Postprocedure Intravenous Patient-Controlled Analgesia Compared to Epidural Patient-Controlled Analgesia Use after Uterine Fibroid Embolization: A Clinical Audit.

PURPOSE: Postprocedure epidural analgesia has a proven benefit over intravenous (i.v.) analgesia for pain management, but has not yet been demonstrated for uterine fibroid embolization (UFE). The objectives of this clinical audit were to determine if epidural patient-controlled analgesia (PCA) was beneficial to patient outcome as compared to i.v. PCA in decreasing parenteral opioid requirements and its associated side effects and determine if there is a difference in required oral opioids after the PCA is stopped.
MATERIALS AND METHODS: This manuscript audited postprocedural pain management of 51 patients after UFE was performed. 20 patients received an i.v. PCA for post-UFE pain control and 31 received an epidural PCA for post-UFE pain control. Total hydromorphone dose, the frequency of anti-nausea medication use, the frequency of anti-pruritus medication use, and patient pain satisfaction data was collected.
RESULTS: Total hydromorphone dose administered to patients post-UFE using epidural PCA was significantly less than patients using an i.v. PCA (P = 0.001). However, the frequency of nausea and pruritus between the two groups did not achieve statistical significance with (P = 0.663) and (P = 0.639) respectively.
CONCLUSION: Our clinical audit found that parenteral opioid requirements administered after UFE can be significantly reduced by using epidural PCA instead of i.v. PCA. However, we found no statistically significant difference in medication related side effects or oral opioid use thereafter.

INTRODUCTION

Patient-controlled analgesia (PCA) has been a major advance in post procedural pain management.[12] Several studies have demonstrated that epidural analgesia provides superior postoperative analgesia compared to intravenous (i.v.) PCA for abdominal, thoracic, gynecologic, and extremity surgeries.[12] This, however, has not yet been proven for post procedural uterine fibroid embolization (UFE) pain control [Figure 1].

Figure 1

(a) Left uterine arteriogram demonstrates vascular blush associated with known uterine fibroids. (b) Left uterine arteriogram post embolization demonstrates near stasis. (c) Pelvic arteriogram prior to uterine fibroid embolization demonstrate widely patent vasculature. (d) Pelvic arteriogram post embolization demonstrating successful bilateral uterine artery embolization

The objective of this clinical audit was to compare patient controlled epidural PCA using an opioid in combination with a local anesthetic to the more standard patient controlled i.v. analgesia (i.v. PCA) after UFE. Our goal was to see whether the overall opioid requirements and systemic side effects such as nausea or pruritus were significantly affected by using one modality versus another.

MATERIALS AND METHODS

This clinical audit was approved by the Institutional Review Board. The reviewed subjects included all of the 51 female patients between the ages of 27 and 55 that presented to the medical center for UFE of symptomatic fibroids between March 2014 and January 2017. Patient demographics are presented in Table 1. No patients were excluded from this review. 20 patients received an i.v. PCA for post UFE pain control and 31 received an epidural PCA. Both groups received scheduled nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen as part of their pain control regimen.

Table 1

Demographics table

Variable	Epidural (n=31), n (%)	i.v. PCA (n=20), n (%)	P
Age - mean (SE)	44.19 (1.20)	42.70 (1.53)	0.444
Insurance - frequency (column percent)
Medicaid	3 (9.7)	6 (30.0)	0.015
Private	22 (71.0)	10 (50.0)	-
Uninsured	6 (19.4)	4 (20.0)	-
Race* - frequency (column percent)
African	17 (54.8)	6 (30.0)	0.003
Caucasian	10 (32.3)	14 (70.0)	-
Other	4 (12.9)		-
Smoking - frequency (column percent)
No	25 (80.6)	13 (65.0)	0.211
Yes	6 (19.4)	7 (35.0)	-
Alcohol use - frequency (column percent)
No	25 (80.6)	17 (85.0)	0.276
Yes	6 (19.4)	3 (15.0)	-
NSAID use - frequency (column percent)
No	25 (80.6)	18 (90.0)	0.220
Yes	6 (19.4)	2 (10.0)	-
Narcotic use - frequency (column percent)
No	30 (96.8)	20 (100.0)	0.608
Yes	1 (3.2)		-

*For race, one subject selected Asian and 3 subjects selected unreported. These 2 groups were combined into another category. PCA=Patient controlled analgesia, i.v.=Intravenous, NSAID=Nonsteroidal anti-inflammatory drugs, SE=Standard error

The epidural catheter was placed preprocedurally by an experienced attending anesthesiologist of at least 10 years’ experience. Under sterile conditions, a 9 cm 17 gauge Tuohy epidural needle was introduced at T11/T12 to L1/L2 and advanced using incremental assessment of injection resistance until loss of resistance was appreciated indicating placement into the epidural space. A 20 gauge polyamide sterile epidural catheter closed tip was advanced through the Tuohy needle. The needle was then withdrawn and the catheter was left in place. An injection adapter cap was applied to the catheter and 3 mL of 1.5% preservative free lidocaine with 1:200,000 epinephrine test dose was administered through the epidural catheter. After a 10–15 min reassessment exam of test dose to confirm negative intrathecal or intravascular placement, the patient was released to the procedural area for fibroid embolization.

Post procedurally, the dedicated pain nursing team bolused the catheters with 3 mL of 0.125% bupivacaine 20 mcg/mL hydromorphone solution (as tolerated by patient's blood pressure) and began infusion of epidural catheter with the same solution. Standard initial settings began at 2 mL/h at a basal rate of 0.125% bupivacaine with 20 mcg/mL hydromorphone and a demand function of 1 mL every 10 min for a maximum total of 8 mL/h based on demand [Table 2]. The catheter was re-assessed every hour for 4 h post procedure to adjust the infusion rate up to 10 ml/h as the blood pressure will tolerate to achieve adequate analgesia in expected dermatomes. When the patient was able to tolerate oral medications post procedurally, the infusion was held for several hours and PO analgesia adequacy was assessed. If analgesia was adequate, the epidural catheter was removed. If analgesia was inadequate, the epidural infusion was restarted and administered for another 24 h with a repeat assessment for transition to PO analgesia. In our study, all patients on epidural PCA had their infusion stopped within 28 h.

Table 2

Typical epidural patient controlled analgesia and intravenous patient controlled analgesia regime

Typical regimen	Epidural PCA	i.v. PCA
Hydromorphone dose (mg/ml)	0.02	0.2
Bupivacaine dose (mg/ml)	1.25	N/A
Basal rate (ml/h)	2	0
Lock out time (min)	10	6

PCA=Patient controlled analgesia, i.v.=Intravenous, N/A=Not available

The i.v. PCA was connected to the patient's peripheral i.v. access at the termination of the procedure. The typical regimen used for i.v. PCA includes hydromorphone 0.2 mg/mL, 1 mL delivered i.v. every 6 min based on patient demand for analgesic requirements with a maximum dose of 2 mg/h allowed [Table 2]. Titration policy allowed for up titration to 1.5 mL (0.3 mg total) every 6 min with a maximum dose of 3 mg/h.

The pumps used for both i.v. PCA and Epidural Pumps are the BodyGuard 575 Color Vision™ (Caesarea Medical Electronics Ltd, Caesarea, Israel). The Infusion pumps are monitored by full time 24/7 dedicated nursing team from the pain service.

A review of the electronic medical record for total hydromorphone administered during the patient's stay was performed. Data for administered oral opioids and other pain medications was also collected. Medication side effects such as nausea and pruritus were recorded as categorical events. Statistical analysis was completed in SAS 9.4 (SAS Institute Inc., Cary, NC, USA) using Fisher's Exact, Chi-square test, and t-test. A significance level of 5% was considered as statistically significant. An analysis of covariance was also performed to determine if the treatment groups were significantly different after adjusting for age, race, and insurance status, history of opioid or NSAID use, smoking and alcohol use. Patient satisfaction with their pain regimen was recorded upon discharge using the following question: “Were you satisfied with your pain control regimen after the procedure and would you like to use the same regimen again if you needed another UFE”. “Yes” or “No” data was collected.

Total hydromorphone dose administered to patients post UFE using epidural PCA was significantly less than patients using an i.v. PCA (P = 0.001) [Table 3]. Total hydromorphone dose in the i.v. PCA group had a mean of 5.24 mg and standard error of 0.96 mg while the PCEA group total hydromorphone dose had a mean of 1.37 mg and standard error of 0.11 mg [Figure 2]. There was no significant difference in the NSAID, acetaminophen and oral opioid dose between the two groups. The frequency of nausea/vomiting and pruritus between the two groups did not achieve statistical significance with (P = 0.663) and (P = 0.639) respectively [Table 3]. The mean frequency of nausea/vomiting in i.v. PCA group was 1.15 with a standard error of 0.18 while the mean frequency of nausea/vomiting in the epidural group was 1.29 with a standard error of 0.26 [Figure 3]. The mean frequency of pruritus in the i.v. PCA group was 1.30 with a standard error of 1.06 while the mean frequency of pruritus in the epidural group was 0.77 with a standard error of 0.33 [Figure 4]. After adjusting for demographic variables, the treatments groups’ hydromorphone dose was still significantly different (P < 0.0001). In the epidural PCA group, 28 patients out of 31 answered “Yes” to our pain regimen satisfaction assessment question, while 13 patients out of 20 answered “Yes” to our question in the i.v. PCA group. The epidural PCA group had a 90.3% satisfaction rate compared with 65% in the i.v. PCA group (P = 0.028). There was one major complication as per Society of Interventional Radiology criteria, which was a cerebrospinal fluid leak from the dural puncture for the epidural requiring 10 days observation and pain management for orthostatic headaches that resolved at discharge. No minor complications were recorded. None of the patients were re-admitted within the following 30 days.

Table 3

Results

Variable	Epidural (n=31)	i.v. PCA (n=20)	P
Total hydromorphone (mg) - mean (SE)	1.37 (0.11)	5.24 (0.96)	0.001
Nausea - mean (SE)	1.29 (0.26)	1.15 (0.18)	0.663
Pruritus - mean (SE)	0.77 (0.33)	1.30 (1.06)	0.639
Oxycodone - mean (SE)	20.65 (7.81)	15.71 (3.27)	0.564
OCT** - mean (SE)	7675.00 (6925.00)	2584.38 (924.34)	0.596

**A new variable OCT is the sum of Ibuprofen and Tylenol use. SE=Standard error, PCA=Patient controlled analgesia, i.v.=Intravenous, OCT=Over the counter medications

Figure 2

Graph comparing total mean hydromorphone (mg) use for epidural patient-controlled analgesia versus intravenous - patient-controlled analgesia

Figure 3

Graph comparing total nausea medication use (mg) for epidural patient-controlled analgesia versus - patient-controlled analgesia

Figure 4

Graph depicting total pruritus medication use (mg) mean for epidural patient-controlled analgesia versus intravenous - patient-controlled analgesia

DISCUSSION

Uterine artery embolization for fibroid treatment is a safe and effective and a well validated procedure nowadays. It is associated with post embolization syndrome (PES) in the majority of patients with postprocedural pain being the most bothersome symptom. PES is thought to be secondary to infarction of all or a portion of the fibroids.[3] Patients usually experience pain, nausea and vomiting, fever, fatigue, and malaise. The symptoms of PES follow a typical pattern after UFE with pelvic pain and cramping worsening the first 2–3 h, reaching a constant level for 8–12 h likely from transient myometrial ischemia.[3] After this, the pain usually subsides to a significantly lower level.[3] There are multiple regimens that have been used for pain control after UFE. At this institution, epidural analgesia has become the standard practice supported by anesthesia availability and patient's overall satisfaction with their pain control.

i.v. PCA is a safe and effective post procedure analgesic technique that has been the gold standard for pain relief after major operations. PCA makes it possible for patients to achieve proper pain control by themselves using self-controlled titrated doses of analgesics. i.v. PCA is relatively quick and simple to set up and administer.[1] However, studies have shown that procedure patient-controlled epidural analgesia provides better post-operative pain control over i.v. PCA.[2] Epidural analgesia can be administered using two agents; local anesthetics and/or opioids both of which can block afferent pain stimulations and efferent sympathetic responses.[1] Also, epidural analgesia is known to cause significantly less generalized sedation than i.v. PCA since direct i.v. infusion of opioids is avoided and a lesser dose of opioids is needed.[1]

Lidocaine is a well-known, widely used local anesthetic agent. Intra-arterial preservative free lidocaine mixed with PVA particles or injected after embolization, has been found to be effective at decreasing pain and opioid dose after UAE.[4] Injection of lidocaine at the end of the embolization may be preferable due to the lower rate of leiomyoma infarction when lidocaine was administered as a mixture with the embolization particles.[4] This may be due to inadvertent uterine artery vasospasm while still delivering embolic particles. High concentrations of intra-arterial lidocaine have been reported to cause severe vasospasm with suboptimal outcomes after UAE.[4]

A lesser known technique is the percutaneous superior hypogastric nerve block (SHNB) which can be performed under CT guidance or intra-procedural fluoroscopic guidance using the Aortic bifurcation into both iliac arteries for accurate targeting of superior hypogastric plexus with subsequent administration of a local anesthetic agent such as bupivacaine. This method of pain control when combined with NSAIDS has been shown to improve patient satisfaction by providing adequate pain control after UFE.[3] However, lack of familiarity among interventionalists and potential associated risks of percutaneous SHNB, including but not limited to bowel transgression make it less appealing as compared with the well validated technique of epidural analgesia or i.v. PCA.

Another alternative pain management approach is to provide a complete oral regimen for post UFE pain control, allowing same day discharge and with the added potential healthcare cost savings. However, pain level after UFE can vary widely due to several procedures and patient related factors and it can become challenging to manage in a completely ambulatory setting.

Epidural analgesia is a well-accepted alternative to conventional i.v. PCA; the cumulative dose of opiates in a 24–48 h period with i.v. PCA can be substantial with a challenging transition to an equivalent oral dosing regimen in preparation for discharge.[56] Epidural analgesia allows for easier transition to an oral opioid regimen as less oral agents are required thereafter as compared with post i.v. PCA transitioning.[5]

Epidural analgesia often uses a local anesthetic (i.e., bupivacaine) in association with an opioid agent; the synergistic effect between these two agents allows for adequate pain control while using a lesser opioid dose. This synergistic effect causes sodium channel blockade of pain pathways with a much lower opiate agonist effect in these pain pathways resulting in satisfactory analgesia.[5]

Unfortunately, no visual analogue pain scores were recorded which would have better validated the results and made them more reproducible/comparable to other studies and future audits, since a simple question on patients’ pain control regimen satisfaction would certainly not suffice as a well validated measure. Also, although there was a 5-fold increase in parenteral opioid requirements in the i.v. PCA group as compared to epidural PCA group, the mean nausea/vomiting scores were not statistically significant. This is likely because PES results in nausea itself, regardless of analgesic method and maybe a confounder that explains why there was no difference in side effects between the two groups. In addition, no cost effectiveness analysis was performed to evaluate the added cost of epidural PCA compared to i.v. PCA; however, it is worth mentioning that all epidurals were billed for and reimbursed.

CONCLUSION

This clinical audit shows that our epidural PCA option is an acceptable alternative for post procedural pain control after UFE and should be considered by all UFE providers. It's most significant advantage is the significant reduction of parenteral opioid requirements after UFE as compared to i.v. PCA. The reduction of overall administered opioids is inevitably becoming a matter of extensive research and debate nowadays given the current opioid epidemic.

However, there was no statistically significant difference in medication related side effects or oral opioid dose use thereafter. A larger study sample is likely needed to further examine this matter. It is worth noting that the epidural PCA group achieved a higher satisfaction rate. A double blinded prospective study is needed to evaluate epidural PCA regimen in post UFE patients as it may offer significant advantages over other methods.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.