Home Pregabalin as adjunct in a multimodal pain therapy after traumatic foot amputation — A case report of a 4-year-old girl
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Pregabalin as adjunct in a multimodal pain therapy after traumatic foot amputation — A case report of a 4-year-old girl

  • Stephanie Wössner , Kirsten Weber , Anna C. Steinbeck , Markus Oberhauser and Matthias Feuerecker EMAIL logo
Published/Copyright: October 1, 2017
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Scandinavian Journal of Pain
From the journal Scandinavian Journal of Pain Volume 17 Issue 1

Abstract

Background and purpose

The purpose of this case report is to describe a multimodal pain therapeutic concept including the adjunct use of pregabalin in a 4.5 year-old child after forefoot amputation.

Phantom limb pain and sensation is a complex pain syndrome that is difficult to treat and prevent. 70–75% of all children develop such a pain syndrome after amputation. We describe here a paediatric patient who underwent forefoot amputation following traumatic foot injury and received multimodal pain therapy including pregabalin.

The current experiment aimed at studying effects of empathic communication, and more specifically validation, on recall during a pain test and possible mediators and moderators of this effect.

Methods

A 4.5 year-old otherwise healthy girl suffered severe injuries of the right foot and lower leg during a motor vehicle accident. Due to development of severe necrosis, forefoot amputation had to be performed during the hospital stay.

Results

Initial pain therapy included paracetamol, ibuprofen, metamizol, morphine and fentanyl. With mounting pain and anxiety, regional anaesthesia of the distal sciatic nerve was administered in combination with a ketamine and morphine patient controlled analgesia pump (PCA). The peripheral blockade of the distal sciatic nerve was placed with the guidance of ultrasound and nerve stimulator. The PCA concept included a continuous basal rate combined with a bolus function. Although the regional anaesthesia was well positioned and functioning, there was inadequate pain control. The pain was described by the patient as short, highly intense and sharp sensations with intensity on the visual analogue scale (VAS) of 10 (out of 10). Furthermore, she suffered from anxiety episodes and sleep disturbance. The medical team decided to treat with pregabalin to resolve these issues while awaiting amputation (Lisfranc line). She received psychological counselling as adjunct treatment. This multimodal concept enabled an early and efficient pain reduction pre- and post-amputation and allowed for the possibility of a hospital discharge without any opioid pain medication.

Conclusion

The multimodal pain therapy including pregabalin was well tolerated, safe and highly effective in this case of traumatic limb injury and subsequent amputation. The use of pregabalin allowed significant pain and anxiety reduction for the patient.

Implications

Pregabalinis frequentlyused in adult patients for severe complex pain syndromes. There are only few reports of such adjunct medication (pregabalin) in paediatric pain syndromes. These reports focus mainly on the paediatric oncologic population. The case reported here encourages physicians to consider adjunct medications when treating complex pain, which are well established in the adult population. The benefits of such therapy in complex pain and anxiety can be extended to the paediatric population in select cases. Of course, one must always take into account that many routine medications used in children are well established but are off-label use. The authors are well aware of this problem and have conducted a critical literature review prior to pregabalin administration, including the search for randomized trials examining safety and tolerability. The parents or legal guardians of a minor must be thoroughly informed and consent to such a constellation of medical treatment.

Keywords: Paediatric traumatic limb amputation; Multimodal pain therapy; Regional anaesthesia; Ketamine; Pregabalin

1 Introduction

Traumatic partial or total limb amputation can lead to complex pain sensations. There is a high prevalence of phantom limb pain (PLP) in patients post amputation. Overall prevalence of PLP ranges between 40% and 80% depending on the amputation site and the patient collective. The elapsed time after amputation also plays an important role in its development [1,2,3]. In the paediatric population, the incidence of PLP seems to be generally lower, though it is described that 70–75% of the children complain about this specific type of pain [4,5]. PLP is most commonly described as a sharp and sudden type of pain in children [4]. Until now, the exact pathophysiology remains unclear. PLP was historically thought to be of psychological nature, recent research however, showed that both neurological (peripheral as well as central nervous system) and psychological components are at play in PLP [6]. Hence, PLP is one of the hardest chronic pain syndromes to treat.

2 Case presentation

A 4.5 year old healthy girl (body weight 20 kg) ran into oncoming traffic while playing with her friends. She sustained severe crush injuries of the right foot and lower leg from the back wheel of a truck (Fig. 1). First aid on site included the sterile bandage of the sub-amputated right foot and leg as well as fentanyl given by the emergency physician. Her vital signs remained stable throughout the transport to hospital and in the emergency room. After an initial advanced trauma life support (ATLS) evaluation in the emergency room, she was immediately transferred to the operating room (OR). General anaesthesia (propofol, remifentanil, fentanyl) was given in combination with a caudal block using ropivacaine and clonidine. Surgical procedures included a degloving-refixation and temporary Kirschner-wire (K-wire) fixation of the right foot. Postoperative analgesic therapy was ordered with paracetamol (12.5 mg/kg every 8h (q8h), per os (p.o.) or rectal), ibuprofen (5 mg/kg q8h, p.o.), metamizol (20 mg/kg q8h, intravenous (i.v.)) and morphine (0.1 mg/kg q3–4 h, i.v.) on demand. The first wound inspection under midazolam sedation was done on day 1 post trauma (pt) and from then on, on a daily basis. Due to the loss of the regional perfusion, venous stasis and increment dry necrosis of the toes and forefoot with mummification, surgical debridement and lateral decompression cuts were performed on day 6 pt under general anaesthesia (propofol, isoflurane, fentanyl, caudal anaesthesia with ropivacaine and clonidine). The postoperative analgesic regime was continued as the patient did not complain about pain in the resting state until the night of day 8 pt. On this night a morphine bolus of 2 mg i.v. had to be given twice with a time interval of four hours. From day 9pt on the patient was transferred daily to the OR for dressing changes under general anaesthesia (propo- fol, isoflurane, fentanyl). Due to increasing intensity and frequency of pain (short, stabbing extreme pain sensations in the right foot, Development of the traumatic foot injury especially at night), a catheter-based peripheral blockade of the distal sciatic nerve was initiated on day 9 pt (0.2 mg/kg/h ropivacaine, regional). Catheter placement was performed under ultrasound guidance and nerve stimulation. Despite a functioning and well placed catheter, we additionally gave an i.v. Patient Controlled Analgesia (PCA) – pump containing a hospital standard solution of ketamine and morphine ([0.5 mg/ml] respectively) with a continuous infusion rate of 10 μg/kg/h and a bolus of 15 μg/kg available every 8min. This allows the patient to self administer additional medication from the pump on top of the basal rate. The pump is programmed to administer a bolus in at least 8 min intervals, meaning pushing the button more often than every 8 min will not result in further bolus application. The maximum injectable amount of the PCA solution allowed was 16 boluses over 4h (240 μg/kg). In addition to the above described therapy with nonsteroidal antiinflammatory medication, the pain was well controlled. Prior to the planned forefoot amputation (Lisfranc line) on day 14 pt we started a concurrent prophylactic neuropathic pain therapy with pregabalin on day 13 pt with 1.25 mg/kg p.o (25 mg capsule). The girl was able to swallow the capsules without any problems. In the next few days we increased the dose to 2.5 mg/kg/d p.o (50 mg capsule). Aside from drowsiness during the first 48 h, there were no other side effects of pregabalin. The patient was adequately alert, while the pain and anxiety episodes dramatically subsided. Throughout the hospital stay, pain was assessed using a visual analogue scale with the tool shown in Fig. 2. The VAS allows a consistent assessment on a numeric scale, with the help of parents or nurses. Overall VAS was below 3 following pregabalin therapy, a significant reduction. From day 16 pt onwards, the bolus function of the PCA was not needed. Her forefoot and lower right leg were covered with mashed skin grafts from both thighs 6 days after amputation. On day 22 pt we were able to stop the sciatic nerve catheter and to reduce the continuous i.v. PCA infusion (5 μg/kg/h). The next day metamizol was prescribed on demand and per os. After 20 days (on day 29 pt the PCA therapy), morphine and ketamine was also discontinued. 37 days after the trauma we were able to discharge the patient in a pain free state with the following medications: ibuprofen 10 mg/kg p.o. on demand up to 3 times/d, metamizol 12.5 mg/kg p.o. on demand up to 3 times/d, pregabalin 2.5 mg/kg p.o. The multimodal pain therapy also included early psychological trauma interventions as well as art-, learning- and physio-therapy.

Fig. 1 Development of the traumatic foot injury
Fig. 1

Development of the traumatic foot injury

Fig. 2 Applied visual analogue scale.
Fig. 2

Applied visual analogue scale.

3 Discussion

This case describes a 4.5 year old girl who underwent a traumatic foot amputation, an initial re-fixation of the foot followed by surgical amputation 14 days later due to necrosis. Of particular note in this report is the specific character of the evolving pain and escalation of pain therapy. By the end of the first week in hospital, the patient developed maximal sudden and sharp pain sensations in the right foot mainly at night. The pain was neuropathic in character, which was increasingly more difficult to control with NSAIDs and morphine. With an inadvertent amputation, the pain medication regimen was definitely lacking, especially in anticipation of possible PLP. With overall inadequate pain management and mounting neuropathic pain, we intensified the therapy with the placement of a sciatic nerve catheter and a morphine/ketamine PCA-pump to reduce the risk of PLP. Fisher and Meller [7] have reported on a postoperative placement of a continuous sciatic nerve blockade in patients undergoing lower limb amputation and its beneficial effect of opioid reduction. We decided to combine the nerve block with the morphine/ketamine PCA-pump as a result. Hayes et al. [8] were able to show in a randomized controlled trial that continuous administration of ketamine in the perioperative period decreases the incidence of PLP from 71% to 47% (control versus ketamine group). Though ketamine is broadly used in the postoperative pain therapy, one has to be aware that it is only approved for pain therapy in mechanically ventilated (intubated) patients. Whereas Wu et al. [9] demonstrated the effectiveness of i.v. morphine in the treatment of PLP compared to placebo or i.v. lidocaine. Another important aspect during her hospitalization was the increasing anxiety and bad dreams of the accident. Despite psychological trauma counselling, we decided to start treatment with pregabalin.

Pregabalin is originally an add-on anticonvulsant drug for the therapy of refractory seizures in adults. It is also effective and beneficial as a medication for neuropathic pain and generalized anxiety disorders [10]. Its safety and tolerability in children ageing 1 month to 16 years has been shown in a phase I randomized controlled study as a powerful and safe drug in the treatment of refractory partial seizures (doses up to 15mg/kg/day) [11]. Few reports are available in the treatment of neuropathic pain and complex regional pain syndrome with pregabalin in children [12,13].There are no previous reports on limb amputation in children and subsequent pain management with pregabalin. Our patient profited greatly from the multimodal pain therapy including pre- gabalin. The latter was well tolerated and had a remarkable effect on the reduction of overall pain medication use.

4 Conclusions

Prevention and treatment of phantom limb pain is a clinically challenging situation, especially in the paediatric population. The medical team should strive for a well-established multimodal pain concept and early pain reduction. Newer adjunct medications such as pregabalin are safe in children and can be a very useful addition in a multimodal pain concept.

Highlights

  • Case report on traumatic fore-foot amputation in a 4 year old child.

  • Multimodal post traumatic pain therapy.

  • Adjunct pain therapy with pregabalin.

Department of Anaesthesiology, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany

  1. Consent:For this publication, a written informed consent was obtained from the patient’s parents who are the legal representatives. The consent also includes the publication of images of the injured extremity. A copy of the written consent is available for review by the Editor-in-Chief of this Journal.

  2. Conflict of interest: All authors declare that there is no competing interest.

  3. Authors’ contributions:SW, KW, MO, MF carried out the treatment and the critical literature review for the use of pregabalin. SW, AS, MO, MF drafted the manuscript. Specific and very significant advice regarding therapy was given by AS. All authors carefully approved the final manuscript.

  4. Funding: This work was financially supported by internal resources of the Department of Anaesthesiology of the Kantonsspital St. Gallen.

Acknowledgements

The authors are grateful to the patient’s family in their great enthusiastic support to this case report. Our special thank goes to Dr. Volker Lesch for his advices on the manuscript. The authors would like to thank Dr. Anne Guo for the language revision.

Abbreviations

ATLS

advanced trauma life support; i.v., intravenous; K-wire, Kirschner wire

NSAIDs

Nonsteroidal Anti-Inflammatory Drugs;

OR

operating room;

PCA-pump

patient controlled analgesia pump; p.o., per os;

PLP

Phantom limb pain; pt, post trauma; q8 h, every 8 hours;

VAS

visual analogue scale.

References

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Received: 2017-05-24
Revised: 2017-08-30
Accepted: 2017-09-01
Published Online: 2017-10-01
Published in Print: 2017-10-01

© 2017 Scandinavian Association for the Study of Pain

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https://doi.org/10.1016/j.sjpain.2017.09.001
Keywords for this article
Paediatric traumatic limb amputation; Multimodal pain therapy; Regional anaesthesia; Ketamine; Pregabalin

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  2. Perceived sleep deficit is a strong predictor of RLS in multisite pain – A population based study in middle aged females
  3. Clinical pain research
  4. Prospective, double blind, randomized, controlled trial comparing vapocoolant spray versus placebo spray in adults undergoing intravenous cannulation
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  6. The Functional Barometer — An analysis of a self-assessment questionnaire with ICF-coding regarding functional/activity limitations and quality of life due to pain — Differences in age gender and origin of pain
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  8. Clinical outcome following anterior arthrodesis in patients with presumed sacroiliac joint pain
  9. Observational study
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  12. Management of patients with pain and severe side effects while on intrathecal morphine therapy: A case study
  13. Clinical pain research
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  19. Topical review
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  21. Clinical pain research
  22. A multi-facet pain survey of psychosocial complaints among patients with long-standing non-malignant pain
  23. Clinical pain research
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  28. COMBAT study – Computer based assessment and treatment – A clinical trial evaluating impact of a computerized clinical decision support tool on pain in cancer patients
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  33. Original experimental
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  74. Lateral Cutaneous Nerve Entrapment Syndrome (LACNES): A previously unrecognized cause of intractable flank pain
  75. Editorial comment
  76. Towards a structured examination of contextual flexibility in persistent pain
  77. Clinical pain research
  78. Context sensitive regulation of pain and emotion: Development and initial validation of a scale for context insensitive avoidance
  79. Editorial comment
  80. Is the search for a “pain personality” of added value to the Fear-Avoidance-Model (FAM) of chronic pain?
  81. Editorial comment
  82. Importance for patients of feeling accepted and understood by physicians before and after multimodal pain rehabilitation
  83. Editorial comment
  84. A glimpse into a neglected population – Emerging adults
  85. Observational study
  86. Assessment and treatment at a pain clinic: A one-year follow-up of patients with chronic pain
  87. Clinical pain research
  88. Randomized, double-blind, placebo-controlled, dose-escalation study: Investigation of the safety, pharmacokinetics, and antihyperalgesic activity of L-4-chlorokynurenine in healthy volunteers
  89. Clinical pain research
  90. Prevalence and characteristics of chronic pain: Experience of Niger
  91. Observational study
  92. The use of rapid onset fentanyl in children and young people for breakthrough cancer pain
  93. Original experimental
  94. Acid-induced experimental muscle pain and hyperalgesia with single and repeated infusion in human forearm
  95. Original experimental
  96. Swearing as a response to pain: A cross-cultural comparison of British and Japanese participants
  97. Clinical pain research
  98. The cognitive impact of chronic low back pain: Positive effect of multidisciplinary pain therapy
  99. Clinical pain research
  100. Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia
  101. Topical review
  102. Targeting cytokines for treatment of neuropathic pain
  103. Original experimental
  104. What constitutes back pain flare? A cross sectional survey of individuals with low back pain
  105. Original experimental
  106. Coping with pain in intimate situations: Applying the avoidance-endurance model to women with vulvovaginal pain
  107. Clinical pain research
  108. Chronic low back pain and the transdiagnostic process: How do cognitive and emotional dysregulations contribute to the intensity of risk factors and pain?
  109. Original experimental
  110. The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury
  111. Educational case report
  112. Erector spinae plane (ESP) block in the management of post thoracotomy pain syndrome: A case series
  113. Original experimental
  114. Hyperbaric oxygenation alleviates chronic constriction injury (CCI)-induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord
  115. Observational study
  116. Predictors of chronic neuropathic pain after scoliosis surgery in children
  117. Clinical pain research
  118. Hospitalization due to acute exacerbation of chronic pain: An intervention study in a university hospital
  119. Clinical pain research
  120. A novel miniature, wireless neurostimulator in the management of chronic craniofacial pain: Preliminary results from a prospective pilot study
  121. Clinical pain research
  122. Implicit evaluations and physiological threat responses in people with persistent low back pain and fear of bending
  123. Original experimental
  124. Unpredictable pain timings lead to greater pain when people are highly intolerant of uncertainty
  125. Original experimental
  126. Initial validation of the exercise chronic pain acceptance questionnaire
  127. Clinical pain research
  128. Exploring patient experiences of a pain management centre: A qualitative study
  129. Clinical pain research
  130. Narratives of life with long-term low back pain: A follow up interview study
  131. Observational study
  132. Pain catastrophizing, perceived injustice, and pain intensity impair life satisfaction through differential patterns of physical and psychological disruption
  133. Clinical pain research
  134. Chronic pain disrupts ability to work by interfering with social function: A cross-sectional study
  135. Original experimental
  136. Evaluation of external vibratory stimulation as a treatment for chronic scrotal pain in adult men: A single center open label pilot study
  137. Observational study
  138. Impact of analgesics on executive function and memory in the Alzheimer’s Disease Neuroimaging Initiative Database
  139. Clinical pain research
  140. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [11C]-D-deprenyl PET/CT
  141. Original experimental
  142. Developing a model for measuring fear of pain in Norwegian samples: The Fear of Pain Questionnaire Norway
  143. Topical review
  144. Psychoneuroimmunological approach to gastrointestinal related pain
  145. Letter to the Editor
  146. Do we need an updated definition of pain?
  147. Narrative review
  148. Is acetaminophen safe in pregnancy?
  149. Book Review
  150. Physical Diagnosis of Pain
  151. Book Review
  152. Advances in Anesthesia
  153. Book Review
  154. Atlas of Pain Management Injection Techniques
  155. Book Review
  156. Sedation: A Guide to Patient Management
  157. Book Review
  158. Basics of Anesthesia
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