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Anesth Analg 2001;93:414-418
© 2001 International Anesthesia Research Society

OBSTETRIC ANESTHESIA

Predictors of Breakthrough Pain During Labor Epidural Analgesia

Philip E. Hess, MD, Stephen D. Pratt, MD, Tanya P. Lucas, MD, Carolyn G. Miller, MD, Tanya Corbett, BA, Nancy Oriol, MD, and Mukesh C. Sarna, MD, FRCA

Department of Anesthesiology and Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Address correspondence and reprint requests to Philip E. Hess, Ste. 308, Department of Anesthesiology and Critical Care, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Address e-mail to phess{at}caregroup.harvard.edu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Parturients who receive labor epidural analgesia may experience breakthrough pain that requires supplemental medications. We investigated the factors associated with breakthrough pain. This prospective observational study included 1963 parturients who received epidural analgesia. Subjects were categorized into two groups on the basis of the number of episodes of breakthrough pain: the Recurrent Breakthrough Pain (RBP) group experienced three or more episodes. Univariate and multivariate regression analyses were used to evaluate factors associated with the RBP group. By multivariate analysis, nulliparity, heavier fetal weight, and epidural catheter placement at an earlier cervical dilation were found to be independently associated with the RBP group. These factors may predict which parturients’ analgesia may be complicated by breakthrough pain. Parturients who received a combined spinal/epidural technique were less likely to be associated with the RBP group. The combined spinal/epidural technique may be superior to conventional epidural anesthesia, because breakthrough pain occurred less often. It is interesting to note that the characteristics that are associated with the RBP group are similar to those that have been associated with increased severity of maternal pain.

IMPLICATIONS: Nulliparity, heavier fetal weight, and epidural catheter placement at an early cervical dilation are predictors of breakthrough pain during epidural labor analgesia. The combined spinal/epidural technique may be associated with a decreased incidence of breakthrough pain.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Epidural analgesia is the most effective method for providing pain relief for women in labor (1). Most women who receive epidural analgesia via continuous infusion remain comfortable, but some may experience episodes of breakthrough pain that require supplemental epidural medication (2). We believe that parturients who request epidural pain relief will be less satisfied if they experience recurrent periods of breakthrough pain during labor. Therefore, the treatment and prevention of breakthrough pain might improve maternal satisfaction with the labor epidural experience. Classifying parturients into high- and low-risk groups may allow for more effective treatment of labor pain in the high-risk group while minimizing the side effects of excessive treatment in the low-risk group. Matching an analgesic technique to an individual parturient, however, requires an accurate set of predictors. Therefore, we conducted this investigation to determine the factors that predict breakthrough pain during labor epidural analgesia (LEA) as practiced at our hospital.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The hospital committee on clinical investigations approved this observational study. Data were collected from all parturients who delivered at our center between July 28, 1997, and July 31, 1998. All data were collected by two obstetric anesthesia fellows and a research assistant. Inclusion criteria for this investigation consisted of singleton live-born delivery between 36 and 41 wk gestation from spontaneous labor in the vertex position. Labor analgesia was provided via continuous infusion by using either LEA or a combined spinal/epidural (CSE) technique. The epidural solution used in all patients consisted of 0.04% bupivacaine with 1.67 µg/mL fentanyl. When LEA was performed, subjects received a 15-mL epidural bolus for initiation and 15 mL/h as infusion. When the CSE technique was used, subjects received a uniform intrathecal injection of 2 mg of bupivacaine with 12.5 µg of fentanyl for initiation, with immediate institution of the epidural infusion at 15 mL/h. All epidural catheters were inserted by residents under the supervision of an attending anesthesiologist or by an attending anesthesiologist.

After admission, demographic and obstetric data were recorded during patient interview, including maternal age, height, and weight, gestational age, and parity. Maternal height and weight were converted to body mass index (BMI) for analysis. Obstetric data were obtained from the patient’s chart, including cervical dilation at admission, cervical dilation immediately before, or within 1 h of, the epidural catheter placement, trial of labor (attempted vaginal delivery after prior cesarean delivery), and the use of oxytocin for augmentation. Neonatal weights were measured by the labor nurse and were then obtained from the patient’s chart. Anesthetic data included the intervertebral site of epidural catheter placement and the technique used (LEA or CSE).

Outcome data consisted of the number of episodes of breakthrough pain. Episodes of breakthrough pain were defined as maternal complaints of pain or pressure that required and were successfully treated with one or more doses of supplemental epidural medications. The indications for supplementation and the type and amount of medications used for treatment were recorded. For analysis, all supplemental medications given within 20 min of the episode were considered as a single treatment. The medications used for supplementation were determined by the anesthesiologist evaluating the patient. The indications for supplementation were reviewed, and episodes related to technical complications (e.g., catheter disconnect) or nonlabor analgesic medications (e.g., anesthesia for instrumental delivery) were eliminated from analysis. The anesthesia team was responsible for evaluation of catheter efficacy and catheter replacement. A persistent unilateral block, the lack of sensory level to cold or pinprick despite supplemental medication, and excessive breakthrough pain despite an apparently adequate sensory level were indications for catheter replacement. Parturients who had their epidural catheter replaced for any reason were excluded from analysis.

On the basis of previous work, we defined excessive breakthrough pain as >1 SD from the mean number of episodes (3). Parturients exceeding this level were labeled as the Recurrent Breakthrough Pain (RBP) group, whereas those with fewer episodes were labeled as the Minimal Breakthrough Pain (MBP) group. Univariate analyses comparing the RBP and MBP groups were performed by using the t-test for continuous variables and the {chi}2 test for frequencies. Multiple logistic regression analysis, using those factors that could be known or estimated at the time of epidural placement, was used to evaluate associations with the RBP group. Only factors found during univariate analysis to be associated with the RBP group with a significance of P < 0.15 were included in the multivariate analysis. P values <0.05 were considered significant. Data analysis was performed with SPSS for Windows 9.0.0 (SPSS Inc., Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Our center is a tertiary care academic center serving a large urban population. Information regarding choices for analgesia is actively disseminated from multiple sources during prenatal visits and childbirth classes, as well as free-of-cost anesthesia classes. Only 5% of our parturients have poor prenatal care (fewer than three prenatal visits). A total of 3489 parturients received LEA during the study period, representing 78% of all laboring women; however, only 2327 met our inclusion criteria. Of these, we excluded 76 who did not receive the study solutions, 8 who had unintentional intrathecal catheters, 111 who had their epidural catheters replaced, and 1 whose record was unavailable for review. Of the 2131 parturients who met our inclusion and exclusion criteria, 168 (8.6%) were excluded because of incomplete data. Missing data consisted of lack of reported cervical examination performed at admission, lack of reported cervical examination performed at epidural catheter placement (43%), missing demographic information (31%), lack of recorded fetal weight (21%), or other (5%). Thus, we had complete information on 1963 subjects (91.4%).

Overall, 44.5% of parturients did not experience breakthrough pain, 43.2% of parturients experienced one or two episodes, and 12.3% experienced three or more periods of breakthrough pain (the RBP group). The average rate of breakthrough pain was 1.1 ± 1.3 episodes per labor. Thus, the RBP group consisted of parturients with three or more episodes of breakthrough pain, whereas the MBP group included those with two or fewer episodes. The absolute rate of breakthrough pain was more frequent in the RBP group (0.53 ± 0.23 episodes per hour versus 0.19 ± 0.28 episodes per hour, P < 0.001), despite a longer duration of analgesia (8.3 ± 3.4 h versus 3.9 ± 2.5 h, P < 0.001). The number of supplemental epidural medication required to successfully treat each episode of breakthrough pain was similar between the MBP (1.3 ± 0.7) and RBP groups (1.3 ± 0.8) (P = 0.64). Also, the dose of bupivacaine (MBP = 6.7 mg versus RBP = 7.2 mg, P = 0.23) and fentanyl (MBP = 42 µg versus RBP = 47 µg, P = 0.34) used for treatment was similar between groups. The technique used for analgesia was CSE in 657 women (33.5%) and LEA in 1306 (66.5%). Women who received CSE were significantly less likely to be in the RBP group than were those who received LEA (5.9% vs 15.5%, P < 0.001). However, there were several significant differences among the subjects who received CSE and those who received LEA (Table 1). Because of these significant differences, multivariate analysis was performed with and without the CSE group as a factor.


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  		Table 1. Analysis by Technique: Combined Spinal Epidural (CSE) Versus Epidural (LEA)
 
By univariate analysis, significant differences in maternal and obstetric characteristics were found between the RBP and MBP groups (Table 2). Parturients in the RBP group were younger, had a higher BMI, were more likely to be nulliparous, and had larger infants. The women in the RBP group were admitted to the labor floor and received a labor epidural at an earlier cervical dilation than those in the MBP group. Their cervical dilation rates were less before placement of an epidural catheter. The women in the RBP group were significantly more likely to receive oxytocin for labor augmentation. No difference was found for the site of placement and the RBP group (P > 0.20). The groups did not differ in the height or weight of parturients (P = 0.26 and P = 0.14, respectively).


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  		Table 2. Univariate Analysis of Factors Associated with Breakthrough Pain
 
Multiple logistic regression was used to determine the influence of the various covariates on the RBP and MBP groups (Table 3). Three independent factors were identified: parturients in the RBP group were more likely to be nulliparous, had heavier fetal weights, and had epidural catheters placed at lesser cervical dilation than their counterparts in the MBP group. After controlling for these factors, the CSE technique was associated with a decreased incidence of RBP. No association was found between the RBP group and maternal age, BMI, cervical dilation at admission, or cervical dilation rate before epidural placement.


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  		Table 3. Results of Multivariate Regression
 
Analysis of the 168 subjects who were eliminated because of missing data revealed small differences in the percentage of women who were receiving oxytocin augmentation (completed = 27.9 versus missing = 35.7, P = 0.04) and in the cervical dilation at the time of epidural placement (completed = 4.65 ± 1.85 versus missing = 5.07 ± 1.95, P = 0.01). No difference was detected in the age, maternal BMI, fetal weight, parity, trial of labor rate, cervical dilation at admission, or cervical dilation rate before analgesia.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
The majority of our parturients had successful analgesia with little requirement for supplementation. However, 12% of parturients (the RBP group) experienced three or more episodes of breakthrough pain that were successfully treated with supplemental medication. Breakthrough pain leading to the request for supplemental medication is common during epidural analgesia via continuous infusion. In studies of continuous infusion epidural analgesia, the requirement for supplementation occurs with rates between 34% and 71% (4–7). The 55% incidence of breakthrough pain in our study is within this range. To develop strategies for the prevention of breakthrough pain, clinicians would be aided by knowing which parturients are at high risk. Previous investigations have highlighted associations between the need for analgesic supplementation and factors that cannot be known at the time of epidural placement. For example, Le Coq et al. (8) found an association between a longer duration of analgesia and abnormal fetal presentation at birth, and the requirement for repeated supplementation. Likewise, Hess et al. (3) found evidence that dysfunctional labor, characterized by cesarean or instrumental delivery, was associated with the requirement for repeated supplementation. Because the factors identified by these two studies cannot be known at the time of epidural placement, they cannot aid the practitioner in making clinical management choices. Effective clinical management requires a set of predictors that can be identified before epidural analgesia is initiated. By multivariate analysis, only four factors were found to be independent predictors. These were nulliparity, neonatal weight, epidural catheter placement at an earlier cervical dilation, and the LEA technique (as compared with the CSE technique). Except for the choice of technique, each of these factors is a preexisting condition that can be obtained or estimated at the time of epidural catheter placement.

In this investigation, parturients who received a CSE were less likely to experience multiple episodes of breakthrough pain than those who received a LEA. Conceivably, because the CSE technique provides more immediate relief of labor pain than the LEA technique, the parturient who received a CSE may have been more satisfied, resulting in fewer requests for supplementation as labor progressed. Collis et al. (7) found increased satisfaction among parturients who received a CSE, and they attributed this satisfaction to a faster onset of successful analgesia. Conversely, Le Coq et al. (8) found that parturients who had a slower onset of analgesia experienced increased analgesic failure, defined as the requirement for at least two supplemental epidural medications. When considering treatment of the parturient at high risk for breakthrough pain (nulliparous, request at an early cervical dilation, and large estimated fetal weight), the CSE technique may be the option of choice.

Tailoring an analgesic regimen to a high-risk parturient by means such as alterations in local anesthetic or narcotic dosing, or the addition of other analgesic medication (e.g., epinephrine, neostigmine, or clonidine), could possibly decrease the recurrence of breakthrough pain. Ideally, the choice of therapy should be tailored toward a specific cause. Breakthrough pain during epidural analgesia is likely to have multiple etiologies. Clearly, technical issues, such as catheter misplacement, migration, and dislodgement, would lead to inadequate analgesia. Technical factors may lead to a loss of function of the epidural catheter that would not be corrected with supplemental medications, requiring catheter replacement. Our exclusion of parturients in whom the epidural catheter needed to be replaced would have limited the effect of technical problems on our results. Despite this, it is possible that technical problems led to the requirement for supplementation in some cases. For example, multiport catheters can deposit medication in more than one space (9). Thus, one of the three holes could lie in the epidural space while the remaining holes lie outside. A parturient with this configuration may have inadequate analgesia, with multiple episodes of breakthrough pain, while being temporarily relieved by supplementation. However, if technical problems were the sole cause of breakthrough pain, then parturients who required supplementation should have had the same distribution of fetal weights and nulliparity as those who remained comfortable. We found the reverse to be true, indicating that some other etiology was responsible for the need for epidural supplementation.

We believe that the severity of maternal pain has a significant influence on the appearance of breakthrough pain; that is, an increased noxious stimulation requires more medication to achieve adequate pain control. As labor advances, parturients report an increased intensity of pain (10). As expected, the median local anesthetic concentration required for the initiation of epidural analgesia increases nearly threefold between early and late labor (11). Additionally, Viscomi et al. (12) found that a single dose of intrathecal sufentanil has a significantly shorter duration of action in parturients with advanced cervical dilation. Thus, the greater severity of pain experienced by the parturient as labor advances affects both the amount of medication required to achieve analgesia and also the duration of action of that medication. Our data suggest that the severity of maternal pain also influences the amount of medication required to maintain continuous analgesia throughout labor. In support of this hypothesis, we note that the parturient characteristics that predict breakthrough pain are identical to those that are associated with increased maternal pain (13–15). Thus, the population of parturients at risk for more severe labor pain is the same population at risk for recurrent episodes of breakthrough pain during epidural analgesia. It is conceivable that repeated episodes of pain lead to either peripheral or central sensitization, resulting in a decreased effectiveness of epidural analgesia. Laboratory evidence also suggests that the transmission of abnormal pain from the uterus may involve alternative nerves, possibly including the vagus nerve (16). It could be hypothesized that pain arising from abnormal uterine stimulation during dysfunctional labor may be conducted via nerves that are not adequately blocked by epidural medications (17). Alternately, the transmission of excessive sensory stimulation may overwhelm the partial local anesthetic blockade, resulting in breakthrough pain. An observational study cannot establish a cause and effect relationship, but merely an association; however, within this hypothesis, breakthrough pain would be a surrogate measure of the severity of labor pain during epidural analgesia.

We acknowledge several limitations to our conclusions. Requests for supplementation may be caused by various cognitive factors, such as maternal expectation, anxiety, and previous experience. It is possible that mental or emotional state may lead to repeated requests for supplementation despite a level of pain relief that would otherwise be acceptable. The elimination of subjects because of incomplete data should be considered. Because the number of patients eliminated was relatively small (8.6%), and there were only minor differences among those parturients who were eliminated and the study population, it seems unlikely that the results would change dramatically had the data been complete. Our hypothesis that breakthrough pain is a result of a greater noxious stimulation cannot be objectively analyzed. Unfortunately, there is no method for evaluating the intensity of noxious stimulation during epidural analgesia, because at least some of the nociceptive transmission is eliminated. Thus, we cannot know whether the parturients in the RBP group were experiencing a greater noxious stimulation when they requested supplementation than did those who remained comfortable. The number of episodes of breakthrough pain may be related to the duration of analgesia; that is, the longer the duration of analgesia, the more likely the requirement for adjustment. However, we found that the absolute rate of breakthrough pain was significantly more frequent in the RBP group, suggesting that these episodes of breakthrough pain were not merely a chance event during a long labor. To assess whether breakthrough pain is caused by tachyphylaxis or by the dynamic nature of pain would require further investigation.

In conclusion, the need for analgesic supplementation is a common finding in studies involving LEA. Identification of maternal and obstetric characteristics at the time of epidural catheter placement may allow the clinician to prepare for episodes of breakthrough pain and, possibly, to adjust medications to improve analgesia. Future investigations of treatment options may be aided by the knowledge of which parturients are likely to experience breakthrough pain.


   Acknowledgments
 
Supported, in part, by the Beth Israel Anesthesia Foundation.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication April 18, 2001.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press