What is the evidence to support the use of methocarbamol for acute post-op pain management?

What is the evidence to support the use of methocarbamol for acute post-op pain management?

Comment by InpharmD Researcher

Limited studies are mixed regarding the benefit of methocarbamol in reducing postoperative pain and opioid use. However, the surgical setting and treatment regimen differ greatly between studies. Some surgeries, such as cholecystectomy, cardiac surgery, and posterior fusion surgery, may benefit from methocarbamol for postoperative pain, but the available studies are mostly limited in quality and scope.

Background

A study performed a data analysis of 687 consecutive augmentation mammaplasty patients. Patients received an indwelling catheter for postoperative instillation of bupivacaine. Methocarbamol was started 2 days preoperatively and continued four times daily for approximately 3-5 days postoperatively. Pain tolerance (scored 1-10) and narcotic-free days were assessed. While the main outcome focused on self-administration of bupivacaine, it was noted that patients tend to score lower on pain scales with use of methocarbamol (mean pain score rating 3.27;n= 242). Methocarbamol was more effective in patients with interscapular pain compared to those without (p= 0.0196). Yet overall, there was a wide variation in response to methocarbamol use, and overall response appears to be poor. [1]

A 2012 randomized, double-blind clinical trial evaluated the effect of methocarbamol on postoperative pain following cholecystectomy in 60 patients with American Society of Anaesthesiologists physical status of I and II, aged between 30-50 years, and weighted lower than 100 kg. Participants in both groups underwent elective surgeries without premedications and under similar conditions of general anesthesia. The interventional group received intravenous methocarbamol 500 mg, and the control group received a 5 mL placebo slowly postoperatively. The mean pain score (measured by visual anesthesia scale [VAS]) was only significantly lower for the interventional group at 6.24 hours after operation (p<0.05), but not at 1, 3, and 12 hours. The frequency of prescribed narcotics (indicated when VAS > 4) in the interventional group was lower compared to controls (p<0.05). While the study demonstrates a promising role of postoperative methocarbamol in patients undergoing cholecystectomy, the full publication is not available in English, and limited numerical data can be extrapolated from the study abstract. [2]

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

What is the evidence to support the use of methocarbamol for acute post-op pain management?

Please see Tables 1-3 for your response.

The Role of Methocarbamol and Intercostal Nerve Blocks for Pain Management in Breast Augmentation
Design	Prospective, randomized, single-blinded clinical trial N= 100
Objective	To investigate the efficacy of intercostal nerve blocks and oral methocarbamol for postoperative pain control
Study Groups	Methocarbamol with block (n= 25) Methocarbamol without block (n= 25) Block without methocarbamol (n= 25) No block nor methocarbamol (n= 25)
Inclusion Criteria	Scheduled primary bilateral subpectoral breast augmentation, aged 18 to 60 years
Exclusion Criteria	Other significant procedures scheduled concomitantly, anticipated sub-glandular implant placement, history of narcotic or substance abuse, chronic pain or long-term use of pain medication, seizure disorder
Methods	Bilateral intercostal nerve block was performed by attending surgeons using bupivacaine 0.25% (total volume 40 mL, 20 mL per side). Methocarbamol was administered as an oral dose of 1,500 mg preoperatively in related groups and was continued every 6 hours in 500 mg tablets. Use of methocarbamol was not blinded by patients or nurses.
Duration	7 days
Outcome Measures	Primary: postoperative visual analog scale (VAS) score (1-10) Secondary: narcotic use
Baseline Characteristics		Methocarbamol with block (n= 25)	Methocarbamol without block (n= 25)	Block without methocarbamol (n= 25)	No block nor methocarbamol (n= 25)
	Age, years	34	37	35	36
	Implant volume, mL	312	304	280	300
	Transaxillary placement	88	88	80	80
Results	Endpoint	Methocarbamol	No methocarbamol	Block	No block	p-value
	VAS pain score 1 hour 3 hour 6 hour 24 hour 48 hour 72 hour	4.84 3.92 4.4 5.64 5.04 3.84	5.96 4.64 4.6 4.84 4.52 3.08	5.32 3.8 4.68 5.6 5.28 4.04	5.96 4.64 4.6 4.84 4.52 3.76	0.03 for methocarbamol; NS for block NS NS NS NS NS
	No significant differences were reported in postoperative narcotic use among patients. Specific datasets were not provided.
Study Author Conclusions	This study suggests that intercostal nerve blocks do not significantly decrease postoperative pain following breast augmentation. Preoperative use of methocarbamol may be of benefit to help diminish early perioperative pain. In this outpatient cosmetic surgery population, expeditious pain management with minimization of nausea and sedation is critical. A preoperative dose of methocarbamol may be of benefit and merits further investigation.
InpharmD Researcher Critique	While frequently associated with pain, breast augmentation is cosmetic surgery. The extrapolation of use in other surgical fields remains limited.

References:

Hidalgo DA, Pusic AL. The role of methocarbamol and intercostal nerve blocks for pain management in breast augmentation. Aesthet Surg J. 2005;25(6):571-575. doi:10.1016/j.asj.2005.09.003

Impact of an Enhanced Recovery after Surgery Protocol on Postoperative Outcomes in Cardiac Surgery
Design	Single-center, retrospective cohort study N= 318
Objective	To determine if the utilization of an enhanced recovery after surgery (ERAS) protocol improves recovery outcomes and decreases the use of postoperative opioids following cardiac surgery
Study Groups	Historic control (n= 185) ERAS protocol (n= 133)
Inclusion Criteria	Aged ≥ 18 years, admitted to the cardiovascular intensive care unit (CVICU), received postoperative care after coronary artery bypass graft (CABG) or valve procedures
Exclusion Criteria	Historic control: received gabapentin or methocarbamol prior to admission or during the stay; received intra-operative methadone, had a history of intravenous (IV) drug abuse, underwent transcatheter aortic valve replacement (TAVR) procedures, pregnant, remained intubated more than 18 hours after surgery
Methods	The study institution implemented a new ERAS protocol for pain management in patients who undergo cardiac surgery, including non-opioid analgesia with acetaminophen (1,000 mg Q8H), gabapentin (100-300 mg Q8H), and methocarbamol (250-500 mg Q6H) for 5 days with the option of extending therapy or making dose adjustments based on renal function, as well as tolerability and response. Doses were reduced based on age and renal function; specifically for methocarbamol, 250 mg was indicated for those aged ≥ 75 years and 500 mg for those aged ≤ 75 years. Of note, no protocol drugs were given pre-operatively.
Duration	Intervention: From July 1, 2019, to December 31, 2019, and April 1, 2020, to September 30, 2020
Outcome Measures	Primary: total cumulative opioid consumption 72 hours postoperatively (as reported Median Morphine Equivalents [MME]) Secondary: average pain scores for the first 72 hours postoperatively (Behavior Pain Scale [BPS] scores during intubation), postoperative length of stay, and incidence of opioid-related complications
Baseline Characteristics		Historic control (n= 185)	ERAS protocol (n= 133)
	Age, years	65	65
	Male	70.8%	69.2%
	White*	74.6%	72.2%
	Weight, kg*	88.0	83.3
	Past medical history* Diabetes Depression Chronic kidney disease Chronic pain Home opioid use	43.8% 3.8% 12.4% 2.7% 3.8%	39.1% 3.8% 18.0% 12.8% 8.3%
	Underwent CABG procedure	78.9%	78.9%
	Postoperative length of mechanical ventilation, hours	8.85	10.8
	*p< 0.05
Results	Endpoint	Historic control (n= 185)	ERAS protocol (n= 133)	p-value
	Cumulative opioid use postoperatively, MME (interquartile range [IQR]) 12 hours 24 hours 48 hours 72 hours	30.0 (7.9 to 67.9) 49.1 (22.5 to 86.6) 83.3 (37.5 to 135.8) 105.4 (37.9 to 165.0)	25.0 (7.9 to 47.5) 38.5 (22.5 to 68.7) 67.9 (37.5 to 111.6) 75.8 (40.6 to 128.7)	0.29 0.18 0.12 0.09
	Median BPS scores at 72 hours postoperatively	3.59 ± 1.32	3.36 ± 1.93	< 0.05
	Postoperative length of stay, hours (IQR)	145.5 (119.7 to 191.8)	140.3 (117.7 to 169.3)	0.89
	Incidence of opioid-related complications Constipation Respiratory depression Incidence of ileus	60.5% 62.7% 2.7%	47.4% 57.1% 0.75%	< 0.05 < 0.05 0.18
	Incidence of patient-controlled analgesia (morphine/hydromorphone) use	36.2%	0%	< 0.05
	Of the patients with an incidence of ileus seen on imaging, a nasogastric tube was inserted in 4 of the historic control patients vs. 1 patient in the ERAS group.
Adverse Events	See results
Study Author Conclusions	Use of an ERAS protocol shows a promising trend toward less postoperative opioid use in cardiac surgery patients. Lower rates of opioid-related adverse events, including constipation and respiratory depression, were observed in the ERAS protocol group. This study indicates that ERAS protocols have a potential role for cardiac surgery patients postoperatively.
InpharmD Researcher Critique	The study is limited by certain inherent weaknesses of a single-center retrospective study, with potentially unadjusted confounding factors and decreased generability. Additionally, as the ERAS protocol group is compared to the historic control, the differences in general practice during the two time periods could also have contributed to the differences in results.

References:

Bills S, Wills B, Boyd S, Elbeery J. Impact of an Enhanced Recovery after Surgery Protocol on Postoperative Outcomes in Cardiac Surgery [published online ahead of print, 2022 Aug 13]. J Pharm Pract. 2022;8971900221119013. doi:10.1177/08971900221119013

Methadone-based Multimodal Analgesia Provides the Best-in-class Acute Surgical Pain Control and Functional Outcomes With Lower Opioid Use Following Major Posterior Fusion Surgery in Adolescents With Idiopathic Scoliosis

Design

Retrospective matched cohort study

N= 122

Objective

To test the hypothesis that a multimodal analgesia regimen, including multiple and small doses of methadone and nonopioid analgesics and adjuncts, would promote earlier hospital discharge, improve pain scores, and lower opioid consumption in adolescents undergoing posterior spinal fusion (PSF)

Study Groups

Multimodal analgesia protocol (n= 61)

Control (n= 61)

Inclusion Criteria

Idiopathic scoliosis patients with posterior instrumented spinal fusion.

Exclusion Criteria

Patients with neuromuscular scoliosis, congenital QT prolongation, and allergy to any of the protocol drugs during the intervention period

Methods

Enrolled patients received a multimodal analgesia regimen consisting of (scheduled methadone, methocarbamol, ketorolac/ibuprofen, acetaminophen, and oxycodone with intravenous [IV] opioids as needed) according to the new protocol. Before implementing the new protocol, patients received intrathecal morphine 5 mcg/kg and postoperative oral gabapentin (100 mg per dose) 3 times a day, morphine patient-controlled analgesia (PCA) on postoperative day 0 (POD0) and transitioned to oxycodone or hydrocodone on POD1 with IV morphine as needed for breakthrough pain. Patients also received ketorolac, acetaminophen, and diazepam as needed. The median LOS on this regimen prior to implementing the new protocol was 3 to 4 days. Comparison was done between patients treated according to the new protocol and those treated with the old analgesia regimen; study groups were matched based on age, sex, and the number of levels fused. A single pediatric spine surgeon performed all procedures.

The new protocol evaluated during the study is detailed in the table below:

Acute Pain Service (APS) Intervention Protocol
	Scheduled	As needed
PreOp POD0	PO acetaminophen 1 dose PO methadone 1 dose IV methocarbamol Q8H X 6 IV ketorolac Q6H X 7 doses IV ondansetron Q8H x 5 doses PO methadone Q12H X 3 doses PO acetaminophen Q6H	IV morphine/hydromorphone Q3H PO diazepam Q6H IV nalbuphine Q6H Scopolamine patch 72H
POD1	PO oxycodone Q6H PO naloxegol QD	IV morphine/hydromorphone Q3H PO diazepam Q6H IV nalbuphine Q6H
POD2	PO ibuprofen Q6H PO methocarbamol Q8H	PO ondansetron Q6H SC methylnaltrexone
PO, oral; SC, subcutaneous; IV, intravenous

Duration

November 2012 to January 2019

Outcome Measures

Primary: hospital length of stay (LOS)

Secondary: pain scores, total opioid use (morphine milligram equivalents), time to a first bowel movement, and postdischarge phone calls

Baseline Characteristics

Control (n= 61)

Multimodal analgesia protocol (n= 61)

p-value

Median age, years

13.8

13.9

0.92

Female

83.6%

83.6%

1.00

Median body mass index, kg/m2

20.5

20.3

0.35

Median preoperative major Cobb, degrees

57

61

0.29

Median number of levels fused

13

12

0.80

Median number of osteotomies

6

7

< 0.001

Results

Endpoint

Control (n= 61)

Multimodal analgesia protocol (n= 61)

p-value

Median LOS, days (interquartile range [IQR])

3 (3 to 4)

2 (2 to 2)

< 0.001

Pain scores

POD 0

POD 1

POD 2

POD 3

2.9 ± 2.0

3.9 ± 1.4

4.2 ± 1.3

3.9 ± 1.5

4.3 ± 1.5

3.7 ± 1.5

3.2 ± 1.4

2.9 ± 1.9

< 0.001

0.97

0.001

< 0.001

Opioid use^*

POD 0

POD 1

POD 2

POD 3

Total (IQR)

9.9 ± 9.2

41.4 ± 23.3

44.4 ± 18.8

33.2 ± 19.9

127.5 (98.3 to 171.4)

29.3 ± 7.9

45.8 ± 10.7

21.5 ± 7.9

14.5 ± 8.8

98.1 (87.9 to 113.5)

< 0.001

0.55

< 0.001

< 0.001

< 0.001

Time to first bowel movement, days

2 (2 to 3)

1 (1 to 1)

< 0.001

Postdischarge phone calls, n

0 (0 to 1)

0 (0 to 0)

0.006

^*Opioid usage in MME (MME, Morphine Milligram Equivalents: 1 mg of methadone = 3 MME, 1 mg of hydromorphone = 4 MME, 1 mg of oral oxycodone = 1.5 MME, 1 mg oral hydrocodone = 1 MME).

Adverse Events

There were no significant adverse events reported in the new protocol group. The mean corrected QT interval increased from baseline to POD1 (416 to 431 ms), remaining within normal limits (< 440 ms).

Study Author Conclusions

Methadone-based multimodal analgesia resulted in significantly lower LOS compared with the conventional regimen. It also provided improved pain control, reduced total opioid consumption, and early bowel movement compared with the control group.

InpharmD Researcher Critique

The study is inherently limited by its retrospective cohort design. Since patients could receive some analgesia medications as needed, this could be a confounding factor, limiting the validity of the results.

References:

Ye J, Myung K, Packiasabapathy S, et al. Methadone-based Multimodal Analgesia Provides the Best-in-class Acute Surgical Pain Control and Functional Outcomes With Lower Opioid Use Following Major Posterior Fusion Surgery in Adolescents With Idiopathic Scoliosis. Pediatr Qual Saf. 2020;5(4):e336. Published 2020 Jul 27. doi:10.1097/pq9.0000000000000336