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Intravenous regional sympathetic block
Summary of the evidence

There is consistent evidence from three high quality studies (one health
technology assessment (HTA), one systematic review, one randomised
controlled trial (RCT)), two medium quality systematic reviews and one low to
medium quality non- randomised controlled trial that intravenous regional
sympathetic block with guanethidine is not effective in the treatment of adults
with complex regional pain syndrome. There is some evidence from two very
small trials that intravenous regional sympathetic block with bretylium or
ketanersin may be effective. Study size varied between 6 to 60 patients, most
trials had less than 20 participants.

There is evidence from one medium quality RCT of 23 patients that
intravenous regional sympathetic block with magnesium and lignocaine is
effective in the short-term compared to intravenous sympathetic regional
block with lignocaine alone for the treatment of adults with chronic limb pain.

Significant adverse effects which include hypotension, hypertension and
tachycardia have been reported with guanethidine and bretylium. Magnesium
Bier’s block is a painful procedure with post treatment aching in muscles or
bones.
Clinical practice recommendation
Complex Regional Pain Syndrome: Intravenous regional sympathetic
blocks1 are not recommended for the treatment of complex regional
pain syndrome (B).
Chronic Limb Pain: No recommendation was made because there was
insufficient evidence to support or refute the effectiveness of magnesium
/ lignocaine intravenous regional sympathetic blocks for the treatment of
adults with chronic limb pain (I).
Good practice points
The use of magnesium in intravenous regional sympathetic blocks should be
restricted to the research setting.
Currently the clinical relevance of intravenous regional sympathetic block is in the
multimodal setting, for which we have no evidence on which to comment. There
is potential severe risk from intravenous injection of guanethidine and bretylium.
What is IV regional sympathetic nerve block?
IV regional sympathetic nerve block (also called IV regional anaesthesia) is a
technique used to anaesthetise one particular region of the body, for example an
arm or a leg, without affecting the rest of the body.
One of guanethidine; reserpine; atropine; guanethidine with prilocaine; bretylium
with lignocaine; guanethidine with lignocaine; bupivacaine; or ketorolac with
lignocaine.
What conditions is IV regional sympathetic nerve block
used for in the studies appraised?

complex regional pain syndrome I (reflex sympathetic dystrophy)

complex regional pain syndrome II (causalgia)

Raynauld’s disease

sympathetically maintained pain in arm/leg

lateral epicondylitis

chronic limb pain
How is IV regional sympathetic nerve block done?
A large vein in the affected limb is cannulated with a 22-gauge venous catheter.
Once the affected limb is elevated and drained by using elastic bandage, a cuff is
inflated up to 100 mmHg above the patient’s systolic blood pressure (ie a
tourniquet). The limb is then returned to the horizontal position, and the diluted
drug solution is administered over 20 minutes. The drug is allowed to circulate
round the affected region for long enough to cause nerve blocking and to fix
enough of the drug to the tissues. This is important so that when the tourniquet
is released there is not a large flood of the drug into the circulation which would
have toxic effects.
Where is IV regional sympathetic nerve block done?
The procedure is carried out in a procedure room with full resuscitation
equipment and monitoring, or an operating room.
Who does IV regional sympathetic nerve block?
The procedure is carried out by an anaesthetist.
How effective is IV regional sympathetic nerve block?
Complex Regional Pain Syndrome
One health technology assessment (HTA), four systematic reviews, one
experimental study and one comparative study provided information on IV
regional sympathetic nerve block for complex regional pain syndrome.
The high quality HTA (McQuay, 1997) included eight controlled trials (96 patients
total). There were conflicting results reported in the studies and most were
reported to have serious methodological flaws. The authors concluded that there
was no support for guanethidine as the active drug to manage pain associated
with reflex sympathetic dystrophy (RSD).
A high quality systematic review (Perez, 2001) included nine randomised
controlled trials (six of which were reported by McQuay) comparing IV
sympathetic nerve blocks (in six trials the active agent was guanethidine) to
control or placebo. Outcome data from these nine studies (226 patients total)
were pooled. Meta analysis showed that IV regional sympathetic blocks (including
guanethidine) did not provide better analgesia than control or placebo
treatments. All trials were noted to have methodological weaknesses, including
lack of statistical power due to heterogeneous patient populations and small
sample sizes; inadequate randomisation procedures; lack of statistical data;
absence of follow-up; unevaluated or absent blinding procedures; insufficient
washout periods or incomplete crossover; and lack of information about possible
co-interventions or side effects.
Three other systematic reviews (Forounzanfar, 2002; Kingery, 1997; Jadad,
1995) also concluded that guanethidine IV sympathetic nerve block did not
appear to be effective but the lack of quality evidence prevented strong
conclusions. The HTA and two reviews noted that the evidence was more
promising for bretylium and ketanserin, but this was based on a small body of
evidence.
In one high quality randomised controlled trial, 57 patients with complex regional
pain syndrome type 1 of the hand received IV regional nerve blocks with
guanethidine and prilocaine, or saline placebo (Livingstone, 2002). Guanethidine
provided no significant therapeutic advantage over placebo, and patients
receiving guanethidine blocks had slower resolution of symptoms of vasomotor
instability. The Authors noted that natural history studies suggested that CRPS
type 1 may resolve spontaneously.
In contrast, one comparative, non-randomised low to medium quality study of 28
patients with hand pain associated with sympathetic dystrophy (Glynn, 1981)
found that pain level was no different after placebo intravenous regional block
compared to baseline but was significantly lower after guanethidine regional block
administered 1 hour later.
Chronic Limb Pain
One medium quality experimental study provided information on IV regional
sympathetic nerve block for chronic limb pain (Tramer, 2002). In 23 patients
given two IV regional nerve blocks (magnesium sulphate with lignocaine and
saline with lignocaine given at least seven days apart and in random order), the
magnesium sulphate nerve block provided more marked and longer-lasting pain
relief (mean 23 days) than the saline block (mean 6 days).
How safe is IV regional sympathetic nerve block?
Complex Regional Pain Syndrome I and II
Adverse effects were monitored in most included studies, two of which reported
that there were none or none that were clinically significant. Adverse effects
reported included prolonged hypotension after repeated guanethidine blocks,
hypertension and tachycardia followed by orthostatic hypotension after bretylium.
One of the trials in Perez et al. (Jadad, 1995) reported that one patient
experienced severe postural hypotension, bradycardia, dizziness, and chest pain
starting five minutes after tourniquet release, the other had severe postural
hypotension starting five minutes after tourniquet release and lasting 20 hours.
Investigators stopped the study because of these adverse effects.
An additional study (a low quality case series) noted no “life-threatening” side
effects but some minor side effects which resolved within 30 minutes, related
mainly to the use of the tourniquet (Connelly, 1995). These included dizziness
and lightheadness on deflation of the tourniquet (41% of patients); numbness of
the extremity after tourniquet deflation (16%); and nausea after tourniquet
deflation (5%).
Chronic Limb Pain
Tramer, 2000 noted that magnesium Bier’s block is painful with aching in muscles
or bones lasting 24 hours. Some patients reported an immediate hot sensation in
the treated limb after tourniquet release. The authors reported ‘severe’ adverse
effects (an increase of over four points on a visual analogue scale) during 52% of
injections and 48% of tourniquet releases, although there were not episodes of
hypotension or bradycardia.