Trial Outcomes & Findings for Four Quadrants Transverse Abdominus Plane (4Q-TAP) Block With Plain and Liposomal Bupivacaine vs. Thoracic Epidermal Analgesia (TEA) in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) on an Enhanced Recovery Pathway (NCT NCT03359811)

Last Updated: 2022-02-18

Results Overview

To compare the efficacy of 4 quadrants TAP blocks (4Q-TAP) versus Thoracic Epidural Analgesia (routine care) on the quality of recovery 48 hours after CRS-HIPEC surgery, measure by QoR-15 changes from Pre-Op to POD2. The QoR scale is a validated scoring system that allows for the quantification of a patient's early postoperative health status. The minimum score 0 and maximum score 150. The higher score mean a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

75 participants

Primary outcome timeframe

48 hours after CRS-HIPEC surgery

Results posted on

2022-02-18

Participant Flow

Patients were recruited from November 2017 to February 2020.

A total of 75 participants consented, 5 participants were inevaluable.

Participant milestones

Participant milestones
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Overall Study STARTED	35	35
Overall Study COMPLETED	33	35
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Overall Study Protocol Violation	2	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.	Total n=68 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=33 Participants	0 Participants n=35 Participants	0 Participants n=68 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=33 Participants	29 Participants n=35 Participants	53 Participants n=68 Participants
Age, Categorical >=65 years	9 Participants n=33 Participants	6 Participants n=35 Participants	15 Participants n=68 Participants
Age, Continuous	58 years n=33 Participants	57 years n=35 Participants	58 years n=68 Participants
Sex: Female, Male Female	18 Participants n=33 Participants	21 Participants n=35 Participants	39 Participants n=68 Participants
Sex: Female, Male Male	15 Participants n=33 Participants	14 Participants n=35 Participants	29 Participants n=68 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	33 participants n=33 Participants	35 participants n=35 Participants	68 participants n=68 Participants
Median BMI	26.6 kg/m^2 n=33 Participants	25.4 kg/m^2 n=35 Participants	26.6 kg/m^2 n=68 Participants
History of Depression No	27 Participants n=33 Participants	27 Participants n=35 Participants	54 Participants n=68 Participants
History of Depression Yes	6 Participants n=33 Participants	8 Participants n=35 Participants	14 Participants n=68 Participants
Preoperative antidepressants No	27 Participants n=33 Participants	28 Participants n=35 Participants	55 Participants n=68 Participants
Preoperative antidepressants Yes	6 Participants n=33 Participants	7 Participants n=35 Participants	13 Participants n=68 Participants
Preoperative Opioids No	32 Participants n=33 Participants	34 Participants n=35 Participants	66 Participants n=68 Participants
Preoperative Opioids Yes	1 Participants n=33 Participants	1 Participants n=35 Participants	2 Participants n=68 Participants
Median Anesthesia Duration	649 Minutes n=33 Participants	634 Minutes n=35 Participants	641 Minutes n=68 Participants
Volatile anesthesia No	3 Participants n=33 Participants	5 Participants n=35 Participants	8 Participants n=68 Participants
Volatile anesthesia Yes	30 Participants n=33 Participants	30 Participants n=35 Participants	60 Participants n=68 Participants
Median propofol consumption	672.7 milligrams n=33 Participants	200 milligrams n=35 Participants	235 milligrams n=68 Participants
Dexmedetomidine use No	4 Participants n=33 Participants	4 Participants n=35 Participants	8 Participants n=68 Participants
Dexmedetomidine use Yes	29 Participants n=33 Participants	31 Participants n=35 Participants	60 Participants n=68 Participants
Median Crystalloids use	3000 mililiters n=33 Participants	3050 mililiters n=35 Participants	3050 mililiters n=68 Participants
Red blood cell transfusion intraoperatively No	32 Participants n=33 Participants	33 Participants n=35 Participants	65 Participants n=68 Participants
Red blood cell transfusion intraoperatively Yes	1 Participants n=33 Participants	2 Participants n=35 Participants	3 Participants n=68 Participants
Frozen plasma transfusions intraoperatively No	33 Participants n=33 Participants	34 Participants n=35 Participants	67 Participants n=68 Participants
Frozen plasma transfusions intraoperatively Yes	0 Participants n=33 Participants	1 Participants n=35 Participants	1 Participants n=68 Participants
Perfusion completed No	4 Participants n=33 Participants	4 Participants n=35 Participants	8 Participants n=68 Participants
Perfusion completed Yes	29 Participants n=33 Participants	31 Participants n=35 Participants	60 Participants n=68 Participants
Urinary output	665 mililiters n=33 Participants	900 mililiters n=35 Participants	783 mililiters n=68 Participants

PRIMARY outcome

Timeframe: 48 hours after CRS-HIPEC surgery

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2	-45 score on a scale Interval -89.0 to 0.0	-50 score on a scale Interval -88.0 to 23.0

SECONDARY outcome

Timeframe: 48 hours after CRS-HIPEC surgery

Pain intensity at rest and cough measure using a Validity and Reliability of the Verbal Numerical Rating Scale (VNRS) (0 = no pain - 10 = worst pain ever). Higher numerical scores on the scale indicate more pain, thus a worse outcome. Data reported as time-weighted pain scores from discharge from the PACU until 48 hours after the end of surgery.

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
4Q-TAP Versus TEA on Postoperative Pain Pain at Rest	3 score on a scale Interval 0.0 to 10.0	4 score on a scale Interval 0.0 to 10.0
4Q-TAP Versus TEA on Postoperative Pain Pain with Cough	5 score on a scale Interval 1.0 to 10.0	5 score on a scale Interval 1.0 to 10.0

SECONDARY outcome

Timeframe: During the 48 hours after CRS-HIPEC surgery

Opioid Consumption reported as morphine equivalents required during the 48 hours after the end of surgery.

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Comparison of the Total Opioid Consumption Between Patients With 4Q-TAP Versus TEA	4.5 morphine milligram equivalents (MME) Interval 0.0 to 51.0	21 morphine milligram equivalents (MME) Interval 1.8 to 108.8

SECONDARY outcome

Timeframe: Length of stay calculated from day of surgery to date of hospital discharge, up to 46 days

Length of stay calculated from day of surgery to date of hospital discharge.

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Comparison of the Length of Stay (LOS) Between Patients With 4Q-TAP Versus TEA	11 days Interval 4.0 to 24.0	11 days Interval 4.0 to 46.0

SECONDARY outcome

Timeframe: 48 hours after CRS-HIPEC surgery

An adverse event is any symptom, sign, illness, or experience which develops or worsens during the course of the study, whether or not the event is considered related to study drug. Adverse events (AEs) related to the study interventions recorded within the first 48 hours after the end of surgery.

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Number of Participants With Adverse Events Related to 4Q-TAP Versus TEA	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Within the first 48 hours after the end of CRS-HIPEC surgery

Opioid-related adverse (i.e. respiratory depression, pruritus, sedation, delirium) within the first 48 hours after the end of surgery.

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Number of Participants With Incidence of Opioid-Related Adverse Events Related to 4Q-TAP Versus TEA 48	7 Participants	7 Participants

SECONDARY outcome

Timeframe: 48 hours after CRS-HIPEC surgery

Postoperative complications recorded using Clavien-Dindo scale and POMS.

Outcome measures

Outcome measures
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 Participants Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 Participants Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA Pulmonary Complications	5 Participants	8 Participants
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA Renal Complications	5 Participants	5 Participants
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA Gastrointestinal Complications	1 Participants	0 Participants
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA Cardiac Complications	7 Participants	4 Participants
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA Hematological Complications	2 Participants	6 Participants

Adverse Events

Standard-of-Care Thoracic Epidural Analgesia (TEA)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 participants at risk Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 participants at risk Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
General disorders Intraabdominal Abscess	0.00% 0/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	2.9% 1/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days

Other adverse events

Other adverse events
Measure	Standard-of-Care Thoracic Epidural Analgesia (TEA) n=33 participants at risk Participants allocated to the TEA group had an epidural catheter placed before induction of anesthesia. The catheter was placed between the thoracic vertebral spaces 8 and 12 according to standard procedure. A bolus or infusion of local anesthetic solution with or without the addition opioids (bupivacaine 0.075% ± hydromorphone 2-5 mcg/mL or bupivacaine 0.075% ± fentanyl 5 mcg/mL, basal rate 8 mL/h, bolus 3 mL every 10 min) were given before surgical incision according to the anesthesiologist's clinical judgment. If deemed appropriate, a precision epidural bolus of hydromorphone (300-800 micrograms) was administered.	Four Quadrant Transverse Abdominus Plane (4Q-TAP) Block n=35 participants at risk Participants in 4Q-TAP group received maximum of 80. cc of a solution consisting of 150 mg of bupivacaine HCl and 266 mg of liposomal bupivacaine divided between each of the four quadrants after induction of anesthesia. All 4Q-TAP were done after induction of general anesthesia and under ultrasound guidance.
Gastrointestinal disorders Dry mouth	6.1% 2/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	11.4% 4/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days
Cardiac disorders Hypotension	42.4% 14/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	22.9% 8/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days
Gastrointestinal disorders Ileus	3.0% 1/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	0.00% 0/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days
Renal and urinary disorders Low urinary input	3.0% 1/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	2.9% 1/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days
Gastrointestinal disorders Nausea	51.5% 17/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	45.7% 16/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days
Skin and subcutaneous tissue disorders Pruritus	9.1% 3/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	8.6% 3/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days
General disorders Sedation	6.1% 2/33 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days	0.00% 0/35 • Adverse event data were collected within the first 48 hours after end of surgery, up to 30 days

Additional Information

Dr. Juan Cata, MD, Associate Professor, Anesthesiology & PeriOper Med

UT MD Anderson Cancer Center

Phone: (713) 792-7452

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place