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Programmed Intermittent Epidural Bolus Time Interval and Injection Volume

Effect of Manipulation of the Programmed Intermittent Bolus Time Interval and Injection Volume on Total Drug Use for Labor Epidural Analgesia: a Randomized Controlled Trial

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00417027
Enrollment
190
Registered
2006-12-28
Start date
2006-08-31
Completion date
2009-04-30
Last updated
2014-04-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Labor Pain

Keywords

Patient controlled epidural analgesia, Labor analgesia, Epidural analgesia

Brief summary

Studies suggest that administration of maintenance epidural solutions as programmed or automated intermittent boluses, rather than continuous infusions, result in lower bupivacaine consumption, decreased need for manual boluses by the anesthesiologist, and greater patient satisfaction. In this technique, the epidural maintenance dose is administered as a bolus by the infusion pump at regular intervals instead of as a continuous infusion. However, the optimal combination of bolus volume and dosing interval has not been determined. At one end of the spectrum, a small volume and short bolus dose interval will likely behave like a continuous infusion. At the other end of the spectrum, a large volume and long bolus dose interval may lead to an increased incidence of breakthrough pain. The purpose of this randomized, double-blind trial was to determine how manipulation of the programmed intermittent time interval and volume influences total drug use, quality of analgesia, and patient satisfaction during maintenance of labor analgesia. We hypothesized that manipulation of the programmed intermittent bolus time interval and volume during the maintenance of epidural labor analgesia influences total drug use, quality of analgesia and patient satisfaction.

Detailed description

Traditionally, neuraxial labor analgesia was maintained for the duration of labor with manual intermittent bolus injection of anesthetic by the anesthesiologist via an in-dwelling epidural catheter. During the last decade, there has been a transition to maintenance of analgesia with a continuous epidural infusion. Analgesia is maintained with fewer episodes of breakthrough pain and parturient satisfaction is increased. The anesthesiologists' workload is less. More recently, use of patient controlled epidural analgesia (PCEA) has become popular; usually a continuous infusion is supplemented by patient-activated bolus injections. Studies have compared the intermittent manual epidural bolus technique to continuous infusion, continuous infusion to PCEA without a background infusion, and PCEA with and without a background infusion. Studies vary in the epidural solution local anesthetic mass (volume and concentration), and lock-out intervals. The incidence and intensity of motor blockade is greater with continuous infusion compared to bolus administration of the same concentration/mass local anesthetic per unit time, whether the bolus is administered manually or by PCEA. Consumption of local anesthetic is less with bolus administration (manual or PCEA) compared to continuous infusion. Therefore, lower concentrations of local anesthetic are frequently used for continuous infusions. Current pump technology supports continuous epidural infusion, PCEA without a background infusion, and PCEA with a background infusion. Current pump technology does not support programmed intermittent bolus administration with or without supplemental PCEA. Further study in this area may motivate pump manufacturers to redesign their pumps to support this type of drug administration. The purpose of the study is to determine how manipulation of the programmed intermittent time interval and volume influences total drug use, quality of analgesia, and patient satisfaction during maintenance of labor analgesia. Eligible women were asked to participate shortly after admission to the Labor and Delivery Unit at Prentice Women's Hospital immediately following the routine preanesthetic interview. Informed, written consent was obtained. At the time of request for labor analgesia the cervix was examined and a baseline Visual Analog Scale (VAS) for pain (100 mm unmarked line with the end points labeled no pain and worst pain imaginable) was determined. Labor analgesia was initiated with a routine combined spinal epidural (CSE) technique. The VAS for pain was determined 10 minutes after the intrathecal injection. If the VAS was less than 10 mm, the parturient was randomized (by a computer generated random number table) to one of three programmed intermittent epidural bolus analgesia maintenance techniques: 2.5 mL every 15 minutes, 5 mL every 30 minutes, or 10 mL every 60 minutes. All epidural solutions consisted of bupivacaine 0.0625% with fentanyl 1.95 micrograms/mL. The initial programmed intermittent bolus dose was initiated 30 minutes after the intrathecal injection in all groups. Programmed intermittent epidural doses were administered via a Hospira Gemstar infusion pump. A commercial pump that can be programmed to administer intermittent boluses and patient controlled boluses does not exist. Thus two pumps were prepared for each subject with the same epidural solution. One pump was programmed to administer the programmed intermittent boluses at a rate of 300 ml/hr at regular intervals. The second pump was programmed to administer the patient's controlled epidural analgesia. VAS scores for pain were determined every 120 minutes until complete cervical dilation beginning 60 minutes after the intrathecal injection. A modified Bromage score was determined every 120 minutes during the 1st stage of labor (0=no motor paralysis; 1=inability to raise extended leg, but able to move knee and foot; 2=inability to raise extended leg and to move knee, but able to move foot; 3=inability to raise extended leg or to move knee and foot). Sensory threshold to a rigid von Frye filament (pressure applied with the rigid tip until the subject reported feeling pressure at the thoracic dermatome of T12, T10, T7, and T4) was determined bilaterally at initiation of epidural and 3 hours after the intrathecal injection. Epidural infusion was discontinued shortly after delivery. Prior to discharge from the Labor and Delivery Unit the parturient was asked to mark her overall satisfaction with labor analgesia using a 100 mm unmarked line with the left end labeled not satisfied at all and the right end labeled extremely satisfied.

Interventions

PROCEDUREProgrammed Intermittent Epidural Bolus (PIEB)

A commercial pump that can be programmed to administer intermittent boluses and patient controlled boluses does not exist. Two pumps were prepared for each subject with the same epidural solution. One pump was programmed to administer the programmed intermittent epidural bolus(PIEB). The second pump was programmed to administer patient controlled epidural analgesia (PCEA)with a dose of 5 mL delivered with a lockout of every 10 minutes.

Sponsors

Northwestern University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes

Inclusion criteria

* Healthy * nulliparous women * term gestation (greater than or equal to 37 weeks gestation) * spontaneous labor or with spontaneous rupture of membranes

Exclusion criteria

* Systemic disease (e.g., diabetes mellitus, hypertension, preeclampsia) * use of chronic analgesic medications * systemic opioid labor analgesia prior to the initiation of neuraxial labor analgesia * cervical dilation less than 2cm or greater than 5cm at time of initiation of neuraxial analgesia * delivery within 90 minutes of intrathecal injection

Design outcomes

Primary

MeasureTime frameDescription
Total Bupivicaine in Milligrams Administered Per Hour of Labor for Analgesia.From initiation of labor analgesia until delivery less than 24 hoursTotal bupivacaine from epidural solution administered for labor analgesia normalized per hour of labor.

Secondary

MeasureTime frameDescription
Patient Controlled Bolus AttemptsDuration of labor analgesiaThe number of attempted self administered bolus doses of epidural analgesia solution for control of pain.
Number of Patient Controlled Bolus Doses of Bupivacaine/Fentanyl AdministeredDuration of labor analgesiaPatient controlled bolus of analgesic solution could be requested by activating a button. Bolus were 5ml of the epidural solution (bupivacaine 6.25mg/ml and fentanyl 1.96mgml). Patient requested administrations were allowed every 10 minutes to a maximum of 30 ml of epidural solution per hour.
Area Under the Visual Analog Pain Scores (0 to 100mm) Per Hour of Labor Analgesia CurveDuration of labor analgesiaThe pain burden calculated as the area under the visual analog pain scale (0 to 100 mm) patient self reported assessment of pain. Pain assessment were made at regular intervals during labor and the area under the pain score per time curve was calculated as the pain burden during labor. Greater pain would be indicated by a larger area. Possible range would be 0 for no pain to 100 for severe pain.
Highest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.3 hours after initiation of labor analgesiaHighest level of sensory loss to ice 3 hours after initiation of epidural analgesia. Thoracic dermatomes specify the level at which the nerves exit the spinal column. Higher thoracic spread of analgesia suggests greater dispersion of the epidural solution and may correlate with better analgesia. Higher levels are given by lower thoracic vertebral number. For example dermatome 4 has greater spread than dermatome 5.
Overall Satisfaction Scores. Higher Scores Represent Greater Satisfaction With Analgesia During Labor and Delivery.24 hours following labor analgesiaPatient satisfaction with analgesia management during labor and delivery. Scores are 0 to 100 with 0 complete dissatisfaction and 100 complete satisfaction with labor analgesia.
Manual Bolus Doses AdministeredDuration of labor analgesia

Countries

United States

Participant flow

Recruitment details

Nulliparous women in spontaneous labor were asked to participate shortly after admission to the Labor and Delivery Unit at Prentice Women's Hospital. Immediately following the routine preanesthetic interview, subjects were approached and informed, written consent was obtained.

Participants by arm

ArmCount
2.5 mL Bolused Every 15 Minutes
Laboring women receiving a programmed intermittent epidural bolus of 2.5 ml of bupivacaine 6.25 mg/ml and fentanyl 1.96 mcg/ml every 15 minutes. Patients could request additional 5 ml of the solution via a patient controlled administration every 15 minutes to a maximum of 30ml per hour.
66
5ml Bolused Every 30 Minutes
Laboring women receiving a programmed intermittent epidural bolus of 5 ml of bupivacaine 6.25 mg/ml and fentanyl 1.96 mcg/ml every 30 minutes. Patients could request additional 5 ml of the solution via a patient controlled activation to a maximum of 30 ml per hour.
65
10ml Bolused Every 60 Minutes
Laboring women receiving a programmed intermittent epidural bolus of 10 ml of bupivacaine 6.25 mg/ml and fentanyl 1.96 mcg/ml every 60 minutes. Patients could request additional 5 ml of the solution via a patient controlled activation to a maximum of 30 ml per hour.
59
Total190

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyProtocol Violation055

Baseline characteristics

Characteristic10ml Bolused Every 60 MinutesTotal2.5 mL Bolused Every 15 Minutes5ml Bolused Every 30 Minutes
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
59 Participants190 Participants66 Participants65 Participants
Age, Continuous31 years31 years31 years30 years
Region of Enrollment
United States
59 participants190 participants66 participants65 participants
Sex: Female, Male
Female
59 Participants190 Participants66 Participants65 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 660 / 600 / 54
serious
Total, serious adverse events
0 / 660 / 600 / 54

Outcome results

Primary

Total Bupivicaine in Milligrams Administered Per Hour of Labor for Analgesia.

Total bupivacaine from epidural solution administered for labor analgesia normalized per hour of labor.

Time frame: From initiation of labor analgesia until delivery less than 24 hours

Population: per protocal

ArmMeasureValue (MEDIAN)
2.5 mL Bolused Every 15 MinutesTotal Bupivicaine in Milligrams Administered Per Hour of Labor for Analgesia.11.3 mg bupivacaine per hour
5ml Bolused Every 30 MinutesTotal Bupivicaine in Milligrams Administered Per Hour of Labor for Analgesia.11.1 mg bupivacaine per hour
10ml Bolused Every 60 MinutesTotal Bupivicaine in Milligrams Administered Per Hour of Labor for Analgesia.10.3 mg bupivacaine per hour
p-value: >0.05Wilcoxon (Mann-Whitney)
p-value: 0.005Wilcoxon (Mann-Whitney)
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary

Area Under the Visual Analog Pain Scores (0 to 100mm) Per Hour of Labor Analgesia Curve

The pain burden calculated as the area under the visual analog pain scale (0 to 100 mm) patient self reported assessment of pain. Pain assessment were made at regular intervals during labor and the area under the pain score per time curve was calculated as the pain burden during labor. Greater pain would be indicated by a larger area. Possible range would be 0 for no pain to 100 for severe pain.

Time frame: Duration of labor analgesia

Population: per protocal

ArmMeasureValue (MEDIAN)
2.5 mL Bolused Every 15 MinutesArea Under the Visual Analog Pain Scores (0 to 100mm) Per Hour of Labor Analgesia Curve15 0 to 100 mm per hour
5ml Bolused Every 30 MinutesArea Under the Visual Analog Pain Scores (0 to 100mm) Per Hour of Labor Analgesia Curve13 0 to 100 mm per hour
10ml Bolused Every 60 MinutesArea Under the Visual Analog Pain Scores (0 to 100mm) Per Hour of Labor Analgesia Curve14 0 to 100 mm per hour
p-value: 0.54Kruskal-Wallis
Secondary

Highest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.

Highest level of sensory loss to ice 3 hours after initiation of epidural analgesia. Thoracic dermatomes specify the level at which the nerves exit the spinal column. Higher thoracic spread of analgesia suggests greater dispersion of the epidural solution and may correlate with better analgesia. Higher levels are given by lower thoracic vertebral number. For example dermatome 4 has greater spread than dermatome 5.

Time frame: 3 hours after initiation of labor analgesia

ArmMeasureGroupValue (NUMBER)
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 511 participants
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 810 participants
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 717 participants
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 46 participants
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Sensory level not tested1 participants
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 96 participants
2.5 mL Bolused Every 15 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 69 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 714 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 45 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 512 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 67 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 88 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 914 participants
5ml Bolused Every 30 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Sensory level not tested0 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 86 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 59 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Sensory level not tested0 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 910 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 716 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 68 participants
10ml Bolused Every 60 MinutesHighest Thoracic Dermatome Sensory Level to Ice. Higher Levels Are Given by Lower Thoracic Vertebral Number.Thoracic dermatome 45 participants
p-value: 0.41Kruskal-Wallis
Secondary

Manual Bolus Doses Administered

Time frame: Duration of labor analgesia

ArmMeasureGroupValue (NUMBER)
2.5 mL Bolused Every 15 MinutesManual Bolus Doses Administered3 doses3 participants
2.5 mL Bolused Every 15 MinutesManual Bolus Doses Administered4 doses4 participants
2.5 mL Bolused Every 15 MinutesManual Bolus Doses Administered1 dose23 participants
2.5 mL Bolused Every 15 MinutesManual Bolus Doses Administered2 doses12 participants
2.5 mL Bolused Every 15 MinutesManual Bolus Doses Administered0 doses24 participants
5ml Bolused Every 30 MinutesManual Bolus Doses Administered1 dose17 participants
5ml Bolused Every 30 MinutesManual Bolus Doses Administered3 doses1 participants
5ml Bolused Every 30 MinutesManual Bolus Doses Administered0 doses30 participants
5ml Bolused Every 30 MinutesManual Bolus Doses Administered4 doses1 participants
5ml Bolused Every 30 MinutesManual Bolus Doses Administered2 doses11 participants
10ml Bolused Every 60 MinutesManual Bolus Doses Administered4 doses2 participants
10ml Bolused Every 60 MinutesManual Bolus Doses Administered0 doses27 participants
10ml Bolused Every 60 MinutesManual Bolus Doses Administered1 dose17 participants
10ml Bolused Every 60 MinutesManual Bolus Doses Administered2 doses7 participants
10ml Bolused Every 60 MinutesManual Bolus Doses Administered3 doses1 participants
Comparison: Analysis apply to all rows. Only 1 comparison was made between the groups in distribution of number of bolus doses.p-value: 0.72Chi-squared, Corrected
Secondary

Number of Patient Controlled Bolus Doses of Bupivacaine/Fentanyl Administered

Patient controlled bolus of analgesic solution could be requested by activating a button. Bolus were 5ml of the epidural solution (bupivacaine 6.25mg/ml and fentanyl 1.96mgml). Patient requested administrations were allowed every 10 minutes to a maximum of 30 ml of epidural solution per hour.

Time frame: Duration of labor analgesia

Population: per protocal

ArmMeasureValue (MEAN)
2.5 mL Bolused Every 15 MinutesNumber of Patient Controlled Bolus Doses of Bupivacaine/Fentanyl Administered7 participants
5ml Bolused Every 30 MinutesNumber of Patient Controlled Bolus Doses of Bupivacaine/Fentanyl Administered6 participants
10ml Bolused Every 60 MinutesNumber of Patient Controlled Bolus Doses of Bupivacaine/Fentanyl Administered6 participants
p-value: 0.69Kruskal-Wallis
Secondary

Overall Satisfaction Scores. Higher Scores Represent Greater Satisfaction With Analgesia During Labor and Delivery.

Patient satisfaction with analgesia management during labor and delivery. Scores are 0 to 100 with 0 complete dissatisfaction and 100 complete satisfaction with labor analgesia.

Time frame: 24 hours following labor analgesia

Population: per protocal

ArmMeasureValue (MEDIAN)
2.5 mL Bolused Every 15 MinutesOverall Satisfaction Scores. Higher Scores Represent Greater Satisfaction With Analgesia During Labor and Delivery.90 Scores on a scale (0 toi 100)
5ml Bolused Every 30 MinutesOverall Satisfaction Scores. Higher Scores Represent Greater Satisfaction With Analgesia During Labor and Delivery.94 Scores on a scale (0 toi 100)
10ml Bolused Every 60 MinutesOverall Satisfaction Scores. Higher Scores Represent Greater Satisfaction With Analgesia During Labor and Delivery.93 Scores on a scale (0 toi 100)
p-value: 0.85Kruskal-Wallis
Secondary

Patient Controlled Bolus Attempts

The number of attempted self administered bolus doses of epidural analgesia solution for control of pain.

Time frame: Duration of labor analgesia

Population: per protocal

ArmMeasureValue (MEAN)
2.5 mL Bolused Every 15 MinutesPatient Controlled Bolus Attempts10 number of bolus attempts
5ml Bolused Every 30 MinutesPatient Controlled Bolus Attempts10 number of bolus attempts
10ml Bolused Every 60 MinutesPatient Controlled Bolus Attempts8 number of bolus attempts
p-value: 0.32Kruskal-Wallis

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026