transcript
- 1. 1 CHAPTER 1 POSTOPERATIVE ANALGESIA FOR THORACOTOMY
PATIENTS: A CURRENT REVIEW PETER H. NORMAN, MD, FRCPC M. DENISE
DALEY, MD, FRCPC ALICIA KOWALSKI, MD It is natural to want to
relieve pain and suffering. None are more aware of this than those
professionals who have devoted their lives to the provision of
anesthesia, yet we have often been prevented from alleviating pain
by not understanding its pathogenesis or by a lack of appropriate
tools to deal with it. Intraoperative pain is now only of historic
concern. It is our fervent hope that postoperative pain will follow
intraoperative pain into the history books. Not so long ago,
certainly within the professional experience of some of us, a
minimalist approach was taken to the management of pain after
thoracic surgery. Anesthesiology residents and faculty alike were
admon- ished to keep total opioid dosage low so the patient would
want to breathe after surgery. During this era, the classic
thoracotomy patient would be nearly apneic from pain in the
postanesthesia care unit. Hypoxic and hypercarbic, diaphoretic and
hypertensive, patients would gradually improve to the point at
which they could actually breathe and complain of pain only after
large doses of opioids. Frequent arterial blood gas analy- ses
often demonstrated the unusual observation that the administration
of opioids led to a decrease in carbon dioxide tension and an
increase in oxygen tension in this setting. In 1973 Gibbons and
colleagues suggested that thoracic epidural blockade was the
treatment of choice for relief of pain after a chest injury.1 The
major limitation was sympathetic blockade causing hypotension. To
prevent this complication, they advocated intercostal blockade for
fractures at or above the fifth rib. The modern era of pain
management after thoracic surgery began with the introduction of
epidural narcotic tech- niques for post-thoracotomy pain.2,3 Soon
continuous infusions were advocated,4 and the effect of better
postop- erative analgesia on pulmonary function was investigated.5
This led to an increased ability to control post-thoraco- tomy pain
and also stimulated the overall interest in find- ing other useful
modalities for post-thoracotomy pain relief. Older or abandoned
techniques were investigated with renewed interest and used singly
or in combinations. For at least the past 10 years, the immediate
postopera- tive pain of most thoracotomy patients has been well
handled. There are occasional patients whose pain is diffi- cult to
manage because of coexisting disease processes that contraindicate
epidural analgesia, anatomic factors, and/or pre-existing chronic
pain, but currently there are techniques to help even these
patients. As an uninten- tional consequence of relieving the
severe, acute incisional pain of surgery, we may have unmasked
other sources of equally troubling pain such as referred pain and
sympa- thetically mediated pain. Much research is focused on
treating these new modalities. This unbundling of post- operative
pain has been termed disaggregation.6 Another area of increasing
interest is the pathogenesis of chronic postoperative pain. Whether
we can affect or even prevent this unhappy outcome remains to be
seen. Post-Thoracotomy Pain Acute Pain Pain in the first few weeks
after a thoracotomy arises from a variety of different mechanisms.
The best charac- terized mechanism is somatic pain, which is
localized to the area around the incision and chest tube
insertion
- 2. sites. It is produced by direct injury to the skin and
underlying subcutaneous tissues, fasciae, ligaments, muscles, and
ribs. Damaged tissue releases a variety of algesic substances,
including substance P, prostaglandins, and serotonin, which
stimulate the peripheral nerve endings.7 Intercostal nerves from
the area conduct these pain impulses to the spinal cord and thence
to the brain via the spinothalamic and spinoreticular tracts.
Somatic pain is responsible for the sharp, severe postoperative
pain that is exacerbated by movement and is believed to be
primarily mediated by type A delta nerve fibers.8 Visceral, or
nonincisional, pain is responsible for the dull, nauseating,
diffuse thoracic wall aching sensation expe- rienced after a
thoracotomy. It is mediated by type C nerve fibers, which travel
with the autonomic nerves. Both the vagus and sympathetic nerves
probably contribute to this type of pain.8 Another form of pain
frequently reported in post- thoracotomy patients is localized to
the ipsilateral shoul- der region. Although it is often moderate to
severe in intensity and present in 75 to 85% of patients who have
had a thoracotomy,911 this type of pain has received little
attention in the literature. It has been attributed to a vari- ety
of factors, including distraction of the posterior thoracic
ligaments or shoulder joint due to patient posi- tioning;
stretching of the brachial plexus, also as a conse- quence of
intraoperative positioning; transection of a major bronchus; and
referred pain from the phrenic nerve.9 As the latter provides
sensory innervation to the pericardium and pleura, mechanical
trauma to these regions during surgery and irritation of the
pleural surfaces by chest tubes postoperatively can result in
phrenic nerve stimulation, with referral to the shoulder. Scawn and
colleagues have demonstrated a reduction in the incidence of
post-thoracotomy shoulder pain from 85 to 33% with the injection of
10 mL of 1% lidocaine into the periphrenic fat at the level of the
diaphragm.9 In this same study, there was a small but insignificant
increase in arterial partial pressure of carbon dioxide (PaCO2) in
the first 2 postoperative hours in patients receiving a phrenic
nerve block, thereby suggesting the possibility of diaphragmatic
paresis. The technique may thus be inappropriate in patients with
severely compro- mised respiratory function. The lack of efficacy
of supras- capular nerve blockade in relieving post-thoracotomy
shoulder pain demonstrated by Tan and colleagues provides further
evidence that distraction of the shoulder joint does not play a
major role in the generation of this type of pain.11 The extent to
which the surgical approach contributes to the severity of
post-thoracotomy pain is unclear. Anteroaxillary and anterior
limited thoracotomies are less painful procedures than are
posterolateral thoraco- tomies.12,13 When muscle-sparing
thoracotomies have been compared with traditional posterolateral
thoraco- tomies (involving a transection of the latissimus dorsi
muscle), some studies have demonstrated less postopera- tive pain
with the former,14 whereas others have revealed no difference
between the two techniques.15,16 It is well appreciated that
thoracoscopic procedures result in less pain than do traditional
thoracotomies in the early post- operative period, but Nomori and
colleagues have demonstrated this benefit to be lost by 14 days
after surgery.17 The lack of a consistent and/or persistent
decrease in post-thoracotomy pain with less extensive surgical
incisions provides further evidence that the actual surgical
incision is just one of several mechanisms responsible for
post-thoracotomy pain. Chronic Pain Post-thoracotomy pain syndrome
is defined as pain that recurs or persists along a thoracotomy scar
at least two months following the surgical procedure.18 There is
usually tenderness, sensory loss, and absence of sweating along the
thoracotomy scar.18 The incidence is variable, ranging from 2 to
67%.19 Dajczman and colleagues stud- ied 59 of 206 sequential
patients who had undergone a unilateral thoracotomy; all procedures
were performed by one surgeon over a period of 5 years.20 Thirty to
73% of the patients available for evaluation were experiencing pain
(Table 1-1), which most rated at a visual analog scale (VAS) of two
to four (Figure 1-1). These results were confirmed by Perttunen and
colleagues,21 who found an incidence of post-thoracotomy pain of
80% at 3 months, 75% at 6 months, and 61% after 1 year. More than
50% of these patients had limitations of their activities of daily
living imposed by the chronic pain. There was also a 3 to 5%
incidence of severe pain. Intriguingly, early consumption of larger
quantities of nonsteroidal anti-inflammatory drugs (NSAIDs) was
associated with an increased incidence of long-term prob- lems. As
suggested by Perttunen and colleagues, this could 2 / Advanced
Therapy in Thoracic Surgery TABLE 1-1. Frequency of
Post-Thoracotomy Pain at Various Intervals following Surgery Time
since No. of Total No. of Percentage of Thoracotomy Patients
Patients Evaluable (yr) with Pain Evaluable Patients with Pain 1* 6
12 50 12 11 15 73 23 7 13 54 34 3 6 50 45 3 10 30 Total 30 56
Adapted from Dajczman E et al.20 *At least 2 months
post-thoracotomy.
- 3. imply that patients with more severe acute postoperative
pain have a greater likelihood of developing chronic pain;
alternatively, it may just imply that patients with a lower pain
threshold are more likely to develop chronic pain. A study by Katz
and colleagues also suggested that increased postoperative pain
intensity at 24 and 48 hours predicted the later development of
chronic pain.22 Better pain relief may not be the only factor and,
in fact, may negatively affect outcome. Although the study was only
carried out to 12 days, Nomori and colleagues found that continuing
epidural analgesia beyond 3 postoperative days led to a rebound
increase in pain when the epidural was removed, such that the
prolonged epidural group had more pain on postoperative days 8 and
9.23 Video-assisted thoracotomy is not a panacea. Although the
acute pain experienced is less, the pain still present from
video-assisted thoracotomy after 1 year (Tables 1-2 and 1-3) is
indistinguishable from that result- ing from conventional
thoracotomy.24 Much work remains to be done, and it is not possible
to predict whether any analgesic approach or combina- tion of
approaches will lessen the development of post- thoracotomy pain
syndrome. Systemic Analgesia Opioids Opioids have been the mainstay
of pain relief for thou- sands of years but were restricted to oral
or inhalation use until the invention of hollow needles by
Alexander Wood in 1853. Intravenous use was employed only in the
operating room until the development of syringe pumps and
patient-controlled systems, giving rise to patient- controlled
analgesia (PCA). From its modest beginnings, PCA has evolved from a
specialized tool of pain special- ists into a routine modality
employed by any surgeon. PCA has also allowed the use of
shorter-acting agents that must be given by continuous infusion
owing to their evanescent action, such as fentanyl, sufentanil, and
remifentanil. Because of the extreme potency of the latter, it
should probably be restricted to perioperative use by an anesthesia
provider. Oral opioids are still very much a part of perioperative
analgesia because most patients are discharged on them and then
maintained on them for months. The past 10 years has seen a
decreasing reluctance to employ stronger opioids such as oxycodone,
hydromorphone, and methadone out of hospital. Typical conversion
ratios are given in Table 1-4. Some novel delivery systems should
be mentioned. Highly lipid-soluble opioids may be absorbed directly
across the skin or mucous membranes. Currently only fentanyl is
used for direct transfer across the skin (Duragesic, Alza
Corporation, Palo Alto, CA). Through the incorporation of a
rate-limiting membrane, the Postoperative Analgesia for Thoracotomy
Patients: A Current Review / 3 FIGURE 1-1. The distribution of
visual analog scale (VAS) scores among patients reporting pain.
Most patients chose a VAS of four or less. Reproduced with
permission from Dajczman E et al.20 0 2 4 6 8 10 0-1 1-2 2-3 3-4
4-5 5-6 6-7 7-8 8-9 9-10 VAS NumberofPatients TABLE 1-2. Chronic
Postoperative Pain Dysfunction Less Than 1 Year after VATS or
Conventional Thoracotomy VATS Thoracotomy p Value Pain 30% 44% .03
Pain scale (05) 1.2 2.2 .01 Pain treatment 11% 18% NS Function 10%
26% .001 Adapted from Landreneau RJ et al.24 NS = not significant;
VATS = video-assisted thoracic surgery. TABLE 1-3. Chronic
Postoperative Pain/Dysfunction More Than 1 Year after VATS or
Conventional Thoracotomy VATS Thoracotomy p Value Pain 22% 29% NS
Pain scale (05) 1.0 1.7 NS Pain treatment 6% 16% NS Function 14%
15% NS Adapted from Landreneau RJ et al.24 NS = not significant;
VATS = video-assisted thoracic surgery. TABLE 1-4. Conversion Table
for Opioids* Opioid IV/SQ Opioid to IV/SQ Morphine IV/SQ Morphine
to IV/SQ Opioid Oral Opioid to Oral Morphine Oral Morphine to Oral
Opioid Hydromorphone 5 0.2 5 0.2 Meperidine 0.13 8 0.1 10 Oxycodone
1.5 0.7 Hydrocodone 0.5 2 Adapted with permission from Cancer Pain
Guideline: M. D. Anderson Cancer Center internal document, 1994.
*Oral morphine to intravenous/subcutaneous (IV/SQ) morphine, divide
by 3; IV/SC morphine to oral morphine, multiply by 3.
- 4. influence of the variable permeability of the skin is
decreased. Nevertheless, there is a significant variability in the
systemic drug levels and analgesic effects. As well, there is an
accumulation of fentanyl under the patch, providing appreciable
serum levels for up to 24 hours after patch removal.25 Because of
the possibility of apnea owing to high serum levels in opioid-naive
patients,26 transdermal fentanyl is not currently recommended for
acute postoperative pain. One approach that may permit its use in
the future is to combine a low-dose transder- mal fentanyl patch
with an NSAID.27 Another possibility is to add electrical control
to enhance the rate of fentanyl absorption across the skin. This
iontophoretic route of administration is currently experimental but
may offer the possibility of patient-controlled transder- mal
fentanyl in the future.28 Fentanyl can be delivered across the
mucous mem- branes of the mouth. Oral transmucosal fentanyl citrate
(OTFC, Actiq Abbott Laboratories, Abbott Park, IL) has been used
for breakthrough chronic cancer pain as well as acute postoperative
pain.29,30 It would be a good choice if the intravenous route was
temporarily unavailable for acute postoperative analgesia.
Fentanyl, sufentanil, butor- phanol, heroin, oxycodone, and
meperidine have been administered through the nasal mucosa, and
morphine, codeine, fentanyl, heroin, and hydromorphone have been
administered by inhalation.31 Ketamine Ketamine is a phencyclidine
derivative occasionally employed as an anesthetic induction agent.
Uniquely among induction agents, it produces what has been termed
dissociative anesthesia. The analgesia does outlast the anesthetic
effects and occurs at lower serum levels, so it can be useful in a
decreased dosage as a postoperative anal- gesic. Ketamine may be
given by intravenous, subcuta- neous, epidural (see below), oral,
and transdermal routes.32 Ketamine produces analgesia by multiple
mecha- nisms, including inhibition of N-methyl-D-aspartate (NMDA)
receptors, depression of the thalamus while activating the limbic
system, and direct spinal effects. NMDA receptors are involved in
hyperalgesia or neuro- pathic pain, which suggests that ketamine
would be a good choice for analgesia for these patients.33 A recent
study in rats demonstrated that ketamine had different mechanisms
of action depending on the presence or absence of inflammation.
Antinociceptive effects were created by activation of the
monoaminergic descending inhibitory system, whereas in a
hyperalgesic state induced by inflammation, inhibition of NMDA
activa- tion was the likely mechanism of the antihyperalgesia.34
Ketamine is a useful agent when narcotics and neurax- ial agents
are contraindicated or working poorly. Chow and colleagues
described a patient undergoing multiple thoracotomies whose pain
management was complicated by infection and the development of
neuropathic pain.35 Low-dose ketamine was used to decrease the need
for narcotics after his fourth thoracotomy, with good results. It
has also been suggested that ketamine should have pre- emptive
effects because of its action at NMDA receptors. A landmark study
in cholecystectomy patients found less postoperative pain, as
measured by VAS scores and morphine consumption, in the group given
low-dose intraoperative ketamine.36 An alternative explanation for
the observed improved analgesia is that ketamine prevents the
development of acute tolerance to opioids.37 Nonsteroidal
Anti-inflammatory Drugs NSAIDs have proven to be a useful component
of postop- erative pain relief. Many oral NSAIDs have been used
including ibuprofen, naproxen, and ketoprofen. The only currently
available parenteral NSAID is ketorolac tromethamine (Toradol,
Roche Laboratories, Nutley, NJ). The addition of ketorolac to a
patient-controlled epidural analgesia (PCEA) regimen employing
hydromorphone alone significantly decreased the incidence of
noninci- sional pain.38 Ketorolac is also employed in the treatment
of breakthrough pain with otherwise satisfactory epidural
analgesia. Ketorolac has several other features that make it useful
in postoperative thoracotomy patients. These include its moderate
potency (equivalent to morphine in some studies39 ); ease of
administration by the intravenous and intramuscular routes; lack of
acute tolerance, which may occur with even a single dose of
opioid40 ; and lack of significant cardiorespiratory or central
nervous system side effects. NSAIDs inhibit cyclooxygenase (COX),
the enzyme that regulates the conversion of arachidonic acid to
prostaglandins. There are two isoenzyme forms of COX. COX-1 is
always present (constitutive). It modulates platelet activity and
gastrointestinal cytoprotection and is involved in maintaining
renal function in hypo- volemic states. COX-2 is thought to be
inducible by inflammatory stimuli and is involved with inflamma-
tion and pain. Conventional NSAIDs, such as indomethacin and
ketorolac, which inhibit both COX-1 and COX-2, have been implicated
in postoperative bleeding and gastric ulceration. They also may
predis- pose to renal failure if the patient is concomitantly hypo-
volemic or even just relatively dry, as post-thoracotomy patients
often are. Specific inhibitors of COX-2 were developed in an
attempt to prevent the side effects of conventional NSAIDs while
maintaining the benefits. Current selective COX-2 inhibitors still
exhibit some predilection for causing renal failure and gastric
ulcera- tion but debatably to a lesser extent than conventional, 4
/ Advanced Therapy in Thoracic Surgery
- 5. nonselective NSAIDs.4143 The selective COX-2 inhibitors do
not affect platelet function and have not been shown to increase
postoperative blood loss. As a result they can be used
perioperatively with relative impunity from hemorrhage. As of this
writing, there is no parenteral COX-2 inhibitor available, although
one is in US Food and Drug Administration trials. Regional
Analgesia Techniques In the past two decades, regional analgesia
techniques have become the primary means of providing optimal pain
relief after a thoracotomy. Although the type C nerve fibers
responsible for autonomically mediated visceral pain have abundant
opioid receptors, type A delta nerve fibers, which mediate somatic
incisional pain, contain a paucity of these receptors.44
Accordingly, systemically administered opioids have limited
efficacy in controlling acute post-thoracotomy pain, especially
that associated with activity. In contrast, local anesthetics,
which are an integral component of most regional anal- gesia
techniques, are very effective in blocking conduc- tion in both
type A delta and C nerve fibers. The main blocks used for
thoracotomy patients are intercostal nerve blocks, interpleural
analgesia, thoracic paravertebral nerve blocks (TPVBs), and
epidural analge- sia. Characteristics of these blocks are
summarized in Table 1-5. Each may be performed as a single
injection through a needle, but owing to the prolonged period of
substantial pain experienced after a thoracotomy, catheter
techniques are used more commonly (with the possible exception of
intercostal nerve blocks, as discussed below). A standard 18- or
20-gauge epidural catheter may be placed through a hollow needle
into the appropriate area for each block, and analgesic medication
is administered through this catheter either as intermittent
boluses or a continuous infusion. The former has the disadvantage
of supplying fluctuating levels of analgesic in the area of the
block and thus providing varying degrees of pain relief for the
patient. The latter has the disadvantages of providing more
analgesic than is necessary during periods of less painful
stimulation, and promoting the accumulation of analgesic medication
over time,45 unless appropriate decrements in infusion rates are
made. With the goal of minimizing the disadvantages of both
methods, low continuous (basal) infusion rates have been combined
with intermittent boluses administered on an as-needed basis (which
is usually patient controlled). Regional analgesia use in
thoracotomies has several unique features compared with use in
other types of surgery. First, all techniques except epidurals may
be performed under direct vision from an internal approach before
the chest is closed. This not only increases the ease with which
the blocks are performed, but may also improve their success rate
when compared with blocks performed via percutaneous techniques
(although no studies have directly addressed this issue). As well,
the risk of developing a pneumothorax, which is a potentially
limiting factor for intercostal nerve blocks and interpleural
analgesia, is irrele- vant because the thoracic cavity is open
intraoperatively and chest tubes are used postoperatively. Finally,
hypov- olemia is a relatively common occurrence in patients after
thoracotomy because extensive fluid administration has been
implicated in the development of postoperative pulmonary edema,
especially after pneumonectomy.46 Therefore, regional analgesia
techniques producing exten- sive blockade of the sympathetic
nervous system and peripheral vasodilation may be accompanied by a
signifi- cant risk of hypotension, and are often avoided.
Postoperative Analgesia for Thoracotomy Patients: A Current Review
/ 5 TABLE 1-5. Summary of Factors Related to Regional Analgesia
Techniques* Technique Ease of Analgesic Preservation Modification
Hypotension Motor Blockade Urinary Retention Respiratory Insertion
Efficacy of Pulmonary of Stress Depression Function Response
Intercostal nerve blocks +++ + + Interpleural analgesia ++++
Thoracic paravertebral block ++ + ++ + Epidural analgesia ++ + + ++
= not a factor; = sometimes a factor; + to ++++ = degrees of being
somewhat a factor to being an important factor. *For
post-thoracotomy pain. With opioid/low-dose local anesthetic
infusions.
- 6. Of the four types of regional analgesia discussed in this
chapter, epidural analgesia is the only technique for which agents
other than local anesthetics have been successfully used. This is
not surprising because the intercostal nerve block, interpleural
analgesia, and paravertebral nerve block techniques depend
primarily on blocking impulse transmission within somatic nerves.
By contrast, blockade of pain pathways within the spinal cord may
be accomplished by other drugs, most commonly opioids, delivered
into the epidural space. Although several local anesthetic agents
are available, bupivacaine has been the most popular choice for
post- thoracotomy blocks over the past couple of decades, primarily
because of its prolonged duration of action. Concentrations of 0.25
to 0.5% are necessary to provide adequate sensory blockade with
most of the blocks discussed below, although lower concentrations
have been used in the epidural space, when combined with opioids.
Since its release in 1996, ropivacaine has been used increasingly
for a variety of intraoperative and postopera- tive situations, and
although the current literature regard- ing post-thoracotomy
regional analgesia focuses on bupivacaine, ropivacaine will
probably play a major role in clinical practice and the literature
in the future. It is an amide local anesthetic structurally similar
to bupivacaine that has the unique quality of being supplied as the
pure S-()-enantiomer. This contrasts with the other local
anesthetics, which exist as racemic mixtures of both the R-(+)- and
S-()-enantiomers. Consequently, ropiva- caine produces less
cardiovascular and central nervous system toxicity,47,48 similar
analgesia, and a less intense and shorter duration of motor
blockade than does bupiva- caine when administered into the
epidural space.49,50 Low concentrations of epinephrine
(1:100,0001:400,000) are frequently added to the solu- tion used
for the regional analgesia techniques to decrease the quantity of
medication absorbed into the systemic circulation. This should
extend the duration and possibly improve the degree of analgesia,
and decrease the risk of systemic toxicity from the drug. Lower
peak plasma concentrations have been convincingly demonstrated when
epinephrine has been added to the solutions used in intercostal
nerve blocks,51 interpleural analgesia,52 and epidural
analgesia,53,54 but data regarding the duration and quality of
analgesia and systemic toxicity are more vari- able. There is even
evidence that the addition of epineph- rine to epidural opioid
solutions may increase the incidence of some opioid-related side
effects, especially pruritus.5557 Epinephrine may also directly
contribute to the pain relief achieved with epidural analgesic
techniques by stimulation of 2-adrenergic receptors in the dorsal
horn of the spinal cord.58 Ultralong-acting local anesthetics and
opioids cur- rently under development have been advocated as a
means of providing prolonged analgesia from a single dose. However,
their eventual role in the management of acute post-thoracotomy
pain is unclear because prolon- gation of analgesic effects is
accompanied by a prolonga- tion of the duration of adverse events,
which has particular relevance in the case of life-threatening
cardio- vascular and respiratory depression. Despite their apparent
usefulness in post-thoracotomy patients, regional analgesia
techniques are not appropriate for all individuals. Absolute
contraindications for all types of regional analgesia include
patient refusal, an allergy to the medication to be used, a lack of
resuscitative equip- ment, a lack of ability to use the
resuscitative equipment, and an infection or tumor at the site of
injection. Relative contraindications are often specific for the
type of block and are discussed below for the individual
techniques. Knowledge of the contraindications may be critical in
choosing the specific block for a particular patient. Intercostal
Nerve Block definition and technique Intercostal nerve block is a
technique in which a local anesthetic is injected into the
immediate vicinity of the intercostal nerve as it lies in the
costal groove on the internal surface of the rib. In this position,
the intercostal nerve traverses between the internal intercostal
and inter- costalis intimus muscles and is located just caudad to
the intercostal artery and vein. Local anesthetic is injected 7 to
8 cm from the posterior midline, proximal to the origin of the
lateral cutaneous branch in the midaxillary line.59 Because there
is a considerable overlap of sensory innervation of the thoracic
dermatomes, it is necessary to block at least one level above and
below the desired dermatomal level. Intercostal nerve blocks are
often performed by a single-shot injection through a needle. There
is limited spread of local anesthetic from one intercostal space to
the next; therefore, separate injections at each level are usually
necessary. For posterolateral thoracotomy inci- sions, intercostal
nerve blocks are usually performed at T3 to T7. Three to 5 mL of
local anesthetic is adminis- tered with each block; thus, a total
of 20 to 25 mL of local anesthetic is used. Analgesia persists for
5 to 12 hours after a single injection,6063 and intercostal nerve
blocks may be repeated as necessary. A variety of catheter tech-
niques have also been described,62,64,65 although most of these
studies involved the use of more than one catheter, which creates a
cumbersome situation. 6 / Advanced Therapy in Thoracic Surgery
- 7. mechanism of action Intercostal nerve blocks produce
analgesia by direct blockade of the intercostal nerves. There is
usually mini- mal or no spread of anesthetic proximally to the
dorsal rami of the intercostal nerves or the sympathetic chain.
efficacy Intercostal nerve blocks are moderately effective for
post-thoracotomy pain. For example, Kolvenbach and colleagues
detected adequate analgesia in approxi- mately 76% of their group
of patients, as measured by the lack of need for supplemental
opioids.62 When compared with placebo or parenteral opioids,
intercostal nerve blocks have usually been shown to produce better
pain control with lower pain scores and/or fewer supple- mental
opioids.6468 Only two studies have compared intercostal nerve
blocks with other regional techniques for post-thoracotomy pain.
Asantila and colleagues compared intercostal nerve blocks with
epidural analgesia with either bupivacaine or morphine, and found
no significant differences between treatments with respect to pain
scores or supplemental parenteral opioid requirements.69 More
recently, Perttunen and colleagues randomized 45 patients to
receive intercostal nerve blocks (performed at T3T7 via an internal
approach and administered as a single injection just prior to wound
closure), TPVBs, or continuous epidural analgesia with
bupivacaine.70 In the first 4 hours after surgery, pain scores
during coughing were significantly lower in the intercostal nerve
block group than in the other two groups. No differ- ences were
noted in supplemental morphine consumption, pain scores at rest, or
pain scores with coughing after the initial 4-hour period. However,
the authors emphasize that pain relief in all patients was only
fair (VAS pain scores of 2862/100 at rest and 6291/100 with
coughing), and opti- mizing the management of these techniques may
have produced different results. Analgesic efficacy may be limited
in intercostal nerve blocks owing to a lack of blockade of the
dorsal rami, which can result in persistent pain at the medial edge
of the incision, and muscles and ligaments in the surround- ing
area. Failure to block the sympathetic chain, vagus, and phrenic
nerves may further limit the ability of inter- costal nerve blocks
to provide optimal pain relief after thoracotomy. Intercostal nerve
blocks also appear to be moderately effective in improving
pulmonary function. This is suggested in several,64,66,71,72 but
not all,65 studies by higher values of forced expiratory volume in
1 second (FEV1), forced vital capacity (FVC), and/or peak
expiratory flow rate (PEFR) in patients receiving these blocks
compared with values in patients receiving a placebo or parenteral
opioids. Compiling the results of several studies, Richardson and
colleagues demonstrated an overall 55% preservation of spirometric
function (vs preoperative values) with intercostal nerve blocks by
48 hours post- thoracotomy.8 Despite the above observations, most
stud- ies have failed to demonstrate that intercostal nerve blocks
decrease the incidence of postoperative complica- tions in
post-thoracotomy patients. Furthermore, although Deneuville and
colleagues showed that inter- costal nerve blocks were associated
with fewer postopera- tive respiratory complications than was
as-needed parenteral opioid, the incidence of complications with
intercostal nerve blocks was identical to that with fixed- schedule
intramuscular opioid injections.65 advantages and disadvantages The
main advantage of intercostal nerve blocks is the ease with which
they can be performed.61 They require little training and no
special equipment. The technique is quite safe, and any significant
complication usually occurs within 30 minutes of performing the
block. As such, no special monitoring is necessary for patients
with these blocks beyond the immediate post-block time period. The
main disadvantages of intercostal nerve blocks are the necessity of
performing separate blocks at multiple levels, and the relatively
short duration of analgesia achieved via the single-injection
techniques. adverse effects The most common adverse effect
associated with the use of intercostal nerve blocks for thoracotomy
is the devel- opment of high systemic blood levels of local
anesthetic. This is a consequence of both the volume needed for
injections at multiple levels and the vascularity of the area of
injection. Peak blood levels of local anesthetic occur at 5 to 20
minutes,61,64,73 and they are higher than with interpleural
analgesia, TPVBs, and epidural analge- sia.70,74 Case reports of
spinal anesthesia associated with the use of intercostal nerve
blocks have also been reported.75,76 This has been postulated to be
due to retro- grade intraneural spread of local anesthetic to the
subarachnoid space. Most cases have involved intercostal nerve
blocks performed by an internal approach during thoracotomy,
possibly because of the more medial injec- tion of the local
anesthetic in these circumstances. contraindications There are no
absolute contraindications specific to inter- costal nerve blocks.
The main relative contraindication of intercostal nerve blocks when
used for post-thoracotomy analgesia is in patients for whom the
effects of high Postoperative Analgesia for Thoracotomy Patients: A
Current Review / 7
- 8. systemic blood levels of local anesthetic may be particu-
larly detrimental, which includes patients with cardiac conduction
defects and seizure disorders. Interpleural Analgesia definition
and technique The term interpleural analgesia refers to a technique
whereby local anesthetic is placed into the interpleural space,
located between the visceral and parietal pleurae. The term
intrapleural analgesia is often used interchange- ably with
interpleural analgesia, but the former is anatomically incorrect.
For thoracotomy patients, a multiorifice epidural catheter is
usually inserted into the interpleural space under direct vision by
the surgeon prior to chest closure, and a local anesthetic is
adminis- tered either as a continuous infusion or intermittent
bolus doses. Some authors emphasize suturing the inter- nal tip of
the catheter high in the interpleural space (in the cranial portion
of the thoracic cage) to prevent dislodgment,77 whereas others
recommend placing the tip at the level of the incision.78 Table 1-6
presents examples of dosage regimens. None has been demonstrated to
be superior to the others. mechanism of action Interpleural
analgesia produces pain relief primarily by diffusion or bulk flow
of local anesthetic through the parietal pleura, into the
subpleural space, and finally to the intercostal nerves. The
resultant effect is a multilevel intercostal nerve block.79
Interpleural analgesia tech- niques may also block other nervous
structures including the vagus and phrenic nerves as they traverse
through the interpleural space,77 pain receptors in the parietal
pleura, and the thoracic sympathetic chain, by diffusion of local
anesthetic into the paravertebral space. The clinical importance of
blockade at these secondary sites is unclear and may contribute to
the variable results in studies examining the efficacy of
interpleural analgesia. efficacy The efficacy of interpleural
analgesia for post-thoracotomy pain is controversial.80 Compared
with placebo or parenteral opioids, interpleural analgesia has been
shown to improve analgesia in some studies,81,82 and to have
minimal or no effect in others.8385 Interpleural analgesia has also
been demonstrated to produce a degree of anal- gesia similar to
TPVB and thoracic epidural analgesia with bupivacaine in some
studies,78,86 but less than thoracic epidural bupivacaine, lumbar
epidural hydro- morphone, and lumbar epidural morphine in
others.74,87,88 The lack of consistent efficacy for
post-thoracotomy pain has been primarily attributed to the loss of
local anesthetic by drainage through chest tubes. Ferrante and
colleagues documented a 30 to 40% loss of an injected dose of
bupivacaine over a 4-hour period through the chest tubes.89 For
interpleural analgesia administered via the bolus method, clamping
the chest tubes for 15 to 30 minutes after each dose has been
advocated to help circumvent this problem,77 although the safety
and effi- cacy of such a maneuver has been questioned.8 Other
factors that may contribute to the lack of anal- gesic efficacy are
dilution of local anesthetic with pleural exudate, and uneven
distribution of local anesthetic throughout the pleural space. The
latter may occur because of inflammation of the pleura by the
current surgical procedure and/or the presence of fibrous tissue
from previous pleural disease or thoracotomy. As well, the
distribution of local anesthetic within the inter- pleural space is
gravity dependent.90 The upright position assumed by
post-thoracotomy patients, because of its beneficial effects on
pulmonary function, encourages pooling of the local anesthetic in
the inferior thoracic cage, thereby contributing to lesser
analgesia at the more cranial thoracic dermatomes. Finally, the
dorsal rami of the thoracic spinal nerves are not blocked by
interpleural techniques; thus, patients may experience pain in the
medial part of the incision and paravertebral surround- ing muscles
and ligaments.64 The effects of interpleural analgesia on
postoperative pulmonary function are likewise unimpressive. Most
studies have failed to demonstrate an improvement in FEV1, FVC,
PEFR, arterial blood gas values, and/or pulmonary complications
compared with these effects when placebo or parenteral opioids are
used.74,83,84 In Richardson and colleagues review of spirometric
function with different analgesic techniques post-thoracotomy, 8 /
Advanced Therapy in Thoracic Surgery TABLE 1-6. Examples of Dosing
Regimens for Interpleural Analgesia Study Intraoperative Regimen
Postoperative Regimen Tartiere et al, 10 mL 0.25% bupivacaine
199181 q8h Richardson et al, 20 mL 0.25% bupivacaine at 0.5%
bupivacaine 199578 chest closure 0.1 mL/kg/h infusion Stromskag et
al, 20 mL 0.375% 199090 bupivacaine prn Schneider et al, 30 mL 0.5%
bupivacaine 199384 q4h Mann et al, 199282 20 mL 0.25% bupivacaine
q4h Silomon et al, 20 mL 0.5% bupivacaine 200083 q4h Raffin et al,
199485 0.15 mL/kg 2% lidocaine with 0.05 mL/kg/h 2% 1:200,000
epinephrine after lidocaine with chest closure 1:200,000
epinephrine infusion prn = according to circumstances.
- 9. an overall 35% preservation of function (vs the preoper-
ative values) was noted for interpleural analgesia by 48 hours
postoperatively.8 This was lower than for all the other techniques
examined, including intercostal nerve blocks, thoracic
paravertebral, and epidural analgesia. In two randomized studies
comparing interpleural analgesia and TPVB, analgesia for the two
techniques was equiva- lent, but patients receiving interpleural
analgesia demon- strated significantly worse FVC and FEV1
values.78,91 This observation led to the suggestion that
interpleural anal- gesia may cause direct impairment of
diaphragmatic and intercostal muscle function, either by diffusion
of local anesthetic into the diaphragm and/or intercostal muscles,
with direct inhibition of their contractile function,91 or by
blockade of the phrenic nerve as it travels through the mediastinum
and/or at its terminal branches innervating the diaphragm. No
studies to date have confirmed the validity of either theory.92
advantages and disadvantages The primary advantage of interpleural
analgesia for post- thoracotomy pain is the ease with which the
technique can be performed. It is also relatively safe, and no
special monitoring is necessary for patients receiving this form of
analgesia.77 The main disadvantage of interpleural analgesia is the
lack of consistent beneficial effects on pain relief and pulmonary
function in the post-thoracotomy patient. Possible explanations for
this have been discussed above. adverse effects The main adverse
effects of interpleural analgesia for post- thoracotomy analgesia
include toxicity owing to excessive systemic absorption of local
anesthetic, blockade of the thoracic sympathetic chain, and
stellate ganglion blockade (with an ipsilateral Horner syndrome).93
Systemic local anesthetic toxicity is rare because plasma
concentrations usually remain below levels associated with
significant toxicity.81,94,95 When administered as a bolus dose,
peak blood levels occur 5 to 30 minutes after injection. Similarly,
blockade of the thoracic sympathetic chain rarely produces
clinically significant hypotension and bradycardia. This lack of
hemodynamic effects has tradi- tionally been attributed to the
unilateral nature of the sympathetic block, although Ramajoli and
De Amici have convincingly demonstrated bilateral sympathetic
blockade of the thorax and abdomen with unilateral interpleural
instillation of both 0.25 and 0.5% bupivacaine.96 Thus, hemodynamic
stability is probably due to incomplete blockade of the upper
thoracic ganglion, resulting in little or no effect on the cardiac
sympathetic fibers and allowing compensatory vasoconstriction of
the upper extremities. contraindications There are no absolute
contraindications specifically related to the technique of
interpleural analgesia. Relative contraindications include
conditions in which there is an anticipated lack of efficacy, such
as with pleural fibrosis, previous surgical or chemical
pleurodesis, and bron- chopleural fistula or empyema; and patients
for whom the effects of high systemic blood levels of local anes-
thetic may be particularly detrimental (as discussed above under
Intercostal Nerve Block). Thoracic Paravertebral Nerve Block
definition and technique After its first performance in 1905 by
Hugo Sellheim, TPVB enjoyed an initial period of popularity,
followed by a dramatic decline in use in the middle of the
twentieth century.97 In the past two decades, however, there has
been a resurgence of interest in the technique, particu- larly in
Europe. TPVB is a technique whereby local anesthetic is injected
into the paravertebral space in the thoracic region. It has also
been referred to as extrapleural, extrapleural paravertebral, and
extrapleural intercostal analgesia. As depicted in Figure 1-2, the
paravertebral space is a wedge-shaped region adjacent to the
thoracic vertebrae in the vicinity where the spinal nerves emerge
from the intervertebral foramina. Its boundaries are as follows:
posteriorly, the superior costotransverse liga- ment; laterally,
the posterior intercostal membrane; ante- riorly, the parietal
pleura; and medially, the posterolateral aspect of the vertebrae,
intervertebral disk, and interver- tebral foramen. The origin of
the psoas muscle forms the inferior boundary of the paravertebral
space; thus, spread of local anesthetic below T12 is uncommon. The
cranial boundary of the paravertebral space has not been
Postoperative Analgesia for Thoracotomy Patients: A Current Review
/ 9 Subserous fascia Sympathetic chain Interpleural space
Extrapleural compartment Subendothoracic compartment Intercostal
nerve Posterior primary rami Superior costotransverse ligament
Right lung Left lung Azygos vein Esophagus Thoracic duct Descending
aorta Pleura Visceral ParietalEndothoracic fascia FIGURE 1-2.
Anatomy of the thoracic paravertebral space. Reproduced with
permission from Karmaker MK.98
- 10. defined, and radiocontrast dye has been observed in the
cervical region after thoracic paravertebral injection.98 The
thoracic paravertebral space is in continuity with the epidural
space medially via the intervertebral foramen, the intercostal
space laterally, and the contralateral paravertebral space via the
prevertebral and epidural spaces.98 The paravertebral space is
traversed by the inter- costal nerves, their dorsal rami, the rami
communicantes, and the sympathetic chain. As with other techniques,
TPVB may be performed by direct injection through a needle or an
indwelling catheter, both of which may be introduced either
percuta- neously or under direct vision before the chest is closed.
Sabanathan and colleagues have described a technique for use during
thoracotomy that involves reflecting the pari- etal pleura from the
posterior wound margin onto the vertebral bodies to form an
extrapleural pocket.99 A percu- taneously placed catheter is then
placed into this pocket and positioned under direct vision so that
it lies against the angles of the exposed ribs. Richardson and
Lonnqvist have employed combined techniques whereby a percuta-
neously placed catheter is inserted before the surgery begins and a
bolus dose of local anesthetic is administered to provide
intraoperative anesthesia.97 Before chest closure, methylene blue
is injected through the catheter, and if the spread of dye is not
optimal, the catheter is reinserted by the surgeon. Video-assisted
placement of a paravertebral catheter during thoracoscopy has also
been reported.100 Table 1-7 presents various dosage regimens for
TPVB. Continuous infusion of local anesthetic through a
paravertebral catheter provides better pain control than do
intermittent bolus injections.101 mechanism of action TPVB produces
analgesia by blockade not only of the intercostal nerves but also
of their dorsal rami and the sympathetic chain. Owing to the
continuous nature of the paravertebral space, local anesthetic
applied at one level spreads to multiple contiguous dermatomes.
Using 15 mL 0.5% bupivacaine, Cheema and colleagues demonstrated a
somatic sensory block extending for a mean of 5 (range 1 to 9)
dermatomes, and a sympathetic block over an average of 8 (range 6
to 10) dermatomes.102 However, the extent of spread is variable, as
is evidenced by these large ranges; thus, it may be necessary to
perform injections at more than one site to reliably anes- thetize
more than three to four segments. A small amount of local
anesthetic may also exit the interverte- bral foramina to enter the
epidural space, but whether this contributes significantly to the
analgesic effects of TPVB is questionable.98 efficacy The efficacy
of TPVB for post-thoracotomy pain control has been well
established. Lower pain score and opioid- sparing effects have been
noted in several studies compar- ing TPVB with placebo and
parenteral opioids,103106 although supplemental opioids were often
still necessary. In comparison to epidural blockade with local
anesthetics and/or opioids, TPVB has frequently demonstrated simi-
lar or better pain relief, accompanied by less nausea, vomiting,
hypotension, and urinary retention.107110 Most studies have
demonstrated a significant improve- ment of post-thoracotomy
pulmonary dysfunction with TPVB compared with placebo or parenteral
opioids, as demonstrated by higher FEV1, FVC, and/or PEFR
values.104,105,106,111 In Richardson and colleagues review of
various techniques for post-thoracotomy analgesia, TPVB
demonstrated the best preservation of pulmonary func- tion.8 FEV1,
FVC, and/or PEFR values had all returned to approximately 75% of
their preoperative value by 48 hours postoperatively in patients
who had received TPVB. When TPVB has been compared directly with
thoracic epidural analgesia, most studies have demonstrated similar
effects on pulmonary function for the two techniques,109,110
although TPVB was associated with higher values of PEFR and oxygen
saturation as measured by pulse oximetry (SpO2) in one study by
Richardson and colleagues group.107 As noted previously (see
Interpleural Analgesia), TPVB has been demonstrated to produce both
better and similar effects on pulmonary function tests when
directly compared with interpleural analgesia.70,112 Likewise,
there is a limited quantity of evidence that 10 / Advanced Therapy
in Thoracic Surgery TABLE 1-7. Examples of Dosage Regimens for
Thoracic Paravertebral Blockade Study Intraoperative Regimen
Postoperative Regimen Carabine et al, 1995103 5 mL 0.25%
bupivacaine after chest closure 0.25% bupivacaine 5 mL/h infusion
Catala et al, 1996101 20 mL 0.375% bupivacaine q6h or 15 mL 0.375%
bupivacaine loading dose, then 5 mL/h 0.375% bupivacaine infusion
Barron et al, 1999105 0.3 mL/kg 1% lidocaine before chest closure
or 0.1 mL/kg/h 1% lidocaine infusion or 0.1 mL/kg/h 0.3 mL/kg 0.25%
bupivacaine before chest closure 0.25% bupivacaine infusion
Berrisford et al, 1990111 20 mL 0.5% bupivacaine after chest
closure Approximately 0.1 mL/kg/h 0.5% bupivacaine Mathews and
Govenden, 1989108 10 mL 0.25% bupivacaine after chest closure 310
mL/h 0.25% bupivacaine Richardson et al, 1999107 20 mL 0.25%
bupivacaine during chest closure 0.1 mL/kg/h 0.5% bupivacaine
infusion
- 11. TPVB may decrease the risk of pulmonary complications
compared with placebo and parenteral opioids. Sabanathan,
Berrisford, and colleagues, in two separate studies (with possibly
overlapping subjects), have reported fewer pulmonary complications
in patients receiving TPVB compared with placebo.104,111 TPVB has
also been shown to suppress the stress response, as measured by
serum cortisol and glucose levels, and in this respect it
functioned better than thoracic epidural analgesia.107 advantages
and disadvantages TPVB has been described as being quick and easy
to perform.98,112,113 This statement should be interpreted
cautiously, however, as it was made by the main authors regarding
TPVB in the literature today, and their experi- ences may not be
applicable to other institutions. This caution may be especially
relevant for centers in North America, where TPVB is rarely taught
in the anesthesiol- ogy and surgery training programs. Other
advantages of TPVB include the lack of urinary retention and motor
blockade of the lower extremities owing to the thoracic and
unilateral location of the block.102,114 As well, the unilateral
nature of the block results in little/no direct effects on
hemodynamics,102 and the doses of local anesthetic are usually less
than those associated with systemic toxicity.70 Even when higher
levels have occurred, there has been no evidence of systemic
toxicity.45,110 Accordingly, no special monitoring is necessary for
patients with these blocks beyond the usual postoperative care.112
As TPVB is dependent on the use of local anesthetics for
postoperative use, opioid- related risks are theoretically avoided.
However, supple- mentation with systemic opioids is often used;
thus, opioid adverse effects may be minimized but not absent. The
main disadvantage of this technique is that it is more difficult to
perform than the intercostal nerve and interpleural blocks. As
well, patients with a previous thoracotomy are usually
inappropriate candidates for the block since the paravertebral
space may be obliterated by scar tissue. The technique may likewise
be unsuitable for patients undergoing a pleurectomy, although
successful use of TPVB has been reported, provided the parietal
pleura covering the vertebral bodies and a few centime- ters
distally is left intact.106 adverse effects The incidence of
adverse effects with TPVB in the post- thoracotomy population is
10% or lower.112,115 The most frequent adverse event is
hypotension,115 which has been primarily attributed to the
unmasking of relative hypo- volemia as hypotension does not occur
in well-hydrated patients receiving TPVB for the treatment of
chronic pain syndromes.98,102,112 Other complications, which occur
much less frequently, are inadvertent puncture of the epidural or
subarachnoid space owing to a faulty tech- nique,97 and unilateral
Horner syndrome because of the cephalad spread of anesthetic to the
cervical sympathetic structures. No fatality directly related to
TPVB has been reported in the literature.98,112 contraindications
As alluded to above, a previous ipsilateral thoracotomy would be a
relative contraindication to the technique because of a possible
obliteration of the paravertebral space. An empyema is not directly
affected by manipula- tions in the paravertebral space, but the
accompanying acidosis and hyperemia may limit the efficacy of the
TPVB and increase the risk of systemic absorption of local
anesthetic. Anticoagulation is a relative contraindi- cation to the
technique, but the paravertebral space is less vascular than the
epidural space; thus, the risk of venous puncture is less than with
epidural analgesia. As well, the consequences of a unilateral
paravertebral space hema- toma are small compared with the
potentially cata- strophic consequences of an epidural hematoma.112
Similarly, TPVB is relatively contraindicated in patients with
raised intracranial pressure because of the possibil- ity of
inadvertent dural puncture and subsequent brain- stem herniation.
However, the risk of puncture is less than with epidural analgesia,
so in this situation, TPVB would be the best choice of the two
techniques. Epidural Analgesia definition and technique Epidural
analgesia refers to the technique of injecting analgesic medication
into the epidural space, surround- ing the spinal cord. As with
most of the other regional techniques discussed heretofore,
epidural analgesia is almost exclusively administered via an
indwelling catheter when used for post-thoracotomy pain relief.
Similar effects may be achieved by injecting analgesic medication
into the subarachnoid space (albeit with lower doses),116 but the
technique is rarely used in the United States because of concerns
with introducing a catheter into this space. The intimate proximity
of the subarachnoid space to the spinal cord poses a risk of injury
to the spinal cord, and an association between the development of
cauda equina syndrome and subarach- noid microcatheters (also known
as spinal micro- catheters) has been suggested.117 Local
anesthetics and opioids are the two main classes of drugs used for
epidural analgesia in post-thoracotomy patients. Other drugs that
have been used in the epidural space, either alone or as adjuncts,
are discussed later (see Postoperative Analgesia for Thoracotomy
Patients: A Current Review / 11
- 12. Other Agents). In the early 1980s, epidural morphine was
popular, primarily because of its hemodynamic stability compared
with epidural local anesthetics and its relatively long duration of
action.5 The latter permitted bolus dosing on an as-needed basis
every 6 to 24 hours. The risk of respiratory depression and slow
onset of action with epidural morphine promoted the search for
alternative opioids,118 thus leading to the use of more lipophilic
epidural opioids such as fentanyl and its analog, sufentanil. Owing
to the short duration of action of these opioids, continuous
infusions are necessary. Most recently the synergistic effects of
combining local anesthetics and opioids in the epidural space have
been recognized.119 This synergism has been attributed to the
facilitation of opioid transport from the epidural space to the
subarachnoid space by local anesthetic,120 and production of a
conformational change in the spinal opioid receptor by local
anesthetic agents, such that opioid binding is facilitated.121
Accordingly, continuous infusions of opioidlocal anesthetic
combinations have become popular, with the goal of providing
similar or improved analgesia with lower doses of both agents, so
that the incidence of adverse effects is reduced. Although similar
or improved analgesia has been achieved in several studies,122126 a
reduction in adverse effects has not been universally accomplished
(see Effects Related to Injection of Epidural Local
AnestheticOpioid Combinations, below). Current literature suggests
that the combination of 10 to 12.5 g/mL fentanyl (or 1 g/mL
sufentanil) and 0.1 to 0.125% bupivacaine is closest to the ideal
for post-thoracotomy patients, producing a maximum of pain relief
and minimum of side effects.6,127 Of interest, the addition of
bupivacaine does not seem to improve analgesia when added to
epidural meperidine.128 This may be because meperidine has
significant local anesthetic properties itself and has even been
used as the sole anesthetic for lower abdomi- nal surgery when
administered in the subarachnoid space.129 Table 1-8 presents
several examples of epidural analgesia regimens. There is
controversy as to whether epidural catheters should be inserted
into the thoracic or lumbar region for thoracotomy patients. Owing
to the proximity of the spinal cord to the epidural space in the
thoracic region and the greater technical difficulty of entering
the epidural space at this level of the spinal column, many
anesthesiologists are hesitant to insert a thoracic epidural
catheter. They are supported by evidence that equivalent analgesia
may be achieved by lumbar and thoracic epidural injections in
post-thoracotomy patients.120,130134 In contrast, advocates of
thoracic epidural catheters emphasize that higher volumes and/or
higher doses of epidural opioids and/or local anesthetics were
needed with the lumbar route to produce equivalent analgesia in
many of these studies, thereby suggesting that the lumbar route may
be acceptable but not optimal. As well, there is no evidence that
complication rates are higher with thoracic than with lumbar
epidural catheters,135 and many of the potential advantages of
epidural analgesia discussed below rely on blockade of the cardiac
sympa- thetic fibers at T1 to T5, which is more easily accom-
plished with a thoracic than with a lumbar epidural catheter. With
these considerations in mind, the approach at our institution is to
preferentially place a thoracic epidural catheter; however, a high
lumbar catheter is used if this is unsuccessful. mechanism of
action The mechanism of action of epidural opioids and local
anesthetics differs. Local anesthetics applied to the epidural
space act primarily by blockade of nerve impulse conduction in the
axonal membrane of the spinal nerve roots as they traverse the
epidural space.136 Diffusion of local anesthetic into the long
tracts of the spinal cord may further contribute to the analgesia
produced by epidural local anesthetics. The various types of nerve
fibers exhibit differential sensitivity to local anesthetics:
sympathetic fibers are the most easily blocked, and motor fibers
are the most resistant.137 Consequently, the concentration of local
anesthetic is the primary determinant of the depth of blockade,
with higher concentrations producing more motor blockade. The
actual extent of blockade along the spinal canal 12 / Advanced
Therapy in Thoracic Surgery TABLE 1-8. Examples of Dosing Regimens
for Epidural Analgesia Solution Infusion Rate Bolus Doses Fentanyl
10 g/mL 0.51 g/kg/h 1015 g q1015 min prn Sufentanil 1 g/mL 0.10.2
g/kg/h 57 g q1015 min prn Morphine 36 mg q612h prn Morphine 0.01%
0.50.8 mg/h 0.20.3 mg q1015 min prn Hydromorphone 0.81.5 mg q46h
prn Hydromorphone 0.005% 0.150.3 mg/h 0.150.3 mg q1015 min prn
Fentanyl 10 g/mL + 68 mL/h 12 mL q1015 min prn bupivacaine
0.750.125% Sufentanil 1 g/mL + 68 mL/h 12 mL q1015 min prn
bupivacaine 0.750.125% Morphine 0.01% + 68 mL/h 12 mL q1015 min prn
bupivacaine 0.750.125% Hydromorphone 0.0025% 68 mL/h 13 mL q1015
min prn 0.005%+ bupivacaine 0.750.125% Data from University of
Texas M. D. Anderson Cancer Center protocol and DeLeon-Casasola OA
and Lema M.154 prn = according to circumstances.
- 13. depends primarily on the volume administered, and because
of the greater sensitivity of the sympathetic fibers, the extent of
sympathetic blockade may be greater than the somatic sensory block.
Epidural opioids exert their primary therapeutic effects by binding
to specific opioid receptors in the substantia gelatinosa of the
dorsal horn of the spinal cord gray mater.136,138 This region
contains interneurons involved in the ascending pain pathways (the
spinothala- mic and spinoreticular tracts). Opioid receptors are
located both presynaptically and postsynaptically, and they
function to inhibit the release of neurotransmitters from primary
sensory neurons and block the depolariza- tion of post-synaptic
neurons, respectively.44 The term selective spinal analgesia has
been used to denote analge- sia attributable to these spinal cord
opioid receptors. Before reaching the spinal cord, opioids injected
into the epidural space must first travel through the dura mater,
subdural space, arachnoid mater, subarachnoid space (containing the
cerebrospinal fluid), and pia mater. The epidural space contains an
abundance of fat tissue and an extensive venous plexus, and 90 to
97% of an injected dose is absorbed into these compartments,139141
thereby never reaching the subarachnoid space. Epidural opioids may
also produce analgesia at a supraspinal level (termed supraspinal
analgesia) by bind- ing to opioid receptors in the brain. Opioids
gain access to these sites via two main pathways: absorption into
the epidural veins and subsequent entry into the systemic
circulation, and rostral travel through the cerebrospinal fluid to
the brain. After a bolus injection of all epidural opioids, plasma
levels peak at approximately the same time as with an intramuscular
injection,139,142,143 and in some studies have achieved values high
enough to contribute to analgesia.139,142,144146 Plasma opioid
levels fall quickly, however, and are of little importance beyond
the first hour after epidural bolus administration for all
agents.139,142,146 A different scenario arises when lipophilic
agents (such as fentanyl and sufentanil) are administered by
continuous epidural infusion or repeat bolus. Continuing systemic
absorption of these agents results in accumulation, and some
studies have recorded systemic plasma levels within the usual
therapeutic range for these drugs, when administered by these meth-
ods.123,143 Similarly, Miguel and colleagues and Sandler and
colleagues have demonstrated that epidural infu- sions of fentanyl
and sufentanil produce plasma levels similar to those with
intravenous infusion, when titrated to equivalent analgesia.1 4 7 ,
1 4 8 This suggests that supraspinal analgesia may be a major
contributor to the overall analgesic effect when lipophilic opioids
are administered in this manner. Rostral travel through the
cerebrospinal fluid of opioids injected into the epidural space is
most promi- nent with morphine, as its relative hydrophilic
properties limit its diffusion out of the subarachnoid space,
thereby allowing greater quantities of morphine to be retained in
the cerebrospinal fluid for a prolonged period of time.149 Morphine
travels cranially via the slow process of cere- brospinal fluid
bulk flow, leading to peak levels of morphine in the cervical cord
region by 3 to 5 hours after lumbar epidural injection.136,150
Movement through the cerebrospinal fluid for more lipophilic
opioids may also occur, especially with large bolus doses, but the
quantities of drug detected in the cervical cord and/or cisterna
magna have been small, and their contribution to the analgesia
achieved with these agents is unknown.146,151 efficacy The efficacy
of epidural analgesia in providing pain relief after thoracotomy
depends on the drug(s) used. Epidural analgesia with local
anesthetics alone is more effective in providing analgesia than are
parenteral opioids, but the concentrations needed to accomplish
this (eg, 0.5% bupivacaine) are accompanied by a signif- icant risk
of hypotension. When lower concentrations have been used,
supplemental parenteral opioids are usually necessary.70,107,152
The efficacy of epidural morphine in providing post-thoracotomy
analgesia is undisputed. It is consid- ered the gold standard for
epidural opioid analgesia. Pain scores and/or the need for
supplemental anal- gesics are universally lower for epidural
morphine than for parenteral morphine, and these effects are accom-
plished using lower doses of epidural morphine, which last longer
than parenteral morphine.5 , 1 5 2 , 1 5 3 The lipophilic opioids
are also effective in providing analge- sia after thoracotomy when
administered via the epidural route. However, as discussed
previously, there is evidence that continuous epidural infusions of
these agents produce post-thoracotomy pain relief primarily by the
systemic absorption of the opioid and may offer little advantage
over the less complicated intravenous route of administration.154
The opioidlocal anesthetic combinations popular today are also very
effective in providing pain relief after thoracotomy. As
combinations are relatively new tech- niques and the efficacy of
epidural analgesia for post- thoracotomy pain has already been
established, there has been little interest in performing studies
comparing the efficacy of combinations to that of parenteral
opioids or placebos. Nevertheless, improved analgesia has been
noted with both epidural morphinebupivacaine and epidural
fentanylbupivacaine infusions compared with parental
opioids.152,155 Postoperative Analgesia for Thoracotomy Patients: A
Current Review / 13
- 14. Studies comparing epidural analgesia with other modes of
regional analgesia in post-thoracotomy patients are few, and their
interpretation has been confounded by the use of a variety of
different medications in the epidural space. Three studies have
used epidural local anesthetics alone. Brockmeier and colleagues
showed no difference in analgesic efficacy between 0.375% epidural
bupivacaine and interpleural analgesia.86 Richardson and colleagues
demonstrated better analgesia with TPVB than with epidural
analgesia, but the TPVB group received 0.5% bupivacaine and the
epidural group received only 0.25% bupivacaine.107 A final study
compared 0.25% epidural bupivacaine with 0.25% TPVB bupivacaine and
0.5% interpleural bupivacaine.70 All techniques produced similar
analgesia at rest, but the intercostal nerve blocks group had
better dynamic pain relief for the first 4 hours after thoracotomy.
In a study of epidural analgesia using a combination of fentanyl
and bupivacaine, analgesia was superior to that produced by
TPVB,114 although this effect did not persist beyond the first
postoperative day. Evidence regarding the efficacy of epidural
analgesia in improving pulmonary function and decreasing pulmonary
morbidity in the post-thoracotomy patient is conflicting. Many
studies have revealed no difference in arterial blood gas results,
spirometry measurements, or pulmonary complications when epidural
analgesia has been compared with parenteral opioids or other types
of regional analgesia in this population.69,88,109,153,156160 In
Richardson and colleagues review of different techniques for
post-thoraco- tomy analgesia discussed previously, epidural
analgesia with local anesthetics and/or opioids resulted in a
moder- ate preservation of pulmonary function.8 By 48 hours after
surgery, FEV1, FVC and/or PEFR values had returned to approximately
55% of their preoperative values in patients who had received
epidural analgesia, which was similar to the results obtained with
intercostal nerve blocks but worse than the 75% values observed
with TPVB. For those studies that have shown an improvement in
pulmonary parameters, most have demonstrated improvement in only
some of the parameters measured. For example, Guinard and
colleagues demonstrated higher FVC and FEV1 values for thoracic
epidural fentanyl when compared with intravenous fentanyl, but no
difference in arterial blood gas results or the number of patients
with abnormalities on chest radiographs.132 Salomaki and colleagues
have shown lower PaCO2 values with epidural fentanyl but similar
PaO2 and incidences of atelectasis compared with intravenous
fentanyl.161 Two articles from Hasenbos and colleagues are the only
stud- ies that have found both improved arterial blood gases (PaCO2
less elevated above preoperative levels) and reduced incidence of
pulmonary complications.162,163 However, these studies were not
blinded, and the opioid examined was nicomorphine, the
3,6-dinicotinoyl ester of morphine, which is not available in North
America. As well, the sole analgesic in the nonepidural groups was
intramuscular nicomorphine, administered in as-needed doses by the
nursing staff. By providing parenteral opioid in this manner,
analgesic therapy in these groups may not have been optimized. A
recent meta-analysis of the pulmonary effects of various analgesic
regimens in a wide variety of surgical procedures (including but
not restricted to thoraco- tomies) revealed only a diminished
incidence of atelecta- sis with epidural opioids and a decreased
incidence of pulmonary infection and overall pulmonary complica-
tions, plus an increased PaO2 with epidural local anes- thetics.164
Of interest, the authors emphasize the lack of difference in
spirometry results between the different methods of analgesia and
suggest that there is no ratio- nale for using these surrogate
measures of pulmonary outcomes. Epidural analgesia has little, if
any, impact on modify- ing the stress response to surgery in the
post-thoracotomy population.107,165 This has been attributed to
incomplete blockade of the afferent sensory nervous input from the
site of surgery and the release of components of the stress
response, such as cytokines, directly into the bloodstream from the
site of tissue injury.166 advantages and disadvantages One major
advantage of epidural analgesia is related to the use of opioids in
the epidural space. Systemic absorp- tion and/or cephalad spread of
epidural opioid may alle- viate the shoulder pain commonly
associated with thoracotomies, and even neck incisions for
esophagec- tomies. In our institution, we do not routinely use
supple- mental parenteral opioids for pain in these two locations.
If necessary, NSAIDs and acetaminophen are almost always sufficient
adjuvants to our epidural analgesia. Thoracic epidural analgesia
with local anesthetics (alone or in combination with opioids) may
have unique advan- tages in patients with coronary artery disease.
Blockade of the cardiac sympathetic fibers innervating the heart
(T1T5) results in small reductions in heart rate, systemic vascular
resistance, and possibly cardiac output,167,168 thereby decreasing
myocardial oxygen demand. At the same time, myocardial oxygen
supply may improve, particularly in areas at most risk of ischemia.
Thoracic epidural analgesia with local anesthetic has been
demonstrated to produce dilatation of stenotic coronary
arteries,169 redistribution of blood flow from the epicardium to
endocardium,170 and redistribution of blood flow specifically
toward ischemic regions of the myocardium.170 Maintaining the
systemic blood pressure close to the normal range (eg, mean
arterial 14 / Advanced Therapy in Thoracic Surgery
- 15. pressure < 20% below baseline) is necessary for these
effects to be most evident.171 Another potential benefit of
epidural analgesia in the patient with coronary artery disease
relates to coagulation. Local anesthetic may be absorbed from the
epidural space in quantities sufficient to interfere with platelet
aggrega- tion,172,173 thereby counteracting the hypercoagulable
state associated with major surgery and potentially diminishing the
risk of coronary artery thrombosis formation. Despite the above
observations, there have been no properly conducted randomized
controlled trials demon- strating decreased risk of myocardial
ischemia/infarction through the use of epidural analgesia in any
group of patients postoperatively, let alone those having thoraco-
tomies. As well, there is concern that blockade of the sensory
innervation of the upper thoracic region may simply obliterate the
pain of myocardial ischemia, thus removing an important warning
signal of impending myocardial infarction.174 Epidural analgesia
may also decrease the risk of postop- erative arrhythmias. This is
of particular relevance in the post-thoracotomy situation as
supraventricular arrhyth- mias (especially atrial fibrillation)
occur in approximately 15% of patients after lung surgery, and
recurrent episodes have been associated with increased
perioperative mortal- ity.175 Animal studies suggest that thoracic
epidural analge- sia with local anesthetic may reduce the risk of
ventricular tachyarrhythmias and reentry supraventricular arrhyth-
mias,176178 an effect that has been attributed to cardiac
sympathetic blockade. In humans a retrospective review by Groban
and colleagues noted a significantly lower inci- dence of atrial
arrhythmias while thoracic epidural analge- sia (with opioid or
opioid plus local anesthetic) was in use compared with the
incidence after the epidural was removed on the second or third
postoperative day.179 In a prospective, randomized study comparing
thoracic epidural bupivacaine with thoracic epidural morphine, Oka
and colleagues demonstrated a lower incidence of supraventricular
tachyarrhythmias with epidural bupiva- caine when administered for
3 days after thoracotomy.180 The aforementioned cardiovascular
benefits of thoracic epidural analgesia with local anesthetics
cannot be extrapolated to the use of epidural opioids or to
epidural local anesthetics administered by the lumbar route. In the
former instance, there is no direct inhibition of sympathetic input
to the heart. In the latter, blockade of T1 to T5 would require
such an extensive blockade of the sympathetic nervous system that
the resultant decrease in blood pressure would very likely
counteract any beneficial effects attributable to the blockade of
the cardiac sympathetic fibers. The main disadvantage of epidural
analgesia is that, of the regional techniques described heretofore,
it is probably the most difficult to perform and is almost
exclusively performed by an anesthesiologist or nurse anesthetist.
Although many of these individuals have had extensive training
and/or experience in performing epidurals for obstetric
indications, and thus can facilely insert an epidural in the lumbar
region, thoracic epidu- rals for analgesia after thoracotomy are
different. Not only is the thoracic epidural space more difficult
to identify owing to anatomic differences in the spinal
architecture of the thoracic region, but the majority of
thoracotomy patients are elderly, with calcified supra- spinous and
interspinous ligaments and compressed intervertebral spaces, all of
which add to the difficulty of successfully inserting an epidural.
adverse effects Effects Related to Insertion of a Needle or
Catheter into the Epidural Space. Adverse effects of epidural anal-
gesia related to the insertion of the needle and/or catheter into
the epidural space include inadvertent spinal puncture, inability
to insert a needle or catheter into the epidural space, premature
dislodgment of the catheter from the epidural space, temporary back
pain at the insertion site, epidural hematoma, epidural abscess,
and permanent neurologic deficits. The most common of these is an
inadvertent spinal puncture, which occurs with an incidence of
approximately 0.3 to 5%.136,181,182 Although rare, subdural
hematoma and pneumocephalus have been reported after spinal
puncture.182 More commonly, a medication intended for the epidural
space is injected into the subarachnoid space instead, which may
have disastrous consequences. An epidural dose of either local
anesthetic or opioid would be clearly exces- sive in the
subarachnoid space, potentially producing major motor blockade,
hypotension and total spinal anesthesia with the former class of
drugs, and life- threatening respiratory depression with opioids.
An inadvertent spinal puncture may also produce a headache, which
can be incapacitating. This postdural puncture headache may be
frontal and/or occipital, usually develops 24 to 72 hours after the
spinal puncture, and is due to leakage of cerebrospinal fluid
through the hole in the subarachnoid membrane and subsequent
traction on pain-sensitive structures at the base of the
brainstem.183 It may be associated with nausea/vomiting and cranial
nerve palsies and auditory disturbances,184,185 and it is clearly
differentiated from other causes of headache by its prominent
exacerbation with the upright position and complete resolution with
the supine posi- tion. Therapy is important, not only from a
humanitar- ian point of view, but because the headache may
discourage the patient from coughing and assuming the upright
position, thereby potentially interfering with Postoperative
Analgesia for Thoracotomy Patients: A Current Review / 15
- 16. recovery. In addition to nonopioid and opioid analgesics,
more specific therapy with oral or intravenous caffeine and
aggressive fluid intake instillation is usually success- ful in
alleviating the postdural puncture headache. The latter is often
undesirable in the post-thoracotomy patient, however. When these
measures fail, instillation of 10 to 30 mL of normal saline or 20
mL of freshly obtained autologous blood (an epidural blood patch)
into the epidural space, is indicated.186 The potentially
catastrophic complications of epidural needle or catheter
insertion, epidural hematoma and abscess, and permanent neurologic
deficits are, fortu- nately, very rare. Incidence rates have been
estimated to be 1 in 150,000 to 190,000,187,188 1 in 1,000 to
6,500,189191 and 1 in 3,000 to 4,500,135,192 respectively.
Permanent neurologic deficits (usually paraplegia) may occur as a
consequence of cord compression and ischemia induced by an epidural
hematoma or abscess. Additionally, they may be related to
mechanical trauma from the epidural needle or catheter, inadvertent
injection of a neurotoxic substance into the epidural space, or
spinal cord ischemia from other causes, such as epinephrine-induced
vasocon- striction of arteries supplying the cord, pressure effect
from the volume of epidural injectate, and hypotension induced by
the sympathetic block.193 Epidural abscesses may arise from direct
extension of infection in the local area of the epidural insertion
site, or from infection at a remote part of the body, with
bacteremia and subsequent seeding of the epidural space.194,195
Factors associated with the occurrence of epidural abscesses are
duration of epidural catheteriza- tion 3 days190 ; immunocompromise
associated with one or more complicating disease, such as cancer,
acquired immunodeficiency syndrome, diabetes, multiple trauma,
chronic renal failure, or chronic obstructive pulmonary
disease190,195,196 ; multiple attempts at inserting the epidural
needle/catheter191 ; and the use of low-dose unfractionated or low
molecular weight heparin.190 The association with the latter two
factors may reflect the development of a hematoma within the
epidural space, which subsequently acts as a nidus for infection.
Direct puncture of the extensive epidural venous plexus during
epidural needle or catheter insertion may result in the development
of an epidural hematoma. Although it may initially be small and
clinically unimportant, this hematoma may later enlarge when the
clot is disrupted by a coagulation abnormality or direct trauma.
The latter may occur at any time while the catheter is being used
as epidural catheters are well-known to migrate within the spinal
canal.182 However, a clot is most likely to be disrupted when an
epidural catheter is removed from the patient. Approximately half
of the epidural hematomas attributed to epidural analgesia in
Vandermeulen and colleagues 1994 review of the literature occurred
immedi- ately upon removal of the epidural catheter.197 Risk
factors associated with the development of an epidural hematoma
include increased age,198 multiple attempts at inserting the
epidural needle or catheter,198 and coagulation defects.188,198 It
is controversial whether the appearance of blood in the needle or
catheter during epidural insertion (known as a traumatic
needle/catheter insertion) is a risk factor for the development of
a significant epidural hematoma. Given the extensive vascularity of
the epidural space and the 3 to 12% incidence of puncture of a
blood vessel or vessels during epidural catheter insertion,182
there are obvi- ously a large number of epidural hematomas that are
too small to attain clinical importance. The association between
epidural hematomas and coagulation defects has been recognized for
decades.197 Defects in either the platelet-mediated or coagulation
factordependent phases of the coagulation system enhance the
possibility of epidural hematoma formation, and combinations of
defects increase the risk further.198200 Therapeutic
anticoagulation with heparin, warfarin, and antifibrinolytics are
known offenders, as are therapeutic and prophylactic doses of low
molecular weight heparin.187,197,201 The use of NSAIDs and low-dose
prophy- lactic unfractionated heparin has not been associated with
a significantly increased risk of epidural hematoma
formation.187,188,202 Effects Related to Epidural Injection of
Local Anesthetics. Adverse effects of local anesthetics injected
into the epidural space include hypotension, motor block- ade,
urinary retention, and systemic toxicity. These effects are usually
dose related, being most pronounced when higher concentrations of
local anesthetic are used. Hypotension is a frequent occurrence as
the sympathetic blockade produces peripheral vasodilation and
bradycar- dia, and it is generally the limiting factor in the use
of high concentrations of local anesthetic. For example, El-Baz and
colleagues reported a 23% incidence of systolic blood pressure <
60 mm Hg with heart rate < 60 beats per minute in the first 24
hours after surgery, using 5 mL bolus doses of 0.5% bupivacaine
administered on an as-needed basis through a thoracic epidural
catheter.4 Motor block- ade of the legs interfering with ambulation
is uncommon if the epidural catheter is inserted in the thoracic
region.203 In contrast, weakness of the upper extremities may
develop with an epidural at this level and may be distress- ing to
patients.4 Urinary retention should not occur with thoracic
epidurals if the volume of local anesthetic is limited to that
necessary for blockade of just the thoracic dermatomes. Toxicity
owing to systemic absorption is a rare occurrence at the usual
recommended doses. Effects Related to Epidural Injection of
Opioids. Epidural opioid adverse effects are similar to those
antici- 16 / Advanced Therapy in Thoracic Surgery
- 17. pated with parenteral administration of this class of
drugs. The most frequent are nausea/vomiting, pruritus, urinary
retention, and intestinal hypomotility and somnolence, and the most
important is respiratory depression. Many of these effects are dose
related and occur more frequently in patients who are opioid
naive.204 They are usually mediated by opioid receptors, such that
opioid antagonists should be effective in the prevention and
treatment of these effects.205 Unfortunately, the doses of
antagonist needed for this purpose may overlap with the doses that
will antagonize the analgesic effects; there- fore, other treatment
modalities are usually employed first, and opioid antagonists are
reserved for instances when they fail. Compared with parenteral
opioid admin- istration, the epidural route is associated with a
greater incidence of pruritus and urinary retention, a lower inci-
dence of somnolence, and an equivalent incidence of nausea/vomiting
and respiratory depression.204 Pruritus, nausea/vomiting, and
urinary retention occur less frequently when epidural morphine is
administered as a continuous infusion than as intermittent bolus
injec- tions.4 Respiratory Depression. Respiratory depression is
the most feared complication of epidural opioids. Large series have
reported 0.1 to 3% incidences of clinically signifi- cant
respiratory depression,118,189,203,206208 defined as that requiring
intervention. These represent combined data from patients having a
wide variety of surgical procedures, who have received different
types of medication, adminis- tered by varying protocols, through
catheters inserted at both lumbar and thoracic levels of the spinal
column. The incidence appears to be similar for most opioids,209
with the possible exception of an increased incidence with high
bolus doses of sufentanil.210 After a single bolus dose of epidural
opioid, respiratory depression classically follows two distinct
patterns, which have been designated early and late.204 Early
respiratory depression occurs within the first 2 to 4 hours after
administration of the epidural opioid, has been observed with most
opioids used during epidural analgesia, correlates with high peak
plasma levels, and is thus thought to be primarily due to systemic
absorption of the opioid. Late depression occurs at > 2 to 4
hours after a dose of epidural opioidmost often at 6 to 12
hours204,211 but there have been reports of respiratory depression
persisting as long as 22 hours after administra- tion of a bolus
dose of epidural opioid.205,212,213 This type of respiratory
depression has been evidenced almost exclu- sively with morphine
and is due to the rostral spread of opioid through the
cerebrospinal fluid to the respiratory control centers in the
brainstem. With the frequent use of infusions in recent years, the
concepts of early and late have become obscured, and respiratory
depression may occur at any time. Respiratory depression with
epidural opioids usually presents with a slow respiratory rate,
although there have been reports of severe hypercarbia with a
normal respira- tory rate.214,215 In these examples, somnolence was
present; hence, there is a need for the assessment of the level of
consciousness as an indicator of respiratory depression.
Well-established risk factors for the development of respiratory
depression include older age, American Society of Anesthesiologists
physical status classes III to IV, respiratory disease, sleep apnea
syndrome, elevated intrathoracic pressure, and concomitant use of
systemic opioids and/or other central nervous system depres-
sants.118 More controversial risk factors are bolus injec- tions,
compared with continuous epidural infusions154,216 ; and thoracic
epidural catheters, in contrast to lumbar epidurals.118,130 The
latter has been demonstrated only with morphine. Efforts to prevent
postoperative respiratory depression associated with epidural
opioids have focused on using the minimally effective dose of
epidural opioid, limiting the quantity of all opioids and sedatives
used intraopera- tively, and avoiding concomitant use of parenteral
opioids and other central nervous system depressants.214 Frequent
monitoring of patients for evidence of respiratory depres- sion is
necessary, most often with intermittent assessment of respiratory
rate and level of consciousness every 0.5 to 2 hours, plus
continuous pulse oximetry. Reliance on pulse oximetry alone is not
recommended as a decrease in oxyhemoglobin saturation may be a late
sign of respira- tory depression when supplemental oxygen is used.
Arterial blood gases and/or continuous ventilatory moni- tors may
be considered for high-risk patients.215 Monitoring should be
applied throughout the course of administration of the epidural
opioids and continued for 4 to 6 hours after the last dose or after
stopping an infu- sion.118,204 Morphine is the exception as the
risk of delayed respiratory depression mandates a more protracted
period of monitoring: 12 to 24 hours after the last dose has been
recommended.118,182,204,205,214 The location of the monitoring has
changed over the last few years. In the 1980s it was recommended
that all patients with epidural opioids (with the possible
exception of the obstetric population) be observed in a setting
such as an intensive care unit or postanesthesia care unit.118 More
recently, large series have demonstrated the apparent safety of
caring for these patients on a ward, provided the staff is well
educated and the aforementioned level of monitoring is
maintained.189,203,208,217 Effects Related to Injection of Epidural
Local AnestheticOpioid Combinations. The currently popu- lar
technique of using combinations of opioids and local anesthetics to
decrease the dose of each may reduce the incidence of drug-related
adverse effects, although the Postoperative Analgesia for
Thoracotomy Patients: A Current Review / 17
- 18. evidence for this varies between studies. Most consis-
tently, the incidence and severity of hypotension is less than that
associated with local anesthetic alone,126,171,218 and the
incidence of somnolence is lower than that asso- ciated with
epidural opioids alone.123 At our institution we usually initiate
epidural analgesia therapy with a solu- tion containing fentanyl 10
g/mL and bupivacaine 0.075% and subsequently adjust the two drugs
indepen- dently, in accordance with the adverse effect profile of
the individual patient. contraindications Relative
contraindications to the use of epidural analge- sia include
elevated intracranial pressure, preexisting disease of the spinal
cord or peripheral nervous system, infection, and coagulopathy.
Elevated intracranial pres- sure is listed here because of the risk
of inadvertent dural puncture and subsequent brainstem herniation.
With neurologic disease, there is concern that the epidural
analgesia may exacerbate the underlying disease, as has been
suggested for demyelinating diseases such as multiple sclerosis,219
or that a coincidental deteri- oration in neurologic function may
be incorrectly attrib- uted to the epidural