Minimum Effective Volume of Crystalloid Co-Loading to Prevent Spinal Anesthesia-Induced Hypotension in Cesarean Section

Determination of the Minimum Effective Volume of Crystalloid Co-Loading for Preventing Spinal Anesthesia-Induced Hypotension in Cesarean Section: A Biased Coin Design Study

The goal of this clinical trial is to find the minimum effective volume of IV crystalloid that should be given with phenylephrine to prevent hypotension caused by spinal anesthesia in healthy, term pregnant adults having elective cesarean delivery.

The main questions are:

What is the minimum effective volume (MEV90, mL/kg) of crystalloid co-loading that prevents spinal-anesthesia-induced hypotension in ≥90% of participants?

What maternal side effects and newborn outcomes occur with this strategy (e.g., nausea/vomiting, need for extra vasopressors, total fluids/blood loss, Apgar scores, and umbilical cord blood gases)?

There is no separate comparison group; this is a single-arm, adaptive dose-finding study.

Participants will:

Receive a predefined volume of IV crystalloid over ~10 minutes during spinal anesthesia while phenylephrine is infused. Have blood pressure and symptoms monitored; receive rescue treatment if needed. Allow the next participant's fluid volume to be adjusted based on whether hypotension occurred (biased-coin design). Be followed through postoperative day 2 for maternal and newborn outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Induced Hypotension in Cesarean Delivery
• Intervention / Treatment: Other: Intravenous Crystalloid Co-Loading

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant adults ≥19 years scheduled for elective cesarean delivery under spinal anesthesia
• Term pregnancy (≥37 weeks' gestation)

Exclusion Criteria:

• Emergency cesarean delivery
• Hypertensive disorders of pregnancy (preeclampsia/eclampsia) or hypertension
• Multiple gestation
• Body weight <50 kg or BMI >35 kg/m²
• Renal impairment or eGFR ≤90 mL/min/1.73 m²
• Heart failure or other heart disease
• History of bronchial asthma or other pulmonary disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Crystalloid Co-Loading; Participants undergo spinal anesthesia for elective cesarean delivery. Immediately after intrathecal injection, a predefined volume of balanced crystalloid (co-loading) is infused over ~10 minutes while a prophylactic phenylephrine infusion is initiated per protocol. The crystalloid volume for each successive participant is adjusted using a biased-coin up-and-down algorithm to identify the minimum effective volume that prevents spinal-anesthesia-induced hypotension in ≥90% of patients (MEV90, mL/kg). Blood pressure is monitored frequently; rescue phenylephrine and/or fluids are permitted to maintain predefined blood pressure ranges. Maternal adverse events and neonatal outcomes are recorded through postoperative day 2.

Other: Intravenous Crystalloid Co-Loading; Balanced crystalloid is infused intravenously immediately after intrathecal injection as a co-load. A predefined volume (mL/kg) is administered over ~10 minutes. The volume for successive participants is adapted by a biased-coin up-and-down algorithm to estimate the minimum effective volume (MEV90) that prevents spinal-anesthesia-induced hypotension. Rescue fluids are allowed per protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Effective Volume (MEV90) of Intravenous Crystalloid Co-Loading (mL/kg)	The smallest crystalloid co-loading dose (mL/kg) that prevents spinal-anesthesia-induced hypotension in ≥90% of participants when given with prophylactic phenylephrine.	From intrathecal injection (start of spinal anesthesia) to end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of intraoperative hypotension (mmHg)	Hypotension is defined as a drop in systolic blood pressure (SBP) to < 80% of the participant's baseline SBP (mmHg). Baseline SBP is the mean of the last three ward SBP measurements obtained before operating room admission.	From intrathecal injection to end of surgery
Incidence of intraoperative hypertension (mmHg)	Hypertension is defined as any occurrence of systolic blood pressure (SBP) > 120% of baseline SBP (mmHg) after spinal anesthesia. Baseline SBP is the mean of the last three ward SBP measurements obtained before operating room admission.	From intrathecal injection to end of surgery
Additional bolus phenylephrine requirement	Administration of rescue phenylephrine bolus in addition to the protocolized prophylactic phenylephrine infusion to treat or prevent hypotension after spinal anesthesia. Hypotension is defined as SBP < 80% of baseline SBP (mmHg) or MAP < 65 mmHg. Baseline SBP is the mean of the last three ward SBP measurements obtained before operating room admission. When hypotension occurs, phenylephrine 100 µg is administered as an IV bolus to restore blood pressure. The outcome is recorded as number of phenylephrine boluses.	From intrathecal injection to end of surgery
Total Phenylephrine Dose (µg)	Total intraoperative phenylephrine dose administered after spinal anesthesia, defined as the sum of the prophylactic infusion dose and all rescue bolus doses. he prophylactic infusion starts at 1,500 µg/h and the infusion rate is reduced if systolic blood pressure (SBP) exceeds 120% of baseline SBP (mmHg). Baseline SBP is the mean of the last three ward SBP measurements obtained before operating room admission. Rescue bolus protocol: phenylephrine 100 µg IV per hypotensive episode (SBP < 80% of baseline SBP [mmHg] or MAP < 65 mmHg), repeated as needed. Dose will be abstracted from the anesthesia record (infusion rate × time plus boluses) and summarized in micrograms (µg).	From intrathecal injection to end of surgery
Estimated blood loss (mL)	Calculated as (suction canister volume - irrigation volume) + gravimetric estimate of soaked sponges/drapes (1 g ≈ 1 mL). For cesarean delivery, amniotic fluid is excluded.	From skin incision to end of surgery
Incidence of Maternal Nausea Associated With Hypotension	Occurrence of nausea temporally associated with hypotension after spinal anesthesia. Recorded as yes/no (≥1 episode) and number of episodes.	From intrathecal injection to end of surgery
Incidence of Maternal Vomiting Associated With Hypotension	Occurrence of vomiting temporally associated with hypotension after spinal anesthesia. Recorded as yes/no (≥1 episode) and number of emetic events.	From intrathecal injection to end of surgery
Incidence of Maternal Dizziness/Lightheadedness Associated With Hypotension	Occurrence of dizziness/lightheadedness temporally associated with hypotension after spinal anesthesia. Recorded as yes/no (≥1 episode) and number of episodes.	From intrathecal injection to end of surgery
Neonatal Apgar score at 1Minute	The Apgar score (range 0-10) assessed 1 minute after birth by clinical staff according to standard practice. It is the sum (0-2 each) of heart rate, respiratory effort, muscle tone, reflex irritability, and skin color. Recorded as the total score (0-10) and, if available, the five component scores.	At 1 minute after birth
Neonatal Apgar Score at 5 Minutes	The Apgar score (range 0-10) assessed 5 minutes after birth by clinical staff according to standard practice. It is the sum (0-2 each) of heart rate, respiratory effort, muscle tone, reflex irritability, and skin color. Recorded as the total score (0-10) and, if available, the five component scores.	At 5 minutes after birth
Umbilical Arterial pH	Umbilical cord arterial blood gas pH obtained immediately after birth from a double-clamped cord segment and analyzed per routine laboratory practice.	At delivery (immediately after birth)
Umbilical Arterial Base Excess (mmol/L)	Umbilical cord arterial blood gas base excess measured immediately after birth from a double-clamped cord segment, processed per routine laboratory practice.	At delivery (immediately after birth)
Pulmonary edema	New-onset pulmonary edema within 48 hours after surgery, defined by physician diagnosis supported by clinical findings (e.g., dyspnea, crackles) and/or objective evidence (e.g., new supplemental oxygen requirement or SpO₂ ≤ 92% on room air, chest imaging consistent with interstitial/alveolar edema). Record as yes/no (≥1 event).	Through postoperative day 2
Clinically Significant Generalized Edema	Generalized pitting edema present within 48 hours after surgery, defined by ≥1 of the following objective criteria (excluding localized, surgical-site-limited edema): (A) Physical exam: pitting grade ≥2+ in ≥2 anatomic regions (e.g., bilateral pretibial/ankle, hands/forearms, sacral, or periorbital), using the standard indentation scale - 2+: ~4 mm pit, brief rebound; 3+: ~6 mm pit, 10-60 s rebound; 4+: ~8 mm pit, >60 s rebound. (B) Anthropometry: body weight increase ≥2% (or ≥2 kg) from the preoperative baseline or bilateral mid-calf circumference increase ≥2 cm from baseline. (C) Therapeutic criterion: initiation or escalation of diuretic therapy (e.g., IV/PO loop diuretic) for generalized edema as judged by the treating clinician. Recorded as yes/no (≥1 criterion met)	Through postoperative day 2
Acute Heart Failure	New diagnosis of acute heart failure within 48 hours after surgery, characterized by symptoms/signs (e.g., dyspnea, orthopnea, pulmonary congestion), objective evidence (e.g., chest radiographic congestion, elevated BNP/NT-proBNP if available, or echocardiographic findings), and requirement for treatment (e.g., IV diuretics, vasodilators, inotropes, or noninvasive ventilation). Record as yes/no (≥1 event).	Through postoperative day 2

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 27, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 14, 2025
• First Submitted That Met QC Criteria: December 30, 2025
• First Posted (Actual): January 7, 2026

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2508-038-1665

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No