The Prevention of Hypotension After Epidural Analgesia After Major Surgery

The Prevention of Hypotension After Epidural Analgesia After Major Surgery by Adding Epinephrine to Infusions to Counteract Sympathectomy: a Double- Blind, Controlled, Randomized, Prospective Dose-finding Study

Epidural analgesia via continuous epidurally infused local anesthetic agent (LA) is widely and very successfully used routinely for perioperative pain control in patients undergoing major orthopedic and abdominal surgery since 1928. The choice currently depends on the preference of the APS physician in charge of the case. A frequent unwanted side effect of epidural block is hypotension due to the epidurally injected LA blocking the sympathetic nerves and thus the patient's response to hypotension, which is usually due to hypovolemia and/or an unopposed parasympathetic (via the vagus nerve) nervous system. The purpose of this research study is to see if adding epinephrine, to the epidural anesthetic will decrease possible side effects, such as low blood pressure, and lead to a better effect of the epidural anesthetic.

Study Overview

• Status: Completed
• Conditions: Pain; Hypotension
• Intervention / Treatment: Drug: Ropivacaine; Drug: Epinephrine

Detailed Description

Participants undergoing epidural analgesia to treat perioperative pain associated with major surgery will be approached for their willingness to participate in the study. Participants undergoing major thoracic, abdominal, or orthopaedic surgery for whom thoracic or lumbar epidural block would be indicated and planned for intraoperative and postoperative analgesia as per the University of Florida Acute Pain Service (APS) usual and routine practice will be included in this study.

All participants will receive a standardized continuous epidural block at the appropriate level for the planned surgery by the APS physicians in the block room that day. For the standardized continuous epidural block, placement will be confirmed with loss of resistance technique (LORA), wave form analysis or nerve stimulation.

Participants will be randomly allocated by computer-generated randomization to one of four groups. This will be a quintuple blinded prospective study. The anesthesiologist managing the intraoperative anesthesia, the anesthesiologists (APS) placing the blocks and following the participants on the floors, the research nurse taking the measurement, the surgeons, nor the participants will be aware of what combination of drugs are used for the epidural block infusion.

The three groups will consist of:

1. Group A (Ropivacaine 0.2% infusion; Control group)
2. Group B (Ropivacaine 0.2% + 2 mcg/mL epinephrine)
3. Group C (Ropivacaine 0.2% + 5 mcg/mL epinephrine)

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• undergoing epidural analgesia to treat perioperative pain associated with major surgery
• undergoing major thoracic surgery
• undergoing major abdominal surgery
• undergoing major orthopaedic surgery

Exclusion Criteria:

• sepsis
• acute trauma
• coagulopathy
• preoperative hemodynamic instability
• symptomatic coronary artery disease
• patients from the ICU whose tracheas were intubated for any cause
• allergies to medications in the protocol
• primary or secondary block failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Ropivacaine only Control group; The participants in this group will receive standard anesthesia, epidural analgesia with 0.2% ropivacaine with no epinephrine added during the procedure.	Drug: Ropivacaine; Epidural block infusion with Ropivacaine 0.2% will be provided as the anesthesia per standard of care during the procedure.; Other Names: Naropin
ACTIVE_COMPARATOR: Ropivacaine + 2 mcg/mL epinephrine; The participants in this group will receive standard anesthesia (Ropivacaine 0.2%) with the addition of 2mcg/mL of epinephrine during the procedure.	Drug: Ropivacaine; Epidural block infusion with Ropivacaine 0.2% will be provided as the anesthesia per standard of care during the procedure.; Other Names: Naropin; Drug: Epinephrine; Participants will receive epinephrine in their epidural block infusion during the procedure. The amount of epinephrine provided during the procedure will be based on the group assignment.; Other Names: Adrenalin
ACTIVE_COMPARATOR: Ropivacaine + 5 mcg/mL epinephrine; The participants in this group will receive standard anesthesia (Ropivacaine 0.2%) with the addition of 5mcg/mL of epinephrine during the procedure.	Drug: Ropivacaine; Epidural block infusion with Ropivacaine 0.2% will be provided as the anesthesia per standard of care during the procedure.; Other Names: Naropin; Drug: Epinephrine; Participants will receive epinephrine in their epidural block infusion during the procedure. The amount of epinephrine provided during the procedure will be based on the group assignment.; Other Names: Adrenalin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes between the 3 groups assessed by blood pressure measurement	Hypotension will be assessed by systolic blood pressure (SBP) > 20% below the baseline preoperative measurements and acquired before the epidural or any sedation has been administered and the intra-operative period	Change from baseline to end of the intra-operative period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes between the 3 groups assessed by the spread of local anesthetic (block) effect	Spread of local anesthetic (block) effect as tested by sensitivity to cold recorded every hour postoperatively and every 8 hours for the subsequent 72 hours after discharge from the PACU.	Change from baseline to 72 hours after discharge from the post anesthesia care unit (PACU)
Changes between the 3 groups assessed by ambulation after surgery	Ambulation on post-op day 1, post-op day 2 and post-op day 3, will be recorded by distance ambulated per 24-hour period.	From post-operative (post-op) day 1 to post-op day 3
Changes between the 3 groups assessed by opioid usage	Opioid usage data will be recorded and converted to morphine equivalents and averaged for day 0, and post-op days 1, 2, and 3 per group.	From day of surgery (0) to post-op day 3
Changes between the 3 groups assessed by opioid-related side effects	Side effects such as pruritus, nausea/vomiting, and respiratory depression (defined as respiratory rate less than 10 breaths per minute of oxygen saturation more than 7 points lower that the patients preoperative value on room air) will be recorded.	From day of surgery (0) to post-op day 3
Changes between the 3 groups assessed by fluid balance	24 hour intake and output for the first 72 hours to assess fluid balance	From post-op day 1 to post-op day 3
Changes between the 3 groups assessed by length of hospitalization	Length of hospitalization	From post-op day 1 to post-op day 3
Changes between the 3 groups assessed by amount of days before return to oral intake status	Return to oral intake status	From post-op day 1 to post-op day 3

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: I. Heermann Anesthesia Foundation
• Investigators: Principal Investigator: Olga C. Nin, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2016
• Primary Completion (ACTUAL): October 4, 2017
• Study Completion (ACTUAL): September 14, 2018

Study Registration Dates

• First Submitted: March 23, 2016
• First Submitted That Met QC Criteria: March 23, 2016
• First Posted (ESTIMATE): March 30, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 19, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Epidural Analgesia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Ropivacaine; Epinephrine
• Other Study ID Numbers: IRB201600185

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