What is the safety and efficacy data to support methocarbamol use in pediatric patients (specifically less than 16 years old)?

Comment by InpharmD Researcher

While some societies and expert recommendations suggest that use of muscle relaxants like methocarbamol is reasonable in pediatric patients, data is limited regarding the use of methocarbamol. Available studies for surgical pain and cerebral palsy suggest methocarbamol may potentially improve clinical parameters without significant adverse outcomes, with use in pediatric post-surgery patients limited to an adjunct role for analgesic treatment. More robust data, as well as further research with isolated methocarbamol, is warranted to understand potential benefit with monotherapy and confirm safe and effective use of methocarbamol in pediatrics.

Background

While a few articles from medical organizations and expert societies briefly discuss the use of methocarbamol in pediatric surgical patients, there remains a notable lack of robust evidence supporting their use. One study examining spinal fusion surgeries for pediatric patients with idiopathic scoliosis proposed intravenous (IV) methocarbamol at 15 mg/kg (up to 1000 mg) Q8H, transitioning to an oral formulation of 500-1000 mg Q8H. However, the author acknowledged the absence of systematic research evaluating its efficacy for pain relief. Similarly, other articles provided comparative dosing suggestions for utilizing muscle relaxants to manage intraoperative pain in children, despite little supporting data. Overall, it appears guidance statements are primarily based on expert opinion, highlighting the need for more rigorous investigations in pediatric surgical populations. [1], [2], [3]

A 2021 systematic review summarized outcomes associated with post-operative analgesia after posterior spinal fusion for adolescent idiopathic scoliosis. Three studies included methocarbamol use combined with gabapentin, opioid, ketorolac, ibuprofen, or acetaminophen for post-operative pain management. One study treating patients with both methocarbamol and gabapentin resulted in a trend towards improvement in infection, postoperative gastrointestinal retention, and length of stay, though these findings were not statistically significant (see Table 1 for details). Another study combining methocarbamol with multiple analgesic agents showed outcomes with significant decreases in opioid use, pediatric intensive care unit utilization, and allogeneic blood transfusions. A third study again combining methocarbamol with various analgesics, resulted in decreased total morphine consumption, length of stay, median time to first bowel movement, and number of post-discharge pain-related phone calls. This review, however, did not find or include any studies that evaluated methocarbamol monotherapy in pediatric pain management after surgery. While two studies indicated the potential benefit of methocarbamol as an adjuvant treatment for postoperative analgesia in pediatric patients, further research with isolated methocarbamol is warranted to understand the benefit of monotherapy. [4]

A 2011 retrospective study compared postoperative pain management outcomes of adolescents who did or did not self-select self-hypnosis training before Nuss procedure. Post-operative in-hospital analgesic medications included a variety of agents, including epidurals with local anesthetic, intravenous opioids by patient-controlled analgesia, and IV ketorolac; patients transitioned to oral opioids and ibuprofen. Methocarbamol 500 mg every 6 hours as needed was used to control pain and/or complaints of chest tightness when other analgesic treatments were not effective. Of 22 patients included in this study, 54% were treated with methocarbamol. The majority of patients who did not receive self-hypnosis training required methocarbamol compared to those who did receive self-hypnosis training (71% vs. 25%, p= 0.04). Initiation of methocarbamol ranged from postoperative day 2 to day 4 with hypnosis patients requiring earlier introduction of therapy compared to non-hypnosis patients. Opioid-related adverse effects were reported and included nausea, vomiting, constipation, and hypoventilation. Although this study did not evaluate outcomes specific to methocarbamol therapy, it does summarize the use of therapy for analgesia and chest tightness relief in postoperative pediatric patients. [5]

A 2003 retrospective review study compares outcomes of open repair versus minimally invasive repair of pectus excavatum (MIRPE) in 68 pediatric patients. A key finding is that MIRPE resulted in significantly shorter hospital stay (2.4 vs 4.4 days; p<0.001) and lower overall hospitalization costs compared to open repair, despite higher operating room costs. A significant factor contributing to the shorter stay with MIRPE was the postoperative pain management regimen used. The study used a multi-modal regimen of intravenous and oral analgesics without epidural catheters. This regimen included methocarbamol, a centrally-acting muscle relaxant. Methocarbamol was given intravenously for the first 48 hours after surgery at a dose of 10 mg/kg every 6 hours, then orally as needed. The article notes internists have effectively used methocarbamol for many years to treat low back pain in adults. It is considered good for treating muscle spasms with a low risk of abuse or other complications. By using this methocarbamol-containing regimen without epidurals, satisfactory pain control was achieved more rapidly, allowing faster transition to oral medications and shorter hospital stay after MIRPE. This was a significant factor in reducing the overall costs of MIRPE compared to open repair in this pediatric population undergoing pectus excavatum repair. However, the focus was on MIRPE itself, so the results for the methocarbamol analgesic regimen remain exploratory; it is likely the surgical technique had a greater impact on the results. [6]

References:

[1] Lee CS, Merchant S, Chidambaran V. Postoperative Pain Management in Pediatric Spinal Fusion Surgery for Idiopathic Scoliosis. Paediatr Drugs. 2020;22(6):575-601. doi:10.1007/s40272-020-00423-1
[2] Gal DB, Clyde CO, Colvin EL, et al. Management of routine postoperative pain for children undergoing cardiac surgery: a Paediatric Acute Care Cardiology Collaborative Clinical Practice Guideline. Cardiol Young. 2022;32(12):1881-1893. doi:10.1017/S1047951122003559
[3] Mavi J. Update of postoperative pain management following pectus excavatum repair. SOJAPM. 2014;1(1). doi: 10.15226/2374-684X/1/1/00106
[4] Shah A, Pey EP, Bowen S, Barsi J. Postoperative analgesia after posterior spinal fusion for adolescent idiopathic scoliosis. Journal of the Pediatric Orthopaedic Society of North America. 2021;3(3):293. doi:10.55275/JPOSNA-2021-293
[5] Manworren RCB, Girard E, Verissimo AM, et al. Hypnosis for postoperative pain management of thoracoscopic approach to repair pectus excavatum: retrospective analysis. Journal of Pediatric Surgical Nursing. 2015;4(2):60-69. doi:10.1097/JPS.0000000000000061
[6] Inge TH, Owings E, Blewett CJ, et al. Reduced hospitalization cost for patients with pectus excavatum treated using minimally invasive surgery. Surg Endosc. 2003;17(10):1609-1613. doi:10.1007/s00464-002-8767-0

Literature Review

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

What is the safety and efficacy data to support methocarbamol use in pediatric patients (specifically less than 16 years old)?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-3 for your response.


 

Elastomeric Pain Pumps for Scoliosis Surgery

Design

Retrospective chart review

N= 81

Objective

To evaluate the effect of elastomeric pain pumps for postoperative pain management following scoliosis surgery

Study Groups

Patient controlled analgesia (PCA; n= 12)

Elastomeric pain pump (EPP; n= 28)

Multimodal pain pump (MPP; n= 41)

Inclusion Criteria

Adolescent patients (age 18 years or younger), underwent scoliosis surgery by a single orthopedic surgeon

Exclusion Criteria

Surgeries for adjustment of growing rods and anterior surgeries

Methods

Patients were divided into three groups:

PCA which used intravenous opioids with oral opioids;

EPP which added the use of three-day elastomeric pain pumps containing 270 ml of 0.125% or 0.25% bupivacaine;

MPP which added gabapentin PO preoperative at 15 mg/kg (continued at 5 mg/kg TID for 7 days) and methocarbamol PO 500 mg Q6H if patients weighed over 33 kg.

Duration

Enrollment period: March 2007 to December 2014

Outcome Measures

Infection, postoperative gastrointestinal retention, and length of stay

Baseline Characteristics

 

PCA (n= 12)

EPP (n= 28)

MPP (n= 41)  

Age, years

13.4 ± 2.7 13.5 ± 2.6 13.8 ± 2.4  

Female, n

10 23 28  

Neuromuscular, n

No

Yes

 

8

4

 

19

9

 

27

14

 

Results

Endpoint

PCA (n= 12)

EPP (n= 28)

MPP (n= 41)

p-Value

Infection

Yes

No

 

3 (25%)

9 (75%)

 

2 (7.1%)

26 (92.9%)

 

0

41 (100%)

0.005

Postoperative gastrointestinal retention

Yes

No

 

3 (25%)

9 (75%)

 

5 (17.9%)

23 (82.1%)

 

1 (2.4%)

40 (97.6%)

0.014

Length of stay, days

8.2 ± 6.4

5.1 ± 1.2

4.3 ± 1.3

0.00094

Adverse Events

N/A

Study Author Conclusions

To our knowledge, this is the first study on the use of elastomeric pain pumps in conjunction with multimodal pain medication following scoliosis surgery. The use of elastomeric pain pumps was associated with clinically and statistically significant improvements in the postoperative course. The addition of methocarbamol and gabapentin was associated with a trend toward further improvements.

InpharmD Researcher Critique

Data provided in this study was limited by its retrospective nature and lack of equivalent sizes between the small group populations. Therefore, the favorable benefits seen with a multimodal pain regimen that contains methocarbamol remains suspect.
References:

Kriel HH, Yngve D. Elastomeric Pain Pumps for Scoliosis Surgery. Cureus. 2019;11(2):e4042. Published 2019 Feb 11. doi:10.7759/cureus.4042

 

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 chart review

N= 122

Objective

To determine whether a methadone-based multimodal analgesia protocol will decrease the length of hospital stay (LOS), improve pain control, and decrease the need for additional opioids

Study Groups

Control (n= 61)

Multimodal analgesia (n= 61)

Inclusion Criteria

Idiopathic scoliosis patients with posterior instrumented spinal fusion (PSF)

Exclusion Criteria

Neuromuscular scoliosis, congenital QT prolongation, allergy to any of the protocol drugs

Methods

A single pediatric spine surgeon performed all procedures. Prior to implementation of the new protocol, all patients received intrathecal (IT) morphine and postoperative morphine as patient-controlled analgesia (PCA), as well as gabapentin, and transitioned to oxycodone or hydrocodone on POD1 with IV morphine as needed for breakthrough pain; ketorolac, acetaminophen, and diazepam were administered as needed.

In September 2017, the new Acute Pain Service (APS) protocol utilized scheduled methadone, methocarbamol, ketorolac/ibuprofen, acetaminophen, and oxycodone with intravenous (IV) opioids as needed. Intervention patients were compared against historical matched controls who received analgesia for PSF prior to the new protocol. The protocol is listed as follows:

  Scheduled PRN

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 nalogexol QD

IV morphine/hydromorphine q3h
PO diazepam q6h
IV nalbuphine q6h

POD2

PO ibuprofen q6h
PO methocarbamol q8h

PO ondansetron q6h
SC methylnaltrexone

Duration

Historical: November 2012 to August 2017

Intervention: September 2017 to January 2019

Outcome Measures

Primary: Time to hospital discharge

Secondary: opioid consumption (in morphine milligram equivalents [MME]), pain scores, opioid-related side effects

Baseline Characteristics

 

Control (n= 61)

Multimodal analgesia (n= 61)

 

Age, years

13.8 13.9  

Female

51 (83.6%) 51 (83.6%)  

Body mass index, kg/m2

20.5 20.3  

Immediately after implementation, pregabalin was removed from the APS protocol due to significant urinary retention in the first 3 patients. 

Results

Endpoint

Control (n= 61)

Multimodal analgesia (n= 61)

p-value

Length of stay, days

3 2 < 0.001

Pain scores

POD 0

POD 3

 

2.9 ± 2.0

3.9 ± 1.5

 

4.3 ± 1.5

2.9 ± 1.9

 

< 0.001

< 0.001

Opioid use, mg

POD 0

POD 3

 

9.9 ± 9.2

33.2 ± 19.9

 

29.3 ± 7.9

14.5 ± 8.8

 

< 0.001

< 0.001

Total opioid consumption, MME

127.5 98.1 < 0.001

Time to first bowel movement, days

2 1 < 0.001

Adverse Events

No significant adverse events related to opioid usage observed in APS group.

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

Use of a historical cohort and small sample sizes may confound the results, as standard of care, surgical management, and institutional protocols outside of analgesia may have changed. Minute changes in the APS protocol after implementation and the retrospective observational design of the study also limit applicability of the findings. As methocarbamol was only a small part of the analgesic protocol, efficacy/safety conclusions cannot be drawn based on this study alone.

 

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

 

Methocarbamol in the treatment of cerebral palsy in children

Design

Double-blind, cross-over study

N= 44

Objective

To investigate the use of methocarbamol in children with cerebral palsy

Study Groups

Children (N= 44)

Inclusion Criteria

4 to 18 years, cerebral palsy

Exclusion Criteria

N/A

Methods

Children were recruited from therapeutic centers located in Helsingborg and Malmo, Sweden. The children then participated in a double-blind study where, for the first two months, one group was administered methocarbamol doses ranging from 75 to 110 mg per kg of body weight while the other group received a placebo. Results were evaluated by parents and physiotherapists.

The exact division of patients into methocarbamol and placebo groups is not directly stated.

Duration

up to 10 months

Outcome Measures

Improvement of cerebral palsy based on objective motor tests and parental opinions.

Baseline Characteristics

 

Children (N= 44)

Cerebral palsy type

Hemiplegia spastica

Diplegia spastica

Tetraplegia spastica

Tetraplegia dystonica

 

12

12

9

3

Results

Endpoint

Methocarbamol

Improved for greater than 10 months based on motor tests

Hemiplegia spastica

Diplegia spastica

Tetraplegia spastica

Tetraplegia dystonica

 

3

6

4

0

Parents opinion of effect of methocarbamol

Better

Unchanged

Worse

 

5

13

1

Adverse Events

Exanthema (1), fatigue (2), nausea (1), hypotonia (2), cannot swallow tablets (6)

Study Author Conclusions

The results of the investigation must be evaluated with due allowance for the difficulties in obtaining a representative series and lack of really objective methods for measuring the effect of treatment.

InpharmD Researcher Critique

Due to its older design, the study may not be relevant to current clinical practice.



References:

Bjerre I, Blennow G. Methocarbamol in the treatment of cerebral palsy in children. Neuropadiatrie. 1971;3(2):140-146. doi:10.1055/s-0028-1091806