Cesarean delivery (CD) is one of the most common surgical procedures performed in the United States, making up over 32% of all live births, or about 1.3 million procedures per year.1 Women undergoing CD are unique because in addition to their own recovery, they must also begin bonding with and caring for their newborns immediately after their surgery. The need for early mobilization and avoidance of oversedation is also important in this population due to an increased risk of thromboembolic complications.2 Approximately 1 in 5 women who undergo CD will experience severe acute postoperative pain.3 The severity of pain in the acute postoperative period is a significant predictor for the development of chronic pain,3,4 which occurs in 9.2%–18% of women who undergo CD.5–7 Furthermore, severe acute postcesarean pain triples a woman’s risk of developing postpartum depression and negatively affects breastfeeding and infant care.3,8 For these reasons, it is imperative to provide adequate postoperative analgesia in this patient population. The challenge for physicians is that pain associated with CD is complex, involving the interplay of many factors with significant interindividual variability in pain perception.9 Therefore, the current standard “one-size-fits-all” approach to postoperative analgesia is often inadequate for a significant portion of patients who experience more severe pain after CD.3
Preoperative identification of women at greater risk for severe postoperative pain might allow for targeting this population with more intensive analgesic interventions to improve postoperative analgesia. Several studies in the general surgical population have attempted to utilize preoperative tests or questionnaires to test the hypothesis that patients with more severe pain after surgery or with increased postoperative analgesic consumption may be identified preoperatively. A systematic review in the general surgical population found that preoperative pain, anxiety, younger age, and type of surgery were significant predictors of postoperative pain, and that type of surgery, younger age, and psychological distress were significant predictors of analgesic consumption.10 Likewise, a growing body of research has investigated modalities attempting to predict which women will experience more severe acute postcesarean pain. However, to our knowledge, there is no current review of the studies that investigate methods to predict acute postcesarean pain. Therefore, with the unique needs of patients undergoing CD in mind, we performed this review to evaluate the utility of various tools to predict severe pain and/or opioid consumption in the first 48 hours after CD.
We performed a literature search of MEDLINE, the Cochrane database, and Google Scholar on August 26, 2017, using the terms “Cesarean,” “Pain,” and “Predict” to identify articles investigating ways to predict acute pain after CD. The MEDLINE search identified 34 articles, the Cochrane search 9 articles, and the Google Scholar search over 30,000 articles. Due to the overwhelming results of the Google Scholar search, we added the terms “Acute Pain,” “Quantitative Sensory Testing,” and “Questionnaire” to the search, which narrowed the results to 2340 articles. Abstracts were manually reviewed for relevance. Because we were interested in the prediction of acute pain outcomes, we only included studies that reported pain scores and/or opioid consumption in the first 48 hours after CD.
Thirteen studies investigating preoperative pain testing in women undergoing CD were identified. Five studies utilized quantitative sensory testing (QST),11–15 1 study utilized hyperalgesia testing,16 1 study used response to local anesthetic infiltration,17 4 studies utilized questionnaires,18–21 and 2 studies utilized both QST and questionnaires.22,23 Four studies were from Israel,13,17,20,23 3 from the United States,19,21,22 3 from Europe,11,12,14 1 from South Africa,15 1 from Brazil,18 and 1 study took place jointly in Brazil and the United States.16 The average age of participants ranged from 25 to 35 years. Seven studies included data on parity of participants,11,15,19–23 and for these studies, the average parity was between 1 and 2. For the 5 studies that reported primary versus repeat status,12,16–18,21 repeat CD patients made up the majority of participants in all but 2 studies.12,18
QST, Scar Hyperalgesia, and Local Anesthetic Infiltration
QST is a term that refers to noninvasive methods that evaluate individuals’ sensory perception in response to different quantifiable mechanical, thermal, or electric stimuli.24 “Static” QST measures, which include pain thresholds, pain tolerance levels, and ratings of suprathreshold painful stimuli, depict a single point on the continuum of pain experience and are less useful for measuring pain modulation processes.25 “Dynamic” QST measures, on the other hand, are used in an attempt to measure certain mechanisms of pain processing and include mechanical temporal summation (mTS), a test of central integration, and diffuse noxious inhibitory control, a test of descending pathways/endogenous analgesia systems.25
There are 3 types of QST stimuli that have been investigated as possible tools to predict postcesarean pain: pressure, electric, and thermal stimulation. We have also included in this section scar hyperalgesia (SHA), which has been put forward as an indicator of central nervous system sensitization,16 and the stimulation produced by local anesthetic infiltration, which, while not technically a QST, is part of routine clinical practice of administration of spinal anesthesia. A summary of the relevant studies, arranged by stimulation modality, is displayed in Tables 1 and 2.
Pressure Stimulation and SHA.
In 2 studies, pressure pain tolerance and threshold were tested using algometers (Table 1).11,12 These devices use a small probe to apply increasing pressures to the pulp of the middle finger of patients’ right hand. Patients are instructed to indicate when they first experienced pain (pain threshold) and when they could no longer bear the pain (pain tolerance). Another study applied a 180 g von Frey filament around the area of prior CD scars; the distance from the scar that pain was felt was used to calculate SHA index (Table 2).16 Both methods showed correlations with some measures of postcesarean pain, but the correlations were inconsistent and weak to moderate in strength. The study assessing wound hyperalgesia also measured mTS, a dynamic quantitative sensory test, in which a 180 g von Frey filament was used to apply repetitive stimuli to the volar aspect of the dominant forearm, and the pain rating of the last stimulus was compared to that of the first. While the authors did not report whether mTS correlated with postoperative pain measures, they found that preoperative SHA index was correlated with preoperative mTS.16 This suggests that mTS may also be able to predict pain after CD, but studies are needed that specifically assess and report the correlation between mTS and postoperative pain outcomes.
Four studies used electricity as the painful stimulus for QST.11,12,14,15 An electrocutaneous stimulation device or nerve stimulator was used to generate electric discharges of increasing intensity to measure sensation threshold (the point at which patients report feeling an electric sensation) and/or pain threshold (the point at which patients report feeling pain). Preoperative electric pain and sensation thresholds were inversely correlated with some measures of postoperative pain scores and analgesic consumption (Table 1). For example, in the study by Nielsen et al,14 patients’ preoperative electric pain thresholds, but not electric sensation thresholds, were shown to be inversely correlated with a “composite post-operative pain endpoint” at rest and with mobilization, which was calculated as the area under the curve of 4 pain scores collected during the first 56 hours after CD. Taken as a whole, the literature shows that preoperative electric QST is possibly predictive of some aspects of postcesarean pain. The strength of the correlation varied in different studies but was at least moderate to strong in 1 study.14
Three studies have evaluated pain modulation in CD patients using heat as the pain stimulus.13,22,23 These studies used a thermode, a hand-held device with a small contact probe that can generate a range of temperatures. The investigators measured patients’ thermal pain threshold, the temperature at which the heat stimulus became painful, or their pain scores in response to a suprathreshold heat stimulus. In 1 study,22 7 potentially predictive factors were identified and tested for their utility in predicting postcesarean pain. These factors were pain and unpleasantness ratings in response to suprathreshold heat stimulus, preoperative blood pressure, preexisting pain during pregnancy, expectation for postoperative pain and analgesic needs, thermal pain threshold, duration of surgery paired with sensory blockade level, and responses to the State-Trait Anxiety Inventory (STAI). Interestingly, pain and unpleasantness ratings in response to suprathreshold heat stimulus and thermal pain threshold were both significantly correlated (with similar strengths of correlation) with resting pain at 24 hours, evoked pain at 24 hours, and recovery room analgesic consumption. However, only suprathreshold heat stimulus pain and unpleasantness ratings were correlated with total analgesic consumption. This seems to suggest that both methods of thermal QST are useful for predicting postcesarean pain, with responses to suprathreshold heat stimuli having a slight edge when it comes to anticipating analgesic consumption. Taken as a whole, the available literature demonstrates that QST using various types of heat stimulation might be used to help predict postcesarean pain.
Local Anesthetic Infiltration.
Local anesthetic skin infiltration is performed as part of standard practice when placing neuraxial blocks for women undergoing CD. A recent study reported that patients’ ratings of pain with local anesthetic infiltration before placement of spinal anesthesia were significantly correlated with their postcesarean pain scores at rest and with mobilization and with analgesic requests (Table 2).17 Furthermore, this study showed that pain scores on local anesthetic infiltration were able to predict severe acute postoperative pain (as measured by a pain score ≥70 of 100) with 91.6% sensitivity and 93.3% specificity, the highest of any study published to date.
Application and Limitations of QST, Hyperalgesia, and Local Anesthetic Infiltration.
The studies evaluating experimental models of pain with pressure, electric, and heat noxious stimuli all demonstrated some correlation with postcesarean pain outcomes, although the findings were not consistent and correlations were not robust. A recent review of QST in the general surgery population also found that patients’ responses to preoperative tests may predict 4%–54% of the variance in the postoperative pain experience.24
Pressure, electric, and thermal QST techniques share similar drawbacks. First, these tests evaluate sensory perception in response to noxious stimuli in experimental settings, and as such, they can only be performed in women undergoing nonurgent CD. Second, these tests require specialized equipment such as algometers, electrocutaneous stimulators, and thermodes that are not currently readily available in most clinical settings. Third, these methods cause discomfort and therefore may be challenging to perform in an anxious patient if done just before CD. Finally, the major shortcoming of these tests in regard to being adapted in clinical practice is the amount of time it takes to perform them. Each of these methods is time consuming, and possibly prohibitively so in a fast-paced clinical environment. Furthermore, assessing SHA can only be performed in women who have previously undergone CD.
Using pain rating of local anesthetic infiltration does not have many of the drawbacks of the QST measures; it does not require any additional or new equipment, is quick to perform, requiring only a single question to be asked of the patient, and the discomfort associated with it is already part of standard practice for performing neuraxial techniques. Furthermore, because local anesthetic infiltration is performed in the clinical setting, it can be used in both nonurgent and urgent CDs. In addition, the study investigating this modality has reported high sensitivity and specificity for predicting which patients will experience more severe pain. This technique has, however, only been evaluated in 1 study, and while the sample size of that study was larger than that of all the QST studies, further studies are needed to confirm the utility of this method for predicting postoperative pain. One final caveat that applies to local anesthetic infiltration as well as the QST modalities is that none of these methods have yet been tested to show whether the patients predicted to experience more severe pain actually benefit from higher analgesic doses or from incorporation of other analgesic adjuncts in their postoperative regimen. These gaps in our current knowledge represent areas that should be targeted by future research.
Preoperative questionnaires have also been investigated as a means to predict postcesarean pain based on patients’ preoperative anxiety, personality, and expectations. The questionnaires that have been studied for this purpose include the STAI, the Pain Catastrophizing Scale (PCS), simple questions regarding anxiety and anticipated pain and analgesic needs, the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). Table 3 is a summary of the relevant studies, arranged by date of publication.
State-Trait Anxiety Inventory.
The STAI, a validated psychological tool that uses 20 questions to assess state anxiety (feelings related to current situation) and 20 questions to assess trait anxiety (enduring personality characteristics),26 was evaluated in 1 study to predict postcesarean pain and analgesic need (Table 3).22 In that study, patient’s preoperative total STAI scores correlated with total analgesic consumption after CD and recovery room analgesic consumption, but not with pain scores. Further analyses with regard to state versus trait components of the questionnaire were not reported in this study.22
Pain Catastrophizing Scale.
The PCS is a validated psychological questionnaire that contains 13 items and is used to assess patients’ attitudes toward pain, namely rumination, magnification, and helplessness.27 In 1 study, preoperative PCS scores were found to be moderately correlated with patient’s pain scores on postoperative day 1 and postoperative day 2 after CD, but not with analgesic consumption (Table 3).23
Simple Questions About Anxiety and Anticipated Pain and Analgesic Needs.
In addition to the STAI, the study mentioned above examined 6 other potential predictive factors for pain after CD: pain and unpleasantness scores in response to a suprathreshold thermal stimulus, preoperative blood pressure, preexisting pain, a pain expectation factor, thermal pain threshold, and an intraoperative factor, which consisted of duration of surgery and sensory blockade level at the time of incision.22 The “expectation factor” in this study consisted of patients’ ratings of the amount of pain they anticipated experiencing after CD and the amount of pain medication they anticipated needing after the surgery. Interestingly, responses to these questions were found to be moderately correlated with patients’ actual pain scores at rest after CD (Spearman ρ = 0.41; P <.05), and these results were used in a later study to evaluate the utility of “three simple questions” to predict postoperative pain.21
In this follow-up study, those three simple questions assessed patient’s anxiety, anticipated postcesarean pain, and anticipated analgesic need (Table 4).21 Answers to these questions were moderately correlated with evoked pain scores at 24 hours postoperatively (r = 0.24–0.33; P < .001).21 Using the data from this study, the authors constructed a model whereby they were able to use this simple questionnaire to predict women at the top 20th percentile of postcesarean pain scores with a sensitivity of 68% and a specificity of 67%. In a follow-up study, the three simple questions were used to develop a cohort of patients undergoing CD who were predicted to have pain scores above the 80th percentile.28 These patients were then randomly assigned to receive either standard doses of spinal morphine (150 μg) plus placebo or an increased dose of spinal morphine (300 μg) plus scheduled acetaminophen. Both groups received regular scheduled nonsteroidal anti-inflammatory drugs. Women in the control group had higher postcesarean pain scores with movement at 24 hours compared with the treatment group. The incidence of pruritus was, however, higher in the treatment group (70% vs 50%), but the difference was not statistically significant since the study was not powered for this end point. This was the only study to date demonstrating that modifying the standard analgesic protocol for patients predicted to experience more intense pain can lead to improved pain control for this population. The study, however, lacked a group of low-risk women randomized to the same interventions.
More recently, another study tested the ability of a comparable simple screening tool (see Table 4) to predict pain after CD.19 This study compared the simple screening tool with 4 validated psychological questionnaires: the Anxiety Sensitivity Index, which assesses anxiety associated with potentially unpleasant events; the Fear of Pain Score III, which evaluates fear that is generated from physical insult or injury; the PCS, discussed above; and the Eysenck Personality Questionnaire Revised-Short Scale, with questions to assess psychoticism, extroversion, neuroticism, and lying. None of the individual psychological questionnaires were significantly correlated with opioid use or pain scores over 48 hours. Multiple linear regression analyses of all 4 questionnaires combined with the simple screening tool revealed significant correlations with opioid consumption and pain scores (r2 = 0.421 and r2 = 0.443, respectively).19 However, analysis of the simple screening tool questions alone also yielded a significant correlation with opioid consumption and pain scores (r2 = 0.212 and r2 = 0.447, respectively), leading the authors to conclude that due to the ease of administration, the simple screening tool was a more clinically useful option compared to other questionnaires.19
Pittsburgh Sleep Quality Index.
The PSQI is a validated self-report questionnaire that assesses sleep quality over the prior month.29 A recent study used the PSQI to divide patients into a “good sleep” (score of ≤5 of 21) and “poor sleep” (score of >5 of 21), and found that patients in the poor sleep group reported significantly higher peak pain scores with movement at 24 hours after CD (OR = 2.64; P = .006).20 Importantly, the authors of this study found that although scores on the PSQI had little positive predictive value, the negative predictive value of a score ≤5 on the PSQI (good sleep) for severe postoperative pain (defined as ≥70 of 100) was 87.2%.20 Also of note, this study compared preoperative STAI and PCS scores for both the good sleep and bad sleep groups, and found no significant difference between groups for the STAI scores, but did find significantly higher scores on the PCS among women in the poor sleep group.
Hospital Anxiety and Depression Scale.
The HADS is a self-assessment tool that has been shown to be a reliable instrument for detecting depression and anxiety in the inpatient hospital setting.30 The questionnaire is made up of 7 items that assess depression and 7 questions that assess anxiety, and these subscales are validated measures of severity of emotional disorder.30 Using the HADS, 1 study found that women’s preoperative anxiety scores were predictive of their incidence of moderate to severe pain (pain score of ≥5 of 10) after CD (OR [95% confidence interval], 1.60 [1.16–2.20]; P = .001).18
Application and Limitations of Questionnaires.
The STAI, the PCS, simple screening questions, the PSQI, and the HADS have all demonstrated modest correlations with some elements of postoperative pain. When compared to QST, these questionnaires are less costly, involve no additional discomfort for patients, and generally take less time to complete. Another advantage is that patients could possibly complete them at home before hospital admission. The longest of these tests is the STAI (40 items) then the PSQI (19 items); the HADS (14 items), the PCS (13 items), and finally both sets of simple screening questions (3 items) are the shortest. The longer length of the STAI, PSQI, HADS, and PCS does not seem to confer much advantage over the simple screening questions, so it would seem that shorter surveys would be the best option to be adopted for clinical use. One of the simple screening tools, the three simple questions, also holds the distinction of being the only questionnaire to be validated for the purpose of predicting postcesarean pain at present,28 even though it has not been subjected to validation outside its group or center of origin. Importantly, when patients who are predicted by the three simple questions survey to experience more severe pain were actually given higher doses of postoperative analgesics, they reported lower pain scores than a group who was given standard postoperative analgesic regimen.28 This suggests that the three simple questions survey might have measurable clinical utility in improving pain outcomes after CD, but those findings need to be confirmed in other studies from other institutions. Studies also need to include low-risk women receiving the same interventions as those predicted to be at high risk, to assess whether increasing the analgesic doses are only of benefit in high-risk patients. Further research using the STAI, PQSI, PCS, HADS, or other questionnaires will need to demonstrate the same clinical utility to be adopted in clinical use. Finally, future studies should focus on evaluating these questionnaires head to head and finding the optimal timing for administration of such questionnaires.
Combination of Multiple Factors.
One study investigated multiple modalities to predict postcesarean pain, using responses to the STAI, patient expectation, audio sensitivity, thermal pain threshold and sensitivity, and suprathreshold pain intensity and unpleasantness to assess if a combination of factors would be more accurate at predicting postcesarean pain or analgesic consumption than a single modality.22 For most of the end points measured, either 1 factor or a combination of just 2 factors yielded the strongest relationship. Additionally, no 1 factor or combination of 2 factors was most effective at predicting all of the end points. These data seem to suggest that combination of factors might not always be beneficial for the prediction of postcesarean pain. Further, the amount of testing required to measure even 2 of the factors from this study would be prohibitively time consuming for clinical use. The results of this study, however, were used to create the three simple questions survey mentioned above, which, when compared to the multivariable model incorporating several predictive factors, was shown to provide similar predictive power in a more clinically oriented form.21,22 However, further research is needed to determine whether 2 or more factors that are easy to implement in clinical practice can be used in combination to predict postcesarean pain with greater accuracy than individual factors alone.
Several different testing methods may be used to predict postcesarean pain. A number of these methods, however, while associated with statistically significant results in the research setting, might not be clinically feasible. The correlations with postoperative pain outcomes were also weak to modest in most studies, and it is therefore unclear if the adoption of such tests in clinical practice would improve patients’ outcomes. With the exception of 1 study,28 there is a striking lack of investigation into the potential clinical impact of using any predictive test. Of the methods studied, pain with local anesthetic infiltration and the simple screening questions show promise for clinical use, but need to be validated outside their institution of origin. More work must be done to incorporate simple, clinically applicable prediction tests in a decision algorithm for analgesia after CD.
Name: Brock H. Gamez, BS.
Contribution: This author helped write the manuscript and approve the final version.
Name: Ashraf S. Habib, MBBCh, MSc, MHSc, FRCA.
Contribution: This author helped design the study, write the manuscript, and approve the final version.
This manuscript was handled by: Jill M. Mhyre, MD.
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