Plasmatic Catecholamines: Randomized Controlled Trial Comparing Epidural Versus Combined Spinal-epidural

Plasmatic Catecholamines After Neuraxial Labor Analgesia: a Randomized Controlled Trial Comparing Epidural Versus Combined Spinal-epidural

Combined spinal-epidural (CSE) for labor analgesia has been associated with fetal bradycardia and uterine hypertonia, possibly due to asymmetric decrease in catecholamine levels, when compared with epidural analgesia (EP).

Study Overview

• Status: Completed
• Conditions: Fetal Bradycardia; Hypertonic Uterine; Catecholamines
• Intervention / Treatment: Drug: Epidural bupivacaine with vasoconstrictor 0.125%; Drug: Epidural sufentanil; Procedure: Placement of the epidural catheter; Drug: Intrathecal hyperbaric bupivacaine solution 0.5%; Drug: Intrathecal morphine; Procedure: Placement of an epidural catheter to the catheter through technical needle; Drug: Intrathecal sufentanil

Detailed Description

Background: Combined spinal-epidural technique for labor analgesia has been associated with fetal bradycardia and uterine hypertonia, when compared with epidural analgesia, possibly due to asymmetric decrease in catecholamine levels (epinephrine and norepinephrine) following neuraxial block. However, there are no studies comparing plasmatic catecholamine levels between those two techniques. This study aimed to compare spinal-epidural versus epidural regarding pre and post-analgesia catecholamine levels, uterine tone and fetal heart rate.

Methods: Randomized clinical trial with 47 laboring patients divided in two groups. Primary outcome was plasmatic catecholamine measurements before and after neuraxial block. Secondary outcomes were fetal heart rate changes, uterine hypertonia, hypotension episodes, pain relief and fetal outcomes.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05408000
    • Shirley Andrade Santos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Parturients aged over 18 years were included when they requested labor analgesia. The inclusion criteria were: patients between 37 and 42 gestational weeks, single pregnancy, in active labor (induced or spontaneous), requesting analgesia with 7 cm or less of cervical dilation. As it is a center that attends only high-risk pregnancies, ASA II or III

Exclusion Criteria:

Contraindications to interventions, either due to severe comorbidity or contraindication to neuraxial block; previous use of systemic opioids during labor, maternal amniotic infection or known fetal diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Puncture epidural; Women in labor the epidural group will receive epidural bupivacaine with vasoconstrictor 0.125% 10 ml plus 20 micrograms sufentanil, followed by the placement of the epidural catheter	Drug: Epidural bupivacaine with vasoconstrictor 0.125%; 10 ml; Drug: Epidural sufentanil; 20 mcg; Procedure: Placement of the epidural catheter; Placement of the epidural catheter
ACTIVE_COMPARATOR: Puncture combined spinal-epidural; The mothers of the combined spinal-epidural analgesia group will receive intrathecal hyperbaric bupivacaine solution 0.5% 2.5 mg plus 5.0 micrograms of sufentanil and plus 60 micrograms of morphine, followed by placement of an epidural catheter to the catheter through technical needle	Drug: Intrathecal hyperbaric bupivacaine solution 0.5%; 2.5 mg; Drug: Intrathecal morphine; 60 mcg; Procedure: Placement of an epidural catheter to the catheter through technical needle; Placement of an epidural catheter to the catheter through technical needle; Drug: Intrathecal sufentanil; 5 mcg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cathecolamines levels	Pattern of cathecolamines levels	at the moment of analgesia and 20 minutes after
Fetal bradycardia	Fetal bradycardia is defined as the baseline drops to less than 100 bpm	15 minutes before analgesia and 30 minutes after continuously
Increase in uterine tone	Increase in uterine tone (qualitative measure)	15 minutes before analgesia and 30 minutes after continuously

Secondary Outcome Measures

Outcome Measure	Time Frame
Maternal hipotension	30 minutes after analgesia (measures every 5 minutes)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores		20 minutes after analgesia (measures every 5 minutes)
APGAR score		At birth
Fetal acidosis	umbilical arterial blood	At birth

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Shirley Santos, MD, Anesthesiologist

Publications and helpful links

General Publications

• Baschat AA. Fetal growth restriction - from observation to intervention. J Perinat Med. 2010 May;38(3):239-46. doi: 10.1515/jpm.2010.041.
• Abrao KC, Francisco RPV, Miyadahira S, Cicarelli DD, Zugaib M. Elevation of uterine basal tone and fetal heart rate abnormalities after labor analgesia: a randomized controlled trial. Obstet Gynecol. 2009 Jan;113(1):41-47. doi: 10.1097/AOG.0b013e31818f5eb6.
• Van de Velde M, Vercauteren M, Vandermeersch E. Fetal heart rate abnormalities after regional analgesia for labor pain: the effect of intrathecal opioids. Reg Anesth Pain Med. 2001 May-Jun;26(3):257-62. doi: 10.1053/rapm.2001.22258.
• Nielsen PE, Erickson JR, Abouleish EI, Perriatt S, Sheppard C. Fetal heart rate changes after intrathecal sufentanil or epidural bupivacaine for labor analgesia: incidence and clinical significance. Anesth Analg. 1996 Oct;83(4):742-6. doi: 10.1097/00000539-199610000-00014.
• Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet. 1995 Jun 3;345(8962):1413-6. doi: 10.1016/s0140-6736(95)92602-x.
• Nakamura G, Ganem EM, Rugolo LM, Castiglia YM. Effects on mother and fetus of epidural and combined spinal-epidural techniques for labor analgesia. Rev Assoc Med Bras (1992). 2009 Jul-Aug;55(4):405-9. doi: 10.1590/s0104-42302009000400014.
• Patel NP, El-Wahab N, Fernando R, Wilson S, Robson SC, Columb MO, Lyons GR. Fetal effects of combined spinal-epidural vs epidural labour analgesia: a prospective, randomised double-blind study. Anaesthesia. 2014 May;69(5):458-67. doi: 10.1111/anae.12602.
• Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna AM. Combined spinal-epidural versus epidural analgesia in labour. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD003401. doi: 10.1002/14651858.CD003401.pub3.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 12, 2017
• Primary Completion (ACTUAL): October 16, 2020
• Study Completion (ACTUAL): October 16, 2020

Study Registration Dates

• First Submitted: December 21, 2015
• First Submitted That Met QC Criteria: January 24, 2016
• First Posted (ESTIMATE): January 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 4, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: analgesia; fetal bradycardia; hypertonic uterine
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Bradycardia; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Anesthetics, Local; Bupivacaine; Morphine; Sufentanil; Dsuvia; Vasoconstrictor Agents
• Other Study ID Numbers: 45992815000000068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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