+++
Local Anesthetic Considerations
++
Lidocaine is the prototypical local anesthetic used for IVRA in the
United States. In Europe, however, prilocaine has been the subject of most
clinical trials to date. Attempts have been made to maximize the efficacy of
lidocaine, while minimizing side effects or toxicity of the agent.
Alkalinization of 0.5% lidocaine (using 1.4% sodium bicarbonate) for
IVRA was studied in 31 patients. The authors found no clinical advantage to
the practice of alkalinization of lidocaine with respect to sensory block,
motor block, or the appearance of postoperative pain.22
When lidocaine was compared with alkalinized and nonalkalinized
2-chloroprocaine, both used as 0.5% concentrations and used for hand
surgery, alkalinized chloroprocaine behaved similarly to lidocaine, but
plain chloroprocaine offered no benefit and produced more minor side effects
than seen with lidocaine.23 Lidocaine has been compared
with ropivacaine for upper extremity IVRA in two separate studies. Two doses
of ropivacaine (1.2 and 1.8 mg/kg) were compared with one dose of lidocaine
(3.0 mg/kg) in 15 volunteers. Recovery of sensory and motor block after
tourniquet release was slowest with the high-dose ropivacaine group. More
patients in the lidocaine group (5 out of 5) experienced light-headedness
following tourniquet release, vs only 1 in the high-dose ropivacaine
group.24 In the second study, 51 patients were randomized
to receive either ropivacaine 0.375% or lidocaine 0.5% in a volume of
0.4 mL/kg up to 25 mL. Postoperative analgesia as measured by first request
for analgesics was superior in the ropivacaine group.25
++
Prilocaine has been compared with lidocaine, as well as with other local
anesthetics used for IVRA. Forty milliters of 0.5% prilocaine (100 mg)
was compared with the same volume and same concentration of chloroprocaine
in 10 volunteers undergoing IVRA, while evaluating onset of sensory and motor
block. Motor block onset did not differ between groups, and sensation
recovered almost equally well. However, recovery of motor function was
shorter in the prilocaine group, and more chloroprocaine patients
demonstrated signs of venous irritation or antecubital urticaria for 30–45
min after tourniquet deflation. Heart rate changes were also more notable in
the chloroprocaine group.26 The same group of
investigators expanded their study to include 60 patients; 30 in each of the
two respective groups detailed earlier. Now, the investigators found that
complete recovery of sensory block was faster in the prilocaine group (7.1
vs 9.8 min). Otherwise, the incidence of side effects remained higher in the
chloroprocaine group.27 Next, these investigators compared
0.5% prilocaine with the same concentration of articaine (a newer amino
amide–type local anesthetic that contains thiophene and that is
pharmacologically similar to mepivacaine) for upper extremity IVRA.
Articaine, a potent local anesthetic with a low degree of toxicity by virtue
of its rapid metabolism with esterases, was felt to be a suitable
alternative to prilocaine. Ten volunteers participated in this
double-blinded, crossover comparison of the two agents. They found no
significant difference between the two with respect to onset of anesthesia
or motor block, or in recovery of sensory or motor function. However, 80%
of the subjects experienced skin rashes after receiving articaine, vs 20%
in the prilocaine group.28 When 0.5% prilocaine was
compared with the same concentrations of articaine or lidocaine in three
groups of 10 patients each for IVRA, it was found that the onset of sensory
block was significantly shorter in the articaine group, which also had the
lowest peak plasma concentrations of local anesthetic following tourniquet
release.29 Plain prilocaine 1% has been compared with
the same local anesthetic combined with four different additives for IVRA;
bupivacaine 0.25%, clonidine 150 mcg, sufentanil 25 mcg, or tenoxicam 20
mg. The sufentanil-added group demonstrated the most rapid onset of sensory
block; postoperative pain scores were improved by adding either clonidine or
tenoxicam. Otherwise, there were no significant differences among the five
groups with respect to onset and duration of sensory and motor
block.30 Unlike the situation noted for lidocaine with the
addition of bicarbonate as an adjuvant, the addition of bicarbonate to
prilocaine does seem to shorten onset time and prolong the duration of
anesthesia.31,32
++
The use of mepivacaine for IVRA has been studied. Sixteen patients were
evaluated using 1.4 mg/kg in 40 mL for IVRA vs saline IVRA blocks performed
in the same individuals on the contralateral arm. Arterial occlusion was
maintained for 20 min. Reactive hyperemia was attenuated in the
mepivacaine-treated arm for the 60-min evaluation period, indicating that
mepivacaine is a potent vasoconstrictor of long duration of action. This
finding has implications for the use of mepivacaine in individuals with
either compromised upper extremity blood flow, or in those suffering from
CRPS, wherein it probably should not be considered the local anesthetic of
choice.33 The same study group evaluated the effects of
mepivacaine IVRA on intracutaneous capsaicin-induced burning pain and on
microvascular skin blood flow as measured by Doppler perfusion imaging. The
reactive hyperemia was less in the mepivacaine-treated arm 10 min after
tourniquet release, and the area of the flare was smaller after capsaicin in
the mepivacaine-treated arms. The authors concluded that mepivacaine IVRA
had no effect on post-IVRA sensory function of thin afferents, but
differentially decreased the spread of capsaicin-induced
flare.34
+++
Adjuncts to Local Anesthetics for IVRA
++
A systematic review of the literature was undertaken to evaluate the
use of adjuncts to local anesthetics for IVRA. Twenty-nine studies met the
criteria of being randomized, double-blinded, and controlled. Data on 1217
study subjects were reviewed, and the agents studied included opioids
(fentanyl, sufentanil, meperidine, morphine), clonidine, muscle relaxants
(atracurium, pancuronium, mivacurium), tramadol, nonsteroidal
antiinflammatory agents (NSAIDs) (ketorolac, tenoxicam, acetylsalicylate),
alkalinization using sodium bicarbonate, and the addition of potassium, and
temperature alterations. The authors found solid evidence supporting the use
of NSAIDs in general, and ketorolac in particular, for improving
postoperative analgesia. Clonidine 1 mcg/kg also appeared to improve
postoperative analgesia and prolong tourniquet tolerance. Opioids fared
poorly when used for IVRA, with only meperidine in doses of ≥30 mg
showing substantial postoperative benefit at the expense of postdeflation
nausea, vomiting, and dizziness. Muscle relaxants improved postoperative
motor block and were beneficial in fracture reduction in which muscular
relaxation is imperative for good results.35
++
Clonidine has been added to both prilocaine and lidocaine as an adjunct
to IVRA, both for surgery and for the management of CRPS. When 2 mcg/kg was
added to prilocaine 0.5% in a randomized, double-blind fashion in 56
patients undergoing upper extremity surgery, there was no difference between
groups regarding sensory or motor block onset or duration. The patients who
had clonidine added had a significant reduction in arterial blood pressure
after tourniquet release (24–48%), while heart rate remained unchanged.
The authors concluded that clonidine was of limited benefit as an adjunct to
IVRA local anesthetics.36 When a dose of 1 mcg/kg in a
total volume of 50 mL of 0.5% lidocaine was used for lower extremity IVRA
for patients suffering from CRPS, five of seven subjects obtained complete
pain relief after four to six blocks. The remaining two study patients
derived partial benefit from the blocks. There were no cases of significant
hypotension, bradycardia, hypoxemia, or excessive
sedation.37 The addition of clonidine to prilocaine did
dramatically suppress tourniquet pain, but it did not alter postoperative
pain following tourniquet deflation.38 Dexmedetomidine is
approximately eight times more selective toward the
α2-adrenoreceptors than is clonidine. As such, it
has been used in IVRA to determine if it might advance some of the
beneficial findings noted with the latter agent. Thirty patients undergoing
hand surgery under IVRA received 0.5% lidocaine alone or lidocaine plus
dexmedetomidine 0.5 mcg/kg. The dexmedetomidine group showed a more rapid
onset of sensory and motor block, a prolonged sensory and motor block
recovery, prolonged tolerance for the tourniquet, and improved quality of
analgesia compared with the group that received local anesthetic
only.39
++
Since opiate receptors were discovered to exist in the peripheral
nervous system40,41 and with the demonstration that
opioids may produce effective, long-lasting analgesia when injected in
conjunction with local anesthetics for brachial plexus block,42–46 several investigators have attempted to decrease the potential
for toxicity from local-anesthetic-only IVRA by adding opioids to reduce the
concentration of lidocaine. Although it has not been proven that the
addition of fentanyl to lidocaine for IVRA results in improved analgesia
while reducing the risks,47,48 the addition of fentanyl in
200-mcg doses to prilocaine 0.5% did result in more complete anesthesia
than in patients who had 100 mcg added, or when plain prilocaine was used
for IVRA. Postoperative nausea and central nervous system side effects were
higher in the fentanyl-added groups vs those who received local anesthetic
alone.49 Two other studies, however, found that the
addition of opioids to prilocaine did not improve success with the
technique.50,51 More research on the effects of the
addition of opioids to prilocaine for IVRA may ultimately resolve this
apparent discrepancy.
++
Some investigators have found that adding opioid and muscle relaxants to
0.25% lidocaine provides the same analgesia and muscular relaxation as
that provided by 0.5% lidocaine alone, while reducing the likelihood of
systemic toxicity. Adjuvants added to lidocaine have included fentanyl 50
mcg plus pancuronium 0.5 mg,52,53 fentanyl plus
rocuronium,54 and fentanyl plus
d-tubocurarine.55 In each case, the
authors reported outstanding operating conditions, and since the lidocaine
concentration was able to be reduced to 0.20%, the potential for systemic
toxicity was at least halved.
++
When meperidine 0.25%, 40 mL (100 mg), was used as a solitary agent for
IVRA, complete motor block was produced, just as effective as that produced
by lidocaine. Motor block onset was as rapid or more rapid than sensory
block onset in each of the 15 patients in this study group. However, when
compared with plain lidocaine in this study, there was a higher incidence of
dizziness, nausea, and pain at the injection site.56
++
Tramadol has been evaluated for use in IVRA of the upper extremity.
Sixty volunteers divided into four groups of 15 patients each received IVRA
with 40 mL of tramadol 0.25% (100 mg), 0.9% NS, lidocaine 0.5%, or
lidocaine plus tramadol 0.25%. The onset and recovery of sensory and
motor block was similar between the tramadol and NS-only groups. However,
the addition of tramadol to lidocaine resulted in faster onset of sensory
block at the expense of an increase in skin rash development and painful
burning sensations at the injection site. The conclusion of the authors was
that tramadol alone does not possess local anesthetic effects, but might
modify the effect if added to a local anesthetic like
lidocaine.57 In another study comparing 0.5% lidocaine
with and without 50 mg of tramadol for upper extremity IVRA, the
tramadol-added group experienced less tourniquet pain than the local-only
group, but, as in the study mentioned earlier, there were several cases of
skin urticaria in the tramadol group, but not in the lidocaine-only
group.58 Tramadol (100 mg) added to lidocaine for IVRA for
upper extremity anesthesia acted similarly to sufentanil (25 mcg) or
clonidine (1 mcg/kg) added to the local anesthesia with respect to
intraoperative hemodynamic data, time to recovery of sensory block, onset
and recovery of motor block, sedation scores, and postoperative
pain.59 In summary, tramadol is ineffective as a solo
agent for IVRA, but may confer some advantage when added to lidocaine. This
advantage, however, may be offset by the significant incidence of
dermatologic side effects of tramadol given intravenously in an
exsanguinated extremity.
++
A small dose of nondepolarizing muscle relaxant may be chosen as an
adjunct to the local anesthetic administered for IVRA; however, since
d-tubocurarine releases histamine even in judicious
doses, it is probably best to avoid this agent altogether. Atracurium has
been added to lidocaine in an effort to improve muscular relaxation during
IVRA, particularly during the reduction of upper extremity fractures and
dislocations. Adding 3 mg of atracurium to lidocaine for IVRA resulted in a
decrease in the onset time of analgesia in the hand, but not at the
tourniquet site. There was no added benefit to adding this agent, or adding
alfentanil to lidocaine in the same study.60 A prior study
using 2 mg of atracurium added to 40 mL of 0.5% lidocaine for IVRA for
hand surgery in 40 patients randomized to one of two groups found that the
addition of the atracurium provided a greater degree of muscular relaxation,
easier reduction of fractures, and better operating conditions, as well as
less pain after surgery.61
++
Neostigmine has been suggested as a co-analgesic when used for epidural
and intrathecal analgesia and anesthesia, but evidence of its benefit in the
peripheral nervous system is controversial. In two studies, one using
neostigmine added to lidocaine, and the other using the adjuvant added to
prilocaine, there have been conflicting findings. When neostigmine (1 mg)
was added to 0.5% lidocaine for IVRA in a study of 54 volunteers
randomized into one of three study groups, it was found that the addition of
the adjuvant provided no benefit in terms of analgesia or anesthesia
compared with controls.62 When one-half the dose of
neostigmine (0.5 mg) was added to prilocaine (3 mg/kg) for IVRA in 30
patients randomized to one of two treatment groups, it was found that the
adjuvant group demonstrated shortened sensory and motor block onset times,
prolonged sensory and motor block recovery times, improved quality of
anesthesia, and prolonged time to first analgesic requirement vs the plain
prilocaine group.63 It appears that these conflicting
findings with neostigmine added to two distinct local anesthetics for IVRA
will need to be confirmed by additional work incorporating larger patient
sample sizes to resolve the apparent discrepancy in the two small studies
mentioned earlier.
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Nonsteroidal Antiinflammatory Agents
++
Other attempts to improve IVRA with lidocaine have included using
NSAIDs like ketorolac64 to suppress tourniquet pain while
enhancing postoperative analgesia. Although ketorolac has shown some
efficacy, other NSAIDs have not fared as favorably. Ketorolac has been added
to lidocaine for IVRA for the treatment of sympathetically mediated pain
syndromes. In a retrospective review of 61 patients referred to a university
pain center with a diagnosis of reflex sympathetic dystrophy (RSD) who all
underwent IVRA with the combination of ketorolac-lidocaine, 26% (16/61)
had a complete analgesic response to the block(s). Forty-three percent
(26/61) had a partial response, and 31% had no response. The authors
stated that the only symptom predicting failure was the presence of
allodynia. However, allodynia is the hallmark of RSD, so one must wonder
whether the clinicians correctly categorized the patients as being afflicted
with RSD, vs an alternative diagnosis.65 When used for
upper extremity surgery, ketorolac added to lidocaine for IVRA was shown to
be safe and effective, and furthermore, using a forearm tourniquet instead
of an upper arm tourniquet in this study demonstrated that the dose of both
agents could be reduced by 50%, while also providing for prolonged
sensory block and prolonged postoperative analgesia. Twenty milligrams of
ketorolac was added to lidocaine 0.5% for the upper arm tourniquet group,
and half the dose of both agents (by virtue of halving the volume
administered of an equipotent concentration of both drugs) was used in the
forearm tourniquet group.66
++
Another NSAID, tenoxicam, was added to prilocaine in one study of 45
total patients. A 20-mg dose of the NSAID was used in patients undergoing
IVRA for reduction of Colles' fractures, with patients divided into three
groups. One group received local anesthetic only, one received local plus
tenoxicam, and one group had IVRA with local anesthetic only plus IV NSAID.
In this last group, the tenoxicam (20 mg) was injected into the
contralateral arm, opposite the IVRA procedure arm. The group receiving the
NSAID added to the local had superior analgesia and lower pain scores than
either of the other two groups of patients.67
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Other Specific Agents: Corticosteroids
++
The antiinflammatory properties of steroids have been evaluated when
these agents have been added to local anesthetics for IVRA in patients with
rheumatoid arthritis (RA). In a randomized, double-blind, crossover,
placebo-controlled study, 20 RA patients received either 50 mg
methylprednisolone in mepivacaine 0.25% or mepivacaine plain for upper
extremity IVRA. The other extremity received the opposite treatment. One
week later, the same medications were injected into the contralateral
extremities, respectively. Fifty percent of patients reported subjective
improvement at 1 and 6 weeks; objective parameters like grip strength did
not change until the 6-week evaluation, at which time a significant increase
was noted, as was the reduction in grip diastasis and movement-invoked pain.
This report suggests that corticosteroids administered by IVRA may provide
sustained analgesia in certain RA sufferers.68 Steroid
IVRA has also been used as adjunctive treatment of CRPS type I.
Methylprednisolone (40 mg) was added to lidocaine for IVRA in a randomized,
double-blinded, placebo-controlled fashion in 22 patients. Treatments were
applied once per week, for up to three sessions of blocks. The investigators
found no benefit in adding the steroid to the local with regard to
improvement in pain severity or shortening the course of the
disease.69
+++
Specific IVRA Treatments for CRPS
++
Adrenergic blocking agents or antagonists, particularly those effective
at the alpha receptor, have shown promise in the treatment of CRPS,
particularly when these agents are used for IVRA. Other adrenergic adjuvants
release and then subsequently prevent the reuptake of norepinephrine at the
neurovascular junction. Their use in CRPS is intuitive, since the
pathophysiology of the disease is suspected to include the alpha receptor
and to be mediated by norepinephrine. However, there is significant
controversy regarding this topic, particularly when current research is
compared with the findings of studies conducted almost 40 years ago.
Guanethidine, reserpine, and bretylium have all been evaluated for IVRA for
CRPS. When 15 mg guanethidine was added to 0.5% prilocaine in a group of
57 patients with CRPS of the upper extremity and hand, the guanethidine was
found not to be more effective than NS in treating allodynia and burning
pain of CRPS, following distal radius fractures.70 These
findings corroborated work done in a double-blind, randomized, multicenter
study 7 years earlier. Sixty patients with RSD/causalgia received four IVRA
blocks at 4-day intervals with either guanethidine or placebo in 0.5% lidocaine. Long-term, there was no difference noted between the placebo
group and the guanethidine group, and only 35% of patients overall in all
groups had a resolution of their pain problem.71 Bretylium
has been used as well in CRPS. In a randomized, controlled trial, 0.5%
lidocaine was compared with the same local anesthetic to which bretylium 1.5
mg/kg was added. A decrease in pain of ≥30% was considered
significant. The bretylium-local group had pain relief for 20
± 17.5 days, as opposed to the lidocaine-only group,
wherein analgesia persisted for only 2.7 ± 3.7 days.
The bretylium was far superior to the local anesthetic alone in treating
CRPS in this study.72 IVRA with bretylium was utilized to
demonstrate that a reduction in sympathetic tone to exercising forearm
muscles would increase blood flow, reduce muscle acidosis, and attenuate
reflex responses. IVRA with bretylium increased blood flow as well as oxygen
consumption in the exercising forearm, although both venous potassium and
hydrogen ion content were elevated during the exercise phase, implying that
reflex effects are unaffected by bretylium block.73