REVIEW

CURRENT
OPINION New developments in the treatment of acute pain
after thoracic surgery
Cory Maxwell and Alina Nicoara

Purpose of review
This review examines recent advances and findings in the field of pain management in patients undergoing
thoracic surgery.
Recent findings
Acute and chronic postoperative pain continues to remain a major problem and a primary concern
for patients. Although thoracic epidural analgesia is still considered a ‘gold standard’, more evidence
exists that paravertebral blockade has similar efficacy with a better side-effect and safety profile. The
cornerstone of pain management remains a multimodal therapeutic strategy that provides both a central
and a peripheral block by combining regional techniques with opioid and nonopioid analgesics.
Summary
Pain after thoracic surgery has a profound impact on perioperative outcome. Beyond the immediate
perioperative period, acute pain contributes to the development of the debilitating chronic pain syndrome.
Going forward, both procedural and pharmacologic interventions for acute and chronic pain should be
studied in definitive multicenter, well designed randomized clinical trials.
Keywords
epidural analgesia, multimodal, pain, paravertebral block, thoracic surgery

INTRODUCTION to control immediate incisional and inflammatory

Lung cancer is the most common cancer worldwide
and is predicted to be a leading cause of cancer death
in the USA in 2013. Also, in the USA, an estimated
17 990 cases of esophageal cancer will be diagnosed
in 2013, and 15 210 deaths are expected from the
disease [1]. Thousands of patients annually undergo
surgical resection of the lung and esophagus. In
addition, thoracotomies are increasingly utilized
to provide access in patients undergoing cardiac,
vascular, orthopedic, and neurosurgical procedures.
Despite our increased knowledge in the pathophysi-
ology and pharmacology of nociception, acute and
chronic postoperative pain continues to remain a
major problem and a primary concern for patients.
Acute surgical pain also contributes to altered
pulmonary mechanics, increased stress response
with altered hormonal and immune response, and
development of chronic surgical pain [2]. In fact, the
severity of acute postoperative pain has been linked
to the development of persistent postoperative
pain [3]. An ideal perioperative analgesia regimen
should facilitate not only relief of acute post-
operative pain but also decrease the burden of
chronic postoperative pain. Although our ability
acute postoperative pain has increased with the
combined use of systemic opioids, regional analge-
sia technique, and other systemic anti-inflamma-
tory medications, a reduction in the incidence and
severity of chronic postoperative pain has not
occurred [4]. Chronic post-thoracotomy pain is
defined as ‘ pain that recurs or persists along a
thoracotomy scar at least 2 months following the
surgical procedure’ [5]. Thoracotomy, along with
limb amputation, represents one of the highest risk
procedures for the development of chronic pain due
to inevitable neurologic injury, which can lead to
a cascade of postinjury neural sensitization and
neuropathic pain. The incidence of chronic pain
varies widely because of difference in the criteria
Division of Cardiothoracic Anesthesiology and Critical Care Medicine,
Department of Anesthesiology, Duke University Medical Center, Durham,
North Carolina, USA
Correspondence to Alina Nicoara, MD, FASE, Box 3094/5691F HAFS,
DUMC Anesthesiology, Erwin Rd, Durham, NC 27710, USA. Tel: +1 919
681 0862; fax: +1 919 681-8994; e-mail: alina.nicoara@dm.duke.edu
Curr Opin Anesthesiol 2014, 27:6–11
DOI:10.1097/ACO.0000000000000029

www.co-anesthesiology.com Volume 27
Number 1
February 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Treatment of acute pain after thoracic surgery Maxwell and Nicoara
KEY POINTS

Pain relief after thoracic surgery is paramount not only
for ethical considerations and patient satisfaction but
also for reducing postoperative pulmonary and cardiac
morbidity and mortality.

Although TEA is still considered a ‘gold standard’,
more evidence exists that paravertebral blockade has
similar efficacy with better side-effect and safety profile.

A multimodal therapeutic strategy that provides both a
central and a peripheral block by combining regional
techniques with opioid and nonopioid analgesics
remains the cornerstone of pain management in
thoracic surgery.
used to classify individuals. It has been reported
at approximately 20–50% for both thoracotomy
and video-assisted thoracic surgery (VATS) with
less clinically relevant and severe pain after VATS
[6,7].
IMPACT OF SURGICAL TECHNIQUE
Possible sources of nociceptive input after thoracic
surgery are multiple and include surgical incision,
intercostal nerve injury or irritation and inflam-
mation of the chest wall, pulmonary parenchyma,
and pleura. Although damage to neural structures
has been identified as the major source of chronic
pain, more recent studies have shown that chronic
pain may have both a neuropathic and a visceral
component (i.e., extensive surgery and pleurec-
tomy). However, the presence of a neuropathic
component correlated with more severe chronic
pain [8]. Intercostal nerve dysfunction can result
from the surgical incision, retraction, trocar place-
ment, and torqueing orentrapment in sutures
during chest closure. Multiple studies have shown
that techniques offering some form of protection to
the intercostal nerve are associated with signifi-
cantly reduced postoperative pain and analgesic
consumption, even up to 12 months after surgery
[9]. Koop et al. [10] compared intercostal nerve
preservation through careful dissection during
surgical incision and protection during retraction
with intercostal nerve sacrifice for surgical reasons
(massive pleural adhesions, tumor infiltration,
and extrapleuralpneumonectomy) and found that
patients with preserved intercostal nerves had
less acute postoperative pain by visual analogue
score (VAS), earlier mobilization, a lower rate
of pneumonia, lower mean hospital stay, and less
post-thoracotomy pain syndrome at 3 and 6 months
follow-up. Allama [11] prospectively randomized
0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
patients undergoing thoracotomy into two groups:
one group underwent closure with an intercostal
muscle flap and intracostal sutures (made by drilling
holes in the rib) and one group underwent closure
with pericostal sutures (placing sutures around the
rib). The postoperative pain score throughout the
first week was significantly lower in the intercostal
muscle flap/intracostal suture group, which also
had significantly earlier ambulation, return to daily
activities, and lower doses of analgetic use. How-
ever, no difference in pain score at 3 or 6-month
follow-up was observed. Even if intracostal sutures
are placed, Bayram et al. [12] showed that rib
approximation without intercostal nerve com-
pression was associated with less post-thoracotomy
pain by VAS. Numerous studies in the past have
focused on the type of surgical incision for thora-
cotomy. Sakakura et al. [13] retrospectively reviewed
patients who underwent posterolateral or antero-
axillary thoracotomy. The investigators found that
up to 2 months postoperatively, antero-axillary
thoracotomy patients had less pain compared with
the posterolateral thoracotomy patient group. It was
also found that intercostal bundle sparing edge-
closure techniques reduced postoperative pain sig-
nificantly (up to 12 months) when compared with
the conventional closure. The use of an intercostal
muscle flap prior to rib retraction resulted in less
postoperative pain up to 1 month after the opera-
tion. More recently, a meta-analysis of relevant
studies compared the muscle-sparing thoracotomy
with the conventional posterolateral thoraco-
tomy [14]. The investigators found that the
muscle-sparing thoracotomy group experienced less
postoperative pain up to 1 month after surgery,
however, there was no difference in spirometry,
mortality, or perioperative complications. Although
the existent literature has inherent limitations,
there is growing evidence supporting the hypothesis
that avoidance of nerve injury and entrapment
helps reduce postoperative pain.
REGIONAL TECHNIQUES
Over the years, a large number of techniques and
various pharmacologic treatments have been devel-
oped and implemented for an adequate control
of acute post-thoracotomy pain and a reduced
incidence of chronic pain. The Procedure Specific
Postoperative Pain Management (PROSPECT) group
has published a proposed algorithm for acute
pain management after thoracotomy based on exist-
ing evidence (Fig. 1) on the use of regional tech-
niques and multimodal analgesia [15]. It is unclear,
however, how this algorithm applies to minimally
invasive procedures.
www.co-anesthesiology.com 7
 Thoracic anesthesia

Overall recommendations for postoperative pain management for thoracotomy

Preoperative Preoperative patient assessment

Recommended regional analgesic techniques: Alternative regional analgesic techniques:

Either may be used if possiblea If epidural analgesia and paravertebral block
are not possible

Thoracic epidural Paravertebral LA Single bolus

LA+opiod+epinephrine Bolus dose spinal opioid
Bolus dose

Thoracic epidural
Operative techniques
Intraoperative

LA+opiod+epinephrine
Continuous infusion – Muscle–sparing thoracotomy if
surgical requirements allow
– Consider closure technique
(nerve compression)
Paravertebral LA Intercostal LA
Continuous infusion Continuous infusion

Thoracic epidural Paravertebral LA Intercostal LA

LA+opiod+epinephrine Continued Continued
Continued 2–3 days postop 2–3 days postop 2–3 days postop

Expected high intensity pain

IV PCA strong opiod
VAS ≥ 50 mm
Postoperative

+ COX–2INSAIDI
Paracetamol
Expected medium intensity pain
VAS > 30 < 50 mm

Paracetamol
+ NASAIDICOX–2
+ weak opiod

Expected low intensity pain

VAS ≤ 30 mm

Paracetamol
+ NASAIDICOX–2

a
Either thoracic epidural LA + opiod + epinephrine or paravertebral block with LA is recommended as the primary analgesic
approach; further studies on efficacy and safety are necessary to determine which technique is superior

FIGURE 1. Algorithm proposed by the PROSPECT Working Group for pain management following thoracotomy
(www.postoppain.org) [15]. COX-2, cyclooxygenase 2; LA, local anesthetic; PROSPECT, Procedure Specific Postoperative
Pain Management; VAS, visual analog scale.

A widespread belief among clinicians is the con-
cept of pre-emptive analgesia. The assumption that
introducing an analgesic regimen before the appli-
cation of noxious stimuli will prevent sensitization
of the nervous system and reduce the incidence and
severity of chronic pain is very appealing. However,
the supporting evidence is conflicting [16,17].
Epidural analgesia and paravertebral block
Thoracic epidural analgesia (TEA) remains the gold
standard for pain relief following thoracic surgery
[15]. A recent prospective, randomized, double-
blinded trial compared the results of continuous
epidural bupivacaine analgesia with and without
hydromorphone to continuous paravertebral anal-
gesia with bupivacaine in patients undergoing
&
thoracotomy [18 ]. Of note, the paravertebral
catheters were placed by the surgeons under direct
visualization at the conclusion of the surgical pro-
cedure. This study found that TEA with bupivacaine
and a hydrophilic opioid, hydromorphone, pro-
vided enhanced analgesia compared with TEA or
continuous paravertebral infusion with bupivacaine
alone. Also, in the TEA with bupivacaine alone
group, the increased basal rates required to achieve
analgesia resulted in hypotension more frequently
underscoring the benefit of synergistic activity. The

8 www.co-anesthesiology.com Volume 27
Number 1
February 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Treatment of acute pain after thoracic surgery Maxwell and Nicoara
study is in agreement with previous retrospec-
tive studies, which suggests that continuous para-
vertebral infusion of local anesthetic appears to
provide acceptable analgesia for post-thoracotomy
pain. A prospective, multicenter, observational
study in the UK looked at the relationship between
mode of analgesia and outcome in patients under-
going pneumonectomy [19]. The investigators
found that the most common type of analgesia used
was epidural (61%) followed by paravertebral infu-
sion (31%). The primary outcome was defined as
major complications such as significant arrhyth-
mias requiring antiarrhythmic, hemodynamic
instability requiring inotropes, severe respiratory
complications requiring mechanical support (con-
tinuous positive airway pressure and noninvasive or
invasive ventilation), unexpected ICU admissions,
further surgery, or 30-day mortality. The most inter-
esting finding of the study was the increased inci-
dence of major complications in the epidural group
spread across multiple complications. Some of these
complications are known to be associated with the
use of epidural (such as hypotension) but others,
such as arrhythmias requiring antiarrhythmic
therapy, respiratory complications requiring venti-
latory support, and the need for further surgery, are
not. This finding could not be explained through
difference in acuity of the surgical patients, extent of
surgery, or differences in postoperative care across
centers. As previous studies have suggested a high
rate of epidural failure [20,21], it is possible that the
failure of epidurals led to inadequate analgesia,
which resulted in higher major complications in
the epidural group; however, the data on epidural
failure rate were not available in this study. The
authors of the study suggest using caution in inter-
preting and extrapolating these results to other
patient populations because of the inherent limita-
tions of a nonrandomized, observational study
design. In patients undergoing Ivor-Lewis esopha-
gectomy, a dual-epidural technique targeting thora-
cic and abdominal surgical sites has been compared
with a single thoracic epidural catheter [22]. The
dual-epidural technique significantly improved
analgesia and was associated with a 50% reduction
in the combined rate of major postoperative com-
plications such as anastomotic leak, pulmonary
complications, sepsis, and new-onset atrial fibrilla-
tion.
Paravertebral nerve blockade (PVB) can be used
as single injections at multiple dermatomes or
paravertebral catheters with continuous infusion.
PVB can be placed percutaneously using a loss-of-
resistance technique, however, ultrasound guidance
is well described and can improve the accuracy of
paravertebral catheter placement and minimizes the
0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
risk of pleural puncture [23]. Recent studies suggest
that PVB provides comparable analgesia to epidural
infusion with greater hemodynamic stability, a
better short-term side-effect profile, and better pres-
ervation of pulmonary function [24,25]. Because of
its similar pain relief efficacy and seemingly superior
safety profile, PVB is particularly useful when
epidural placement is contraindicated. In a recent
study, Katayama et al. [26] observed no compli-
cations related to the paravertebral catheters placed
by the surgeon under direct vision in patients who
underwent thoracotomy and were not eligible for
epidural catheter placement.
Often reported advantages of paravertebral
blocks over epidurals include lower risk of compli-
cations such as bleeding, spinal, and local anesthetic
toxicity. However, in all regional anesthetic tech-
niques the incidence of clinically significant side-
effects is low, making it challenging to achieve
sufficient power for clinical study. Systemic local
anesthetic toxicity from continuous paravertebral
infusion leading to seizure, aspiration, and ulti-
mately death has been reported [27]. Potential con-
tributing factors in this case could have been small
patient size, malnutrition, extensive surgical disrup-
tion of the pleura, and inappropriate bolus admini-
stration.
Although there is no definite proof that PVB is
superior to epidural analgesia in the quality of pain
control, there is a trend in literature that favors the
use of PVB because of its similar efficacy and better
safety and side-effect profile. Of note, in most
studies the paravertebral catheters have been placed
under direct vision by the surgeon. There is no defi-
nite evidence that the use of PVB has an impact on the
incidence or severity of chronic pain.
INTERCOSTAL AND INTRAPLEURAL
BLOCKS
Intercostal analgesia has appeal because of ease of
placement; it can be administered as single injection
or as a continuous infusion via placement of a
catheter. A recent prospective, randomized trial
compared TEA with single-shot intercostal block
and intravenous patient-controlled analgesia with
morphine in patients undergoing thoracotomy [28].
The patients in the intercostal group experienced
higher pain scores. Also, pulmonary function eval-
uated by spirometry was better preserved in the
epidural group. Intrapleural analgesia has been
advocated as an alternative to intercostal nerve
block. Major limitations of this technique are the
unpredictability of systemic absorption of the local
anesthetic and loss of local anesthetic delivered
&&
through the chest tubes [29 ].
www.co-anesthesiology.com 9
 Thoracic anesthesia
MULTIMODAL ANALGESIA
Although regional anesthesia remains a mainstay in
the treatment of pain associated with thoracic
surgery, many patients may not be candidates for
regional analgesia techniques due to coagulopathy,
infection, or refusal. Multimodal analgesia follows
the concept that agents with different mechanisms
of analgesia may have synergistic effects in prevent-
ing and treating acute pain when used in combi-
&&
nation [30 ]. In addition, circulating humoral
inflammatory factors induce central sensitization
and may contribute to the development of chronic
pain, providing further scientific justification for
using multimodal systemic analgesia.
Oral acetaminophen has a well established role
in perioperative analgesia. After gaining approval by
the Food and Drug Administration in the USA in
2010, intravenous acetaminophen quickly became
adopted for utilization in thoracic surgery. In the
perioperative period, the intravenous formula-
tion may have some advantages given its reliable
pharmacokinetics and ease of administration. In
a double-blind, randomized, placebo-controlled
study, acetaminophen decreased post-thoracotomy
ipsilateral shoulder pain when given pre-emptively
and for the first 48 h postoperatively in patients
receiving TEA [31].
NSAIDs have been extensively investigated in
the perioperative period; their use improves analge-
sia, reduces opioid requirements, and reduces
opioid-related side-effects [32]. Cyclooxygenase-2
inhibitors are sometimes preferred in the peri-
operative period given their decreased effect on
platelet function. A recent randomized, double-
blind, placebo-controlled study in patients under-
going thoracotomy investigated the potential
benefits of oral celecoxib on postoperative analgesia
when combined with TEA. Pain scores were signifi-
cantly lower at rest and with coughing in the
celecoxib group compared with the control group.
Satisfaction with postoperative analgesia was also
significantly greater at postoperative day 2 in the
celecoxib group [33]. In a small randomized, double-
blind study, Esme et al. [34] found that the addition
of flurbiprofen to tramadol in patients undergoing
thoracotomy, resulted in reduced postoperative
pain, reduced mean additional analgesic consump-
tion, and a mitigated inflammatory response as
demonstrated by reduced levels of acute phase reac-
tants such as C-reactive protein and interleukin-6.
There is no current evidence, however, that the
NSAID use prevents the development of chronic
post-thoracotomy pain.
Ketamine is an antagonist of the N-methyl
D-aspartate receptor known to be involved in cen-
tral sensitization and neuropathic pain. Addition of
10 www.co-anesthesiology.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
low-dose ketamine to opiate patient-controlled
analgesia following thoracic surgery showed the
practice to be safe while reducing pain [35], reducing
opiate consumption, and possibly improving respir-
atory mechanics [36], with an incidence of central
nervous system side-effects comparable to mor-
phine [37]. Unfortunately, recent studies have failed
to show the hypothesized benefit of a reduced inci-
dence of chronic pain with ketamine [38,39].
Gabapentin and pregabalin have demonstrated
efficacy in multiple neuropathic pain conditions
[40]. The results of multiple trials with gabapenta-
noid agents in patients undergoing thoracic surgery
have been disappointing. Kinney et al. found that a
single 600 mg dose of gabapentin in addition to
epidural analgesia did not reduce pain scores
or opioid consumption following thoracotomy.
Similarly, Huot et al. found that a single 1200 mg
dose of gabapentin administered preoperatively
did not reduce the incidence or severity of post-
thoracotomy shoulder pain in patients receiving
TEA. Multiple dosing regimens may be beneficial
in reducing acute or chronic post-thoracotomy
pain, however, more robust studies are required.
OTHER TECHNIQUES
Cryoanalgesia has been proposed as an adjunct to
managing acute postoperative pain and preventing
chronic pain in thoracic surgery. Recent studies
have raised concerns regarding cryoanalgesia. Ju
et al. [41] showed that more patients rated their
chronic pain intensity as moderate or severe in
the cryoanalgesia group and stated that their pain
interfered with daily activities. A more recent study
showed similar results. Mustola et al. [42] found that
the cryoanalgesia group had more neuropathic type
pain compared with the epidural-alone group after
posterolateral thoracotomy.
Transcutaneous electrical nerve stimulation
(TENS) has also been studied in the setting of thora-
cic and cardiac surgery. A recent systematic review
and meta-analysis of 11 randomized placebo-con-
trolled trials in patients undergoing thoracic surgery
or cardiac surgery, has shown that TENS associated
with pharmacological analgesia promoted greater
pain relief after thoracic surgery [43].
CONCLUSION
Growing evidence shows that multimodal analgesia
combining regional analgesia techniques and
systemic analgetics reduce the severity of acute
pain after thoracic surgery with still unknown
impact on the incidence and severity of chronic
pain. According to the PROSPECT group, 70% of
Volume 27
Number 1
February 2014
 Treatment of acute pain after thoracic surgery Maxwell and Nicoara
patients experience moderate-to-severe pain after
surgery [15]. It is, therefore, imperative to treat
the high-risk patient population undergoing thora-
cic surgery with a combination of the tools at our
disposal. Further, randomized trials are required to
establish the role of promising techniques and con-
cepts such as the paravertebral block or pre-emptive
analgesia.
Acknowledgements
No funding was received.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA: Cancer J Clin
2013; 63:11–30.
2. Gerner P. Postthoracotomy pain management problems. Anesthesiol Clin
2008; 26:355–367; vii.
3. Reuben SS, Yalavarthy L. Preventing the development of chronic pain after
thoracic surgery. J Cardiothorac Vasc Anesth 2008; 22:890–903.
4. Buchheit T, Pyati S. Prevention of chronic pain after surgical nerve injury:
amputation and thoracotomy. Surg Clin North Am 2012; 92:393–407; x.
5. Classification of chronic pain. Descriptions of chronic pain syndromes and
definitions of pain terms. Prepared by the international association for the
study of pain, subcommittee on taxonomy. Pain Suppl 1986; 3:S1–S226.
6. Mongardon N, Pinton-Gonnet C, Szekely B, et al. Assessment of chronic pain
after thoracotomy: a 1-year prevalence study. Clin J Pain 2011; 27:677–681.
7. Wildgaard K, Ravn J, Nikolajsen L, et al. Consequences of persistent pain after
lung cancer surgery: a nationwide questionnaire study. Acta Anaesthesiol
Scand 2011; 55:60–68.
8. Steegers MA, Snik DM, Verhagen AF, et al. Only half of the chronic pain after
thoracic surgery shows a neuropathic component. J Pain 2008; 9:955–961.
9. Visagan R, McCormack DJ, Shipolini AR, Jarral OA. Are intracostal sutures
better than pericostal sutures for closing a thoracotomy? Interact Cardiovasc
Thorac Surg 2012; 14:807–815.
10. Koop O, Gries A, Eckert S, et al. The role of intercostal nerve preservation in
pain control after thoracotomy. Eur J Cardio-Thorac Surg 2013; 43:808–
812.
11. Allama AM. Intercostal muscle flap for decreasing pain after thoracotomy: a
prospective randomized trial. Ann Thorac Surg 2010; 89:195–199.
12. Bayram AS, Ozcan M, Kaya FN, Gebitekin C. Rib approximation without
intercostal nerve compression reduces postthoracotomy pain: a prospective
randomized study. Eur J Cardio-Thorac Surg 2011; 39:570–574.
13. Sakakura N, Usami N, Taniguchi T, et al. Assessment of long-term post-
operative pain in open thoracotomy patients: pain reduction by the edge
closure technique. Ann Thorac Surg 2010; 89:1064–1070.
14. Li S, Feng Z, Wu L, et al. Analysis of 11 trials comparing muscle-sparing with
posterolateral thoracotomy. Thorac Cardiovasc Surg 2013. [Epub ahead of
print]
15. Procedure specific postoperative pain management. Thoracotomy 2011.
http://www.postoppain.org [Accessed 2 October 2013].
16. Bong CL, Samuel M, Ng JM, Ip-Yam C. Effects of preemptive epidural analgesia
on postthoracotomy pain. J Cardiothorac Vasc Anesth 2005; 19:786–793.
17. Moiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review
of pre-emptive analgesia for postoperative pain relief: the role of timing of
analgesia. Anesthesiology 2002; 96:725–741.
18. Grider JS, Mullet TW, Saha SP, et al. A randomized, double-blind trial
& comparing continuous thoracic epidural bupivacaine with and without opioid
in contrast to a continuous paravertebral infusion of bupivacaine for post-
thoracotomy pain. J Cardiothorac Vasc Anesth 2012; 26:83–89.
An excellent clinical trial comparing different regimens of epidural analgesia and
continuous paravertebral analgesia.
19. Powell ES, Cook D, Pearce AC, et al. A prospective, multicentre, observa-
tional cohort study of analgesia and outcome after pneumonectomy. Br J
Anaesth 2011; 106:364–370.
0952-7907 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
20. Davies RG, Myles PS, Graham JM. A comparison of the analgesic efficacy and
side-effects of paravertebral vs epidural blockade for thoracotomy: a sys-
tematic review and meta-analysis of randomized trials. Br J Anaesth 2006;
96:418–426.
21. Pratt WB, Steinbrook RA, Maithel SK, et al. Epidural analgesia for pancrea-
toduodenectomy: a critical appraisal. J Gastrointest Surg 2008; 12:1207–
1220.
22. Brown MJ, Kor DJ, Allen MS, et al. Dual-epidural catheter technique and
perioperative outcomes after ivor-lewis esophagectomy. Reg Anesth Pain
Med 2013; 38:3–8.
23. Renes SH, Bruhn J, Gielen MJ, et al. In-plane ultrasound-guided thoracic
paravertebral block: a preliminary report of 36 cases with radiologic
confirmation of catheter position. Reg Anesth Pain Med 2010; 35:212–
216.
24. Pintaric TS, Potocnik I, Hadzic A, et al. Comparison of continuous thoracic
epidural with paravertebral block on perioperative analgesia and hemody-
namic stability in patients having open lung surgery. Reg Anesth Pain Med
2011; 36:256–260.
25. Scarci M, Joshi A, Attia R. In patients undergoing thoracic surgery is para-
vertebral block as effective as epidural analgesia for pain management?
Interact Cardiovasc Thorac Surg 2010; 10:92–96.
26. Katayama T, Hirai S, Kobayashi R, et al. Safety of the paravertebral block in
patients ineligible for epidural block undergoing pulmonary resection. Gen
Thorac Cardiovasc Surg 2012; 60:811–814.
27. Fagenholz PJ, Bowler GM, Carnochan FM, Walker WS. Systemic local
anaesthetic toxicity from continuous thoracic paravertebral block. Br J
Anaesth 2012; 109:260–262.
28. Meierhenrich R, Hock D, Kuhn S, et al. Analgesia and pulmonary function after
lung surgery: is a single intercostal nerve block plus patient-controlled
intravenous morphine as effective as patient-controlled epidural anaesthesia?
A randomized noninferiority clinical trial. Br J Anaesth 2011; 106:580–589.
29. Kaplowitz J, Papadakos PJ. Acute pain management for video-assisted
&& thoracoscopic surgery: an update. J Cardiothorac Vasc Anesth 2012;
26:312–321.
Excellent review of analgesic modalities with specific application for patients
undergoing VATS.
30. Young A, Buvanendran A. Recent advances in multimodal analgesia.
&& Anesthesiol Clin 2012; 30:91–100.
Excellent review on recent advances in pharmacologic agents for multimodal
analgesia.
31. Mac TB, Girard F, Chouinard P, et al. Acetaminophen decreases early
postthoracotomy ipsilateral shoulder pain in patients with thoracic epidural
analgesia: a double-blind placebo-controlled study. J Cardiothorac Vasc
Anesth 2005; 19:475–478.
32. Maund E, McDaid C, Rice S, et al. Paracetamol and selective and non-
selective nonsteroidal anti-inflammatory drugs for the reduction in morphine-
related side-effects after major surgery: a systematic review. Br J Anaesth
2011; 106:292–297.
33. Senard M, Deflandre EP, Ledoux D, et al. Effect of celecoxib combined with
thoracic epidural analgesia on pain after thoracotomy. Br J Anaesth 2010;
105:196–200.
34. Esme H, Kesli R, Apiliogullari B, et al. Effects of flurbiprofen on crp, tnf-alpha,
il-6, and postoperative pain of thoracotomy. Int J Med Sci 2011; 8:216–
221.
35. Carstensen M, Moller AM. Adding ketamine to morphine for intravenous
patient-controlled analgesia for acute postoperative pain: a qualitative review
of randomized trials. Br J Anaesth 2010; 104:401–406.
36. Michelet P, Guervilly C, Helaine A, et al. Adding ketamine to morphine for
patient-controlled analgesia after thoracic surgery: influence on morphine
consumption, respiratory function, and nocturnal desaturation. Br J Anaesth
2007; 99:396–403.
37. Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant
analgesic to opioids: a quantitative and qualitative systematic review. Anesth
Analg 2004; 99:482–495; table of contents.
38. Mendola C, Cammarota G, Netto R, et al. Sþ -ketamine for control of
perioperative pain and prevention of post thoracotomy pain syndrome: a
randomized, double-blind study. Minerva Anestesiologica 2012; 78:757–
766.
39. Ryu HG, Lee CJ, Kim YT, Bahk JH. Preemptive low-dose epidural ketamine for
preventing chronic postthoracotomy pain: a prospective, double-blinded,
randomized, clinical trial. Clin J Pain 2011; 27:304–308.
40. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuro-
pathic pain and fibromyalgia in adults. The Cochrane database of systematic
reviews 2011; CD007938.
41. Ju H, Feng Y, Yang BX, Wang J. Comparison of epidural analgesia and
intercostal nerve cryoanalgesia for postthoracotomy pain control. Eur J Pain
2008; 12:378–384.
42. Mustola ST, Lempinen J, Saimanen E, Vilkko P. Efficacy of thoracic epidural
analgesia with or without intercostal nerve cryoanalgesia for postthoracotomy
pain. Ann Thorac Surg 2011; 91:869–873.
43. Sbruzzi G, Silveira SA, Silva DV, et al. Transcutaneous electrical nerve
stimulation after thoracic surgery: systematic review and meta-analysis of
11 randomized trials. Rev BrasCir Cardiovasc 2012; 27:75–87.
www.co-anesthesiology.com 11