Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion for Termination of Pregnancy Analgesia

• Sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy (Other)
• Overall Status: Completed
• CT.gov ID: NCT01860521
• Collaborator: (none)
• Enrollment: 104
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 5

Study Details

Study Description

Brief Summary

This study included women who underwent voluntary second trimester termination of pregnancy. Patients were randomized to programmed intermittent epidural anesthetic bolus or continuous epidural infusion for pain analgesia. In this randomized, double-blind study, the investigators assess the incidence of motor block (primary outcome), degree of satisfaction of the patients, total levobupivacaine and sufentanil consumption and adverse events (secondary outcomes) between the two study groups.

Condition or Disease	Intervention/Treatment	Phase
Medical; Abortion, Fetus	Procedure: Programmed Intermittent Epidural Bolus; Procedure: Continuous Epidural Infusion; Procedure: Procedure of interruption of pregnancy; Drug: Drug used for analgesia procedures; Device: Pump for programmed intermittent bolus.; Device: Pump for continuous epidural infusion.; Drug: Drug used for termination of pregnancy procedure.	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion for Second Trimester Voluntary Termination of Pregnancy Analgesia: a Randomized Study.
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Programmed Intermittent Epidural Bolus	Procedure: Programmed Intermittent Epidural Bolus; An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.; Procedure: Procedure of interruption of pregnancy; Patients were administered 1 mg of gemeprost pessaries (Cervidil®, Merck Serono SPA, Roma, Italy) in the posterior fornix of the vagina every 3 hours up to 5 doses. If the expulsion of the fetus did not occur, the therapeutic regimen was repeated after 24 hours from the initiation of the treatment. Induction-to-abortion time (hours) was considered the period of time comprised between the first gemeprost pessary administration and fetal expulsion. Failure of induction of abortion was defined as women undelivered after two completed cycles (48h).The evacuation of the uterus under general anesthesia was performed if ultrasonography showed retained productions of conception.; Drug: Drug used for analgesia procedures; Levobupivacaine (Chirocaine®, Abbott, Chicago, IL, USA) and sufentanil(Fentatienil®, Angelini, Rome, Italy) were administered in both study groups according to the regimen of each intervention arm (Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion).; Other Names: Levobupivacaine: Chirocaine®, Abbott, Chicago, IL, USA. Sufentanil: Fentatienil®, Angelini, Rome, Italy. ; Device: Pump for programmed intermittent bolus.; Pump administering programmed intermittent epidural bolus for the maintenance of analgesia was used.; Other Names: Pump: Gemstar®; Hospira, Lake Forest, USA. ; Drug: Drug used for termination of pregnancy procedure.; Gemeprost pessaries.; Other Names: Gemeprost pessaries: Cervidil®, Merck Serono SPA, Rome, Italy.
Active Comparator: Continuous Epidural Infusion	Procedure: Continuous Epidural Infusion; An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.; Procedure: Procedure of interruption of pregnancy; Patients were administered 1 mg of gemeprost pessaries (Cervidil®, Merck Serono SPA, Roma, Italy) in the posterior fornix of the vagina every 3 hours up to 5 doses. If the expulsion of the fetus did not occur, the therapeutic regimen was repeated after 24 hours from the initiation of the treatment. Induction-to-abortion time (hours) was considered the period of time comprised between the first gemeprost pessary administration and fetal expulsion. Failure of induction of abortion was defined as women undelivered after two completed cycles (48h).The evacuation of the uterus under general anesthesia was performed if ultrasonography showed retained productions of conception.; Drug: Drug used for analgesia procedures; Levobupivacaine (Chirocaine®, Abbott, Chicago, IL, USA) and sufentanil(Fentatienil®, Angelini, Rome, Italy) were administered in both study groups according to the regimen of each intervention arm (Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion).; Other Names: Levobupivacaine: Chirocaine®, Abbott, Chicago, IL, USA. Sufentanil: Fentatienil®, Angelini, Rome, Italy. ; Device: Pump for continuous epidural infusion.; Pump administering continuous epidural infusion for the maintenance of analgesia was used.; Other Names: Pump: Gemstar®; Hospira, Lake Forest, USA. ; Drug: Drug used for termination of pregnancy procedure.; Gemeprost pessaries.; Other Names: Gemeprost pessaries: Cervidil®, Merck Serono SPA, Rome, Italy.

Outcome Measures

Primary Outcome Measures

1. Incidence of Motor Block [Assessed every hour from starting the analgesia procedure (up to 66 hours from starting of the procedure).]

   The assessment of the degree of motor block was performed in the right and left lower extremities using the Breen modified Bromage score: 1 = complete block (unable to move feet or knees), 2 = almost complete block (able to move feet only), 3 = partial block (just able to move knees), 4 = detectable weakness of hip flexion while supine (between scores 3 and 5), 5 = no detectable weakness of hip flexion while supine (full flexion of knees), and 6 = able to stand and to perform partial knee bend. Patients with a Bromage score < 6 were considered to have motor block.

Secondary Outcome Measures

1. Degree of Satisfaction of the Patients With the Analgesia Procedure [At discharge from the hospital (up to 72 hours from starting of the procedure).]

   At discharge from the hospital, patients were requested to answer the following question "Taking into consideration the variations in pain symptoms, as well as the adverse events experienced, if any, how would you define the grade of satisfaction with your analgesic treatment?" The grade of satisfaction was assessed using a visual analog scale (VAS) where 0 corresponded to "completely unsatisfied" and 100 to "completely satisfied".

2. Total Levobupivacaine Consumption [At the moment of fetal expulsion (up to 66 hours from starting of the procedure).]

3. Total Sufentanil Consumption. [During the whole analgesia procedure (assessed between the starting of the procedure until 66 hours).]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• age ≥ 18 years

• pregnancy at second trimester

• willingness of voluntary interrupt the pregnancy

• comprehension of Italian Language

• baseline pain score ≥ 30 on a 100-mm visual analog pain scale (VAPS)

Exclusion Criteria:

• contraindication to epidural analgesia and to narcotics

• history of drug abuse or chronic use

• maternal disease (such as severe asthma, cardiac, liver or kidney disease)

• inability to comprehend or comply with the analgesia pain management procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Obstetrics and Gynecology, San Martino Hospital and National Institute for Cancer Research, University of Genoa	Genoa	Ligury	Italy	16132

Sponsors and Collaborators

• IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Investigators

• Study Director: Simone Ferrero, PhD, University of Genoa
• Principal Investigator: Umberto Leone Roberti Maggiore, MD, University of Genoa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Umberto Leone Roberti Maggiore, Principal Investigator, Research Fellow., IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• ClinicalTrials.gov Identifier: NCT01860521
• Other Study ID Numbers: SCUL 4022
• First Posted: May 22, 2013
• Last Update Posted: Oct 28, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Umberto Leone Roberti Maggiore, Principal Investigator, Research Fellow., IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy: Termination of pregnancy; Second trimester; Programmed intermittent epidural bolus; Continuous epidural infusion; Epidural analgesia; Legally Induced Abortion
• Additional relevant MeSH terms: Sufentanil; Levobupivacaine; Gemeprost

Study Results

Participant Flow

Recruitment Details	September 2011 - June 2013. University Hospital.

Arm/Group Title	Continuous Epidural Infusion	Programmed Intermittent Epidural Bolus
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.
Period Title: Overall Study
STARTED	52	52
COMPLETED	52	52
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Continuous Epidural Infusion	Programmed Intermittent Epidural Bolus	Total
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Total of all reporting groups
Overall Participants	52	52	104
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	52 100%	52 100%	104 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.3 (4.7)	32.4 (5.3)	32.8 (5.0)
Sex: Female, Male (Count of Participants)
Female	52 100%	52 100%	104 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Italy	52 100%	52 100%	104 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Motor Block
Description	The assessment of the degree of motor block was performed in the right and left lower extremities using the Breen modified Bromage score: 1 = complete block (unable to move feet or knees), 2 = almost complete block (able to move feet only), 3 = partial block (just able to move knees), 4 = detectable weakness of hip flexion while supine (between scores 3 and 5), 5 = no detectable weakness of hip flexion while supine (full flexion of knees), and 6 = able to stand and to perform partial knee bend. Patients with a Bromage score < 6 were considered to have motor block.
Time Frame	Assessed every hour from starting the analgesia procedure (up to 66 hours from starting of the procedure).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Continuous Epidural Infusion	Programmed Intermittent Epidural Bolus
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.
Measure Participants	52	52
Number [participants]	24 46.2%	3 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous Epidural Infusion, Programmed Intermittent Epidural Bolus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Degree of Satisfaction of the Patients With the Analgesia Procedure
Description	At discharge from the hospital, patients were requested to answer the following question "Taking into consideration the variations in pain symptoms, as well as the adverse events experienced, if any, how would you define the grade of satisfaction with your analgesic treatment?" The grade of satisfaction was assessed using a visual analog scale (VAS) where 0 corresponded to "completely unsatisfied" and 100 to "completely satisfied".
Time Frame	At discharge from the hospital (up to 72 hours from starting of the procedure).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Continuous Epidural Infusion	Programmed Intermittent Epidural Bolus
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.
Measure Participants	52	52
Mean (Standard Deviation) [mm]	73.2 (19.6)	84.4 (15.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous Epidural Infusion, Programmed Intermittent Epidural Bolus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Total Levobupivacaine Consumption
Time Frame	At the moment of fetal expulsion (up to 66 hours from starting of the procedure).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Continuous Epidural Infusion	Programmed Intermittent Epidural Bolus
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.
Measure Participants	52	52
Mean (Standard Deviation) [mg]	86.2 (27.0)	75.5 (26.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous Epidural Infusion, Programmed Intermittent Epidural Bolus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Total Sufentanil Consumption.
Time Frame	During the whole analgesia procedure (assessed between the starting of the procedure until 66 hours).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Continuous Epidural Infusion	Programmed Intermittent Epidural Bolus
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.
Measure Participants	52	52
Mean (Standard Deviation) [microg]	69.0 (21.6)	60.4 (21.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous Epidural Infusion, Programmed Intermittent Epidural Bolus
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Continuous Epidural Infusion		Programmed Intermittent Epidural Bolus
Arm/Group Description	Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Continuous Epidural Infusion : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL at a rate of 10 mL/h, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.		Pump : Pump administering either programmed intermittent epidural bolus or continuous epidural infusion for the maintenance of analgesia was used. Programmed Intermittent Epidural Bolus : An initial epidural loading dose consisting of 0.0625% levobupivacaine 20 mL (Chirocaine®, Abbott, Chicago, USA) plus sufentanil 10 µg (Fentatienil®, Angelini, Rome, Italy) was followed by 0.0625% levobupivacaine with sufentanil 0.5 µg/mL, 10 mL every hour, starting 60 minutes after the administration of the initial epidural loading dose until expulsion of the fetus. If the patient still felt pain (VAPS score ≥ 30mm), despite the analgesia, additional manual incremental boluses of 5-mL levobupivacaine 0.125% until the VAPS score was < 30 mm were administered.
All Cause Mortality
	Continuous Epidural Infusion		Programmed Intermittent Epidural Bolus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Continuous Epidural Infusion		Programmed Intermittent Epidural Bolus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/52 (5.8%)		3/52 (5.8%)
Pregnancy, puerperium and perinatal conditions
Hemorrhage	1/52 (1.9%)		3/52 (5.8%)
Uterine perforation	2/35 (5.7%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Continuous Epidural Infusion		Programmed Intermittent Epidural Bolus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/52 (63.5%)		21/52 (40.4%)
Gastrointestinal disorders
Nausea	18/52 (34.6%)		7/52 (13.5%)
Vomiting	3/52 (5.8%)		1/52 (1.9%)
General disorders
Hypotension	2/52 (3.8%)		4/52 (7.7%)
Pruritus	14/52 (26.9%)		17/52 (32.7%)
Shivering	11/52 (21.2%)		9/52 (17.3%)
Sedation	3/52 (5.8%)		0/52 (0%)
Respiratory depression	2/52 (3.8%)		0/52 (0%)
Pregnancy, puerperium and perinatal conditions
Failure of induction	1/52 (1.9%)		1/52 (1.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.