Parturient-controlled epidural analgesia (PCEA) has accorded laboring women autonomy in pain relief for labor as well as being very effective and desirable (1). Even so, the optimal regimen of PCEA has not been resolved, especially with regard to the role of a basal infusion. Although omitting a basal infusion has been shown to reduce analgesic consumption (2,3), an increased need for analgesic supplementation administered by the anesthesiologist has been demonstrated in other studies (4). The use of a basal infusion has also been recently shown to produce lower pain scores in parturients using PCEA during labor (5,6).
Our earlier work suggested that, compared with a continuous infusion, automated regular boluses could increase maternal satisfaction and decrease the incidence of breakthrough pain during the maintenance of labor epidural analgesia (7). This result was further supported by a recent publication (8), which demonstrated that the use of an intermittent epidural bolus was associated with a reduced dose of local anesthetic and better patient satisfaction than a continuous epidural infusion. This could be attributed to a more extensive spread of an analgesic solution in the epidural space when infused via intermittent boluses, when compared with a continuous infusion (9).
We devised a computer program that enables an ordinary continuous infusion pump to function as a PCEA pump with the ability to deliver basal intermittent boluses. These mandatory, basal intermittent boluses are discharged in addition to PCEA. We hypothesized that epidural ropivacaine consumption would be lower if basal intermittent boluses were used instead of an infusion for maintenance of analgesia with PCEA after combined spinal epidural (CSE) was used to initiate labor epidural analgesia. This could potentially reduce drug consumption and make the delivery of basal boluses, instead of a continuous infusion, another alternative to providing PCEA in labor.
This study was conducted with the approval of the IRB and informed written consent (including the liberty of withdrawing from the study at any point) was obtained from every parturient who participated in the study. Forty-two healthy (ASA I), nulliparous parturients with cephalic presentation at ≥36 wk of gestation who were in early spontaneous labor (cervical dilation ≤5 cm) and who had requested neuraxial blocks for analgesia were recruited. Parturients who had received parenteral opioids in the last 4 h, or those who had contraindications to neuraxial blocks (e.g., coagulopathy) were excluded. Parturients who had multiple pregnancies, noncephalic presentations, premature labor, and obstetric complications (e.g., preeclampsia, gestational diabetes, and premature rupture of amniotic membranes) were also excluded.
After establishing IV access, baseline systolic blood pressure and heart rate were measured noninvasively from the right brachial artery (Dinamap, Critikon, FL). A baseline visual analog pain score (VAPS based on a 0–10 cm scale, 0 cm = no pain and 10 cm = worst pain imagined) during a contraction was also obtained. Only parturients who had a VAPS of >3 cm were recruited. After explaining the procedure to the parturient, CSE analgesia was instituted by using the single space, needle-through-needle technique. The time of spinal injection during the CSE (Time0) was recorded. All the blocks were performed by a single operator (YL) at the L3–4 interspace with the patient in the right lateral position. The loss of resistance to air technique was used to identify the epidural space with a 18-gauge Tuohy needle (Espocan, B.Braun, Melsungen, Germany) and <2 mL of air was injected into the epidural space. A 27-gauge pencil point needle was then passed into the subarachnoid space and free flow of cerebral spinal fluid was ensured before the standard dose of intrathecal analgesics, comprising 2 mg ropivacaine (Naropin, Astra Zeneca, Sweden) and 15 μg of fentanyl (David Bull, Australia) was injected over 15 s with the orifice of the needle in the cephalad direction. A multiorifice epidural catheter was inserted 3–5 cm. Once negative aspiration was observed (signifying a low risk of intravascular catheterization), the catheter was flushed with 2 mL of 1.5% lidocaine (Xylocaine, Astra Zeneca, Sweden). The parturients were then turned supine with 15% left lateral tilt.
The assignment of parturients to group was done by another investigator (ATS) not involved in performing the block or subsequent monitoring of the parturients. Neither the parturients nor the investigators who monitored and collected data were aware of the patient group. The parturients were randomized using a sealed opaque envelope containing a computer generated number, to receive one of the following regimens of 0.1% ropivacaine plus 2 μg/mL of fentanyl solution to maintain epidural analgesia:
- PCEA + basal continuous infusion (Group PCEA+BCI, n = 21, BCI 5 mL/h, PCEA bolus of 5 mL, lockout interval = 10 min, maximal dose per hour = 20 mL), initiated the minute after Time0.
- PCEA + automated mandatory boluses (Group PCEA+AMB, n = 21, based on an empirical algorithm, as shown in Fig. 1, maximal dose per hour = 20 mL), initiated the minute after Time0. In this group, apart from PCEA boluses of 5 mL per demand, the parturients received mandatory boluses of 5 mL/h with the first AMB dose delivered 30 min after the initiation of the pump and every hour after that if no PCEA demands were made. The lockout period for both PCEA and AMB boluses was 10 min. If a PCEA demand was made within 10 min of an AMB dose, no further bolus would be given. This would be recorded as an unsuccessful PCEA attempt. Provided that no further PCEA demands were made, the next AMB bolus would then be delivered one hour after the last AMB. If there had been a successful PCEA bolus, the next AMB bolus would be delivered one hour after the last successful PCEA bolus.
In both regimens, the same infusion pump, IVAC P700 (Alaris, UK) was used. The PCEA+AMB and PCEA+BCI program source codes were compiled in the Borland Pascal language on Windows Operating Systems. The reliability of the communications was performed by parity and cyclic redundancy checks based on the communication protocol provided by the service manual of the infusion pump. The two-way communications between the pump and the laptop computer (IBM Thinkpad) were accomplished by using their respective RS232 serial ports. The 5-mL boluses (which were time-cycled, based on an infusion rate of 150 mL/h) took 2 min to complete.
If the parturients were pain free (VAPS <1 cm) 15 min after CSE, they were given a remote controlled (wireless), modified hand-held computer “mouse.” They were then instructed to self-administer an epidural bolus dose by clicking a button on this computer mouse if a recurrence of pain was felt. This served as the interface between the parturient and the Computer Integrated-PCEA/infusion pump, analogous to the PCEA “button” for the parturient's self-administration of analgesics. They were counseled to self-bolus before pain reached an unbearable intensity, with the concept of a lockout period clearly explained. We recorded the time when the patient first self-bolused (TimeSB), defined as the need for patient-activated bolus. The duration of painless labor after CSE (Tpainless after CSE) was taken mathematically as TimeSB − Time0.
In our institution, the onset of a profound lower limb motor block (defined as the inability to flex either knee) and significant hypotension (defined as reduction of systolic blood pressure of more than 25%) within the next 10 min of Time0 would suggest a possible misplacement of the epidural catheter in the intrathecal space and result in exclusion of the parturient from the study. Failure to obtain cerebrospinal fluid after two attempts at dural puncture with the spinal needle also excluded the parturient from recruitment (“failed” block). In the event of an inadvertent intravascular or dural puncture by the epidural needle or catheter, the parturient was disqualified from recruitment into study and managed according to the departmental protocols.
The following variables were monitored after the block:
- Systolic blood pressure and heart rate every 5 min for the first 30 min and then every 2 h until delivery.
- Continuous fetal heart rate monitoring.
- VAPS every 10 min for the first 30 min and then every 2 h until delivery.
- Sensory block at midline (loss of cold sensation to ice) every 10 min for the first 30 min and then every 2 h until delivery.
- Lower limb motor block every 10 min using the modified Bromage scale (0 = no block, 1 = unable to flex either hip joint but able to move knee and ankle joints, 2 = unable to move hip and knee of either limb but able to move either ankle, 3 = unable to move hip, knee or ankle joint of either lower limb) for the first 30 min and then every 2 h until delivery.
- Side effects: shivering (0 = no, 1 = yes), significant hypotension, nausea (0 = no, 1 = yes), vomiting (0 = no, 1 = yes) and fetal bradycardia (0 = no, 1 = yes). The presence of an abnormality of the fetal heart tracing was diagnosed and assessed by an attending obstetrician who was blinded to the patient's group assignment. Treatment of fetal bradycardia was based on its cause, e.g., IV terbutaline 0.2 mg if uterine hyperstimulation was diagnosed.
If VAPS remained >1 cm at 15 min postblock and/or the patient complained of pain at that time, an incremental dose of epidural supplementation of 5 mL of 0.2% ropivacaine every 10 min (up to a maximum of 15 mL) was offered. This would be classified as an “ineffective” CSE and the parturient would be removed from the study.
At any time during the study, the parturients were instructed to ask for immediate help from the anesthesiologist if they felt that their pain was inadequately relieved despite their PCEA therapy. This event would be recorded as “breakthrough pain requiring anesthesiologist's intervention,” defined as the need for additional pain relief instituted by the anesthesiologist despite PCEA+BCI or PCEA+AMB. The time when the parturient experienced breakthrough pain requiring anesthesiologist's intervention (TimebpAN) was recorded and the duration of analgesia before the intervention of the anesthesiologist (TAN top-up) was taken mathematically as TimebpAN − Time0. Pain scores, cervical dilation and use of oxytocin at TimebpAN were recorded. At TimeAN top-up, after ensuring that blood was not aspirated through the epidural catheter, the anesthesiologist instituted an incremental dose of epidural supplementation of 5 mL of 0.2% ropivacaine every 10 min (up to a maximum of 20 mL) and epidural fentanyl 50 μg (after 10 mL of 0.2% ropivacaine has been instituted) until pain was relieved. A failure to achieve analgesia would render the catheter ineffective and the parturient would also be removed from the study.
Time of delivery (recorded as Timeend), mode of delivery, Apgar scores and overall satisfaction scores with labor analgesia (based on a 0–100 scale, 0 = very dissatisfied, 100 = extremely satisfied) were assessed and documented within 2 h of delivery.
All data and statistical analyses were managed with SPSS version 9 (Chicago, IL). The Student's t-test was used for the analysis of interval data, which were normally distributed. Otherwise, the Mann Whitney test was used. For nominal data and proportions, the χ2 test with Yates correction when appropriate, was used. In the comparison of Tpainless after CSE and TAN top-up, Kaplan Maier survival analysis was used. As there was no actual Tpainless after CSE and TAN top-up for subjects who had delivered before the need for patient-activated bolus and breakthrough pain requiring anesthesiologist's intervention occurred, respectively, the duration of time from Time0 to the time of delivery of the neonates was computed as the censored data in the eventual Kaplan Maier analysis. The mean survival to anesthesiologist intervention was analyzed using log rank test. The sample size was determined (α = 0.05, β = 0.2) to detect a 20% reduction in the time weighted epidural ropivacaine consumption for PCEA+AMB compared with PCEA+BCI.
There were 21 parturients recruited in each study group. There were no differences in patients' anthropometric and preanalgesia data between groups. (Table 1) None of the parturients had an ineffective block. There was a significant difference in the time-weighted epidural ropivacaine consumed per hour, i.e., the primary outcome measure (mean = 6.5 mL, sd = 3.4 in the PCEA+AMB group vs 7.5 mL, sd = 2.0 PCEA+BCI group, P = 0.011). A larger proportion of parturients in the PCEA+AMB group did not self-bolus (6/21 vs 1/21 in PCEA+BCI, P = 0.03). The time to the first self-bolus after CSE was longer in the PCEA+AMB group (mean survival time 315 min, 95% confidence interval [CI] = 213–416 vs 190 min, CI = 119–260 in PCEA+BCI group, P = 0.04 by log rank test) (Fig. 2). However, there was no significant difference in the incidence of breakthrough pain requiring an anesthesiologist's intervention (5/21 in PCEA+AMB vs 3/21 in PCEA+BCI, P = 0.26). There was no difference in TAN top-up (mean survival time 660 min, CI = 590–744 in PCEA+AMB vs 760 min, CI = 581–880 in PCEA+BCI group, P = 0.39 by log rank test). There was no significant difference in the median ration of successful to total patient demands between the two groups (median = 0.9, minimum-maximum = 0.2–1 for PCEA+AMB vs 1, 0.5–1 for PCEA+BCI, P = 0.6). There were also no differences in the characteristics of labor analgesia, sensory level, side effects, patient's satisfaction with the epidural analgesia, and obstetric outcome between the two regimens even though two of the parturients from the PCEA+AMB group had had significant hypotension during the study. (Table 2) There was no reported fetal bradycardia within 30 min of Time0 that required uterine relaxation or cesarean delivery.
In this study, we found that there was a significant reduction in the time-weighted epidural ropivacaine consumed per hour, as well as a reduced proportion of parturients who needed to self-bolus in the PCEA+AMB group when compared with the PCEA+BCI group. The time taken for the parturients who had required a self-bolus after CSE (Tpainless after CSE) was longer in the PCEA+AMB than PCEA+BCI group. Indeed, our earlier study (10) had also demonstrated that, at the rate of 5 mL/h, the use of continual intermittent boluses prolonged the duration of analgesia induced by CSE to a greater degree than a continuous infusion at the same rate. Unlike that study, PCEA was used in the current study, hence allowing parturients to supplement the degree of analgesia to a desired level, if necessary. This could partially explain the lack of difference in the highest level of sensory block or pain scores between the PCEA+AMB and PCEA+BCI groups.
Our study also showed that fewer parturients had required self-supplementation of analgesics with the current regimen of PCEA+AMB when compared with PCEA+BCI. This is consistent with the findings of our earlier study (7) that demonstrated the reduced need for at least one episode of manual supplementation of analgesia when intermittent boluses, totaling 10 mL/h but without PCEA were used instead of a continuous infusion at the same hourly rate (also without PCEA), to maintain labor analgesia induced by CSE. Our results are also consistent with another study by Wong et al. (8) which demonstrated that the use of an intermittent epidural bolus was associated with a reduced dose of local anesthetic and better patient satisfaction than continuous epidural infusion. Experimentally, the use of intermittent boluses had been found to result in a greater spread of infusate when compared with a continuous infusion, despite a similar rate of infusion (11). Based on a study in human cadavers, the distribution of solution in the epidural space is nonuniform and the spread of epidural solution is directed among paths between structures according to pressures by which they are compressed. Thus, the use of intermittent boluses with higher infusion pressure may aid in producing a more uniform epidural spread as compared to a continuous infusion (12). We suggest that the reduced need for parturients' self-supplementation in the PCEA+AMB group in our current study could be attributed to the improved spread of analgesics with continual boluses compared with a continuous infusion. This could have contributed to a reduction of time-weighted consumption of local anesthetics in the PCEA+AMB group.
In this study, we deliberately programmed the first hourly AMB bolus at 30 min but started BCI immediately after CSE to reduce the likelihood of any disparity in the amount of drug consumption arising from the study design. In fact, a parturient in the PCEA+BCI group would consume more analgesics than her counterpart in PCEA+AMB group during the first 30 min, although the situation would be reversed during the next 30 min. This pattern would repeat itself if no PCEA demands were made. Even though the overall hourly consumption of epidural ropivacaine was lower with the PCEA+AMB regimen, the proportion of parturients in PCEA+AMB group who had required the anesthesiologist's intervention for breakthrough pain was not statistically different from the PCEA+BCI group. We could infer that as pain intensified with the progress of labor (13), the current PCEA+AMB needed to be refined to customize analgesia and reduce the requirement for supplementation by the anesthesiologist. Further research is needed to determine if delivering AMB sooner after PCEA bolus, or if using smaller AMB boluses at more regular intervals, would help in addressing this issue. Intuitively, we deem the occurrence of breakthrough pain to be clinically significant because a delay in providing rescue analgesia in our busy labor and delivery floor could potentially undermine the quality of labor analgesia. In our study, we were unable to demonstrate a difference in maternal satisfaction scores, but the sample size was small. In addition, all parturients were closely monitored and frequently reviewed by the caregivers. This could have enhanced the overall analgesic experience, hence making any difference in the quality of analgesia between the two regimens difficult to distinguish.
Our preliminary results suggested that PCEA+AMB is another alternative to PCEA+BCI in maintaining labor epidural analgesia by allowing the parturients the flexibility of receiving pain relief on demand on top of continual basal boluses. The bolus volume of 5 mL was chosen for both AMB and PCEA because a previous study that had demonstrated that regardless of concentration, this minimal volume was desirable to ensure an appropriate spread of block (14). In this study, we did not observe any adverse clinical side effects in the two groups, given the small sample size. The PCEA+AMB program was tested in vitro by the investigators independently before the initiation of the clinical trial. Throughout the study, we did not encounter any problem with regard to equipment errors. The built-in alarm, which activates when further analgesic demands are made and when maximal basal infusion has been reached, is a safety mechanism which would trigger the need for a closer assessment of the parturient for situations such as a dislodged epidural catheter or a patchy block.
In conclusion, our study showed that PCEA+AMB could be useful as the mode of maintenance for epidural analgesia. PCEA+AMB reduced analgesic consumption and the need for parturients' self-bolus of analgesics. The time to the loss of analgesia induced by CSE was also longer with PCEA+AMB. Further developments of the PCEA+AMB program and its incorporation into an infusion pump will hopefully allow us to convert an ordinary infusion pump to one that could deliver mandatory bolus, in addition to and in synchrony with, doses on demand. More research is required to define and refine the clinical role of PCEA+AMB for labor analgesia.
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