Download Iv regional diamorphine for analgesia after foot

British Journal of Anaesthesia 84 (1): 95–6 (2000)
I.v. regional diamorphine for analgesia after foot surgery
M. G. Serpell1*, E. Anderson2, D. Wilson2 and N. Dawson2
1Department
of Anaesthesia and 2Department of Orthopaedic Surgery,
Western Infirmary, Glasgow G11 6NT, UK
*Corresponding author
Opioids administered to peripheral tissues can have significant analgesic effects in doses which
would not be effective centrally. We have assessed the effects of regional diamorphine 2.5 mg
i.v. in 14 patients undergoing surgical correction of bilateral arthritic foot deformities in a
prospective, randomized, double-blind study. Patients acted as their own controls as only one
foot received the active drug. Visual analogue scale (VAS) pain scores and wound tenderness
were measured over 72 h. Diamorphine did not improve median VAS area under the curve
pain scores during the first 6 h after surgery (33 (95% confidence intervals (CI) 25–46) vs 24
(17–35)). It also did not effect wound hypersensitivity when tested at 72 h after surgery (95
(47–125) vs 90 (50–125) g). There were no significant adverse effects.
Br J Anaesth 2000; 84: 95–6
Keywords: analgesics opioid, diamorphine; anaesthetic techniques, regional, i.v.; surgery,
orthopaedic
Accepted for publication: July 16, 1999
When opioids are applied peripherally to tissues, they can
have significant analgesic effects in doses which would not
be effective centrally.1 This action may be explained by
activation of opioid receptors at peripheral sites located in
inflamed tissue. Our previous study failed to show any
improvement in analgesia or hyperalgesia after peripheral
administration of morphine for bilateral foot surgery.2 We
postulated that this may have been because of poor access
of morphine to the receptors in the tissues of the foot.
Therefore, we have repeated this prospective, randomized,
double-blind, placebo-controlled study with a more lipophilic opioid and a larger volume of injectate.
Methods and results
After obtaining approval from the Hospital Ethics Committee and written informed consent, we studied 14 patients
undergoing elective surgery for correction of bilateral arthritic deformities of the feet. Patients were ASA I–II, aged
18–80 yr and weighed 45–90 kg. All anti-inflamatory
medication was stopped 72 h before surgery; paracetamol
was taken if required for analgesia.
Anaesthesia was induced with propofol and maintained
with 1–2% enflurane and 66% nitrous oxide in oxygen,
with the patient breathing spontaneously via a laryngeal
mask. Each foot was cannulated with a 22-gauge i.v. Venflon
and exsanguinated using an Esmarch bandage. Tourniquets
were applied just above the ankle and inflated to 100 mm Hg
above systolic arterial pressure. Patients received 15 ml of
0.9% saline containing diamorphine 2.5 mg into the cannula
of one foot and 15 ml of saline into the other over 60 s.
This procedure was randomized (Kwickstat 3.01 TexaSoft)
and double-blinded. The cannulae were removed and surgery
commenced 10 min later on each foot by two operators
simultaneously using the same technique. Morphine was
administered systemically after commencement of surgery,
as required, by i.v. injection. After surgery, the tourniquets
were deflated and analgesia was provided in the recovery
room by bolus doses of morphine 1–2 mg i.v., as requested,
until satisfactory relief was obtained.
After 2 h, patients returned to the ward and analgesia
was provided by paracetamol 1 g, ibuprofen 400 mg or
morphine 7.5–10 mg i.m. Pain scores were measured
separately for each foot at 1, 2, 4, 6, 24, 48 and 72 h using
a 100-mm visual analogue scores (VAS). At 72 h, sensitivity
thresholds were assessed by applying wires to the dominant
forearm and to both feet on an area 2 cm lateral to the
proximal end of the wound. The six calibrated wires of
increasing gauge allowed application of a range of forces
to the skin (5, 10, 40, 50, 135 and 230 g). The force values
were recorded when touch was first detected and when the
stimulus first became uncomfortable, and are expressed as
relative thresholds (forearm minus foot) so that each patient
acted as their own control.
Power analysis indicated that 12 patients would be needed
to detect a 50% difference in pain levels with a power of
80% and significance of 0.05 (from area under the curve
(AUC) data–SD of 42%).3 4 Data were analysed using
Mintab 10.5 for Windows 95.
© The Board of Management and Trustees of the British Journal of Anaesthesia 2000
Serpell et al.
feet. In support of this, during the pilot phase of the study,
when diamorphine 5 mg was given, one patient required
naloxone to reverse respiratory depression which occurred
immediately after deflation of the tourniquet. These systemic
effects did not occur with the dose of 2.5 mg.
Similarly, the dose of morphine given systemically and
paracetamol and ibuprofen analgesic consumption would
have had a central analgesic effect which would be equal for
both feet and may have attenuated any potential differences.
However, it would have been unethical to withhold these
drugs as optimal analgesia must remain a priority for
patients after surgery.
Analgesia has been reported with morphine 1 mg administered arthroscopically1 but the area is relatively avascular
and so the drug is likely to remain localized when the
tourniquet is deflated. Consequently, application of opioids
into the knee joint seems to be beneficial while other
peripheral routes of administration do not.6
The main analgesic effect would be expected to occur in
the early postoperative period and we doubt the clinical
significance of the 24-h VAS recording. The lower pain
thresholds in the feet are indicative of secondary hyperalgesia which can result from both peripheral and central
sensitization. The fact that diamorphine was not effective
despite being administered peripherally and before surgery
was commenced, supports a larger role for central sensitization in this phenomenon.
We used a sensitive model for this investigation.3 Patients
were their own controls and therefore differences in the
comprehension and reporting of pain, and the pharmacodynamic and kinetic profile of any drug, would not be responsible for differences seen in either foot.
In summary, i.v. regional diamorphine 2.5 mg had no
beneficial effect on pain scores or wound hypersensitivity
during the first 72 h after surgical correction of arthritic
foot deformities.
Fig 1 Median, interquartile and full range of visual analogue scale (VAS)
pain scores for the diamorphine and control groups at various individual
postoperative times. *P⫽0.05 (Wilcoxon sign rank test).
One patient was withdrawn from the study because the
injectate leaked from the Venflon. There were no differences
between groups in operator seniority or tourniquet time.
Relative median pain thresholds were 95 (95% confidence
intervals (CI) 47–125) g and 90 (50–125) g for the diamorphine and control groups, respectively. Mean doses of
systemic morphine given during and after operation were
6.5 (SD 3) and 9.3 (7.9) mg, respectively.
VAS values at individual times are presented in Figure
1. Median (interquartile) scores tended to be higher in the
diamorphine group but this only just reached significance
at 24 h (42 (18–59) vs 21 (9–36), respectively; P⫽0.05
Wilcoxon sign rank test). AUC pain scores for the first 6 h
were not significantly different (median 33 (95% CI 25–
46) for diamorphine and 24 (17–35) for controls).
The only adverse effect noted was flushing of the foot
which occurred in one patient in each group.
Comment
Diamorphine did not appear to have an effect on postoperative pain or secondary hyperalgesia. Diamorphine may have
failed to gain access to the peripheral receptors. Some
leakage of drug into the general circulation can occur
through both intraosseous and other veins, but we took steps
to prevent this by ensuring that the tourniquet completely
encircled the lower calf, that exsanguination was performed
and the injection was given slowly. We did not observe any
seepage of the injectate from the wound during surgery.
Diamorphine is lipophilic and would be expected to have
high tissue uptake and gain access to the peripheral receptors
in the nerve and joint tissue.5 However, when the tourniquet
is deflated, the drug may be washed out rapidly and any
peripheral effect of the opioid could then be obscured by
the central effects which would produce analgesia of both
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