytocin Infusion for Maintaining Uterine Contractility During Elective Cesarean Delivery: A Prospective Randomized Clinical Trial. Anesth Analg. 2017;124(3):857–62. Qian XW, Drzymalski DM, Lv CC, Guo FH, Wang LY, Chen XZ. The ED50 and ED95 of oxytocin infusion rate for maintaining uterine tone during elective caesarean delivery: a dose-finding study. BMC Pregnancy Childbirth. 2019;20(1):6. Mohta M, Chowdhury RB, Tyagi A, Agarwal R. Efficacy of different infusion rates of oxytocin for maintaining uterine tone during elective caesarean section: A randomised double blind trial. Anaesth Intensive Care. 2021;49(3):183–9. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin during elective Caesarean delivery. Br J Anaesth. 2010;104(3):338–43. Additional Declarations No competing interests reported. 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The World Health Organization (WHO) recommends administering oxytocin, a uterotonic agent, at a dosage of 10 IU as the standard for preventing and treating PPH due to inadequate uterine contractions (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, the Royal College of Obstetricians and Gynecologists (RCOG) in the United Kingdom suggests reducing the oxytocin dosage to 5 IU (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Both 5 IU and 10 IU doses of oxytocin have been associated with significant side effects, particularly hypotension (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Additionally, studies have reported higher mortality rates in patients receiving higher doses of oxytocin (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePrevious studies have compared the administration of intravenous oxytocin as a bolus followed by continuous infusion with continuous infusion alone, showing no significant differences in uterine contractions between the two methods (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Studies examining low-rate oxytocin infusion have also demonstrated that uterine contraction outcomes are comparable to those with high-rate infusion (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Thus, avoiding immediate intravenous bolus administration before continuous infusion may reduce the risk of oxytocin-related side effects while effectively initiating and sustaining uterine contractions.\u003c/p\u003e \u003cp\u003eCurrently, oxytocin administration practices, including dosage and regimens for preventing and managing inadequate uterine contractions during cesarean sections, vary among hospitals. At Srinagarind Hospital, there is no standardized protocol for oxytocin administration in cesarean deliveries, despite a general trend towards reducing oxytocin doses in alignment with RCOG recommendations. In clinical practice, the standard 5 IU intravenous bolus of oxytocin is still commonly used, though it can result in adverse side effects. This study aims to evaluate the efficacy of low-rate oxytocin infusion as a standalone intervention compared to the standard 5 IU intravenous bolus, assessing its impact on uterine contractions within the first 3 minutes and comparing associated side effects.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSetting and Participants\u003c/h2\u003e \u003cp\u003eThis study was designed as a randomized, controlled, non-inferiority trial. The protocol was approved by the Khon Kaen University Ethics Committee in Human Research, following the Declaration of Helsinki, the ICH Good Clinical Practice guidelines (HE651289), and registered with the Thai Clinical Trials Registry on November 12, 2022 (TCTR20221113003). The study was conducted at Srinagarind Hospital, Khon Kaen University, between October 2022 and August 2023. Written informed consent was obtained from all pregnant women scheduled for cesarean sections who agreed to participate.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003ePregnant women aged 18\u0026ndash;40 years, with a gestational age of 37\u0026ndash;42 weeks and classified as ASA physical status class II, undergoing cesarean section under spinal anesthesia, were eligible for enrollment. Exclusion criteria included a history of prior uterine surgery (excluding prior cesarean section) and conditions associated with a higher risk of inadequate uterine contractions, such as estimated fetal weight\u0026thinsp;\u0026gt;\u0026thinsp;4000 grams, twin pregnancies, chorioamnionitis, polyhydramnios (amniotic fluid index\u0026thinsp;\u0026gt;\u0026thinsp;25 cm), or a history of uterine fibroids during pregnancy. Patients at elevated risk for PPH, including those with a low-lying placenta, prior history of PPH, coagulopathy, thrombocytopenia, and pre-eclampsia, were also excluded. Participants who experienced failed spinal anesthesia were withdrawn from the study.\u003c/p\u003e\n\u003ch3\u003eRandomization and Allocation\u003c/h3\u003e\n\u003cp\u003eParticipants were randomly assigned to groups using sealed opaque envelopes prepared in advance with a computer-generated sequence. Baseline characteristics and anesthesia details were documented for analysis. Qualified anesthesia personnel performed the spinal anesthesia, positioning each patient in either a left lateral or sitting position. A spinal needle (No. 25 or No. 27) was used to administer 0.5% heavy Marcaine (10\u0026ndash;15 mg) combined with morphine (0.2 mg), followed by left uterine displacement after the spinal injection. Upon delivery of the infant, the investigational drug was administered immediately (slow push over 15 seconds) according to the randomized group, followed by an intravenous infusion rate of 125 ml/h.\u003c/p\u003e \u003cp\u003eThe investigational drug was prepared by a non-research anesthesia staff member who was not involved in data collection. The two groups received the following preparations:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLow-rate oxytocin infusion group (Intervention Group)\u003c/b\u003e: Normal Saline Solution (NSS) in a 5 ml syringe was prepared for intravenous bolus. Additionally, a low-rate oxytocin infusion was prepared using Lactated Ringer\u0026rsquo;s Solution (LRS) 1,000 ml\u0026thinsp;+\u0026thinsp;oxytocin 20 IU for intravenous infusion.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eOxytocin bolus group (Control Group)\u003c/b\u003e: Oxytocin 5 IU was prepared in a 5 ml syringe for intravenous bolus, along with Lactated Ringer\u0026rsquo;s Solution (LRS) 1,000 ml for intravenous infusion.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eAt 3 minutes post-delivery, a blinded obstetrician assessed uterine contraction adequacy, categorizing it as either \u0026ldquo;adequate\u0026rdquo; or \u0026ldquo;inadequate.\u0026rdquo; Uterine tone was evaluated on a linear analog scale (LAS) from 0 to 10, where 0 represents absent uterine tone and 10 indicates optimal tone. Uterine tone, blood pressure, heart rate, and adverse events were recorded at 0, 3, 6, 9, and 15 minutes, with standard monitoring every 5 minutes until the surgery was completed.\u003c/p\u003e \u003cp\u003eIf inadequate uterine tone was observed, or if the obstetrician required additional medication to stimulate uterine contractions, uterotonic drugs were administered per the anesthesiologists\u0026rsquo; rescue protocol. In the oxytocin bolus group, the first rescue agent was 5 IU oxytocin. In the low-rate infusion group, oxytocin 5 IU, repeatable up to two times, was administered intravenously over 15 seconds. Subsequent rescue agents in both groups included methylergonovine maleate (0.2 mg, intravenous), misoprostol (800 \u0026micro;g, rectal suppository), and sulprostone (500 \u0026micro;g, intravenous drip over 30 minutes). Any observed side effects were managed according to established standards and guidelines under the anesthesiologist\u0026rsquo;s supervision.\u003c/p\u003e\n\u003ch3\u003ePrimary and Secondary Objectives\u003c/h3\u003e\n\u003cp\u003eThe primary objective of this study was to assess adequate uterine contraction at 3 minutes following oxytocin administration. Secondary objectives included evaluating uterine tone on a linear analog scale (0\u0026ndash;10) at 3 minutes, as well as the total amount of uterotonic drugs used, additional obstetric interventions (e.g., uterine artery ligation, B-Lynch procedure, hysterectomy), mild adverse effects of oxytocin (e.g., nausea, vomiting, flushing, tachycardia), and severe adverse effects (e.g., hypotension, chest pain, ECG changes).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eA rigorous methodology was applied to evaluate whether low-rate oxytocin infusion was non-inferior to the intravenous 5 IU oxytocin bolus in achieving adequate uterine contraction during cesarean delivery. Power analysis was based on a previous study, where the rate of adequate uterine contraction was reported as 84.6%. To detect a 15% difference in uterine contraction rates between groups (non-inferiority margin\u0026thinsp;=\u0026thinsp;0.15) with a 5% significance level and a power of 90%, a sample size of 72 patients per group was calculated. To account for a 5% dropout rate, 80 patients per group were recruited.\u003c/p\u003e \u003cp\u003eCategorical data were analyzed using Fisher\u0026rsquo;s exact test or the Chi-square test, with results presented as numbers and percentages. Continuous data were analyzed using the independent sample T-test, and findings were reported as Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Additionally, relative risk (RR) with a 95% confidence interval (CI) was calculated for relevant outcomes. Analyses were conducted using STATA 10 statistical software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFrom the initial pool of 181 registered participants, 160 participants were ultimately enrolled in the study and randomized into two groups: the low-rate oxytocin infusion group (Group L) and the bolus oxytocin group (Group B), with 80 participants in each group (Figure 1). Baseline characteristics were similar between the two groups are presented in Table 1.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eL group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eB group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean age, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.06 (4.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.79 (4.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (31.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (26.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Body Mass Index, kg/m2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.04 (4.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.56 (3.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNulliparous, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean gestational age, week\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.09 (0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.26 (0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication of cesarean section, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious Cesarean section\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (68.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49 (61.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCephalopelvic disproportion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (16.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (16.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFetal condition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnesthetic level, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (48.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (8.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (51.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreoperative baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean arterial pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.96 (9.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.31 (11.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean heart rate (beat/mins)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.96 (11.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.89 (14.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntravenous fluid preload (mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e923.13 (232.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e922.31 (222.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematocrit (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.24 (51.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.19 (4.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight, g\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3140.88 (356.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3151.53 (327.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003ePrimary Outcome\u003c/h3\u003e\n\u003cp\u003eAdequate uterine contraction at 3 minutes post-oxytocin administration was achieved in a total of 120 participants. A significant difference was observed between the two groups, with 47 participants (58.75%) in the low-rate oxytocin group achieving adequate uterine contraction, compared to 73 participants (91.25%) in the bolus oxytocin group (RR\u0026thinsp;=\u0026thinsp;0.64; 95% CI 0.53 to 0.78).\u003c/p\u003e\n\u003ch3\u003eSecondary Outcomes\u003c/h3\u003e\n\u003cp\u003eSecondary outcomes are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. The mean uterine tone at 3 minutes, categorized on a scale from poor to strong, showed a statistically significant difference between groups. Group L exhibited a lower mean uterine tone (4.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35) compared to Group B (6.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.78) (P-value\u0026thinsp;=\u0026thinsp;0.000).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePrimary and secondary outcome\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;160)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eL group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eB group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdequate uterine contraction at 3 minutes, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47 (58.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73 (91.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.53, 0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eUterine tone at 3 minutes, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePoor (0\u0026ndash;5)\u003c/p\u003e\n \u003cp\u003eModerate (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003eStrong (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e87 (54.37)\u003c/p\u003e\n \u003cp\u003e67 (41.88)\u003c/p\u003e\n \u003cp\u003e6 (3.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59 (73.75)\u003c/p\u003e\n \u003cp\u003e21 (26.25)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (35)\u003c/p\u003e\n \u003cp\u003e46 (57.5)\u003c/p\u003e\n \u003cp\u003e6 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.11 (1.52, 2.92)\u003c/p\u003e\n \u003cp\u003e0.45 (0.30, 0.69)\u003c/p\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdditional uterotonic agents, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eOxytocin\u003c/p\u003e\n \u003cp\u003eMethylergonovine maleate\u003c/p\u003e\n \u003cp\u003eMisoprostol\u003c/p\u003e\n \u003cp\u003eSulprostone\u003c/p\u003e\n \u003cp\u003eEstimate blood loss\u0026thinsp;\u003cspan class=\"Underline\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;500 ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e91 (56.88)\u003c/p\u003e\n \u003cp\u003e24 (15)\u003c/p\u003e\n \u003cp\u003e1 (0.63)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1 (0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59 (73.75)\u003c/p\u003e\n \u003cp\u003e13 (16.25)\u003c/p\u003e\n \u003cp\u003e1 (1.25)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1 (1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (40)\u003c/p\u003e\n \u003cp\u003e11 (13.75)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.84 (1.37, 2.49)\u003c/p\u003e\n \u003cp\u003e1.18 (0.56, 2.48)\u003c/p\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eApgar score at 1, 5 min\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are presented as number (percentage). Low-rate oxytocin is the reference group.\u003c/p\u003e\n\u003cp\u003eRR, relative risk; CI, confidence interval\u003c/p\u003e\n\u003cp\u003eThe low-rate oxytocin group required significantly more additional oxytocin than the bolus oxytocin group (73.75% in Group L vs. 40% in Group B; RR\u0026thinsp;=\u0026thinsp;1.84, 95% CI 1.37 to 2.49). Group L also received a higher proportion of methylergonovine maleate compared to Group B, though this difference was not statistically significant (16.25% vs. 13.75%; RR\u0026thinsp;=\u0026thinsp;1.18, 95% CI 0.56 to 2.48). One participant in Group L experienced blood loss exceeding 500 ml and subsequently received additional sulprostone.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eNeonatal Outcomes\u003c/h2\u003e\n \u003cp\u003eNeonatal outcomes were favorable in both groups, with all Apgar scores exceeding 7, and no cases requiring neonatal resuscitation or NICU admission.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eAdverse Effects\u003c/h2\u003e\n \u003cp\u003eMild adverse effects, including nausea, vomiting, flushing, and tachycardia, were minimal and not statistically significant between groups (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). However, a statistically significant difference was noted in the incidence of severe adverse effects, particularly hypotension. Group L had a lower incidence of hypotension (11.25%) compared to Group B (26.25%), with a relative risk of 0.43 (95% CI 0.21 to 0.88). No cases of chest pain or ECG changes were reported in either group.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eOxytocin- related adverse effects outcomes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAdverse effects\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;160)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eL group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eB group\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;80)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild adverse effects, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNausea/Vomiting\u003c/p\u003e\n \u003cp\u003eFlushing\u003c/p\u003e\n \u003cp\u003eTachycardia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (3.13)\u003c/p\u003e\n \u003cp\u003e5 (3.13)\u003c/p\u003e\n \u003cp\u003e10 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (1.25)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2 (2.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (5.0)\u003c/p\u003e\n \u003cp\u003e5 (6.25)\u003c/p\u003e\n \u003cp\u003e8 (10.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.50 (0.05, 5.40)\u003c/p\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003cp\u003e0.25 (0.05, 1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere adverse effects, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHypotension\u003c/p\u003e\n \u003cp\u003eChest pain\u003c/p\u003e\n \u003cp\u003eECG change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (18.75)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9 (11.25)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (26.25)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.43 (0.21, 0.88)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eData are presented as number (percentage).\u003c/p\u003e\n \u003cp\u003eRR, relative risk; CI, confidence interval; ECG, electrocardiographic.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis double-blind, randomized study demonstrated that low-rate oxytocin infusion was less effective than an intravenous 5 IU oxytocin bolus for initiating adequate uterine contractions during cesarean delivery. The reduced effectiveness observed with the 0.04 IU/min infusion rate in the low-rate group likely stems from its lower initial dose, which may delay achieving adequate plasma levels of oxytocin necessary for effective uterine contractions. Consequently, the low-rate group required a greater use of additional uterotonic agents to achieve comparable outcomes. Importantly, both groups experienced a low incidence of postpartum hemorrhage (PPH).\u003c/p\u003e \u003cp\u003eOur findings contrast with Duffield et al.\u0026rsquo;s study (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), which compared oxytocin infusion rates of 2.5 IU/h and 15 IU/h following a 1 IU bolus. In their study, approximately 73% of participants in the low-rate group achieved adequate contractions, whereas our study observed only 58%. This discrepancy may be attributed to protocol differences, as the Duffield study administered a 1 IU bolus for rescue, while we used a 5 IU bolus. Additionally, the Duffield study reported a higher PPH rate, potentially due to the lower bolus dosage in their rescue protocol.\u003c/p\u003e \u003cp\u003eSimilarly, Qian et al. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) examined oxytocin infusion rates ranging from 0 to 8 IU/h after a 1 IU bolus, with adequate uterine tone rates varying from 48\u0026ndash;92% across groups. Our study observed lower adequate tone rates in the low-rate group, which may be due to differences in administration protocols. Specifically, initiating an infusion without a bolus may delay reaching effective therapeutic levels of oxytocin.\u003c/p\u003e \u003cp\u003eThe definition of postpartum hemorrhage (PPH) classifies blood loss exceeding 500 ml as minor and over 1000 ml as major or severe. Prior studies (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) comparing oxytocin infusion rates of 2.5 IU/h and 5 IU/h reported no significant difference in PPH incidence, aligning with our findings. This suggests that low-rate oxytocin infusion does not increase PPH risk.\u003c/p\u003e \u003cp\u003eOxytocin is associated with dose-dependent cardiovascular effects, including hypotension, tachycardia, and, in rare cases, myocardial infarction. Our study focused on the impact of oxytocin administration on blood pressure, finding that the low-rate infusion group (2.5 IU/h) experienced significantly less hypotension than the 5 IU bolus group at 3 minutes. This result aligns with Sartain et al. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), who observed a higher incidence of hypotension with a 5 IU bolus compared to lower doses. Similarly, Butwick et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) reported greater hypotension incidence with 5 IU doses compared to lower doses (0.5\u0026ndash;5 IU). This finding underscores the dose- and rate-dependent nature of oxytocin\u0026rsquo;s hypotensive effect. Other oxytocin-related side effects, such as flushing and nausea, were infrequent in both groups, consistent with our study.\u003c/p\u003e \u003cp\u003eOne limitation of our study is the lack of an objective, clinically validated method for assessing uterine tone, necessitating subjective evaluation. We sought to minimize variability by using experienced obstetricians for tone assessments.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study found that low-rate oxytocin infusion at 2.5 IU/h was less effective than a 5 IU oxytocin bolus in initiating adequate uterine contractions during cesarean delivery, leading to a higher requirement for additional uterotonic drugs in the low-rate group. Hypotension was associated with the higher dose and faster rate of oxytocin administration. No significant differences were observed in other oxytocin-related adverse events between the two groups. After establishing adequate uterine tone, estimated blood loss (EBL) did not differ between groups. We recommend further research to identify an optimal oxytocin infusion regimen that achieves effective uterine contractions, maintains uterine contractility, minimizes the need for additional uterotonic drugs, and reduces oxytocin-related adverse events.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Clinical Implications","content":"\u003ch2\u003eWhat is already known on this topic?\u003c/h2\u003e\u003cp\u003eCurrent evidence indicates that a 5 IU intravenous oxytocin bolus is effective for initiating adequate uterine contractions during cesarean deliveries. However, a standardized protocol for oxytocin administration during cesarean sections remains lacking, resulting in dosage and regimen variability across hospitals.\u003c/p\u003e\u003ch2\u003eWhat does this study add?\u003c/h2\u003e\u003cp\u003eThis study suggests that low-rate oxytocin infusion is less effective for initiating adequate uterine contractions during cesarean delivery compared to a 5 IU bolus, indicating that bolus administration may be preferable for achieving prompt uterine contraction.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe study has been reviewed and approved by the Khon Kaen University Ethics Committee for Human Research based on the Declaration of Helsinki and the ICH Good Clinical Practice Guidelines \u003cb\u003e(\u003c/b\u003eHE651289\u003cb\u003e)\u003c/b\u003e, and registered with the Thai Clinical Trials Registry on November 12, 2022 (TCTR20221113003). Written informed consent was obtained from all pregnant women scheduled for cesarean sections who agreed to participate.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors received no specific funding for this review.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: MS, WP, KK; Methodology:MS, WP, CK, KK; Resources: MS, WP, CK, KK; Data collection: MS, WP, CK, DS, MS, NB, KK; Formal analysis: MS, WP, KK; Data Curation: MS, KK; Writing - Original Draft: MS, WP, CK; Writing - Review \u0026amp; Editing: MS, WP, CK, KK; Supervision: KK.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe would like to thank the patients for their participation and the staff at Srinagarind Hospital for their assistance.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe data used to support the findings of this study are available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. WHO recommendation on routes of oxytocin administration for the prevention of postpartum haemorrhage after vaginal birth [Internet]. Geneva: World Health Organization. 2020 [cited 2022 May 13]. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://apps.who.int/iris/handle/10665/336308\u003c/span\u003e\u003cspan address=\"https://apps.who.int/iris/handle/10665/336308\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWedisinghe L, Macleod M, Murphy DJ. Use of oxytocin to prevent haemorrhage at caesarean section\u0026ndash;a survey of practice in the United Kingdom. Eur J Obstet Gynecol Reprod Biol. 2008;137(1):27\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSartain JB, Barry JJ, Howat PW, McCormack DI, Bryant M. Intravenous oxytocin bolus of 2 units is superior to 5 units during elective Caesarean section. Br J Anaesth. 2008;101(6):822\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLangesaeter E, Rosseland LA, Stubhaug A. Haemodynamic effects of repeated doses of oxytocin during Caesarean delivery in healthy parturients. Br J Anaesth. 2009;103(2):260\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas JS, Koh SH, Cooper GM. Haemodynamic effects of oxytocin given as i.v. bolus or infusion on women undergoing Caesarean section. Br J Anaesth. 2007;98(1):116\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKing KJ, Douglas MJ, Unger W, Wong A, King RAR. Five unit bolus oxytocin at cesarean delivery in women at risk of atony: a randomized, double-blind, controlled trial. Anesth Analg. 2010;111(6):1460\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSomjit M, Surojananon J, Kongwattanakul K, Kasemsiri C, Sirisom M, Prawannoa K, et al. Comparison of Low Dose versus High Dose of Oxytocin for Initiating Uterine Contraction During Cesarean Delivery: A Randomized, Controlled, Non-Inferiority Trial. Int J Womens Health. 2020;12:667\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuffield A, McKenzie C, Carvalho B, Ramachandran B, Yin V, El-Sayed YY, et al. Effect of a High-Rate Versus a Low-Rate Oxytocin Infusion for Maintaining Uterine Contractility During Elective Cesarean Delivery: A Prospective Randomized Clinical Trial. Anesth Analg. 2017;124(3):857\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQian XW, Drzymalski DM, Lv CC, Guo FH, Wang LY, Chen XZ. The ED50 and ED95 of oxytocin infusion rate for maintaining uterine tone during elective caesarean delivery: a dose-finding study. BMC Pregnancy Childbirth. 2019;20(1):6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohta M, Chowdhury RB, Tyagi A, Agarwal R. Efficacy of different infusion rates of oxytocin for maintaining uterine tone during elective caesarean section: A randomised double blind trial. Anaesth Intensive Care. 2021;49(3):183\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eButwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin during elective Caesarean delivery. Br J Anaesth. 2010;104(3):338\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Low-rate oxytocin infusion, Uterine contraction, Cesarean delivery, Hypotension","lastPublishedDoi":"10.21203/rs.3.rs-5402053/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5402053/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: Administration of oxytocin is the standard for preventing and treating postpartum hemorrhage. This study aims to evaluate the efficacy of low-rate oxytocin infusion compared to a 5 IU intravenous oxytocin bolus, specifically assessing its impact on uterine contractions at 3 minutes and comparing associated side effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterial and Methods:\u003c/strong\u003e This randomized, controlled, non-inferiority trial was conducted at Srinagarind Hospital, Khon Kaen University, between October 2022 and August 2023. A total of 160 pregnant women undergoing cesarean section under spinal anesthesia were randomized into two groups: low-rate oxytocin infusion (Group L) and oxytocin bolus (Group B), with 80 participants in each group. The primary objective was to assess adequate uterine contraction at 3 minutes post-oxytocin administration. Secondary outcomes included uterine tone (measured on a 0–10 linear analog scale) at 3 minutes, the total amount of uterotonic drugs used, additional obstetric procedures required and adverse effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Adequate uterine contraction at 3 minutes was achieved in a total of 120 patients. Group L had a significantly lower rate of adequate uterine contraction compared to Group B, with 47 (58.75%) in Group L versus 73 (91.25%) in Group B (RR 0.64; 95% CI 0.53 to 0.78). The mean uterine tone at 3 minutes was lower in Group L than in Group B (4.68 ± 1.35 vs. 6.01 ± 1.78, respectively; P \u0026lt; 0.001). The incidence of hypotension was also lower in Group L than in Group B (11.25% vs. 26.25%, RR 0.43; 95% CI 0.21 to 0.88).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eLow-rate oxytocin infusion was found to be inferior to a 5 IU oxytocin bolus in achieving adequate uterine contraction during cesarean delivery. Higher doses of oxytocin were associated with an increased risk of hypotension. Further studies are warranted to identify the optimal oxytocin regimen that achieves effective uterine contraction while minimizing the need for additional uterotonic agents and reducing adverse effects.\u003c/p\u003e","manuscriptTitle":"Comparison of low-rate oxytocin infusion versus bolus oxytocin for initiating uterine contraction during Cesarean delivery: A randomized, controlled, non-inferiority trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-11 06:53:10","doi":"10.21203/rs.3.rs-5402053/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c5b367d0-a8a9-4429-8ef3-b3da2c9aaf9d","owner":[],"postedDate":"December 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-17T14:08:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-11 06:53:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5402053","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5402053","identity":"rs-5402053","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}