Dept. of Neurology

Ketamine-Midazolam Anesthesia for intractable
Complex Regional Pain Syndrome-Type I (CRPS-I)
Klinikum Saarbrücken
Eberhard-Karls-Universität

Ralph-Thomas Kiefer1, Peter Rohr2, Annette Ploppa1, Hans-Jürgen Dieterich1, Karl-Heinz Altemeyer2, John Grothusen3, Klaus Unertl1, Robert J Schwartzman3
1Dept. of Anesthesiology, Eberhard-Karls University, Tuebingen, Germany; 2Dept. of Anesthesiology, Klinikum Saarbruecken, Germany;

Universitätsklinikum Tübingen1210-P126

3Dept. of Neurology, Drexel- University, Philadelphia, U.S.A.

INTRODUCTION
CRPS-I, a debilitating neuropathic pain
state, may be very difficult to treat. The
disease may spread and be intractable
to standard therapy.1 More effective
therapeutic options are desperately
needed.2 Functional and structuralchanges in central pain processing
neurons (central sensitization) arethought to be important for initiating
and maintaining neuropathic pain, ofwhich CRPS-I is a subset. Central
sensitization seems to occur inconsequence of activity dependent NMethyl-D-Aspartate (NMDA) receptor
activation. 3,4 Growing clinical evidence
suggests NMDA-antagonists for thetherapy of neuropathic pain & CRPS.5METHODS
10 ASA I-II patients (intractable CRPS)
Anesthesia Induction
ketamine (0.5-1mg/kg)
midazolam (2.5-5mg), repetitively
Maintenance (5 days)
Infusions: ketamine (3-7 mg/kg/h) &midazolam (0.15-0.3)
Spontaneous breathing (Pat# 1, 2, 4)
Intubation/Mechanical Ventilation
Patients # 3, 5-10
Emergence (day 6)
slowly tapering of infusions

Summary of patient‘s characteristics#AgeSex

116f

228f

324

4

46

56

Initiating InjurySpreadDuration

sprain & brachial plexus traction injury

non-generalized

8 monthsbrachial plexus traction injury

non-generalized

1 yearmlymph node invasion of brachial plexus

non-generalized

1 yearfbrachial plexus traction injury

generalized

6 years

44

fcrush injury footgeneralized

6 years

30

felectrical shock injury to arm

non-generalized

2 years

741

f

traumatic knee injury

non-generalized

2 years828f

L5-S1 radiculopathy

generalized

6 years919

ffoot # & brachial plexus traction injury

generalized

6 years1022

f

traumatic hand injury

generalized

6 years

Table 1: Patient number (#), characteristics, initiating injury,
status of spread, and duration of symptoms.

RESULTS
Summary: Results#total PR

recurrence of[months]

ONP1since 42no2

since 14

yes

3

for 2

yes

4

for 2

5

for 4

6
7

Site

Low dose ketamine-

NPP

CRPS-relapse

nono

bp

no

no

rp

no

no

yes

bp

yes

less severe

not applied

yes

ps

yes

no

yes

for 4

yes

bp

yes

no

yes

for 2

yes

kp

nono

no8

for 1

yes

rp

yes

no

not applied

9

since 2

nono

no

10

for 2

yesnonobpsuccessnot applied

Table 2: Results: Patient #, duration of total pain relief (PR), recurrence of original nociceptive pain (ONP), site (bp:brachial plexus,
rp: radicular back pain; ps: pseudoarthrotic pain, kp:knee pain);recurrence of neuropathic pathological pain (NPP) features (hyperalgesia, allodynia), CRPS-relapse &severity and success ofketamine retreatment (low-dose outpatient).

Initial Observations
Immediate treatment response
total pain relief (10/10)
no hyperalgesia, no allodynia (10/10)
absence of CRPS-I-signs (10/10)

Adverse Treatment Effects
slight psychomimetic effects
up to 3 months (3/10)
urinary infection (2/10)
respiratory infection (5/10)
weaning problems (obesity) (1/10)

Fulminant CRPS-I & full recovery
after ketamine-midazolam
anesthesia (since >3.5 years)

Long-Term Observations
Lasting full pain relief (pathological)
since 3.5 years ( # 1)
since 14 months (# 2)since 5 months (# 7, 8)
since 2 months (# 9)
Recurring original nociceptive pain
after 6-8 weeks (8/10)
at original injury site (7/8)

Figure 1: Clinical Course of the most dramatic case (#1).
Upper row: left: at admission (CRPS-I right hand); right: fulminant
exacerbation of symptoms, clinical failure of standard therapy.
Lower row: left/ right: functional outcome 1 week after ketaminemidazolam anesthesia. Total recovery since 3.5 years.

CONCLUSIONS

Recurrence of pathological pain
hyperalgesia/allodynia (4/10)
ketamine-retreatment (3/4)
treatment success (2/3)

Ketamine-midazolam anesthesia
shows promise as potentially effective
therapeutic option for severe andotherwise intratable CRPS-I

CRPS-relaps (1/10) (#4,less severe)

CHALLENGES

Consumption of Analgesics
Significant reduction (exept #4)
Social/Professional Reintegration
full in (5/10)
improved (3/10)
no improvement (2/10)

Which patients benefit most?
Patient selection criteria?
Best Timing (stages)?
Dose-Response Curves?
Maintenance Strategies?

References: 1. Maleki J et al. Pain 2000; 2. Schwartzman RJ. N Engl J Med 2001; 3. Woolf CJ, Salter MW. Science 2000; 4. Schwartzman RJ et al. Arch Neurol 2001; 5. Sang CN, J Pain Symptom Manag 2000