Abstract
Objectives:
To determine the impact of a multimodal protocol on opiate use and postoperative pain after ambulatory urogynecologic surgery.
Methods:
This was a retrospective cohort study comparing ambulatory urogynecologic surgery patients treated under a standard perioperative pain protocol to those treated under a multimodal perioperative pain protocol. The multimodal protocol consisted of preoperative gabapentin and acetaminophen and postoperative scheduled doses of acetaminophen and non-steroidal anti-inflammatory drugs. Pain scores were obtained from nursing records and assessed on the Numeric Rating Scale (NRS-11) per hospital protocol. All opioid dosages were converted into morphine milligram equivalents (MME) using standardized conversion tables.
Results:
We treated 109 patients under the standard protocol and 112 under the multimodal protocol. Patients had similar baseline characteristics. Overall, a minority of patients (39%) used postoperative opioids; this was similar in the two groups (p=0.45). The two groups also were similar with regard to the total postoperative MME (p=0.35). Postoperatively, patients treated under the standard protocol had higher mean pain scores (2.2 vs 1.4, p=0.002). Patients treated under the standard protocol were also significantly more likely to report postoperative pain (69%) than those treated under the multimodal protocol (52%; p=0.01) and the multimodal protocol was associated with a 25% lower risk of postoperative pain (risk ratio: 0.75; 95% CI: 0.60–0.94) than the standard protocol.
Conclusions:
Patients infrequently use opiates following ambulatory urogynecologic surgery. The use of a multimodal pain protocol was associated with lower pain scores, and patients in a multimodal pain protocol were more likely to report no pain.
Keywords: Enhanced recovery after surgery, postoperative pain
INTRODUCTION
The concept of enhanced recovery after surgery (ERAS) was first developed in the early 1990s and involves multimodal and multiphasic evidence-based interventions to enhance recovery after surgery and reduce length of stay. The first ERAS protocols were developed for patients undergoing colorectal surgery,1–4 and similar protocols have been applied in a variety of surgical settings, including benign gynecology and gynecologic oncology5,6. Key ERAS components include thorough preoperative patient education concerning pre-, intra- and post-operative care; safe and short-acting anesthetics; optimal dynamic pain relief with minimal use of opioids; management of postoperative nausea and vomiting; enteral nutrition and early mobilization; and minimally invasive surgery.
Currently, there is a limited, although growing, body of literature on the use of an ERAS protocol in female pelvic medicine and reconstructive surgery.7 While many of the early studies evaluated the effect of ERAS protocols on length of stay, pain control also is an important component of ERAS. Urogynecologic surgery often is ambulatory, and observational studies have confirmed that poorly controlled pain can delay recovery after ambulatory surgery.8. Pain relief allows for early mobilization and therefore is one of the prerequisites for enhanced recovery.
Opiates have traditionally been used to control pain but commonly contribute to nausea, vomiting and slowing of gastric function, which may decrease patient satisfaction and delay return to normal functional status.9,10 Recent progress in perioperative pain management has focused on non-opioid multimodal analgesia, where increasing evidence has demonstrated that opioid sparing reduces nausea, vomiting, and sedation. Several agents have demonstrated effectiveness in randomized, controlled, single-intervention studies (nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, ketamine, gabapentin, local anesthetic). However, there is limited published literature assessing the influence of multimodal pain protocols on recovery after ambulatory urogynecologic surgery.
The goal of this study was to assess the effect of a multimodal perioperative pain control protocol compared to the standard perioperative pain control protocol on postoperative opiate use and pain scores for patients undergoing ambulatory urogynecologic surgery. Our hypothesis was that a multimodal protocol would improve pain control and decrease overall opiate use without increasing the time patients spent in recovery in the post-anesthesia care unit (PACU).
MATERIALS AND METHOD
This was a retrospective cohort study of patients undergoing ambulatory urogynecology surgery treated under a standard perioperative pain control protocol from July 2017 to December 2017 compared to those treated under the multimodal perioperative pain control protocol from January 2018 through June 2018. Anesthesia induction protocols and induction agents were similar for the duration of the study. We obtained pain scores and opioid dosages from the nursing records. Pain was assessed on the numerical rating scale (NRS-11)11 in fifteen- to thirty-minute intervals while in the PACU per hospital protocol. We defined mild pain as a NRS-11 score of 1–3, moderate pain as a NRS-11 score of 4–6 and severe pain as a NRS-11 score of 7–10.
Our standard protocol for postoperative pain control consisted of acetaminophen and/or NSAIDs for mild pain, oral opiates (oxycodone 5mg) for moderate pain, and intravenous opiates (hydromorphone 0.5mg) for severe pain. Under the multimodal protocol all patients had an order for preoperative oral gabapentin (600mg) and oral acetaminophen (975mg). Patients also had an order for scheduled doses of postoperative acetaminophen (975mg) every six hours and appropriate NSAIDs (intravenous ketorolac 15mg or oral ibuprofen 600mg) every six hours. For patients with a contraindication to components of the multimodal protocol, we withheld the offending medications and administered the remaining perioperative medications. In addition, in the multimodal protocol patients were offered oral opiates as first line therapy and intravenous opiates as second line therapy for breakthrough pain. Under the standard and multimodal protocols, intravenous ketorolac was administered at the conclusion of the surgical procedure in the operating room or immediately upon arrival in the PACU. In both cases, intravenous ketorolac was counted with the postoperative non-opiate pain medications.
Vaginal prolapse procedures included vaginal procedures without a laparoscopic component, such as anterior colporrhaphy, posterior colporrhaphy, perineorrhaphy, sacrospinous ligament fixation, uterosacral ligament suspension and colpocleisis. Primary laparoscopic prolapse procedures included sacrocolpopexy, sacrocervixopexy, sacrohysteropexy, paravaginal repair and laparoscopic uterosacral ligament suspension. Vaginal anti-incontinence procedures included midurethral slings with either a synthetic mesh or a biologic graft. Sacral neuromodulation included stage I or stage II sacral neuromodulation and implantable pulse generator removal, replacement or lead wire replacement. Other procedures performed include vesicovaginal fistula repair, excision of transvaginal mesh, repair of urethral diverticulum, and excision of skene’s gland.
All opioid dosages were converted into morphine milligram equivalents (MME) using standardized conversion tables. For each patient, we calculated the total MME administered intraoperatively and postoperatively. We also determined the mean postoperative pain score for each patient, as well as the maximum pain score they reported while in the PACU. For purposes of comparison with published literature, we also calculated the percent change in mean pain. In addition, we assessed the number of postoperative patient phone calls and the frequency of readmission within thirty days of surgery.
Descriptive statistics were reported as mean with standard deviation, median with interquartile ranges (IQR), or frequency with percent. We compared categorical variables using the chi-square or Fisher’s exact test and continuous variables using a t test or Wilcoxon rank sum test, depending on normality of the data. We used log-binomial regression to calculate risk ratios and 95% confidence intervals (CI) for the primary outcomes of any postoperative opiate use and any postoperative pain. We considered the following as potential confounders: age, body mass index, chronic opioid use, procedure, operative time, and intraoperative MME. All tests were two-sided and p-values <0.05 were considered statistically significant. We stored data using Research Electronic Data Capture12 and analyzed data with SAS 9.3 (SAS Institute, Cary, North Carolina). The institutional review board at Mount Auburn Hospital approved this protocol.
RESULTS
During the study period, we performed 302 urogynecologic surgeries; 221 (71%) were ambulatory surgery and thus eligible for inclusion in the study. There were 109 patients treated under the standard protocol and 112 treated under the multimodal protocol. The two groups were similar at baseline with regard to age; body mass index; prevalence of medication-dependent diabetes and hypertension; and gynecologic or urogynecologic surgical history. Patients treated under the standard protocol were more likely (7%) to have chronic opioid therapy, as defined by a prescription for an opioid in the month prior to surgery, than those treated under the multimodal protocol (1%). The types of surgeries performed were generally similar between groups. Baseline characteristics are shown in Table 1.
Table 1:
Baseline patient characteristics stratified by type of perioperative pain control protocol
| Standard protocol n=109 | Multimodal protocol n=112 | |
|---|---|---|
| Age, years | 57 [48 – 69] | 56 [47 – 66] |
| Caucasian race | 93 (85) | 106 (96) |
| Body mass index, kg/m2 | 28 [24 – 31] | 26 [23 – 32] |
| Comorbidities | ||
| Medication-dependent diabetes mellitus | 4 (4) | 12 (11) |
| Hypertension | 34 (31) | 31 (28) |
| Chronic opioid use prior to surgery | 8 (7) | 1 (1) |
| Gynecologic or urogynecologic surgical history | ||
| Hysterectomy | 29 (27) | 37 (33) |
| Prolapse repair | 25 (23) | 25 (22) |
| Anti-incontinence procedure | 29 (27) | 27 (24) |
| None | 57 (52) | 61 (54) |
| Surgery performed | ||
| Vaginal prolapse surgery | 35 (32) | 45 (40) |
| Laparoscopic prolapse surgery | 16 (15) | 13 (12) |
| Vaginal anti-incontinence procedure | 23 (21) | 31 (28) |
| Sacral neuromodulation | 18 (17) | 11 (10) |
| Other | 17 (16) | 12 (11) |
Data presented as n (%) or median [interquartile range]
The median operative time was shorter under the standard protocol than the multimodal protocol (p=0.15). Estimated blood loss was similar in the two groups, and patients in both groups received a median of 10 intravenous MME intraoperatively (both p≥0.56). Following surgery, the median length of time spent in the PACU was 131 (101–180) minutes for those treated under the standard protocol and 146 (110–225) for those treated under the multimodal protocol (p=0.09). Intraoperative characteristics are shown in Table 2.
Table 2:
Intraoperative characteristics and perioperative pain medication usage stratified by type of perioperative pain control protocol
| Standard protocol n=109 | Multimodal protocol n=112 | p | |
|---|---|---|---|
| Intraoperative characteristics | |||
| Operative time, minutes | 49 [27 – 91] | 68 [28 – 107] | 0.15 |
| Estimated blood loss, CCs | 25 [10 – 50] | 25 [10 – 50] | 0.67 |
| Intraoperative intravenous MME | 10 [10 – 17] | 10 [10 – 17] | 0.56 |
| Post-anesthesia care unit length of stay (minutes) | 131 [101–180]) | 146 [110–225] | 0.09 |
| Postoperative pain medication use | |||
| Neither postoperative opiate or non-opiate use | 42 (39) | 34 (30) | 0.21* |
| Any postoperative opiate or non-opiate use | 67 (61) | 78 (70) | |
| Postoperative non-opiate pain medication use | |||
| Neither acetaminophen nor NSAID | 64 (59) | 49 (44) | 0.03* |
| Any acetaminophen or NSAID | 45 (41) | 63 (56) | 0.25† |
| Acetaminophen only | 6 (13) | 3 (5) | |
| NSAID only | 37 (82) | 55 (87) | |
| Both acetaminophen and NSAID | 2 (4) | 5 (8) | |
| Postoperative opiate use | |||
| Neither oral nor intravenous opiates | 65 (60) | 69 (62) | 0.78* |
| Any oral or intravenous opiates | 44 (40) | 43 (38) | 0.45† |
| Oral opiates only | 17 (39) | 12 (28) | |
| Intravenous opiates only | 14 (32) | 19 (44) | |
| Both oral and intravenous opiates | 13 (30) | 12 (28) | |
| Postoperative MME | |||
| Total postoperative MME | 0 [0 – 8] | 0 [0 – 5] | 0.35 |
| Postoperative oral MME | 0 [0 – 8] | 0 [0 – 0] | 0.27 |
| Postoperative intravenous MME | 0 [0 – 1] | 0 [0 – 1] | 0.98 |
| Total intraoperative and postoperative MME | 15 [10 – 20] | 13 [10 – 21] | 0.74 |
Data presented as n (%) or median [interquartile range]
Compares no use to any use
Compares use across all three categories: acetaminophen only, NSAID only, and both
MME: morphine milligram equivalents; NSAID: non-steroidal anti-inflammatory drug
The proportion of patients who received postoperative pain medication, opiates and/or non-opiates, increased from 61% under the standard protocol to 70% under the multimodal protocol, though this difference was not significant (p=0.21). The proportion of patients who received postoperative non-opiate pain medication increased significantly from 41% to 56% (p=0.03). Patients treated under the standard protocol were as likely to use opiates postoperatively (40%) as those treated under the multimodal protocol (38%; p=0.45), yielding a risk ratio of 1.1 (95% CI: 0.39 −3.0). None of the potential confounders had an appreciable effect on the risk ratio. In addition, the median total intraoperative and postoperative MME administered was similar under the two protocols (p=0.74). Perioperative pain medication use is shown in Table 2.
Patients treated under the standard protocol were significantly more likely to report postoperative pain (69%) than those treated under the multimodal protocol (52%; p=0.01). In other words, the multimodal protocol was associated with a 25% lower risk of postoperative pain (risk ratio: 0.75; 95% CI: 0.60–0.94) than the standard protocol; none of the potential confounders had an appreciable effect on the risk ratio. Further, under the standard protocol, patients reported significantly higher mean pain scores (2.2 ±2.2) than under the multimodal protocol (1.4 ±1.8; p=0.002), yielding a 39% reduction in self-reported pain score. This difference was driven by patients who had vaginal prolapse surgery and vaginal anti-incontinence surgery; mean patient-reported pain was similar under the two protocols among those who had laparoscopic prolapse surgery. Of note, severe pain following ambulatory urogynecologic surgery was reported by 17% of patients treated under the standard protocol and 15% under the multimodal protocol. Postoperative pain scores are shown in Table 3.
Table 3:
Postoperative pain stratified by type of perioperative pain control protocol
| Standard Protocol n=109 | Multimodal protocol n=112 | p | |
|---|---|---|---|
| Postoperative pain | |||
| No pain | 34 (31) | 54 (48) | 0.01 |
| Any pain | 75 (69) | 58 (52) | |
| Numeric rating scale pain scores | 2.2 ± 2.2 | 1.4 ± 1.8 | 0.002 |
| Vaginal prolapse surgery | 2.5 ± 2.2 | 1.3 ± 1.7 | 0.01 |
| Laparoscopic prolapse surgery | 2.1 ± 1.8 | 1.6 ± 1.3 | 0.49 |
| Vaginal anti-incontinence procedure | 2.0 ± 2.2 | 0.7 ± 1.2 | 0.02 |
| Sacral neuromodulation | 1.9 ± 2.0 | 2.6 ± 2.7 | 0.43 |
| Other* | 2.5 ± 2.6 | 1.8 ± 2.5 | 0.54 |
| Maximum numeric rating scale pain score | 0.11 | ||
| Severe: scores 7–10 | 19 (17) | 17 (15) | |
| Moderate: scores 4–6 | 37 (34) | 28 (25) | |
| Mild: scores 1–3 | 9 (8) | 8 (7) | |
| None: score 0 | 34 (31) | 54 (48) | |
| Missing | 10 (9) | 5 (4) |
Data presented as n (%) or mean ± standard deviation
After discharge from the PACU, 55% of patients treated under the standard protocol called the clinic within thirty days of surgery compared with 35% of patients treated under the multimodal protocol (p=0.02). Overall, there were only five patients readmitted. One patient treated under the standard protocol was readmitted for poor pain control. Four patients treated under the multimodal protocol were readmitted; one for urinary retention, one for a urinary tract infection, one for poor pain control and one for a syncopal episode. There was no difference in the incidence of readmission between the two protocols (p=0.35).
DISCUSSION
In all surgical fields, there is not only increasing awareness of the immediate risks of narcotics, including constipation, nausea, and vomiting, but also the significant risks of addiction—potentially affecting both short- and long-term recovery. By implementing a simple perioperative pain control regimen with an added emphasis on multimodal pain control, we were able to reduce the risk of postoperative pain and lower pain scores without increasing opiate use.
In the literature, studies of pain relief have reported that reductions in pain scores of 17%−38% correspond to a clinically significant change in pain.13–16 We demonstrated a 39% reduction in mean pain scores after transitioning from a standard protocol to a multimodal protocol. This clinically meaningful improvement in pain suggests that there may be benefit to more widespread use of multimodal protocols to manage pain among patients undergoing ambulatory urogynecologic surgery. Additionally, multimodal pain control seemed most effective treating pain following vaginal procedures.
Other studies in urogynecology have shown a trend in shortening the length of admission after establishing ERAS protocols.7,17 Given our study included only patients undergoing ambulatory surgery, we hypothesized that patients treated under the multimodal protocol would require less time in the PACU to recover after surgery before discharge home. Given the known pharmacokinetics of gabapentin and acetaminophen, we believed that preoperative administration would allow for maximal therapeutic benefit during the postoperative recovery. Acetaminophen generally reaches peak blood concentration around 90 minutes after ingestion and its subsequent half-life is 1.5 to 2.5 hours.18 The timing of the peak concentration and the half-life of acetaminophen perhaps allows for maximal therapeutic benefit while the patient is in recovery. However, we were concerned that gabapentin, which is known to cause sedation, might delay discharge from the PACU. Gabapentin has a half-life of 5 to 9 hours, which is longer than the typical PACU recovery for ambulatory surgery, suggesting that the drug effects likely extended beyond the immediate postoperative recovery.19 However, patients in our study spent a similar amount of time in the PACU before and after implementation of the multimodal protocol, which may suggest that the length of stay in the PACU is more closely related to the anesthesia provided during surgery. Additionally, preoperative gabapentin and acetaminophen did not seem to impact the amount of intraoperative opiates required for anesthesia. This suggests that preoperative multimodal pain medications may be a safe and effective adjunct treatment to help manage postoperative pain.
This study is limited by its observational nature and the differences between the patients in the two study periods. While the groups were similar with regard to baseline characteristics, patients treated under the multimodal protocol had longer operative times. This may signify an increased complexity of surgeries among these patients, leading to increased pain and subsequent opiate requirements for patients treated under the multimodal protocol. However, adjusting for baseline characteristics of patients and operative time did not alter the risk ratios. Further, protocol adherence was not perfect; despite the fact that the multimodal protocol included scheduled doses of acetaminophen and NSAIDs, many patients did not receive either medication postoperatively. Given that a significant proportion of patients had mild or no postoperative pain, many patients refused non-opioid pain medication because they felt it was unnecessary. Additionally, given many patients spent only a short period of time in the PACU, many were discharged before the schedule dose was due to be administered postoperatively. While these limitations may have obscured some of the potential effects of the multimodal protocol, this study design does provide a realistic assessment of the impact of a multimodal pain protocol since it closely mimics real clinical practice and may improve generalizability.
In conclusion, following ambulatory urogynecologic surgery, most patients do not use opiates for postoperative pain control. A multimodal protocol appears to be associated with lower risk of pain and lower pain scores, particularly for vaginal procedures.
Financial Support:
This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers.
Footnotes
Author Disclosure Statement: The author(s) report(s) no conflict of interest
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