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Eur J Anaesthesiol 2016; 33:160–171
ig
Fro
CoTe
02
REVIEW
Current issues in postoperat
ive pain managementNarinder Rawal
Postoperative pain has been poorly managed for decades.Recent surveys from USA and Europe do not show any majorimprovement. Persistent postoperative pain is common aftermost surgical procedures, and after thoracotomy and mas-tectomy, about 50% of patients may experience it. Opioidsremain the mainstay of postoperative pain treatment in spiteof strong evidence of their drawbacks. Multimodal analgesictechniques are widely used but new evidence is disappoint-ing. Regional anaesthetic techniques are the most effectivemethods to treat postoperative pain. Current evidencesuggests that epidural analgesia can no longer be con-sidered the ‘gold standard’. Perineural techniques are goodalternatives for major orthopaedic surgery but remain under-used. Infiltrative techniques with or without catheters areuseful for almost all types of surgery. Simple surgeon-deliv-ered local anaesthetic techniques such as wound infiltration,preperitoneal/intraperitoneal administration, transversusabdominis plane block and local infiltration analgesia can
ht © European Society of Anaesthesiology. Un
m the Department of Anaesthesiology and Intensive Care, University Hospital, Ore
rrespondence to Narinder Rawal, Professor, Department of Anaesthesiology and Il: +46 70 6305567; e-mail: [email protected]
65-0215 Copyright � 2016 European Society of Anaesthesiology. All rights reser
play a significant role in improvement of postoperative care,and the last of these has changed orthopaedic practice inmany institutions. Current postoperative pain managementguidelines are generally ‘one size fits all’. It is well known thatpain characteristics such as type, location, intensity andduration vary considerably after different surgical pro-cedures. Procedure-specific postoperative pain manage-ment recommendations are evidence based, and also takeinto consideration the role of anaesthetic and surgical tech-niques, clinical routines and risk–benefit aspects. The role ofacute pain services to improve pain management and out-come is well accepted but implementation seems challen-ging. The need for upgrading the role of surgical ward nursesand collaboration with surgeons to implement enhancedrecovery after surgery protocols with regular audits toimprove postoperative outcome cannot be overstated.
Published online 27 October 2015
Introduction
Pain relief after surgery continues to be a major medicalchallenge. Poorly managed postoperative pain may delay
discharge and recovery, and result in the patient’s inability
to participate in rehabilitation programmes, leading to poor
outcomes. Recent advances include better understanding
of pain mechanisms, physiology and pharmacology, pub-
lication of guidelines, establishment of acute pain services
(APSs), initiatives such as ‘pain as the fifth vital sign’ and
availability of new drugs and devices. However, these
advances have not led to any major improvements, and
undertreatment of postoperative pain continues as a con-
siderable problem worldwide.1,2
Prevalence of postoperative pain – stillappalling numbersA leading group of postoperative pain researchers has
commented on the current ‘. . . appalling high rates of
significant postoperative pain’.3 A 2011 report from the
US National Institutes of Health states that more than
80% of patients suffer postoperative pain, with fewer than
50% receiving adequate pain relief.4 US surveys from
1993, 2003 and 2012 have shown that postoperative pain
is common and remains undertreated, and that distri-
bution and quality of perceived pain have remained
largely unchanged.5
A European survey which included 746 hospitals con-
cluded that the management of postoperative pain was
suboptimal. Among the problems identified in this 2008
report were absence of pain assessment in 34% of institu-
tions, absence of documentation in 56% of institutions
and no written protocols in 75% of institutions.6 A simi-
larly disappointing picture emerged from a recent US
survey of 301 hospitals (101 teaching hospitals). There
were no written protocols in 45% of hospitals, and intra-
venous patient-controlled analgesia (PCA) was the most
common method to treat pain. Interestingly, this was
managed by surgeons in 75% of hospitals; nurses were not
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bro, Sweden
ntensive Care, University Hospital, 70132 Orebro, Sweden
ved. DOI:10.1097/EJA.0000000000000366
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Postoperative pain management 161
allowed to adjust PCA in 38% of hospitals, epidurals in
57% of hospitals and perineural catheters in 79% of
hospitals.7
Certain categories of patients are at a greater risk of being
undertreated including the pregnant, the paediatric, the
elderly, the opioid tolerant and the patient undergoing
ambulatory surgery.
Persistent postoperative painPersistent postoperative pain (PPP) is common, causes
disability, lowers quality of life and has economic
implications; it is a major cause of chronic pain and
therefore an important public health problem.8 Severe
PPP affects 2 to 10% of adults undergoing surgery.9
Worldwide, about 235 million patients undergo surgery
annually, and this means that millions of patients suffer
from the consequences of PPP. The reported incidence
of PPP is variable; after some common operations such as
thoracotomy, mastectomy, coronary artery bypass and
hernia repair, the incidence can be 30 to 50%. After limb
amputation, the risk is even higher.10 Over 20 surgical,
psychosocial and patient-related genetic and environ-
mental risk factors have been identified. These include
preoperative factors such as anxiety, depression, impaired
pain modulation, genetic factors, sleep disorders and
catastrophising. In the intraoperative and postoperative
healing phase, the factors to consider are surgical tech-
nique, nerve injury and tissue ischaemia. In the later
postoperative period, the important factors are post-
operative pain hyperalgesia, chemotherapy or radiother-
apy, repeat surgery and a variety of psychosocial
factors.1,8,10,11 No single factor seems to play a dominant
role.
Given the multiplicity of neurotransmitters and pain
pathways involved in the transition from acute to chronic
pain, it is not surprising that there are no definitive
pharmacological interventions to prevent or treat PPP.
It would seem logical that a combination of mechanisms
needs to be targeted by different approaches to inhibit
central sensitisation. Gabapentinoids are considered an
interesting class of drugs because of their analgesic
effects in neuropathic pain as well as their anxiolytic
effects. However, the literature is conflicting. A systema-
tic review of 11 randomised controlled trials (RCTs)
showed that gabapentin decreased the incidence of
PPP,12 whereas a more recent Cochrane review13 and a
meta-analysis 14 dispute this. Of the 11 different analge-
sics evaluated, only intravenous ketamine had a modest
effect.13 A meta-analysis showed that the number needed
to treat for intravenous ketamine versus placebo was 12.
This meta-analysis also reported that reduction of acute
pain intensity may not be linked directly to reduced
prevalence of development of PPP.15 Intravenous keta-
mine may be appropriate in patients undergoing painful
operations, particularly those who are expected to require
large doses of opioids.
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Surgeons can play an important role in reducing PPP by
using minimally invasive and nerve-sparing techniques
such as sentinel node biopsy for mastectomy, thereby
avoiding axillary dissection and intercostal nerve damage.
Thoracoscopic techniques spare intercostal nerves and
avoid the use of rib retractors. Intracostal sutures (versus
pericostal sutures) have been shown to be associated with
lower pain scores up to 3 months after thoracotomy.16
At present, one of the most promising strategies to reduce
PPP seems to be the use of regional techniques. A recent
Cochrane review of 23 RCTs showed that epidural
anaesthesia and paravertebral block, may prevent PPP
after thoracotomy and breast cancer surgery in about one
out of every four to five patients treated. The data
consistently favoured regional anaesthesia, and three
studies favoured wound infiltration for hernia repair, iliac
crest harvesting and vasectomy.17
In conclusion, more than 20 years after the first reports of
development of a chronic pain state lasting months or
years after surgery,1 there is no definitive evidence for the
role of any intervention to prevent or treat this complex
entity. Intravenous ketamine may have a modest role.
Regional anaesthesia techniques show some promise, and
should be used more frequently because they also reduce
the need for opioids. An APS may have a role in identify-
ing at-risk patients and in follow-up after they are dis-
charged home.8 Given the very high prevalence, it is time
to include the risk of PPP in preoperative information
routines, particularly for patients at high risk.
Pharmacological management – no majorbreakthroughsOpioid therapyIn spite of the growing awareness of the value of multi-
modal pain management plans, opioid monotherapy
remains the foundation of postsurgical pain therapy. A
recent retrospective review based on more than 300 000
patients across 380 US hospitals showed that about 95%
of surgical patients were treated with opioids.18 Opioids
are widely used because they are highly effective for
relieving moderate-to-severe postoperative pain, do not
have a ceiling effect and are available in a wide variety of
formulations. There is also a long tradition of decades of
opioid use, familiarity with the technique and accumu-
lated experience. However, opioids have many dose-
limiting side-effects that range from bothersome to
life-threatening, including nausea, vomiting, consti-
pation, oversedation, somnolence and respiratory depres-
sion.1,18 Elderly or sleep apnoeic patients, the obese and
smokers are all at increased risk of oversedation and
respiratory depression. Patients may self-limit their
opioid use to reduce opioid side-effects, but this can lead
to inadequate analgesia. Opioid-related adverse events
have been associated with an increase in overall cost,
length of stay and even decreased survival during in-
hospital resuscitation.19 However, these developments
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162 Rawal
have not resulted in reduced use of opioids. Indeed, the
use of opioids has increased in recent years, both for
inpatients1 and outpatients.20
The introduction of new analgesic drugs has been incred-
ibly slow and hardly any new drugs have come to the
market in the last 50 years.21 Postoperative pain manage-
ment is still based on the use of traditional opioids,
paracetamol, NSAIDs and local anaesthetics. The main
innovations have been in the use of older drugs in new
delivery systems and routes of administration such as
transdermal (fentanyl, buprenorphine), intranasal (fenta-
nyl, sufentanil, diamorphine, ketamine), oral transmuco-
sal (fentanyl) and sublingual (buprenorphine, sufentanil).
The other innovations have been in the development of
extended-release local anaesthetics and epidural mor-
phine (now withdrawn from the market). A transdermal
system using iontophoresis to allow rapid transfer of
fentanyl to the circulation allowed the patient to self-
administer 40 mg of fentanyl with a 10-min lockout time.
This transdermal PCA system was shown to provide
comparable analgesia to that seen with intravenous mor-
phine PCA.22,23 This ‘needle-free PCA system’ was
approved by the US and European regulatory agencies
but was voluntarily withdrawn because of technical pro-
blems. The impressive device is undergoing further
development and might re-emerge.
Multimodal analgesia – much rhetoric, disappointingevidenceThe concurrent use of more than one class of analgesic
drug or technique to target different mechanisms of
analgesia has been advocated to improve analgesia
through additive or synergistic effects while reducing
opioid-induced side-effects.1,24 In general, the main
aim is to reduce or eliminate the use of strong opioids
which are recognised to have many disadvantages and
unacceptable side-effects. A large number of nonopioids
are available including paracetamol, NSAIDs, local
anaesthetics, gabapentinoids, ketamine and glucocorti-
coids. Although the concept of multimodal analgesia is
widely accepted, the literature on the possible harmful
effects of combining analgesics is poorly studied. There is
also surprisingly little evidence to show that using an
arsenal of different analgesics is better than more simple
regimens.25 Meta-analyses have shown beneficial analge-
sic effects when opioids are combined with nonopioid
drugs such as paracetamol, NSAIDs, a2-delta modulators
(gabapentin, pregabalin), a2-agonists (clonidine, dexme-
detomidine), ketamine and magnesium. However, with
the exception of a combination of paracetamol and
NSAIDs, there is no meta-analysis of combinations of
different nonopioids. There is hardly any literature on a
combination of three or more analgesics, which is a
common clinical practice.26 In general, research into
multimodal analgesia has not shown a consistent level
of success because of a large number of variables in
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available studies. These include a variety of analgesics
or analgesic modalities and different doses and drug
combinations, making it difficult to draw relevant con-
clusions.
A recent review of systematic reviews and meta-analyses
showed that the 24-h morphine-sparing effects of non-
opioids as monotherapy are rather modest.27 A systematic
review of adverse effects of nonopioids found that para-
cetamol was associated with trivial adverse effects but the
use of NSAIDs was associated with anastomotic leakage.
Gabapentinoids, especially pregabalin, were associated
with an increased risk of sedation, dizziness and visual
disturbances.14,27,28 There is also increasing concern
regarding substance misuse and abuse of gabapentin29
and pregabalin.30
The concept of multimodal analgesia for managing post-
operative pain was introduced by Kehlet and Dahl in
1993.24 Over the years, they have repeatedly promoted it
in multiple publications.31 However, the implementation
of such techniques in routine clinical practice is appar-
ently challenging.32 A 2012 report from 12 surgical
departments from their own institution showed surpris-
ingly disappointing results. Their data indicated that 75%
of patients were treated with opioids as first choice during
the first three postoperative days and that doses of non-
opioids were inadequate. The quality of pain manage-
ment was unclear because pain scores were not recorded
in most patients. The authors concluded that ‘. . . the use
of multimodal opioid-sparing pain treatment was subop-
timal’.32 In 2006, a group of US experts reviewed the
literature and concluded that there was little evidence of
any benefits of multimodal analgesia, except for the
combination of paracetamol and NSAIDs.33 Eight years
later, a review by one of the two originators of the concept
not only came to a similar disappointing conclusion but
also noted that many patients receiving combination
analgesia may be at increased risk of adverse events.34
So we seem to be back to square one after 20 years of
multimodal analgesia. This does not mean that we should
stop combining nonopioids because the goal of avoiding
strong opioids, though daunting, is still valid. It is time to
shift our focus to evaluate the role of simple, local
anaesthetic-based infiltrative techniques as a primary
component of multimodal analgesia.
The two safest nonopioids available to us are paracetamol
and local anaesthetics. The latter seem to be underused
as an important component of multimodal regimens.
Based on our standard protocol since 1991, every surgical
patient at our hospital receives a combination of para-
cetamol and wound infiltration with bupivacaine (by the
surgeon at the end of surgery).35 Other regional tech-
niques, NSAIDs, opioids or intravenous morphine PCA
are added as necessary. Nearly 25 years of this multi-
modal regimen, in tens of thousands of patients, and
results of repeated audits testify to the remarkable safety
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Postoperative pain management 163
of this regimen (see ‘Acute Pain Services’ below). Wound
infiltration techniques are now recommended as part of
multimodal regimens by several national and inter-
national societies such as the American Society of
Anesthesiologists36 and the Australian and New Zealand
College of Anaesthetists.37
In conclusion, in spite of major drawbacks with the use of
opioids, we have been unable to replace them as the
mainstay of treatment of moderate to severe postopera-
tive pain. In spite of much rhetoric, current evidence
suggests that the advantages of combining paracetamol
and NSAIDs are rather modest, the benefits of combining
other nonopioids overrated, the side-effects generally
ignored and the role of combining more than two non-
opioids largely unknown. Future studies need to address
the role of surgeon-delivered local anaesthetic-based
infiltrative techniques as a first-line component of
multimodal analgesia.
Regional anaesthesia techniquesIn recent years, there has been an increase in the use of
regional techniques for surgery and perioperative pain
management, particularly in patients undergoing obste-
tric, orthopaedic or paediatric surgery.38 By stopping pain
transmission, regional techniques with local anaesthetics
can provide excellent pain control. Multiple routes of
local anaesthetic administration are available. The fol-
lowing is a brief summary of the current status of regional
techniques for postoperative pain.
Epidural techniques – ‘gold standard’ no more!Epidural analgesia is a widely used technique to provide
excellent postoperative pain after major surgery. Several
earlier meta-analyses have shown that the use of the
technique is also associated with other benefits such as
reduced cardiovascular, pulmonary and gastrointestinal
morbidity. Some studies have also shown reduced
mortality. For decades, epidural techniques have been
considered the ‘gold standard’ for pain management after
major surgery. However, more rigorous evaluation of
previous data and newer meta-analyses show less optim-
istic results. Several meta-analyses and data from more
robust trials in patients undergoing major surgery such as
aortic, colonic or gastric procedures failed to show any
reduction in mortality with perioperative epidural analge-
sia compared with general anaesthesia and systemic
opioids.39 The authors of a meta-analysis of 28 RCTs
with more than 2700 cardiac surgery patients did not
recommend epidural analgesia because of its poor risk–
benefit ratio.40 The protective effect of epidural analgesia
against pneumonia after abdominal or thoracic surgery
has decreased over the last 35 years because of an overall
reduction in baseline risk because of changes in surgical
routines including early postoperative mobilisation and
active physiotherapy.41 Furthermore, the debate about
the pulmonary benefits of epidural analgesia is becoming
less relevant with increasing use of endoscopic surgical
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procedures instead of open ones. A review has questioned
the use of epidural analgesia in abdominal surgery.42
There are several meta-analyses showing that the far less
invasive intravenous lidocaine infusion is associated with
many benefits in abdominal surgery such as reduced
duration of ileus, decreased pain scores, lower risk of
postoperative nausea and vomiting (PONV) and shorter
hospital stay.43 There are three meta-analyses showing
that an even simpler and safer evidence-based method to
prevent or ameliorate postoperative ileus is the use of the
humble chewing gum.39,44 Chewing gum therapy is part
of enhanced recovery after surgery (ERAS) protocols in
many institutions.
Epidural analgesia has been promoted as an essential
component of ERAS protocols for colorectal surgery.
Perioperative clinical pathways facilitate postoperative
rehabilitation by optimising analgesia, early oral intake
and ambulation and avoidance of fluid overload.45 ERAS
programmes with a coordinated team approach in imple-
menting the various elements of such protocols have
been shown to reduce morbidity and hospitalisation
times.45,46 Such pathways have been promoted for many
surgical procedures, but those for colorectal surgery are
the most widely studied. However, it remains difficult to
demonstrate supporting evidence for individual com-
ponents.39,45,47 On account of the mediocre to poor
quality of studies, the authors of a Cochrane review
did not recommend ‘fast-track’ (ERAS) as a standard
of care.48 At present, there is no evidence that epidural
analgesia is an essential component of ERAS proto-
cols.39,45 Thus, it appears that the success of ERAS
programmes for colorectal surgery is primarily a result
of a structured, protocol-based approach and a modified
attitude towards postoperative rehabilitation goals. Pain
relief is important, but its role seems to be secondary,
particularly in the increasingly common laparoscopic
procedures. There is no convincing evidence that an
epidural technique is essential or any better than simple
local anaesthetic-based infiltrative techniques.39 The
procedure-specific postoperative pain management
(PROSPECT) group does not recommend epidural
analgesia for the increasingly more common laparoscopic
colonic surgery. Neither is epidural analgesia recom-
mended as the first choice for most other abdominal
procedures including laparoscopic cholecystectomy, hys-
terectomy, prostatectomy and caesarean section.49
The controversy about the role of epidural analgesia in
influencing postoperative morbidity and mortality has
resurfaced with the publication of four new reports50–53
with meta-analyses reporting both reduced50 and
increased51,52 morbidity. A literature review concluded
that epidural analgesia can no longer be considered as a
standard of care after routine surgery.53
Several studies (almost all retrospective) and editorials
have reported that the risks of severe neurological
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164 Rawal
Table 1 Reasons for the diminishing role of epidural analgesia inpostoperative pain management
Re-evaluation of previous data and newer metaanalyses show less impressiveoutcome results regarding postoperative mortality and morbidity
Widespread adoption of prophylactic anticoagulant techniques by surgeons haseliminated the DVT-reducing benefits of EA while creating practical obstaclesfor EA catheter management
EA increasingly unnecessary because of change from open to minimally invasiveand endoscopic surgical techniques – also, many previous inpatientoperations are now day-case or overnight stay procedures
Benefits of EA versus systemic opioids for postoperative pulmonarycomplications have decreased over the years because of overallimprovements in postoperative rehabilitation and physiotherapy routines
EA failure rates can be very high (30 to 47%). Most anaesthesiologists unawareof their failure rates (day 1, day 2, day 3) because audits are not performed inthe vast majority of institutions
Risk of side-effects such as hypotension and urinary retention is relatively high,hindering postoperative mobilisation
Monitoring requirements are labour intensive (at many institutions patientsnursed in high-dependency units or ICU because of shortage of trainedpersonnel)
Availability of several equally effective and far less invasive regional anaesthesiatechniques (see text)
Risks of serious complications (including death) greater than previously believedNo convincing cost-effectiveness data in spite of years of EA useLitigation concerns because of risks of severe neurological complications
DVT, deep vein thrombosis; EA, epidural analgesia.
complications of epidural analgesia are higher than pre-
viously believed.39,54,55 A recent closed claims analysis
from Finland reported six deaths over a period of 9 years.
The risk of neuraxial haematoma was far greater with
epidural analgesia (1 : 26 400) than spinal anaesthesia
(1 : 775 000).56 A much higher risk was noted in a recent
audit report of over 35 000 patients from the USA: cardiac
arrest 1 : 5000, epidural abscess 1:27 000 and epidural
haematoma 1 : 5400.57
In making the decision to use epidural analgesia, the
failure rate has to be taken into consideration. This can
vary from 32% to about 50%.39,53 To be considered
successful, epidurals need to facilitate the early post-
operative mobilisation (‘walking epidural’) that is
required for ERAS protocols and function effectively
for the entire duration of treatment (typically 48 to
72 h). This has to be balanced against the costs of
labour-intensive monitoring requirements; in many hos-
pitals, such patients are still nursed in high-dependency
units or ICUs. Only institutional audits can guide the
clinicians as to whether their epidural analgesia risk–
benefit ratios are acceptable.
Based on current evidence, the main indications for
epidural analgesia could be high-risk patients scheduled
for open major surgery; extensive surgery involving large
areas of the body; centres wherein peripheral regional
techniques have not been introduced and possible future
new indications such as anticancer benefits and preven-
tion of chronic postoperative pain. For labour analgesia,
epidural analgesia remains the ‘gold standard’.
In conclusion, the advantages of epidural analgesia are
not as impressive as formerly believed and the risks are
greater than estimated in the past. Epidural analgesia
may have a role in high-risk patients undergoing open
major vascular or cardiac surgery. In general, the role of
epidural techniques has been decreasing in recent years
for reasons shown in Table 1. Regional anaesthesia
techniques provide the most effective postoperative pain
relief. The risk–benefit equation has shifted away from
epidural analgesia and in favour of less invasive but
equally effective and safer regional anaesthesia tech-
niques (Fig. 1). Epidural analgesia can no longer be
considered the ‘gold standard’ as a routine method for
the management of postoperative pain. The continued
use of epidural analgesia at any institution can only be
justified by results from its own audits. Very few institu-
tions perform regular audits. Consequently, the success
rates of epidural analgesia in each institution remain
largely unknown.
Perineural techniques – effective but underusedIt is well established that perineural techniques are
highly effective and are superior to intravenous opioid
techniques.58 A large number of nerve block techniques
have been reported for almost every part of the body. A
ight © European Society of Anaesthesiology. UnEur J Anaesthesiol 2016; 33:160–171
limitation of the single-injection peripheral nerve block is
the relatively short duration of analgesia. Catheter tech-
niques allow prolonged analgesia. Regardless of the
location of the catheter, continuous perineural tech-
niques are opioid sparing and associated with a reduced
risk of opioid-related side-effects such as PONV and
sedation.58 As these techniques may be as effective as
epidural analgesia but are less invasive with a better
adverse effect profile, they are recommended as the first
choice for major orthopaedic surgical procedures such as
hip or knee replacement surgery.49,59 Several meta-
analyses conclude that peripheral blocks such as femoral
and sciatic are superior to epidural analgesia for knee
replacement.59,60 Systematic reviews have shown that
paravertebral blocks may be as effective as epidural
analgesia after thoracotomy but with a lower risk of
adverse effects such as hypotension, urinary retention,
PONV and pulmonary complications.49,61 Correct identi-
fication of nerves is technically challenging, with an
average failure rate of about 20%.62 Ultrasound-guided
blocks have improved the success rates but have not
eliminated the problem. In some technically challenging
blocks such as 3-in-1 block, catheters may be in an
incorrect position in 60 to 77% of patients.62,63 In
addition, peripheral blocks may be associated with com-
plications such as nerve injury, catheter migration into
blood vessels resulting in local anaesthetic toxicity, pneu-
mothorax despite ultrasound guidance and unintentional
spread of block epidurally or intrathecally. These risks
depend on the site of the block, and fortunately they are
not common. There is an ongoing debate about the risk of
falls due to quadriceps weakness after femoral nerve
block for pain management after total knee replacement.
In recent years, adductor canal block (ACB) performed at
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Postoperative pain management 165
Fig. 1
Before 1980s - GA + i.m. opioids - i.v. opioid PCA after 1990s
1980s - Neuraxial blocks - epidural - spinal opioids - CSE
1990s - Peripheral n. blocks - femoral - femoral-sciatic - lumbar plexus
Currently* - LIA
- Femoral - ACB - Ultra long-acting LA?
*Within multimodal analgesia strategies and ERAS pathways
An example of how postoperative analgesic techniques for knee surgery have evolved over time. Total knee replacement is a common surgicalprocedure and generally considered very painful. ACB, adductor canal block; CSE, combined spinal and epidural; ERAS, enhanced recovery aftersurgery; LA, local anaesthetic; LIA, local infiltration analgesia.
the level of the mid-thigh has been increasingly advo-
cated64 to eliminate the problem (Fig. 1).
Nevertheless, most anaesthesiologists have not been able
to introduce these techniques into their clinical routines.
Studies have shown that the use of perineural techniques
to treat postoperative pain is very low in the USA, Europe
and elsewhere.62,65,66 Data from the US National Center
for Health Statistics showed that regional anaesthesia was
used in only 8% of ambulatory cases.66 A French survey
showed that less than 5% of inpatients received post-
operative analgesia by peripheral nerve blocks and a
surprisingly low 1.5% received epidural analgesia.65 A
recent USA database report from over 400 acute care
hospitals with 191 570 patients undergoing total knee
arthroplasty (TKA) showed that only 12.1% of patients
received postoperative analgesia with a peripheral nerve
block.67
In conclusion, there is convincing evidence about the
efficacy and feasibility of peripheral nerve blocks to
manage pain. Catheter techniques can prolong the
duration of analgesia for an unlimited time. Ultra-
sound-guided blocks have reduced failure rates and
encouraged more anaesthesiologists to use such tech-
niques. However, routine use of these techniques still
remains restricted to a relatively small percentage of
institutions. In ambulatory surgery patients, perineural
yright © European Society of Anaesthesiology. U
catheter techniques for pain management will most likely
be restricted to an even smaller number of institutions
because of safety concerns in the medically unsupervised
patient at home.
Infiltrative techniques – growing andevolving, the way forwardEpidural and perineural catheter techniques are very
effective in controlling postoperative pain, but these
techniques require the expertise of an anaesthesiologist,
are associated with technical failures and catheter man-
agement can be labour intensive. In recent years, several
infiltrative techniques have received increasing attention
as simple and less invasive local anaesthesia-based altern-
atives either alone or as part of multimodal regimens to
treat postoperative pain. These techniques can be single
dose or catheter techniques and are usually surgeon
administered.
The ease of use and safety of local anaesthetics has been
well recognised for decades. Collectively, they serve as
one of the most important classes of drugs in periopera-
tive pain management. The main advantage of local
anaesthetics is that they directly act on the tissue to
which they are applied and do not have the adverse
effects of opioids. Consequently, they should be evalu-
ated further as component of multimodal techniques.
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166 Rawal
Simple surgeon-delivered techniques such as wound
infiltration, preperitoneal/intraperitoneal administration,
transversus abdominis plane (TAP) block and local infil-
tration analgesia (LIA) as single administration or with
catheters placed under direct vision and in collaboration
with anaesthesiologists and the APS can play a significant
role in improvement of postoperative care. A meta-
analysis concluded that even a simple instillation of local
anaesthetic in the peritoneal cavity can provide effective
analgesia, albeit for only about 6 h postoperatively after
gynaecological laparoscopy.68 As some of these tech-
niques are relatively new and others still evolving, there
is a need for further studies to address the many
unanswered questions.
Wound infiltration and catheter infusion techniques –surprisingly effectiveDirect application of local anaesthetics to the surgical site
is a rational approach to block pain transmission from
afferent nociceptive barrage. Local anaesthetics also
inhibit the inflammatory response to injury and may,
therefore, reduce the risk of hyperalgesia. The technique
is simple and inexpensive, and has a good safety profile
with few side-effects. It can be used alone or as part of
multimodal regimens depending on the severity of post-
operative pain. Surgeon-administered wound infiltration
at the end of surgery is a simple and effective technique,
and is used routinely in many hospitals.35,69
Wound catheter infusions (WCIs) should preferably be
called surgical-site catheter infusions because the
catheters are not always strictly in the surgical wound.
The technique involves catheters placed in a number of
sites including subcutaneous, subfascial, preperitoneal,
intraperitoneal, subacromial, intraosseous, intra-articular
and others.62 A systematic review of 44 RCTs showed
that WCI techniques provided effective pain relief at rest
and movement, and reduced opioid use and increased
patient satisfaction, with some limited evidence for
shorter hospital stay. No major adverse effects were
reported, and the rates of wound infection were very
low (0.7%) and similar to those in the control group. WCI
was effective across a variety of surgical procedures
(abdominal, cardiothoracic, orthopaedic and others).70
A more recent meta-analysis of 14 RCTs (756 patients)
focused on ropivacaine for WCI, the authors noting
consistent evidence of effective analgesia and opioid
sparing in a wide range of surgical procedures such as
total knee or hip replacement, and major abdominal and
cardiac surgery.71 Similarly, a meta-analysis of infiltrative
techniques (WCI, TAP, intraperitoneal) versus placebo
for routine analgesia for colorectal surgery concluded that
the infiltrative techniques were associated with lower
pain scores, reduction of opioid requirements, shorter
length of stay and no increase in complications.72
It must be emphasised that all studies with wound
infiltration are not positive. A Cochrane review concluded
ight © European Society of Anaesthesiology. UnEur J Anaesthesiol 2016; 33:160–171
that the beneficial effects of wound infiltration were
modest in patients undergoing laparoscopic cholecystect-
omy.73 Meta-analysis has also shown modest benefits of
wound infiltration in patients undergoing mastectomy
and those undergoing spinal surgery.74
Local infiltration analgesia – game changer inorthopaedic practiceThe LIA technique was introduced by Kerr and Kohan
mainly for controlling pain after total hip arthroplasty
(THA) and TKA.75 In spite of its name, the original LIA
technique is not just infiltration of local anaesthetic but a
multicomponent optimisation package. In addition to
infiltration with a mixture of ropivacaine, adrenaline
and ketolorac into all tissues subject to surgical trauma,
it includes extensive preoperative patient education,
minimally invasive surgery, accelerated postoperative
rehabilitation and structured follow-up care. This is
combined with an intra-articular catheter for analgesic
top-ups, allowing the blockade to last as long as 36 h. Ice
packs and compression bandages are also a part of the
technique. Surgery is performed under spinal anaesthe-
sia. Thrombosis prophylaxis consists of aspirin only.
Postoperative analgesia is provided by paracetamol and
ibuprofen with morphine as a rescue analgesic. Post-
operative mobilisation is started about 4 h after surgery.
In a case series of 325 patients, more than half of those
undergoing surgery could be discharged on the first post-
operative day and most of the remainder were discharged
on the following day. Postoperative pain scores were low
and there were very few thromboembolic complications.
The details of the infiltration technique and the other
components of LIA technique are described elsewhere.75
The LIA technique has achieved widespread acceptance
by orthopaedic surgeons, especially in the Scandinavian
countries, UK, Australia and some other countries.47
Much of the literature is from Denmark, Sweden, Nor-
way, UK, USA and Australia, although none of these
studies has been able to replicate the 1 to 3 days discharge
times reported by Kerr and Kohan. In general, the dis-
charge times are in the range of 3 to 5 days, which is still
much shorter than the pre-LIA hospitalisation times of 6
to 10 days.47 The 2014 report of the Swedish Knee
Arthroplasty Register showed that almost every patient
(97.3%) received LIA for TKA in 2013. However, the
intra-articular catheter was used in only 25.6% of
patients.76
The LIA technique has shown favourable results when
compared with traditional methods of pain relief such as
epidural analgesia77–79 and intrathecal morphine80–82 for
both THA and TKA, and also with femoral nerve block
for TKA.83,84 In comparison with epidural for TKA, LIA
was not only more effective but was also associated with
superior knee function, lower cumulative morphine dose,
faster mobilisation and shorter hospital stay.78,79 LIA with
a catheter for TKA was not only associated with similar
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Postoperative pain management 167
pain scores as with epidural, but also the opioid con-
sumption was reduced and hospital stay was 2 days
shorter in the LIA group.79
A literature review concluded that LIA may be useful for
TKA but not for THA if nonopioid multimodal analgesia
is used.85 However, no evidence was provided to support
this claim. Furthermore, another systematic review of
LIA for THA disagreed and concluded that the tech-
nique was an effective method for THA.86 Two editorials
concluded that LIA for TKA is promising but that further
studies are necessary.69,87
Analgesia for TKA is a good example of how regional
techniques have evolved in recent years. As shown in
Fig. 1, the femoral block was shown first to be an effective
alternative to epidural analgesia49,59 and now there is
increasing evidence that ACB with LIA may be an
effective alternative to femoral block within the frame-
work of ERAS programmes for TKA.64,88,89 LIA was
associated with effective analgesia, improved ambulation
and ability to climb stairs. Combining ACB with LIA was
associated with further increases in ambulation and more
rapid discharge home.88
In conclusion, LIA is a major recent development in
lower extremity joint replacement surgery. In some
institutions, it has been a game changer. In Sweden,
almost every TKA is performed in association with a
LIA technique. Although controlled trials are necessary
to address the many unanswered questions such as the
role of intra-articular catheters and the most appropriate
drug combinations, the technique is here to stay. The
results of ongoing studies with ultra long-acting local
anaesthetics are eagerly awaited.
Intraperitoneal local anaesthetics for abdominal surgery– site of catheter placement may be keyIn a meta-analysis of 30 RCTs, intraperitoneal use of local
anaesthetic in laparoscopic cholecystectomy was shown
to reduce pain, opioid use and the need for rescue
analgesia.90 Literature is now appearing in which WCI
has been compared with other regional techniques. A
meta-analysis of nine RCTs compared WCI with epidural
analgesia in abdominal surgery including liver resection,
colorectal and aortic aneurysm repair concluded that WCI
was associated with comparable pain scores both at rest
and during movement up to 48 h, and with less urinary
retention.91 With increasing published literature, certain
aspects of WCI are becoming clearer. For example, the
importance of catheter positioning was demonstrated in
two studies in patients undergoing open colorectal
surgery. Ropivacaine infusion through a preperitoneally
placed catheter provided effective analgesia, less PONV
and accelerated postoperative recovery.92–94 The tech-
nique has been demonstrated to be superior to epidural
analgesia in terms of analgesia and reduction of hospital
stay.93,94 For caesarean section, the most appropriate
yright © European Society of Anaesthesiology. U
position is subfascial rather than subcutaneous and in
this position, WCI was as effective as epidural analgesia95
or better.96 This catheter placement is recommended by
the PROSPECT group.49
Transversus abdominis plane blocks – increasingevidence of efficacyOwing to the ease of administration and efficacy, TAP
infiltration has been used successfully in bowel surgery,
appendicectomy, hernia repair, umbilical surgery and
gynaecological surgery.97 There is a substantial quantity
of safety and efficacy data which has allowed several
meta-analyses98–100 and a Cochrane review.101 Another
meta-analysis has shown TAP block to be effective for
pain after caesarean section,102 and it is also recom-
mended by the PROSPECT group.49
Current management guidelines are ‘one sizefits all’ – need for procedure-specificrecommendationsAll pain management guidelines advocate generalised
‘one size fits all’ recommendations for the use of analgesic
drugs and techniques. Such guidelines are derived from
different surgical procedures with varying pain charac-
teristics such as type (visceral versus somatic), location,
intensity and duration. The efficacy of an analgesic can
vary depending on a surgical procedure.103 Also, even
similar high pain intensities may be associated with
widely different postoperative morbidity, for example
dental extraction pain versus open thoracotomy or upper
abdominal surgery, the latter procedures are associated
with considerable pulmonary dysfunction.26 In clinical
practice, it is well recognised that there are clear differ-
ences in perception of pain intensity and its con-
sequences across different surgical procedures, for
example thoracotomy versus hysterectomy, or knee
replacement versus hip replacement. Furthermore, the
consequences of surgical technique (open versus endo-
scopic surgery) on postoperative pain and morbidity will
influence the choice of analgesic technique and its risk–
benefit ratio. For example, although epidural analgesia is
very effective for analgesia, it may not have risk–benefit
advantages in thoracoscopic versus thoracotomy and
laparoscopic versus laparotomy procedures. Thus, there
is a need for surgical procedure-specific recommen-
dations.
PROSPECT guidelines are such a source of evidence-
based, procedure-specific recommendations from an
international group of anaesthesiologists and surgeons.
The PROSPECT recommendations are based on sys-
tematic reviews of the literature for a particular surgical
procedure and include randomised studies that evaluate
the role of analgesic drugs and techniques and also the
role of anaesthetic and surgical techniques on postopera-
tive pain. The recommendations also take into consider-
ation clinical routines and risk–benefit aspects. For
nauthorized reproduction of this article is prohibited.Eur J Anaesthesiol 2016; 33:160–171
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168 Rawal
Table 2 RequirementsM for establishing an organised Acute PainService (APS) team
Designated personnel responsible for 24-h serviceRegular pain assessment at rest and movement and maintaining scores below
predetermined thresholdDocumentation of pain scores before and after interventionDocumentation of side-effectsActive cooperation with surgeons to implement analgesic protocols as part of
ERAS programmes to achieve preset goals for postoperative rehabilitationOngoing teaching programmes for ward nurses (drugs and modalities used,
‘standard orders’, PCA pump programming, regional anaesthesia cathetertechniques, recognition and management of adverse effects, monitoringroutines)
Patient education regarding their right to good analgesia and treatment optionsOngoing prospective data collection system for regular audits of risk–benefit of
analgesic techniques and patient-related quality of life outcomesPolicies and procedures for continuous quality improvement
ERAS, enhanced recovery after surgery; PCA, patient-controlled analgesia.M Irrespective of the APS model selected, these are considered to be the essentialrequirements (see text for details).
example, the PROSPECT group does not recommend
epidural analgesia as first-line treatment for a number of
surgical procedures (laparoscopic cholecystectomy, hys-
terectomy, laparoscopic colorectal surgery, THA, TKA,
caesarean section) in spite of its documented analgesic
efficacy in all these procedures.49 Readers are presented
with algorithms and different alternatives to help with
clinical decision making. Implementation of procedure-
specific protocols has been shown to be associated with
significant improvement in pain management.104
PROSPECT recommendations are freely available
online (www.postoppain.org). At present, the following
procedures are online: cholecystectomy; hip replace-
ment; knee replacement; thoracotomy; hysterectomy;
prostatectomy; inguinal hernia surgery; haemorrhoidect-
omy; and mastectomy. The latest procedure to go online
is caesarean section. Among the evidence-based (Level
of Evidence 1, Grade of Recommendation A) recommen-
dations are preoperative gabapentin, Joel-Cohen and
similar transverse incisions (superior to the commonly
used Pfannenstiel incision), nonclosure of peritoneum,
infiltrative techniques such as wound infiltration includ-
ing WCI, iliohypogastric and ilioinguinal blocks, and
TAP block. This again illustrates that the PROSPECT
group also evaluates the role of surgical techniques in
improving postoperative pain. It is proposed that 15 to 20
of the most common surgical procedures will be included.
The recommendations are updated regularly. At present,
PROSPECT is funded and administered by a grant from
the European Society of Regional Anaesthesia and
Pain Therapy.
Acute pain services still ‘work in progress’25 years onThe establishment of an Acute Pain Service has been
accepted as an important tool in the improvement of
postoperative pain management on surgical wards and in
providing safe analgesia with the use of more advanced
techniques such as intravenous opioid PCA, epidural
analgesia and other regional techniques. APS with a
multidisciplinary team approach has received widespread
formal acceptance from national and international organ-
isations.105
It is generally accepted that the problem of undertreated
postoperative pain is best addressed by having an appro-
priate APS organisation. Worldwide, the number of hos-
pitals with an APS seems to be increasing.106 However, a
prevalence of APSs does not mean much in the absence of
established standards for structure and function of an
APS.107 There is evidence that many APSs provide only
a token service because of financial constraints and low
priority.106 A literature review concluded that most APSs
worldwide did not meet basic quality criteria, defined as
regular recording of pain scores at least once a day, written
protocols, dedicated personnel and policies for pain man-
agement during nights and weekends (Table 2).107 In
ight © European Society of Anaesthesiology. UnEur J Anaesthesiol 2016; 33:160–171
Norway and Denmark, the APS numbers have decreased
in recent years, apparently because of increasing imple-
mentation of ERAS programmes. An editorial made a
connection between this reduction in APSs with increased
deaths because of opioid overdose on Norwegian surgical
wards and concluded that APSs and ERAS programmes are
not mutually exclusive and that ERAS programmes should
complement, not replace, APSs.108
Various APS models, with significant differences in struc-
ture and function, have been reported.2 The main
examples include the model described above with 24-h
cover by an anaesthesiologist,2,107 and a ‘low-cost’
specialist nurse-based APS supervised by anaesthesiolo-
gists.35,109 A literature review showed that physician-
based APSs were more common than the nurse-based
APSs.2 Whichever the model selected, an APS should
have a collaborative interdisciplinary approach to mana-
ging postoperative pain. Table 2 shows the requirements
that are generally accepted for a good APS.2,107,110 It is
beyond the scope of this review to debate the pros and
cons of the APS models and how to implement APSs;
these have been addressed elsewhere.109 In any model of
an APS, the role of ward nurses needs to be upgraded if
postoperative pain management is to improve on surgical
wards. Even today, in most institutions and countries,
ward nurses are not allowed to administer opioids through
intravenous lines or local anaesthetics through epidural or
perineural catheters. A 2012 US survey of APSs in 301
hospitals showed that PCA was the most common
method to treat pain and was managed by surgeons in
75% of hospitals. Notably, ward nurses were not allowed
to adjust PCA in 38% of hospitals, epidural analgesia in
57% of hospitals and perineural techniques in 79% of
hospitals.7 Similar disappointing results were reported
from European surveys.6 There is very little information
from low-resource countries, and it is probably even more
disappointing. In physician-based APSs, surgical ward
nurses are required to call the APS anaesthesiologist
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Postoperative pain management 169
every time the patient needs dose adjustments for PCA or
epidural. The patient remains in pain until the physician
arrives, and it is not uncommon that this physician is
relatively inexperienced.110 This system seems time-
consuming, cost-ineffective and inhumane.
Specialist nurse-based, anaesthesiologist-supervised APS
models which cover all patients undergoing surgery (not
just those requiring hi-tech services) address the above
issues by allowing ward nurses to administer intravenous
opioids on demand, programme PCA pumps and adjust
PCA, epidural and perineural techniques as necessary.
Details of this model, including the responsibilities of the
APS anaesthesiologist, APS nurses, ‘section anaesthesiol-
ogist’, surgeon, ward nurse and ‘pain representative’
nurse and surgeon on each ward are described else-
where.108–110 Since the implementation of this model
at our hospital in 1991 and based on audit results, many
changes have taken place over the years. Some of the key
changes have been the change from intramuscular or
subcutaneous to titrated doses of intravenous morphine
administered by ward nurses on every surgical ward;
patient information brochures in 16 languages and video;
regular pain assessment at rest and on movement (every
3 h in awake patients) and documentation of pain scores;
pain assessment tool changed to numerical rating scale
from visual analogue scale; increase from one to three
APS nurses (two of these part time) although the total
number of operations decreased gradually from 20 000 to
about 15 000 per year; annual audit feedback to surgeons
and ward nurses; epidural PCA mode instead of continu-
ous infusion to allow better mobilisation with ‘walking
epidural’; modified analgesic routines to adapt to surgical
ERAS protocols; increased use of perineural techniques
on surgical wards; electronic recording of pain scores; and
the use of hand-held computers by APS nurses to pro-
spectively collect audit data and joining the PAIN OUT
international database for benchmarking of our APS.111
The general principles of this APS model have been
recommended for Swedish hospitals by the Swedish
Medical Association (Svenska Lakaresallskapet) in
2001112 and have also been implemented in several other
countries.2,109,113
This ‘office hours only’ APS nurse-based model does
not provide direct hands-on patient care, nor does it
provide out of hours cover. This model is a resource for
education and training and promotion of good clinical
practice. It relies on the on-call anaesthesiologist being
consulted during nights and weekends. The number of
times these anaesthesiologists are consulted has
decreased over the years; at present, this only happens
occasionally.
In conclusion, it is increasingly clear that the decades-old
problem of undertreated postoperative pain is not
because of lack of effective drugs or techniques but to
a lack of an organised, multidisciplinary approach (APS)
yright © European Society of Anaesthesiology. U
which uses existing treatments. Irrespective of the APS
model, teaching programmes to upgrade the role of ward
nurses, standardised protocols and regular audits are
necessary to address the problem. The role of the last
of these to improve outcomes cannot be overstated.
Acknowledgements relating to this articleAssistance with the review: none.
Financial support and sponsorship: none.
Conflicts of interest: none.
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