Programmed Intermittent Epidural Bolus Time Interval and Injection Volume

Condition(s) targeted: Analgesia, Epidural

Intervention: two different drug administration (Procedure)

Phase: N/A

Status: Recruiting

Sponsored by: Northwestern University

Official(s) and/or principal investigator(s):
Cynthia A Wong, M.D., Principal Investigator, Affiliation: Northwestern University

Overall contact:
Cynthia A Wong, M.D., Phone: 312-926-1774, Email: c-wong2@northwestern.edu

Traditionally, neuraxial labor analgesia was maintained for the duration of labor with manual intermittent bolus injection of anesthetic via an in-dwelling epidural catheter. There has been a transition to maintenance of analgesia with a continuous epidural infusion. Advantages include fewer episodes of breakthrough pain, increased parturient satisfaction, and decreased anesthesiologists' workload. More recently, use of patient controlled epidural analgesia (PCEA) has become popular; usually a continuous infusion is supplemented by patient-activated bolus injections. 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, as is consumption of local anesthetic. We recently completed a study that compared programmed intermittent epidural anesthetic bolus with PCEA (PIEB) vs. PCEA with a background infusion. Total bupivacaine consumption and the need for manual "top-up" boluses were lower, and patient satisfaction was higher in women who were randomized to receive PIEB.

Similar results were obtained in two recently published studies. The time to first manual epidural rescue bolus was longer in parturients assigned to intermittent boluses compared to continuous epidural infusion, and pain scores were lower. In another study patients randomized to the programmed intermittent technique had a greater number of blocked dermatomal segments than women who received the same hourly dose of ropivacaine via a continuous epidural infusion.

Taken together, the results of these studies suggest that further studies of automated intermittent bolus injections are indicated, in particular, studies of the optimal bolus time interval and volume. A short interval/low volume protocol may mimic a continuous infusion, whereas a long interval/large volume may negate the inherent safety of a continuous infusion. Current pump technology supports 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 proposed 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.

Official title: Effect of Manipulation of the Programmed Intermittent Bolus Time Interval and Injection Volume on Total Drug Use and Quality of Analgesia During Labor Epidural Analgesia

Study design: Case Control, Prospective

Primary outcome: Total epidural bupivacaine dose

Secondary outcome:

Pain scores/area under the pain/time curve

Patient controlled bolus attempts

Patient controlled bolus doses administered

Manual bolus doses administered

Sensory level at 3 hours

Overall satisfaction scores

Detailed description: Background: 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 (1). 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 (2-4) or by PCEA (5). 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.

We recently completed a study that compared programmed intermittent epidural anesthetic bolus with PCEA (PIEB) vs. PCEA with a background infusion (6). Total bupivacaine consumption was lower, the need for manual "top-up" boluses was lower, and patient satisfaction was higher in women who were randomized to receive PIEB. Pain scores were not different between the groups.

Similar results were obtained in recently published studies of the programmed intermittent technique. Chua and Sia showed that by using an automated intermittent bolus, the time to first manual epidural rescue bolus was longer in parturients assigned to intermittent boluses compared to continuous epidural infusion of the same solution (7). Pain scores were lower in the intermittent group. Fettes and colleagues found that patients required a lower total drug dose and fewer manual bolus injections when epidural labor analgesia was maintained with automated intermittent boluses of ropivacaine compared to a continuous infusion (8). Similarly, Lim and colleagues demonstrated a lower incidence of break-through pain and higher patient satisfaction with intermittent epidural boluses compared to continuous infusion (9). Ueda and colleagues studied postoperative epidural analgesia in gynecologic patients (10). Patients randomized to the programmed intermittent technique had a greater number of blocked dermatomal segments than women who received the same hourly dose of ropivacaine via a continuous epidural infusion.

Solutions injected into the epidural space tend to spread more evenly when injected as a bolus, as compared to a continuous infusion (11). For example, parturient body position has very little influence on the spread of sensory analgesia after a bolus injection, but parturient position may influence the extent of sensory blockade during a continuous epidural infusion.

Furthermore, studies of epidural opioid analgesia suggest that epidural bolus administration of lipid soluble opioids (e. g., fentanyl) results in segmental spinal opioid analgesia, whereas continuous opioid epidural infusion results in systemic opioid analgesia. The analgesic effects of both epidural fentanyl infusion and epidural fentanyl bolus were evaluated using a volunteer, double blinded, cross-over designs study (12). Volunteers received an epidural fentanyl infusion or fentanyl bolus in random order and were then subjected to painful stimuli at the lumbar (thigh) and cranial (cheek and ear) dermatomes. Epidural bolus administration of fentanyl resulted in segmental spinal analgesia (lumbar dermatome analgesia > cranial dermatome analgesia), whereas epidural infusion produced nonsegmental analgesia (lumbar = cranial). The authors suggested that a fentanyl bolus results in a significantly larger amount of fentanyl in the epidural space compared to that which occurs at any single time point during a fentanyl infusion. Thus, even though only a small fraction of the administered fentanyl is able to distribute to the spinal cord opioid receptors, in the case of bolus administration the fraction is sufficient to produce a spinally mediated analgesic effect. This phenomenon may contribute to the dose sparing effect of bupivacaine/fentanyl that we observed in patients who received PIEB in our recent study.

Taken together, the results of these studies suggest that further studies of automated intermittent bolus injections are indicated, in particular, studies of the optimal bolus time interval and volume. At one end of the spectrum, a short interval/low volume protocol may mimic a continuous infusion. At the other end the spectrum, a long interval/large volume may negate the inherent safety of a continuous infusion.

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 proposed 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.

Methods: Eligible women will be asked to participate shortly after admission to the Labor & Delivery Unit at Prentice Women's Hospital immediately following the routine preanesthetic interview. Informed, written consent will be obtained. At the time of request for labor analgesia the cervix will be 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") will be determined. Labor analgesia will be initiated with a routine combined spinal-epidural (CSE) technique. Analgesia will be initiated in the sitting position at the L3-4 or L2-3 interspace. The epidural space will be located with the loss of resistance to air technique and a 27-g x 5 in pencil point spinal needle will be passed through the epidural needle to the subarachnoid space. The intrathecal injection will consist of bupivacaine 1. 25 mg and fentanyl 15 micrograms. The epidural catheter will be threaded and secured 4 cm in the epidural space. A test dose of lidocaine 1. 5% with epinephrine 1: 200,000 will be administered through the epidural catheter. Assuming a negative test dose, the catheter will be secured and the parturient placed in the lateral position. The VAS for pain will be determined 10 min after the intrathecal injection. If the VAS is less than 10 mm, the parturient will be randomized (by a computer generated random number table) to receive maintenance of epidural analgesia by one of three programmed intermittent time intervals/volume protocols (Table).

Group Programmed Interval (min) Bolus volume (mL) Group15 15 2. 5 Group30 30 5 Group60 60 10

All epidural solutions will consist of bupivacaine 0. 0625% with fentanyl 1. 95 micrograms/mL. Maintenance epidural analgesia will begin 18 min, 25min, or 40 min after the intrathecal injection for Group15, Group30, and Group60 respectively. Boluses in Group30 will be delivered over 1 minute and Group60 over 2 minutes to equal a rate of 300 ml/hr. Boluses in Group15 will be delivered over 1 minute at a rate of 150 ml/hr. (Infusion rate is different due to programming restrictions of the Gemstar infusion pump. The infusion duration for each individual bolus cannot be set for a value below 1 minute.) In addition, the patient may activate PCEA (PCEA bolus 5 mL, lockout interval 10 min, maximum hourly dose 20 mL/h, no background infusion). This results in a maximum hourly dose of 30 mL/h (programmed bolus 10 mL plus PCEA 20 mL), which is the maximum hourly dose received by patients at PWH via the current continuous infusion/PCEA protocol normally administered. The PCEA doses will be delivered at a rate of 125 mL/h. The parturient will be instructed to push the PCEA button whenever she feels uncomfortable. If the subject initiates a PCEA dose at the same time as programmed intermittent bolus is being delivered, the largest dose a subject might receive as a bolus is 15 mL 0. 0625% bupivacaine (9. 4 mg).

If the parturient has activated the PCEA bolus twice in 20 min and has not obtained adequate relief, the anesthesiologist will administer manual bolus doses of bupivacaine 0. 125% until the patient's pain score using the Verbal Rating Scale (VRS) ≤ 1. If patient requires more than 2 boluses, the maintenance solution in the PCEA pump will be replaced with 0. 11% bupivacaine and 1. 95 micrograms fentanyl.

Epidural maintenance analgesia will be administered via a Hospira Gemstar infusion pump (an infusion pump approved by the FDA for epidural infusion). The patient and the anesthesiologist will be blinded to group assignment. An anesthesia research nurse will initiate maintenance epidural analgesia according to group assignment.

VAS for pain will be determined every 120 min until complete cervical dilation beginning 120 min after the intrathecal injection. A modified Bromage score will be determined every 120 min during the 1st stage of labor. The cephalad and caudad extent of sensory blockade will be tested using an ElectroVonFrey Anesthesiometer . Values will be measured at time of enrollment and again 3 hours post-intrathecal injection. Extent of sensory blockade to ice will also be tested bilaterally 10 min and 3 hours post-intrathecal injection. The epidural infusion will be discontinued shortly after delivery. Prior to discharge from the Labor & Delivery Unit the parturient will be asked to mark her average VAS for pain while pushing (complete cervical dilation until delivery) as well as 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").

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Healthy, nulliparous, term (gestation greater than or equal to 37 w) women in

spontaneous labor or with spontaneous rupture of membranes will be eligible to participate.

Exclusion Criteria:

- Systemic disease (e. g., diabetes mellitus, hypertension, preeclampsia)

- chronic analgesic medications

- systemic opioid labor analgesia prior to the initiation of neuraxial labor

analgesia

- cervical dilation is less than 2 or greater than 5 at time of initiation of neuraxial

analgesia.

Cynthia A Wong, M.D., Phone: 312-926-1774, Email: c-wong2@northwestern.edu

Northwestern University, Chicago, Illinois 60611, United States; Recruiting

Related publications:

Paech MJ, Pavy TJ, Sims C, Westmore MD, Storey JM, White C. Clinical experience with patient-controlled and staff-administered intermittent bolus epidural analgesia in labour. Anaesth Intensive Care. 1995 Aug;23(4):459-63.

Boutros A, Blary S, Bronchard R, Bonnet F. Comparison of intermittent epidural bolus, continuous epidural infusion and patient controlled-epidural analgesia during labor. Int J Obstet Anesth. 1999 Oct;8(4):236-41.

Bogod DG, Rosen M, Rees GA. Extradural infusion of 0.125% bupivacaine at 10 ml h-1 to women during labour. Br J Anaesth. 1987 Mar;59(3):325-30.

Smedstad KG, Morison DH. A comparative study of continuous and intermittent epidural analgesia for labour and delivery. Can J Anaesth. 1988 May;35(3 ( Pt 1)):234-41.

van der Vyver M, Halpern S, Joseph G. Patient-controlled epidural analgesia versus continuous infusion for labour analgesia: a meta-analysis. Br J Anaesth. 2002 Sep;89(3):459-65. Review.

Paech MJ. Patient-controlled epidural analgesia in labour--is a continuous infusion of benefit? Anaesth Intensive Care. 1992 Feb;20(1):15-20.

Ferrante FM, Rosinia FA, Gordon C, Datta S. The role of continuous background infusions in patient-controlled epidural analgesia for labor and delivery. Anesth Analg. 1994 Jul;79(1):80-4.

Boselli E, Debon R, Cimino Y, Rimmele T, Allaouchiche B, Chassard D. Background infusion is not beneficial during labor patient-controlled analgesia with 0.1% ropivacaine plus 0.5 microg/ml sufentanil. Anesthesiology. 2004 Apr;100(4):968-72.

Petry J, Vercauteren M, Van Mol I, Van Houwe P, Adriaensen HA. Epidural PCA with bupivacaine 0.125%, sufentanil 0.75 microgram and epinephrine 1/800.000 for labor analgesia: is a background infusion beneficial? Acta Anaesthesiol Belg. 2000;51(3):163-6.

Halonen P, Sarvela J, Saisto T, Soikkeli A, Halmesmaki E, Korttila K. Patient-controlled epidural technique improves analgesia for labor but increases cesarean delivery rate compared with the intermittent bolus technique. Acta Anaesthesiol Scand. 2004 Jul;48(6):732-7.

Chua SM, Sia AT. Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labour. Can J Anaesth. 2004 Jun-Jul;51(6):581-5.

Ueda K, Ueda W, Manabe M. A comparative study of sequential epidural bolus technique and continuous epidural infusion. Anesthesiology. 2005 Jul;103(1):126-9.

Hogan Q. Distribution of solution in the epidural space: examination by cryomicrotome section. Reg Anesth Pain Med. 2002 Mar-Apr;27(2):150-6.

Chestnut DH, Owen CL, Bates JN, Ostman LG, Choi WW, Geiger MW. Continuous infusion epidural analgesia during labor: a randomized, double-blind comparison of 0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine. Anesthesiology. 1988 May;68(5):754-9.

Li DF, Rees GA, Rosen M. Continuous extradural infusion of 0.0625% or 0.125% bupivacaine for pain relief in primigravid labour. Br J Anaesth. 1985 Mar;57(3):264-70.

Bernard JM, Le Roux D, Vizquel L, Barthe A, Gonnet JM, Aldebert A, Benani RM, Fossat C, Frouin J. Patient-controlled epidural analgesia during labor: the effects of the increase in bolus and lockout interval. Anesth Analg. 2000 Feb;90(2):328-32.

Gambling DR, Huber CJ, Berkowitz J, Howell P, Swenerton JE, Ross PL, Crochetiere CT, Pavy TJ. Patient-controlled epidural analgesia in labour: varying bolus dose and lockout interval. Can J Anaesth. 1993 Mar;40(3):211-7.

Starting date: August 2006
Ending date: December 2009
Last updated: October 2, 2008