RCT of Epinephrine (None, 100mcg, and 200mcg) in a Hyperbaric Bupivacaine, Fentanyl and Morphine Spinal in C-sections.

NCT03335293 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: IRB201702657 - A
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, randomized, double blind study of 75 patients (n=25 for each group) in which epinephrine (100mcg or 200mcg) or normal saline vehicle is added to intrathecal hyperbaric bupivacaine (0.75% bupivacaine hydrochloride in 8.25% dextrose), fentanyl, and morphine to prolong the duration of the spinal anesthetic in scheduled cesarean deliveries. The primary outcome of duration will be the time to T10 level sensory regression as well as motor level regression that will be graded via the modified Bromage scale. Repeat cesarean sections, in particular, are associated with increased operative time and thus often performed with a spinal-epidural (CSE) technique. The epidural component is, however, untested and may not provide adequate anesthesia, thus the higher risk of conversion to a general anesthesia. Epinephrine is routinely used to prolong spinal anesthesia. If effective for the duration of a repeat cesarean section it would obviate the additional time and risks of performing the epidural and still avoid sufficient duration to avoid conversion to a general anesthetic.

Conditions

Pregnancy; Cesarean Section

Keywords

pregnancy; repeat cesarean section; spinal anesthesia; bupivacaine; epinephrine; intrathecal; analgesia

Outcome Measures

Primary Outcomes (5)

• T4 sensory level

  Time to T4 sensory level (this will be assessed by pin prick at the anterior axillary line)

  15 minutes

• T10 sensory regression

  Time to regression to a T10 sensory level (this will be assessed by pinprick at the anterior axillary line)

  120 minutes

• Analgesia

  Analgesia levels of the patient during the surgery (Pain scores will be measured at the beginning of surgery and during delivery, uterine manipulation, peritoneal suturing and skin closure. 0-10 pan scale)

  120 minutes

• Epidural dosing

  Time elapsed after the spinal dose to the start of epidural dosing (this will be be assessed by review of the anesthesia record as the first recorded supplemental does of local anesthetic)

  120 minutes

• Satisfaction

  Satisfaction levels of the patient during the surgery. (Maternal satisfaction will be quantified using a VAS score (0=no satisfaction and 100=full satisfaction) at the end of surgery and during a postoperative patient examination. )

  120 minutes and up to 24 hours after surgery

Study Arms (3)

Placebo

PLACEBO COMPARATOR

normal saline vehicle added to subarachnoid block

Other: normal saline

100 mcg epinephrine

EXPERIMENTAL

100 mcg epinephrine added to subarachnoid block

Drug: 100 mcg Epinephrine

200 mcg epinephrine

EXPERIMENTAL

200 mcg epinephrine added to subarachnoid block

Drug: 200 mcg Epinephrine

Interventions

100 mcg Epinephrine DRUG

This study will evaluate the optimal dose of epinephrine as an adjunct to spinal doses of 1.6 mL hyperbaric bupivacaine + 20 mcg preservative free fentanyl + 150 mcg preservative-free morphine.

100 mcg epinephrine

normal saline OTHER

placebo comparator

Placebo

200 mcg Epinephrine DRUG

This study will evaluate the optimal dose of epinephrine as an adjunct to spinal doses of 1.6 mL hyperbaric bupivacaine + 20 mcg preservative free fentanyl + 150 mcg preservative-free morphine.

200 mcg epinephrine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Elective C-section patients
• ASA physical status class 1-3
• Age \>18 years
• Height 140-180 cm
• Singleton pregnancy
• Gestational age ≥35 weeks

You may not qualify if:

• Age \< 18 yo
• Prisoner status
• BMI \> 45 Laboring patients with epidural going for emergency C-section Opioid abuse in the past 6 months Allergies to any of the adjuncts added to the spinal drug. Ruptured membranes four or more previous cesarean deliveries intrauterine growth retardation, abnormal placentation

Sponsors & Collaborators

• University of Florida: lead

Related Publications (9)

• Abouleish E, Rawal N, Fallon K, Hernandez D. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg. 1988 Apr;67(4):370-4.

  PMID: 3354872 BACKGROUND

• Abouleish E, Rawal N, Rashad MN. The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: a prospective study of 856 cases. Reg Anesth. 1991 May-Jun;16(3):137-40.

  PMID: 1883770 BACKGROUND

• Abouleish E, Rawal N, Tobon-Randall B, Rivera-Weiss M, Meyer B, Wu A, Rashad MN. A clinical and laboratory study to compare the addition of 0.2 mg of morphine, 0.2 mg of epinephrine, or their combination to hyperbaric bupivacaine for spinal anesthesia in cesarean section. Anesth Analg. 1993 Sep;77(3):457-62. doi: 10.1213/00000539-199309000-00007.

  PMID: 8368545 BACKGROUND

• Ginosar Y, Mirikatani E, Drover DR, Cohen SE, Riley ET. ED50 and ED95 of intrathecal hyperbaric bupivacaine coadministered with opioids for cesarean delivery. Anesthesiology. 2004 Mar;100(3):676-82. doi: 10.1097/00000542-200403000-00031.

  PMID: 15108985 BACKGROUND

• Gurbet A, Turker G, Kose DO, Uckunkaya N. Intrathecal epinephrine in combined spinal-epidural analgesia for labor: dose-response relationship for epinephrine added to a local anesthetic-opioid combination. Int J Obstet Anesth. 2005 Apr;14(2):121-5. doi: 10.1016/j.ijoa.2004.12.002.

  PMID: 15795147 BACKGROUND

• LEIMDORFER A, METZNER WR. Analgesia and anesthesia induced by epinephrine. Am J Physiol. 1949 Apr;157(1):116-21. doi: 10.1152/ajplegacy.1949.157.1.116. No abstract available.

  PMID: 18144412 BACKGROUND

• Moore JM, Liu SS, Pollock JE, Neal JM, Knab JH. The effect of epinephrine on small-dose hyperbaric bupivacaine spinal anesthesia: clinical implications for ambulatory surgery. Anesth Analg. 1998 May;86(5):973-7. doi: 10.1097/00000539-199805000-00011.

  PMID: 9585279 BACKGROUND

• Onishi E, Murakami M, Hashimoto K, Kaneko M. Optimal intrathecal hyperbaric bupivacaine dose with opioids for cesarean delivery: a prospective double-blinded randomized trial. Int J Obstet Anesth. 2017 May;31:68-73. doi: 10.1016/j.ijoa.2017.04.001. Epub 2017 Apr 13.

  PMID: 28623089 BACKGROUND

• PRIDDLE HD, ANDROS GJ. Primary spinal anesthetic effects of epinephrine. Curr Res Anesth Analg. 1950 May-Jun;29(3):156-62. No abstract available.

  PMID: 15414611 BACKGROUND

MeSH Terms

Conditions

Agnosia

Interventions

Epinephrine; Saline Solution

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Paul Mongan, MD

  UF COMJ Department of Anesthesiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: November 7, 2017
• Study Start: October 1, 2019
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: November 25, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share