The Prevention of Hypotension After Epidural Analgesia After Major Surgery

Phase 1

Completed

Conditions: Hypotension
Pain

Interventions: Drug: Ropivacaine
Drug: Epinephrine

Registration Number: NCT02722746

Lead Sponsor: University of Florida

Brief Summary: 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.

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)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ropivacaine only Control group	Ropivacaine	The participants in this group will receive standard anesthesia, epidural analgesia with 0.2% ropivacaine with no epinephrine added during the procedure.
Ropivacaine + 2 mcg/mL epinephrine	Ropivacaine	The participants in this group will receive standard anesthesia (Ropivacaine 0.2%) with the addition of 2mcg/mL of epinephrine during the procedure.
Ropivacaine + 2 mcg/mL epinephrine	Epinephrine	The participants in this group will receive standard anesthesia (Ropivacaine 0.2%) with the addition of 2mcg/mL of epinephrine during the procedure.
Ropivacaine + 5 mcg/mL epinephrine	Ropivacaine	The participants in this group will receive standard anesthesia (Ropivacaine 0.2%) with the addition of 5mcg/mL of epinephrine during the procedure.
Ropivacaine + 5 mcg/mL epinephrine	Epinephrine	The participants in this group will receive standard anesthesia (Ropivacaine 0.2%) with the addition of 5mcg/mL of epinephrine during the procedure.

Primary Outcome Measures

Name	Time	Method
Changes Between the 3 Groups Assessed by Blood Pressure Measurement	Change from baseline to end of the intra-operative period	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. The median time to end of intraoperative period was 2:37 (hours:min), ranging from 0:53 to 7:30.

Secondary Outcome Measures

Name	Time	Method
Changes Between the 3 Groups Assessed by Ambulation After Surgery	From post-operative (post-op) day 1 to post-op day 3	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, calculating mean ambulation in feet per day
Changes Between the 3 Groups Assessed by Opioid Usage	From day of surgery (0) to post-op day 3	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.
Changes Between the 3 Groups Assessed by Opioid-related Side Effects	From day of surgery (0) to post-op day 3	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.
Changes Between the 3 Groups Assessed by Fluid Balance	From post-op day 1 to post-op day 3	24 hour intake and output for, the first 72 hours (up until POD 3) to assess fluid balance, reported as median intake and output per day (in milliliters per day).
Changes Between the 3 Groups Assessed by Length of Hospitalization	post-op period, up until discharge	Length of hospitalization, recorded as median days
Changes Between the 3 Groups Continously Measured Cardiovascular Outcomes - Oxygen Saturation	Change across preoperative, intraoperative, Post Anesthesia Care Unit (PACU), and transfer to floor (up to 72 hours)	Changes in oxygen saturation (SpO2), and heart rate (HR) assesed by area-under-the-curve calculated using pre-op as reference value. Measures were summarized across four time intervals, preoperative, intraoperative, PACU, and transfer to floor, with these intervals as x-axis for AUC
Changes Between the 3 Groups Assessed by Days to Return to Oral Intake Status	post-op period, up until discharge	Return to oral intake (PO) status, recorded in median days
Changes Between the 3 Groups Assessed by the Spread of Local Anesthetic (Block) Effect	Preop, post anesthesia care unit (PACU), Post-op Da 1 (POD 1, 72 hours after discharge from PACU)	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. Cold was applied to dermatomes (i.e. segments/areas of skin primarily assoicated with one spinal nerve), then sensitivty to cold was recorded to determine spread of block across spinal segments.
Changes Between the 3 Groups Continously Measured Cardiovascular Outcomes - Blood Pressure	Change across preoperative, intraoperative, Post Anesthesia Care Unit (PACU), and transfer to floor (up to 72 hours)	Changes in systolic blood pressure (SBP) , diastolic blood pressure (DBP), mean arterial blood pressure (MAP) assesed by area-under-the-curve calculated using pre-op as reference value. Measures were summarized across four time intervals, preoperative, intraoperative, PACU, and transfer to floor, with these intervals as x-axis for AUC
Differences Between the 3 Groups Assessed by Pain	Measured at 12-hour intervals for first 48 hours postopoerative	Pain measured by and visual analog pain score on the Defense and Veterans Pain Rating Scale. This scale ranges from 0 to 10, with higher scores indicating greater pain. Pain scores were average within in 12-hour time interval for comparison.
Changes Between the 3 Groups Continously Measured Cardiovascular Outcomes - Respiratory Rate	Change from preoperative, intraoperative, Post Anesthesia Care Unit (PACU), and transfer to floor (up to 72 hours)	Changes in respiratory rate (RR) assesed by area-under-the-curve (AUC) calculated using pre-op as reference value. Measures were summarized across four time intervals, preoperative, intraoperative, PACU, and transfer to floor, with these intervals as x-axis for AUC
Changes Between the 3 Groups Continously Measured Cardiovascular Outcomes - Heart Rate	Change across preoperative, intraoperative, Post Anesthesia Care Unit (PACU), and transfer to floor (up to 72 hours)	Changes in heart rate (HR) assesed by area-under-the-curve calculated using pre-op as reference value. Measures were summarized across four time intervals, preoperative, intraoperative, PACU, and transfer to floor, with these intervals as x-axis for AUC