A Review of Pre-operative Management of Phantom Limb Pain

Patti Ephraim, M.P.H., Tim Dillingham, M.D., Mathilde Sector, M.P.H., and Ellen MacKenzie, Ph.D.

Phantom and residual limb pain can lead to marked secondary disability following amputation. It is estimated that 72% of patients experience phantom pain following amputation and 57% experience stump pain.¹ These conditions may continue long term, with an estimated 59% and 21% experiencing phantom pain and stump pain at two years, respectively.² 

Pain prior to amputation is thought to be one of the contributing factors in the development of phantom limb pain following amputation.³  Researchers have focused their attention on the prevention of phantom pain prior to amputation using a pre-operative epidural or regional anesthetic blockade.

The purpose of this study was to ascertain the current state of research in the area of pre-operative pain management among amputees.

The reference database was developed from a literature search of fifteen reference databases, including MEDLINE (January 1966 through June 2000). The search strategy was hierarchical, using “pain management,” “amputation,” “pre-operative pain” and “surgery” as medical subject headings or text words linked by “or.” Criteria for inclusion included interventional, prospective, and randomized studies.

Article Selection

A total of fifty-four references were identified. Initial exclusions were based on article title and review of the abstract, if present. Exclusion criteria included non-English language, animal studies, case reports, review articles, letters and editorials.  Six articles were reviewed and four articles were selected.^4-9 

Among the four articles selected, all included controls as part of the study design and three of these were randomized-controlled clinical trials (Table 1.0).

In 1994, Jahangiri et. al. studied the effect of a preoperative epidural infusion of bupivacaine, clonidine and diamorphine in prevention of phantom limb pain among a group of 24 patients undergoing limb amputation (11 control, 13 study group).  Results demonstrated that one-year following surgery, fewer patients in the treatment group had phantom pain than those in the control group who received standard therapy of on demand opioid analgesia (P < 0.002).⁵

In a randomized clinical trial of the effect of lumbar epidural blockade among 25 patients undergoing limb amputation, Bach et. al. found the incidence of phantom pain to be significantly reduced at 6 months, but not 1 year following surgery.⁷  In this study, the treatment group received epidural morphine, bipuvacaine 0.25% or both in combination to achieve pre-operative pain control for three days and the control group received various analgesic drugs.  Outcomes were assessed at 7 days, 6 months, and one year after surgery.  All patients in the treatment group at 6 months were pain free while 5 patients (38%) had pain (p < 0.05).  While all the patients in the blockade group remained pain free at 1 year, this difference was not significant (p < 0.20).

In a randomized-controlled double-blind trial conducted among 60 patients undergoing lower-limb amputation in 1997, Nikolajsen et. al. found no difference in treatment groups one year following surgery.⁶ Patients in the treatment group received epidural bupivicaine 0.25% and morphine 0.16 – 0.28 mg/hour for 18 hours before and during the procedure while those in the control group received epidural normal saline.  Outcomes were assessed at 3, 6, and 12 months post surgery by independent examiners using a visual analog scale for phantom and stump pain. Three months post surgery, 82% in the treatment group and 50% in the control group experienced phantom pain.  Among the 28 patients who completed a one-year follow-up examination, 75% in the treatment group and 69% in the control group experienced phantom pain.

Similarly, one year later, a randomized-controlled study to evaluate the effectiveness of preoperative extradural bupivacaine and morphine on post-operative stump sensation among a group of 31 lower limb amputees found no difference between groups at 1 week or 6 months following surgery.⁸ Patients in the treatment group had a catheter placed one day prior to surgery followed by a bolus of 2 mg. of extradural morphine, 5-10 ml. of bupivacaine 0.25%, an infusion of bupivacaine 0.25% at 4-7 ml./hour and morphine at 0.16-0.28 mg./hour infusion rate prior to surgery.  Those in the control group had an extradural catheter placed and were given a bolus of normal saline followed by an infusion of saline over the next 24 hours.  Additionally, the control group received oral or intra-muscular pain medications.  Outcomes were assessed using a visual analog scale. After one week, the percentage of patients with phantom pain was 57.1% in the treatment group and 58.8% in the control group. After six months, more patients in the treatment group experienced phantom pain (78%) than those in the control group (58%).

Discussion

Phantom limb pain affects the majority of amputees with over half of them experiencing pain long term.¹  The cohort study to measure the effect of preoperative treatments, namely preoperative bupivacaine, demonstrated the promise of a new therapy to reduce the incidence of phantom pain.⁵ However, a major limitation of this study is the introduction of selection bias.  Patients selected for the study may not be representative of the general population and thus the results cannot be generalized.  Additionally, patients receiving the new therapy may be selected according to attributes that may alter the outcome thus leading to treatment bias.  Such a bias leads to an overestimate of the effectiveness of the treatment because only the patients with the best prognosis are chosen for the study.   Randomization, that is the random assignment of patients to a treatment, overcomes the effect of treatment bias by assigning treatment without regard to the attributes of an individual that may contribute to the success or failure of the treatment.

Randomized clinical trials to study the effectiveness of new treatment modalities are few and difficult to compare due to the differences in treatments.  Among the three randomized clinical trials, only one demonstrated a significant benefit of preoperative anesthesia.⁷ The limitations among these studies include an inadequate sample size to detect a difference between treatment groups combined with a high drop out rate.⁸  The randomized clinical trial that demonstrated a treatment difference suffered from the absence of a true placebo group, i.e. an epidural injection, and that lack of a standardized questionnaire for the assessment of phantom limb pain.⁷

Epidural preoperative treatment of pain to reduce the incidence of phantom pain following amputation remains promising.  Phantom limb pain is a debilitating condition that can lead to a decline in daily activities and overall health and well being.  More is needed to investigate the causal pathway of phantom pain among amputees that may lead to new and effective treatments.

Table 1.0

References

1.  Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain. 1983;17:243-56.

2.  Jensen TS, Krebs B, Nielsen J, Rasmussen P. Immediate and long-term phantom limb pain in amputees: incidence, clinical characteristics and relationship to pre-amputation limb pain. Pain. 1985;21:267-78.

3.  Katz J. Prevention of phantom limb pain by regional anaesthesia. Lancet. 1997;43:319-336.

4.  Wall R, Novotny-Joseph P, Macnamara TE. Does preamputation pain influence phantom limb pain in cancer patients? South Med J. 1985;78:34-6.

5.  Jahangiri M, Jayatunga AP, Bradley JW, Dark CH. Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl. 1994;76:324-6.

6.  Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet. 1997;350:1353-7.

7.  Bach S, Noreng MF, Tjellden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain. 1988;33:297-301.

8.  Nikolajsen L, Ilkjaer S, Jensen TS. Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth. 1998;81:348-54.

9.  Roberge CW, McEwen M. The effects of local anesthetics on postoperative pain. AORN-Journal. 1998;68:1003-12.

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