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PROCEDURAL
AND MEDICAL COMPLICATIONS OF CHRONIC PAIN MANAGEMENT
Steven
H. Richeimer, M.D.
Assistant Professor of Anesthesiology
and Psychiatry
Stephen
M. Macres, M.D., Pharm.D.
Assistant Professor of Anesthesiology
INTRODUCTION
An unfortunate but
obvious fact is that where there is medical care, there are complications.
In this paper, we will review the procedure-related and the pharmacological
complications of pain management.
Procedural
Complications
Complications from pain management
procedures are related to the involved anatomy, physiology, and pharmacology.
A thorough understanding of these aspects of neural blockade is critical.
For any procedure or injection, the physician should answer the following
questions:
1(a) What tissues must
the needle pass through?
(b) What vulnerable tissues
and organs are near the path and target of the needle?
2(a) Are any nearby nerves
or vessels vulnerable to trauma, unintended injection, or spread of
injectate?
(b) What are the results
of trauma, bleeding, and infection, or the results of injection or spread
to unintended sites?
Example: The piriformis
muscle injection may produce an unexpected motor block. Unintended
injection into the vertebral artery, during a stellate ganglion
block, will cause loss of consciousness and seizures.
3(a) What are the expected
physiological effects of the injection?
(b) Are there other,
less common effects that need to considered?
4) Does coexisting illness
or prior history make this patient particularly vulnerable to complication?
Considering these questions
will help the physician to appropriately evaluate the risks of direct
nerve damage, infection, vascular, dural or pulmonary compromise, backache,
and undesired spread of drug after placement of a block.12
Besides the risks of immediate complications, some major neurologic
complications may manifest after a number of days or longer, including
epidural hematoma, chemical meningitis, cauda equina syndrome, lumbosacral
radiculopathy and adhesive arachnoiditis.12
Nerve
Damage
Direct nerve damage can be
associated with toxicity of the injected solution or mechanical damage
to the nerve.12 Cytotoxicity appears to be directly related
to the concentration of local anesthetic and the duration of exposure.
The site of deposition of local anesthetic, be it extrafasicular or
intrafasicular, is also directly related to the extent of alteration
in nerve function. Extrafasicular application appears to have subtle
effects on the nerve which include edema formation within the endoneurium
with increased fluid pressure within the fascicle, some inflammatory
changes and myelin and Schwann cell injury. Intrafasicular injection
of local anesthetic is a much more serious matter. Axonal degeneration
and barrier changes have been documented with intrafasicular injection
of local anesthetic.12 Higher concentrations of local anesthetic
can cause correspondingly greater nerve injury. It is good practice
to always use the minimum effective concentration of local anesthetic.
Sodium metabisulfite is an
anti-oxidant found in local anesthetic solutions containing epinephrine.
It has pronounced neurotoxic effects when injected intrathecally; intrafasicular
injection should also be avoided. Likewise, intrafasicular injection
of epinephrine is a potential problem. The vasoconstrictive effects
of epinephrine could theoretically compromise blood flow. This concern
about ischemic damage has also raised questions about the use of intrathecal
or epidural epinephrine; however, this has not been documented to be
a clinical problem. If using epinephrine it is wise, at the time of
the block, to add fresh epinephrine (devoid of sodium metabisulfite)
to your local anesthetic.
Neuropathy has been reported
to occur as a result of exposure to local anesthetic; however, mechanical
trauma to the nerve is likely to be the more common culprit.13
Mechanical damage can occur
when the needle is inserted into the nerve resulting in interruption
of the perineural tissue around nerve fasicles.12, 14 Such
a maneuver, which is often times unavoidable, can manifest itself as
a paresthesia. Whether or not elicitation of a paresthesia has significant
adverse consequences is unknown. In case of a paresthesia, it is our
practice to withdraw the needle slightly, and to confirm resolution
of the paresthesia, before injection of local anesthetic. If the injection
produces intense pain, it should be discontinued and the needle repositioned.
Important guidelines for
perineural injections include: 1) use blunt (B-bevel) instead of a sharp-beveled
needles, 2) use 22 gauge rather than 25 gauge needles, 3) use gentle
technique, preferably in an awake patient who can report parathesias,
4) avoid neural injections in confined fascial spaces, such as the ulnar
nerve at the elbow and the peroneal nerve at the fibular head, and 5)
use a nerve stimulator which can help illicit parathesias without mechanical
damage to the nerve.
Vascular
Injury
Vascular puncture can be an
unavoidable consequence of a nerve block since nerves, arteries, and
veins frequently run in very close proximity to each other. In fact,
some regional blocks utilize arterial puncture as part of the technique,
in order to verify ideal needle placement. Examples of this approach
include the transarterial axillary and transaortic celiac plexus blocks.
Although vascular puncture tends to be common, clinically significant
hematoma formation is rare. Hematoma formation can be minimized by using
gentle technique, preferably with a short beveled needle no larger than
22 gauge. Multiple penetrations of the vessel will increase the risk
of hematoma formation, which can obscure anatomic landmarks and interfere
with the spread of local anesthetic.13 Hematomas, especially
in closed spaces such as the epidural space, can cause major complications,
including nerve compression syndromes such as lumbosacral radiculopathy
or cauda equina syndrome.15,16
Performance of nerve blocks
in the anticoagulated patient presents unique problems. The consensus
is that nerve blocks in general, and central neural blockade in particular,
are contraindicated in the fully heparinized patient or those with known
coagulopathies and significant thrombocytopenia.12,14,17
Placement of an epidural catheter at least one hour prior to heparinization,
in patients about to undergo major vascular surgery, has been reported
to be safe.15,17 Postoperative removal of the catheter should
be performed 4-6 hours after the heparin has been discontinued.17
Perioperative use of thrombolytic agents (TPA, Streptokinase, Urokinase)
are an absolute contraindication to placement of an epidural catheter.13,17
Patients on coumadin therapy should discontinue its use at least 3-5
days prior to a procedure. Regional blockade can then be safely performed,
if the INR is less than 1.3 (some experts say 1.5), the aPTT is within
the upper limit of normal, the platelet count is greater than 80,000/,microliter,
and the bleeding time is less than 8 minutes.
Many of our patients, at
the University of California-Davis Pain Management Center, have compromised
platelet function secondary to the use of aspirin or one of the many
non-steroidal anti-inflammatory drugs (NSAIDs). Most regional blocks
can be performed safely in these patients, particularly if care is taken
to avoid vascular trauma. It is prudent to discontinue aspirin for 7
days and NSAIDs for 2-3 days prior to the procedure. If the patient
is scheduled for a cervical or thoracic epidural procedure, such discontinuance
is mandatory. These guidelines may also be reasonable for patients who
are scheduled for procedures for which the potential bleeding is not
readily treatable with direct pressure, such as the celiac plexus.12
A bleeding time may be helpful for these patients, particularly if the
platelet count is less than one hundred thousand, however, this test
may not be reliably predictive of intraoperative hemostasis.13
For patients with low platelet counts, look for clinical signs of increased
bleeding and carefully weigh the potential benefits of the block against
the increased risks of harm.
Pulmonary
Complications
Pneumothorax is a complication
that is bound to occasionally occur when performing regional blocks
in and about the chest and neck. Procedures commonly associated with
pneumothorax include stellate ganglion, supraclavicular, intercostal
and splanchnic nerve blocks. Symptoms include chest pain, coughing and
shortness of breath. Physical examination may reveal subcutaneous air
and diminished breath sounds on the affected side. Certainly, while
performing any of the above procedures, if you should aspirate air,
presume the subsequent development of pneumothorax. Often, however,
it takes 6-12 hours for interpleural air to accumulate and cause symptoms.
Chest x-ray is diagnostic and if the pneumothorax is less than 25% of
the lung volume it will usually resolve without treatment. Greater volume
loss requires consultation with a surgeon for possible chest tube placement.
If there is concomitant hemodynamic compromise associated with the pneumothorax,
suspect a tension pneumothorax, and be prepared to place a large bore
intravenous needle or catheter into the second intercostal space, at
the midclavicular line on the effected side.
Generally speaking, in healthy
patients, without significant lung disease, blockade of a single phrenic
nerve or blockade of bilateral intercostal nerves from T6 to T12 results
in minimal respiratory compromise. However, even in healthy individuals,
there is a 25% decrease in vital capacity with bilateral phrenic nerve
blocks. We avoid performing almost any bilateral blocks, especially
those with the risk of pneumothorax.
Other
Tissue Trauma
Fortunately, organ damage
is a relatively rare event. However, during the performance of a lumbar
sympathetic block, the kidney may be punctured. This can result in some
hematuria, but this is rarely associated with adverse sequelae. When
neurolytic agents are being used, special care must be taken to assure
accurate needle placement. This should be done with fluoroscopic guidance.
If urine, blood, or CSF is aspirated, the needle should be repositioned.
Bowel puncture is another risk of needle placement, particularly with
an anterior, CT guided approach to the celiac plexus. Radiologists report
that as long as a 22 gauge or smaller needle is used, the small bowel
seals itself without consequence. Puncture of the large bowel must be
avoided.
Dural
Puncture
Headache is a complication
of spinal anesthesia or inadvertent dural puncture. When assessing a
post-procedure headache it is necessary to also consider the full range
of headache etiologies. Classic post-dural puncture headache (PDPH)
is thought to result from a CSF leak through the rent in the dura. The
resulting pressure and tension changes in the neuro-axis is the presumed
cause of the headache. Traction on the trigeminal, glossopharyngeal,
vagal, and upper cervical nerves is thought to contribute to the frontal
and occipital head pain and the diffuse neck pain reported by patients.
The onset of the headache is usually within 72 hours of the dural puncture
and is posture related. The headache is worse when the patient is upright
and relieved when recumbent. Associated symptoms include nausea, dizziness,
tinnitus, photophobia, auditory and visual disturbances. Hearing loss
can occur, and apparently parallels the size of the dural defect. This
appears to be a reversible problem.15
The incidence of PDPH can
be minimized by using the smallest gauge needle reasonable, such as
25 gauge. Needles much smaller than this however, have higher failure
rates and may be associated with poorer mixing of local anesthetic in
the CSF, with potentially higher rates of neurotoxicity. Pencil point
needles, such as the Sprotte, Green, or Whitaker, gently separate rather
than sever dural fibers and appear to decrease the rate of PDPH. Orienting
the bevel of both spinal and Touhy needles parallel to the dural fibers
may also be beneficial. It also appears that the risk of PDPH decreases
with increasing age. The reported incidence of PDPH is approximately
5% in patients over 50 years of age, following dural puncture with a
22 gauge needle. Women, in general, experience PDPH twice as often as
men.15
Postdural puncture headaches
usually resolve spontaneously within 2-3 days. On occasion, a headache
may persist for longer than one week. It is our practice to discuss
with the patient both conservative and blood patch treatment, but to
initially recommend the conservative approach. Conservative therapy
consists of analgesics, bedrest, and hydration (preferably with caffeinated
beverages). Intravenous caffeine - sodium benzoate 500 mg, in one liter
of lactated ringers, infused over approximately one hour, and followed
by ongoing hydration has been recommended. The efficacy of this treatment
is unclear, and many patients cannot tolerate the effects of the caffeine.
Should the headache prove
refractory to conservative treatment, an autologous blood patch can
be attempted. We recommend administering 15-20 milliliters of blood,
obtained aseptically from the antecubital vein and placed into the epidural
space, preferably one level below the previous dural puncture site,
since the blood tends to move primarily in a cephalad direction.18
Use of an autologous blood
patch in a septic patient is problematic and runs the risk of precipitating
an epidural abscess. Likewise, the HIV positive patient with PDPH is
a group at risk for spread of the HIV virus to the CNS. A "dextran
patch" may be useful for these situations or for Jehovah's Witnesses.18
Autologous blood patching has been performed successfully in HIV positive
patients, without any apparent adverse neurologic sequelae.17,18
Backache
Backache after spinal or epidural
procedures can be due to the mild trauma of placing a needle through
skin, muscle, and ligament. This can precipitate hematoma formation,
ligament injury, and reflex muscle spasm. Symptoms tend to be mild in
nature and generally resolve in less than one week. Occasionally, we
will prescribe 3-4 days of muscle relaxants, to treat severe spasms.
Infections
The incidence of infection
associated with central and peripheral nerve blocks is relatively rare.12,15
In fact, local anesthetics are reported to have antimicrobial activity
which may help to decrease the risk of infection. However, local anesthetics
are not adequate antiseptics and meticulous aseptic technique is critical.
Local skin infections at the insertion site of epidural catheters are
not uncommon. Therefore, it is our practice to inspect the epidural
catheter site daily to confirm catheter depth, integrity, security of
the dressing, and the absence of any signs of infection (e.g. induration,
swelling, pronounced tenderness, erythema, or drainage).
Epidural or subarachnoid
space infections, although extremely rare, can be devastating. Epidural
catheters can act as a wick allowing the spread of infection from the
skin to the epidural space. This is of particular concern in the immunocompromised
patient.17 Epidural abscess usually manifests itself several
days after neural blockade with symptoms of severe low back pain, local
tenderness, and fever with leukocytosis. Cord compression can also occur
and manifests with pain or motor and sensory symptoms, including lumbosacral
radiculopathy or cauda-equina syndrome.16 An MRI exam can
rule out epidural abscess or epidural hematomas.16 Surgical
intervention within 12 hours of diagnosis improves neurological outcome.17
Often we are consulted for
placement of an epidural catheter in a trauma victim with rib fractures
and compromised respiratory status. Occasionally, these patients can
show signs of systemic infection which can preclude timely placement
of an epidural catheter. Once appropriate antibiotic therapy is begun,
placement of a catheter in the neuro-axis can be performed with minimal
fear of precipitating meningitis or epidural abscess.19
Patients with Acquired Immune
Deficiency Syndrome (AIDS) may not be ideal candidates for epidural
or spinal analgesia. These patients may be more likely to develop serious
infectious complications. Furthermore, the virus can cause degenerative
changes in the spinal cord; therefore, it is preferable to avoid seeding
virus into the central nervous system. Nevertheless, there are times
when this theoretical risk is overshadowed by the potential benefit.
Unintentional
Effect or Spread of Local Anesthetic
Unintentional spread of a
drug during regional blockade can occur because of communicating tissue
planes. Subarachnoid block has occurred following retrobulbar block,
brachial plexus block, facet joint injection, and intercostal block.
This rare event can occur if drug is injected into a peripheral nerve
fascicle, "which topographically is an extension of the central
nervous system.12" Epidural spread has been reported
after brachial plexus blockade, intercostal blockade, segmental somatic
blocks and facet injections. It is not uncommon to get spread from sympathetic
blocks to adjacent somatic nerves.
Cephalad spread of spinal
or lumbar epidural anesthesia (LEA) can have unintentional consequences.
Interruption of the cardiac sympathetic fibers (T1 - T5) can result
in significant bradycardia and hypotension. With progression of the
block to the C3-5 nerve roots, phrenic nerve paralysis occurs and endotracheal
intubation with positive pressure ventilatory support is necessary.
Even without cephelad spread, hypotension can result from blockade of
sympathetic outflow in the splanchnic distribution. Treatment of hypotension
should include administration of fluids, vasopressors, and elevation
of the legs.
Unintended spread can be
disastrous if a neurolytic agent is used or planned. Abram12
states, "If a diagnosis of a pain mechanism is made on the basis
of a block that is in fact more extensive than believed, inappropriate
therapeutic procedures might be performed, including surgical ablations.
This concern should encourage the use of small volumes when blocks are
done for diagnosis," and when performing a chemical neurolysis.
Cardiovascular and respiratory
complications, unique to epidural anesthesia result from unintentional
injection of local anesthetic into an epidural vein or the subarachnoid
space. One method of ruling out intravascular injection is the administration
of 15 mcg of epinephrine with the local anesthetic solution, (e.g. 3
ml of 2% lidocaine, with 1:200,000 epinephrine). A 30% increase in the
pulse rate 20 seconds following injection confirms intravascular injection.13
Subarachnoid injection is confirmed if the 60 mg of lidocaine produces
rapid anesthesia, possibly up to the thoracic dermatomes.
An unusual cardiovascular
complication can occur with a right sided stellate ganglion block (SGB).
The heart is innervated via the cardiac plexus of nerves which are derived
from the cervical and upper thoracic sympathetic ganglion and vagal
branches. The sino-atrial node has dual innervation with sympathetic
fibers from the right stellate ganglion and parasympathetic innervation
via the vagus. Interruption of sympathetic outflow following a right
sided SGB may precipitate sinus arrhythmias or even transient sinus
arrest, especially if the patient stands up too quickly after the block.20
There is also some evidence that left sided SGB causes a partial sympathetic
dennervation of the left ventricular wall. This may lead to left ventricular
dysfunction which could be of particular significance in those patients
with pre-existing left ventricular disease. 21
PHARMACOLOGICAL
COMPLICATIONS
So far, we have discussed
complications that can arise from disruption of the psyche or the bodily
structure; the remaining major category of complication arises from
disruption of the biochemistry. All medications are associated with
complications; we will highlight some of the most important problems
associated with the more commonly used pain management medications.
Local
Anesthetics
Adverse reactions associated
with the use of local anesthetics include systemic toxicity, tissue
toxicity, and allergic reaction. Probably the most serious and frequent
complication is systemic toxicity which produces either central nervous
system or, more rarely, cardiovascular symptoms.22
The toxicity of local anesthetics
are a direct reflection of plasma concentration. Central nervous system
manifestations of toxicity are both drug and dose related. The common
complaints of lightheadedness, metallic taste, circumoral numbness,
and tinnitus occur at lower plasma levels (3-5 mcg/ml). Skeletal muscle
twitching involving the face or extremities (8 mcg/ml) or decreased
responsiveness can presage loss of consciousness and tonic-clonic convulsions
(10-12 mcg/ml).22,23 An important clinical caveat is that
both hypercarbia and acidemia decrease the seizure threshold, which
are important points to consider during resuscitation of an overdose.
Whenever significant amounts
of local anesthetics are being used in a regional procedure, EKG and
blood pressure monitoring are needed, resuscitation equipment should
be nearby, and intravenous access should be established prior to the
procedure.
Local anesthetics, through
inhibition of sodium channels, interfere with the electrical and mechanical
activity of the myocardium, and therefore, are direct myocardial depressants.
Excessive lidocaine plasma concentrations can prolong both the PR and
QRS intervals and cause profound hypotension. Following unintended intravenous
injection, and without prior symptoms of CNS toxicity, bupivacaine can
precipitate hypotension, cardiac dysrhythmias and atrioventricular heart
block.23 Bupivacaine toxicity appears to be particularly
profound during pregnancy or with hypoxemia, hypercarbia, or acidosis.
Bupivacaine avidly binds to the sodium channel receptor and only slowly
dissociates, resulting in persistent myocardial depression, which requires
prolonged resuscitation in the event of cardiac arrest. Bretylium is
the recommended agent for the treatment of ventricular tachycardia secondary
to bupivacaine toxicity. 13,22,23
The likelihood of toxicity
from local anesthetics varies according to the 1) the dose administered,
2) the vascularity of the injection site, 3) the use of epinephrine
with the local anesthetic, and 4) the choice of drug.23 Obviously,
it is most important to avoid intravascular injection; careful pre-injection
aspiration is essential. This is particularly important when performing
a stellate ganglion or interscalene block, when as little as 1-2 ml
of local anesthetic, if injected into the vertebral artery, can precipitate
a seizure. Significant serum levels of local anesthetic follow all regional
blocks with the highest levels obtained after intercostal blocks, intermediate
levels after epidural block, and the lowest levels after brachial plexus
blockade and subcutaneous administration.
Opiates
Clinically relevant side effects
that occur with acute or chronic administration of opiates include respiratory
depression, sedation, constipation, nausea and vomiting, pruritis, dry
mouth, sleep disturbance, hallucinations, difficult micturition, mood
changes, myoclonus, tolerance, physical dependence, and the potential
for addiction.24 We will briefly discuss the most important
of these side effects.
Respiratory depression is
certainly the most feared complication associated with the use of opiates.
The mechanism for respiratory depression is a direct effect on the brain
stem resulting in decreased ventilatory rate and tidal volumes in response
to increasing PaCO2.25 With chronic use, tolerance develops
to this side effect and apnea is rare. Of particular concern is the
delayed respiratory depression that can occur approximately 6 to 24
hours after the epidural administration of opiates.23 This
is dose dependent, and is more commonly associated with the hydrophilic
agents (morphine, hydromorphone) than the lipophilic ones (fentanyl,
sufentanil). Fortunately, the incidence of delayed respiratory depression
is relatively rare--approximately 1%.23
Sedation and impaired cognition
are also common side effect associated with the use of opioids. Tolerance
can also develop to this side effect. Occasionally we will add methylphenidate
to the drug regimen of patients on long term opiate therapy. This diminishes
sedation and can also enhance analgesia.
Opioids diminish peristaltic
activity in both the large and small intestines, increase the tone of
the pyloric and anal sphincters and the ileocecal valve.23
The result is constipation. Minimal tolerance develops to this side
effect, so it is imperative that the patient be placed on an appropriate
bowel regimen. Combinations of stool softeners or bulk laxatives together
with bowel stimulants are usually effective.
Nausea is a particularly
distressing side effect of the opioids. Stimulation of dopaminergic
receptors in the medullary chemoreceptor trigger zone is the primary
cause but vestibular stimulation and delayed gastric emptying can contribute
to the symptoms. Intravenous administration of opioids may produce less
nausea than intramuscular administration. Ambulation appears to increase
the incidence of nausea and vomiting. Continued use leads to tolerance,
but changing to another opiate can often decrease the side effects.
Mu receptor mediated histamine
release accounts for the pruritis associated with the opioids. Antihistamines
are beneficial. For pruritis precipitated by epidural morphine, small
doses of agonist-antagonists (e.g. nalbuphine) may be especially helpful.
Switching the epidural narcotic may also decrease the pruritis. True
allergic reactions to opioids appears to be a rare event.23,24
Central nervous system effects
include, but are not limited to euphoria, dysphoria, sedation, mood
changes and miosis.25 There are reports of convulsions with
high dose opiates, but no evidence of seizure activity is evident on
EEG.23 Normeperidine, the metabolite of meperidene, can produce
true seizure activity. Skeletal muscle rigidity and myoclonus are complications
associated with opioids, particularly after high dose intravenous fentanyl.23
Finally, sleep disturbance, visual hallucinations, and nightmares have
been reported, especially in the elderly. The treatment includes low
dose haloperidol and a change of opiate.24
Urinary urgency and retention
is associated with all routes of opiate administration. The reported
incidence of this side effect, following epidural administration of
opioids, is unclear, with estimates between 15 - 90%.14
Tolerance, physical dependence
and addiction are major concerns with long term opioid use. Although
the actual pathophysiological changes that occur are not clearly understood,
up-regulation of opioid receptors appears to play a major rule. Tolerance
is demonstrated by a need for ever escalating doses of drug to maintain
analgesia previously provided by lower doses. Tolerance can also occur
with the ventilatory depressant effects of opiates; however, miosis
and constipation seem to persist.
Physical dependence on opioids
is present if withdrawal symptoms appear with abrupt discontinuation
of the drug,. Withdrawal symptoms are reminiscent of an influenza infection
and consist of yawning, lacrimation, rhinorrhea, mydriasis, restlessness,
nausea, vomiting, diarrhea, backache, leg pain, and muscle cramps.
The word "addiction"
is often misused. It is clear that both tolerance and dependence can
be present without the patient being addicted. Most patients with unremitting
and incapacitating chronic pain, who are dependent on opioid analgesia,
fit this picture. Addiction is defined as loss of control, compulsive
use, and continued use of a drug in spite of adverse consequences. Without
coexisting psychopathology or a prior history of addiction problems,
opiate addiction in the context of pain management is rare. Nevertheless,
coexisting psychopathology in the pain clinic population is not rare;
therefore, it is valuable to monitor patients for evidence of functional
improvement and treatment compliance. Lack of compliance or improvement
are indications for a psychological assessment, and it may be appropriate
to consider non-narcotic treatment modalities. Should a patient require
withdrawal from an opioid analgesic, a rational approach would be to
decrease the dose by approximately 10% every 24 - 72 hours; however
it is often necessary to individually tailor this regimen.
Neurolytic
Agents
Neurolytic agents can be extremely
useful in the treatment of intractable, chronic pain, refractory to
other treatment modalities. Although there are several agents available,
alcohol and phenol are the most widely used. Alcohol, the classic agent,
used in concentrations from 50 to 95 % causes extraction of cholesterol,
phospholipid and cerebroside, and causes precipitation of liposomes
and mucuproteins. Phenol, on the other hand, causes protein denaturation.
Both agents can cause wallerian degeneration. Complications that occur
with the use of these agents include:
1) damage to peripheral nerves,
2) spread to neuraxial structures, 3) local tissue effects, and 4) systemic
effects.12,26
Examples of peripheral nerve
damage that can occur include inadvertent spread of neurolytic agent
to 1) the facial nerve during trigeminal block, 2) the glossopharyngeal
nerve during gasserian ganglion block, 3) the brachial plexus during
stellate ganglion block, and 4) the somatic nerve roots during celiac
plexus, splanchnic or lumbar sympathetic blocks.12 Careful
placement of the needle and utilization of fluoroscopic guidance, together
with the use of small volumes of neurolytic drug, can minimize these
problems. Even with correct needle placement, peripheral neurolytic
blockade can cause neuropathic pain such as neuritis and anesthesia
dolorosa. Local tissue effects can include pain, swelling, cellulitis
and abscess formation at the site of injection. Tissue damage can be
minimized if the needle is flushed with local anesthetic prior to it's
removal during neurolytic procedures. The consequences of spread of
a neurolytic agent to the neuraxial structures can include loss of sensation,
motor blockade, loss of bowel and bladder function, paraplegia and even
death.12
Inebriation and sedation
will result from an inadvertent intravascular injection of 50 ml. of
50% alcohol. This is usually of no consequence except in the patient
taking disulfiram (antabuse). Intravascular injection of phenol, on
the other hand, is a more serious matter. Mild symptoms include tinnitus
and flushing, but seizures, loss of consciousness, and hypotension can
also occur.12
Corticosteroids
Pain states amenable to corticosteroid
treatment include the pain of bone cancer, visceral and neuropathic
pain, spinal cord compression, brain metastasis, reflex sympathetic
dystrophy, post-herpetic and post-traumatic neuralgias, and radicular
pain associated with herniated discs or spinal stenosis.27
The side effect profile of
corticosteroids is dependent on the duration of treatment. Short-term
use has been associated with reversible symptoms of hypertension, hyperglycemia,
gastrointestinal bleed, glaucoma, hypokalemic alkalosis, mood disorders,
psychotic reactions, pancreatitis, proximal myopathy, and sodium and
water retention. Long-term adverse effects include amenorrhea, aseptic
necrosis of bone, cataracts, cushingoid appearance, hypothalamic-pituitary
axis suppression, hyperlipidemia, hypertension, mood disorders, muscle
weakness and osteoporosis.27,28
No matter what the route
of administration, side effects can occur. Even the epidural administration
of corticosteroids is not without systemic effects. Cushing's syndrome,
congestive heart failure and adrenal suppression have all been reported
to occur.29 Hyperglycemia is certainly a risk in the insulin
dependent diabetic.30 Hypothalamic- pituitary axis suppression
has been reported to persist for up to 5 weeks following three weekly
injections of epidural triamcinolone 80 mg.31
Nonsteroidal
Anti-inflammatory Drugs
Nonsteroidal anti-inflammatory
drugs (NSAIDs) are valuable analgesics. There is evidence that they
have direct antinociceptive properties distinct from their anti-inflammatory
effects. These drugs do not produce alterations in cognitive functions,
respiratory depression, pruritis, or nausea. Nevertheless, the NSAIDs
are associated with significant side effects, especially with long-term
use. In particular, the elderly have reduced renal clearance of NSAIDs,
and require appropriately reduced doses.32
NSAIDs inhibit the formation
of thromboxane A2 and prostaglandin endoperoxides which are necessary
for platelet aggregation. Bleeding times do increase, but generally
remain below the normal, reference, upper limits. With most NSAIDs,
these effects last only until the drug has been eliminated (1-2 days);
however, aspirin produces prolonged effects of 7-10 days. Regarding
perioperative blood loss, well controlled studies have not clearly demonstrated
increased losses; however, some concern remains regarding this potential
problem.33,34 Regarding wound healing, there is some evidence
for impairment of healing of intestinal anastomoses; but no effect or
even mildly beneficial effects have been documented on corneal wound
healing. Little or no effect of nonsteroidals have been demonstrated
on bone remodelling.33
In hypovolemic patients,
or other patients with reduced renal blood flow, prostaglandins appear
to be important mediators of vasodilation and maintenance of renal perfusion.
In this setting, NSAIDs may decrease the glomerular filtration rate
and result in release of renin from the juxtaglomerular cells, resulting
in a further reduction in renal blood flow and function. This does not
appear to be a clinically significant danger in the relatively healthy
postoperative patient; however, considerable caution must be used when
giving NSAIDs to patients with congestive heart failure, renal insufficiency,
cirrhosis, or other patients with potentially impaired renal perfusion.
For these patients, NSAIDs should only be used together with careful
monitoring of renal function and serum electrolytes.33
Blockade of the cyclo-oxygenase
pathway may lead to the shunting of more arachidonic acid to the lipooxygenase
pathway, where it is converted to leukotrines and slow reacting substances
of anaphylaxis, thereby increasing the risk of an asthmatic episode
in susceptible patients.33
Prostaglandins support gastric
mucosal integrity by inhibiting gastric acid secretion via blockade
of histamine activation of parietal cells, and by other cytoprotective
mechanisms. NSAIDs produce gastroduodenal damage by local irritation
and by inhibiting the production of the protective prostaglandins. Long
term treatment with NSAIDs, increases the risk of serious gastroduodenal
complications 3-fold, and this worsens with age. Short term treatment
with NSAIDs does produce endoscopically detectable mucosal lesions,
but not a clinically significant risk of bleeding or perforation. The
risks of NSAID treatment, even short term, for patients with prior histories
ulcer disease is unknown, and usually considered contraindicated.34,35,36
All NSAIDs are approximately,
equally efficacious, though individuals show considerable variation
of response. There may be some differences in the side effects of the
NSAIDs, but these differences are not well established. Relatively weak
platelet inhibition is seen with choline magnesium trisalicylate, salsalate,
and nabumetone; therefore, these drugs may be cause less alteration
of hemostasis and less gastrointestinal bleeding.33,34 Nabumetone
is not active until after first pass metabolism, and therefore appears
to be associated with less gastric mucosal injury.35
Acetaminophen
Acetaminophen is an analgesic
of equipotency to aspirin, but free of hematologic or ulcerogenic side
effects. The analgesic effect reaches a ceiling at a dose of 1 g. Acetaminophen
is the preferred analgesic in children because of the lack of association
with Reye's Syndrome. Large doses of acetaminophen, 15 g as a single
dose, or chronically more that 5 g per day, may cause severe liver damage
and death. Malnourished or chronic alcohol abusing patients may be particularly
susceptible to toxic hepatic injury. There is also some evidence of
risk of renal injury with chronic use.37
Antidepressant
Medications
There is considerable evidence
that the tricyclic antidepressants are effective for the treatment of
a variety of pain conditions, such as migraine headaches and neuropathic
pain. The practitioner should be aware of the potential risks and side
effects of these drugs. Most of the side effects can be attributed to
the anticholinergic, antihistaminic, anti-alpha-adrenergic, and quinidine-like
effects of the tricyclics. Except for the cardiac, quinidine-like effects,
most the other side effects are less prominent with nortriptyline and
desipramine.38 In the elderly, dose escalation should be
slower and stop earlier. In this population, we typically use nortriptyline
rather than amitriptyline, imipramine, or doxepin.
It is relatively easy to
achieve a lethal overdose with the tricyclic antidepressants. The average
lethal dose is 30 mg/kg in healthy adults, and 20 mg/kg in children.38
Toxic plasma levels can also
occur secondary to drug interactions. Levels are increased by the selective
serotonin reuptake inhibitors (SSRIs), especially fluoxetine and paroxetine.
Neuroleptics, cimetidine, methylphenidate, and estrogens may all increase
TCA plasma levels. The level of phenytoin may be increased by TCAs.
Clonidine may be a less effective antihypertensive when coadministered
with TCAs. TCAs should not be given to patients taking monoamine oxidase
inhibitors (MAOIs); potentially fatal complications can result. Additive
side effects can occur with administration with alcohol, sedatives,
or other anticholinergics. Co-administration with sympathomimetics may
produce hypertension and hyperpyrexia.38,39
Cardiovascular side effects
include sinus tachycardia and conduction changes with potential for
AV or bundle branch blocks, or re-entrant excitation. Marked postural
hypotension may occur in 20% of patients and is a particular problem
in the elderly.
Other fairly common problems
include: constipation, weight gain, dry mouth, and sedation.38,39
Anticonvulsants
Anticonvulsants are extensively
used adjunctive analgesics for central or peripheral neuropathic pain.
The most commonly used drugs are phenytoin, carbamazepine, valproic
acid, clonazepam, and most recently, gabapentin.
Carbamazepine: CNS
side effects include sedation, headache, impairment of cognitive learning,
and visual changes. Other side effects include nausea, vomiting, rash,
thrombocytopenia (reversible), and mild leukopenia (which does not require
discontinuing treatment). There are rare, but potentially fatal complications,
including agranulocytosis, aplastic anemia, Stevens-Johnson syndrome,
cardiac toxicity, hyponatremia, and hepatotoxicity. Carbamazepine is
chemically similar to the TCAs, and may produce additive side effects.
Of note, is that propoxyphene may increase carbamazepine plasma levels.
Appropriate monitoring of drug levels, liver functions, and CBC is necessary.40
Phenytoin: Side effects
include rash and nystagmus (usually at the upper end of the therapeutic
range of serum concentrations). Above 20 mcg/ml the patient may experience
symptoms of drowsiness, ataxia, and diplopia. With long term use there
are risks of gingival hyperplasia, facial coarsening, and hirsutism.
Serious complications, including hepatitis, are rare. Appropriate monitoring
of drug levels, liver functions, and CBC is necessary.40
Valproate (valproic acid):
Side effects include mild drowsiness, nausea, weight gain, tremor, menstrual
disturbances, and dose-related thrombocytopenia. Serious, but rare complications
include liver failure, pancreatitis, and interstitial nephritis.40
Clonazepam: The side
effects of clonazepam are similar to other benzodiazepines, and include
sedation, ataxia, and cognitive impairment.40
Gabapentin: This drug
is not metabolized by the liver, and is primarily excreted by the kidneys.
It does not affect the metabolism of other anticonvulsants or the tricyclic
antidepressants. Side effects are usually mild and include sedation,
dizziness, ataxia, and nystagmus. No special laboratory monitoring is
required.40
CONCLUSION
Efforts to understand pain
require serious attempts to grapple with the intertwining of psyche
and soma. It is impossible to treat either one without affecting the
other. Knowledge of the full variety of psychological, procedural, and
pharmacological complications is necessary if we hope to anticipate
and side-step the hazards that are inherent in our treatments.
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