INTESTINAL SURGERY e II
Perioperative pain
management in colorectal
surgery
Vinay Ratnalikar
Catrin Williams
Thomas Moses
Abstract
Postoperative pain management has a bearing on postoperative
recovery and outcomes. This is particularly so in Enhanced Recovery
After Surgery (ERAS). Use of proven techniques such as central neu-
raxial blockade, advances in regional analgesic block techniques and
the multimodal combination of drugs with newer range of adjuvant
analgesics are presented. This article discusses pain management
options and practices.
Keywords Adjuvant analgesics; colorectal; intrathecal; regional blocks
Introduction
Enhanced Recovery After Surgery (ERAS) involves various,
multimodal interventions which help to reduce the endocrine, metabolic
and inflammatory stress response to surgery. Main-taining and restoring
organ function enables early mobilization and oral intake in the
postoperative period. Extensive work by Kehlet formalized the concept
and successfully shown the ben-efits of it various components which
have already been in practice for many years. A through preoperative
assessment and optimization of co-morbidities is essential for better
outcome and this has been established beyond doubt. Effective
analgesia and optimal fluid administration can have a significant impact
on postoperative recovery. Despite this knowledge, poorly controlled
postoperative pain continues to be one of the most undesirable effects
following surgery.
Pain pathways
Acute pain is a physiological response that warns us of danger. Pain
processing occurs at three primary sites: (1) the peripheral nerve and
dorsal root ganglion; (2) the dorsal horn of the spinal cord; and (3) the
brain or brainstem (Figure 1). Different
Vinay Ratnalikar MBBS MD FRCA is a Consultant Anaesthetist at ABM
University Health Board, Singleton Hospital, Swansea, UK.
Conflicts of interest: none
BSc(Hons) MB BCh FRCA declared.
Catrin Williams
Anaesthesia at ABM University
BMBCh BA FRCA Health Board, Morriston
Hospital, Swansea, UK. Conflicts
of interest: none declared.
Thomas Moses is a Specialist Registrar in
Anaesthesia at Aneurin Bevan University Health Board, Royal
Gwent Hospital, Newport, UK. Conflicts of interest: none declared.
pharmacological agents work by targeting different sites along this
anatomical pathway. Painful stimuli cause release of neu-rotransmitters
at both peripheral and central levels. Neuro-transmitters acting on
specific receptors can either produce excitation and pain or inhibition
and analgesia. Drugs cause analgesia by either antagonizing the effect
of the excitatory neurotransmitters or by stimulating and/or preventing
the breakdown of inhibitory neurotransmitters.
The WHO step ladder approach to pain relief was first pub-lished in
1986 as a guideline for managing cancer pain. This approach has
become widely accepted and used for the man-agement of pain of all
types. There is some debate as to whether this simple step-wise
approach is still valid but there can be no doubt that it has had a major
impact on how the rationale for treating acute pain has been developed.
What is clear is that a multi-modal approach to postoperative pain relief
is essential. Various drugs and techniques are now used to improve
anal-gesia, reduce opioid consumption and opioid related side-effects.
This article aims to give an overview of some of the established
techniques along with some of the newer adjuvant agents.
Regional analgesia for open surgery
Traditionally and in the early days of ERAS, thoracic epidural analgesia
was considered the ‘gold standard’ for laparotomy and colorectal
procedures. It has been shown to be superior to intravenous opioids in
the management of postoperative pain and also in the reduction in the
pituitary, adrenocortical and sympathetic stress responses to surgery
(Box 1).
However, new evidence suggests that epidural analgesia may be
harmful in colonic surgery. Significantly high failure rates have been
associated with management of epidural analgesia, though it may
apparently look effective in the immediate post-operative period. In
contrast, intrathecal analgesia carries higher insertion rates, does not
require further care, makes early ambulation possible and reduces work
1
load on nursing staff.
The MASTER trial (Multicentre Australian Study of Epidural
Anaesthesia) compared adverse outcomes for high-risk patients
undergoing major abdominal surgery with epidural block or alternative
analgesic strategies with general anaesthesia. This study concluded that
they are unable to demonstrate any sig-nificant effect of epidural
analgesia on the overall frequency of complications after major
abdominal surgery, except for a modest reduction in the incidence of
2
respiratory failure.
There is data to suggest that intrathecal analgesia may be effective in
open surgery. We have found that the postoperative opioid requirement
is minimal with satisfactory pain scores, comparable to laparoscopic
surgery. We have also observed a further postoperative opiate sparing
effect of combining intra-thecal analgesia with ultrasound guided
abdominal wall blocks as discussed later.
is a Specialist
Analgesia for Registrar in
laparoscopic surgery
Laparoscopic resection of the colon was first reported in 1991.
Guidance from the UK National Institute for Health and Clinical
Excellence recommended that all patients considered suitable must be
offered laparoscopic surgery due to the perceived ben-efits (Box 2).
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Please cite this article in press as: Ratnalikar V, et al., Perioperative pain management in colorectal surgery, Surgery (2017), http://dx.doi.org/
10.1016/j.mpsur.2017.05.010
 INTESTINAL SURGERY e II
Site of action for adjuvant analgesics along the pain pathway
Opioids,
ketamine,
gabapentinoids
noradrenergic
serotoninergic
Ascending Dorsal horn
spinothalamic
Figure 1
There is relatively little data regarding the optimum analgesic
technique in laparoscopic colorectal surgery but undoubtedly high-
quality analgesia is needed to prevent delayed recovery. In laparoscopic
surgery, parietal pain is less intense due to smaller incisions but the
visceral component remains the same and the majority of patients
require opioids perioperatively. By 24 hours postoperatively, simple
oral analgesics are usually sufficient with a combination of
paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and
weak opioids.
There are several important differences when comparing lapa-
roscopic to open surgery that can affect the neuraxial block. The
presence of a pneumoperitoneum increases intraoperative cardio-
pulmonary stresses; therefore the effects of a block may be magnified.
Positioning can affect block height and cardio-respiratory physiology,
especially extended periods of steep Tren-delenberg positioning.
Pneumoperitoneum or head down posi-tioning before the drug is fixed
to nervous tissue will result in high block. The abdominal incision is
often smaller, transverse and below the umbilicus which may affect the
decision of which level to insert the block. Shoulder tip pain can be a
problem postoperatively and this cannot be covered by a neuraxial
block. Post-laparoscopic shoulder pain is preventable by evacuating
residual CO2
Local anaesthetic (LA) techniques
LA infiltration techniques and abdominal wall blocks have become
commonplace with advances in ultrasound technol-ogy skills allowing
improvements in the reliability and effi-cacy of blocks. They have come
to prominence as a safe
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Opioids, α2 Local Local Local
agonists anaesthetics, anaesthetics anaesthetics,
α2 agonists NSAIDs
Descending
and
Dorsal root
ganglion
Nerve
Primary endings
afferent
nerve
alternative to a central neuraxial technique in patients who are
coagulopathic, have systemic sepsis or in those who may not tolerate
the haemodynamic sequelae often associated with neuraxial block.
However they are increasingly used electively as part of a multi modal
pain management following abdom-inal surgery.
Wound infiltration
Surgical wound infiltration with LA is a simple low cost well-
recognized technique that reduces the postoperative pain originating
from the surgical incision. However, the duration of analgesia is limited
by the time that LA remains effective; normally between 4 and 8 hours
for commonly used agents. Infiltration with local anaesthetics before
surgical incision, as opposed to infiltration at the end of the procedure,
has the advantage of reducing the amount of analgesia and anaesthesia
required intraoperatively. This should also reduce the noci-ceptive input
and hence preemptively block the N-methyl-D-aspartate-induced wind-
up phenomena and release of inflam-matory mediators. There have
been concerns over the use of incisional infiltration. It was suggested
that infiltration with local anaesthetics might increase the risk of
postoperative wound infection. This concern has not been substantiated
by clinical studies and it appears that local anaesthetics, particu-larly
3
bupivacaine, may have both bacteriostatic and bacteri-cidal actions.
Continuous infusion of LA via catheters placed subcutaneously into the
anterior abdominal wall at the time of surgery has been shown to reduce
opiate consumption following laparoscopic surgery.
2 2017 Published by Elsevier Ltd.
 INTESTINAL SURGERY e II

with a lower incidence of postoperative hypotension and no difference

Benefits of regional anaesthesia compared in the rate of lower respiratory tract infections, post-operative wound
with systemic opioids infection or anastomotic leak between the two groups of patients.
4

1. Lower pain scores

Single-shot blocks appear to be effective immediately post-
2. Longer time to first request for rescue analgesia operatively but any benefit is limited to, at most, the first 24 hours.
3. Fewer requests for rescue analgesia and lower total dose needed Bilateral subcostal and lateral TAP catheters have been shown to
4. Reduced opioid-related adverse effects provide ongoing analgesia comparable to thoracic epidurals after
C Respiratory depression (59%) 5
laparotomy for up to 72 hours. Single-shot blocks are done using
C PONV relatively large volumes of local anaesthetic. There is a potential risk of
C Ileus
inadvertent intravascular injection, intraperitoneal injec-tion and local
5. Reduced overall mortality (30%) anaesthetic toxicity. These risks have been reduced with the use of
6. Earlier discharge home ultrasound to accurately place the block. Reducing the systemic toxicity
7. Lower unplanned re-admission rates by the addition of adjuncts after local anaesthetic blocks has been
8. Higher patient satisfaction scores studied extensively; the most commonly used adjunct being adrenaline.
A recent randomized-controlled trial looked at the addition of a low-
DVT, deep vein thrombosis; PE, pulmonary embolism; PONV, molecular weight dextran to the levobupivacaine for TAP and rectus
post-operative nausea and vomiting sheath blocks in patients undergoing laparoscopic colectomy. The study
Modified from Fischer B. Anaesthesia and intensive care found that the addition of a dextran not only reduced the absorption of
medicine 2003;10:545e548 levobupivacaine from the injection site but also resulted in better
6
analgesia on the first postoperative day.
Box 1

Benefits of laparoscopic surgery Non-opioid-based adjuvant analgesia

1. Smaller incisions The desire to avoid opioids has led to the more widespread use of drugs
2. Reduced postoperative pain more traditionally used in the management of chronic neuropathic pain
3. Reduced time to first mobilization including anticonvulsants (gabapentinoids), N-methyl-D-aspartate
4. Reduced time to first oral intake (NMDA) receptor antagonists (ketamine/ magnesium), membrane
5. Shorter recovery time stabilizers (lidocaine) and a-2 agonists (clonidine/dexmedetomidine).
6. Lower incidence postoperative wound infection Current evidence only supports the use of intravenous lidocaine,
7. Reduced perioperative morbidity
ketamine, the gabapentinoids and a-2 agonists perioperative use (Table
8. Overall shorter inpatient stay
1).

Modified from Hayden et al. CEACCP 2011;11:177e180 Intravenous (IV) lidocaine

Box 2
Abdominal wall plane blocks and anatomy
Innervation of the abdominal wall arises from spinal nerves T7 to L1.
T7 to T12 exit the intercostal spaces to run in between the internal
oblique and transversus abdominis muscles in the transversus
abdominis (TAP) plane. These nerves continue anteriorly to pierce the
rectus sheath and innervate the rectus muscles and anterior abdominal
wall.
Transversus abdominis plane (TAP) block
The TAP block is an abdominal field block that provides anal-gesia to
the parietal peritoneum as well as the muscles and skin of the anterior
abdominal wall. The TAP block is an injection into the transversus
abdominis plane. It is technically simple to perform either using
anatomical landmarks, ultrasound guided or via a surgeon-assisted
approach. TAP blocks can be performed laterally to provide lower
abdominal analgesia or with a sub costal approach to provide blocks
higher up the abdomen.
Rectus sheath block
The sensory blockade for the rectus sheath block is between T7 and T10
segments. A recent review found that ultrasound-guided rectus sheath
catheters are as effective as epidural analgesia but
Lidocaine is a widely available and commonly used amide type local
anaesthetic. It exerts its pharmacological actions by block-ing sodium
channels in neural tissues so interrupting neuronal transmission.
Although the exact way in which IV lidocaine provides systemic
analgesia is unknown it is thought to be related to this mechanism. It
has been suggested that the bene-ficial effects of epidural and peripheral
local anaesthetic doses may in part be due to a systemic effect of these
agents. There is an increasing body of evidence for the use of IV
7
lidocaine in both open and laparoscopic colorectal surgery. A meta-
analysis of randomized controlled trials assessing IV lidocaine infusions
on patients undergoing laparoscopic surgery showed a favourable effect
on pain control, postoperative nausea and vomitting (PONV), ileus and
8
pulmonary function postoperatively. Many of the clinical trials looking
at IV lidocaine suggest that the effect on gut motility is secondary to a
reduction in pain and decreased opioid requirements. A case series
looking at patients with ileus secondary to severe spinal cord injury had
9
resolution of their ileus after receiving a lidocaine infusion. These
findings suggest that lidocaine may have a more direct action on
intestinal function.
Dose recommendations for lidocaine are complicated by the fact that
the concentration of free lidocaine is affected by plasma

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 INTESTINAL SURGERY e II

Current evidence for use of non-opioid adjuvant agents in perioperative pain

Drug Acute perioperative pain Side-effects
Doses Pain intensity Analgesia/opioid consumption

Ketamine >30 mg not associated with Decreased (20e25%) Decreased (30e35%) Psychotomimetic e
improved analgesia hallucinations/nightmares
Sedation
Nausea and vomiting
Pregabalin 50e600 mg per day in divided Decreased but Decreased Visual disturbance dizziness
doses (Average 300 mg) inconsistent
Gabapentin 300e1200 mg 1e2 hours Decreased Decreased (20e62%) Dizziness sedation
preoperatively
IV Lidocaine No consensus on dose needed Decreased Decreased None but needs caution
Systemic a-2 Best dose and route of Decreased Decreased Hypotension bradycardia
agonist administration to produce
maximal benefit largely
unknown

Modified from Ramaswamy et al. CEACCP 2013;13:152e157.

Table 1

protein concentration and acid-base status both of which can cause
considerable variability in pharmacokinetics and toxic ef-fects.
Lidocaine is metabolized in a perfusion dependent manner in the liver
to active metabolites, therefore cardiovascular instability or the
concomitant use of drugs that alter hepatic blood flow can significantly
affect clearance.
Ketamine
Painful stimuli cause glutamate release which activate NMDA receptors
causing pain. Ketamine, an NMDA receptor antagonist that non-
competitively blocks NMDA receptors, is already widely used in
subanaesthetic doses as an adjuvant perioperative anal-gesic. There is a
widening body of evidence that perioperative ketamine is effective in
the management of postoperative pain. A systematic review in 2005
looked at 53 randomized controlled trials where ketamine was used.
Ketamine was associated with a statistically significant reduction in
10
pain scores consistently up to 48 hours post surgery.
Ketamine is well known for causing psychotomimetic effects such
as hallucinations, out of body sensations, vivid dreams and dysphoria.
The incidence of these effects is dose-dependent and clinical experience
suggests that a dose of <0.5 mg/kg generally does not cause major
11
psychotomimetic disturbance. At high doses ketamine produces a
‘dissociative’ anaesthetic state resembling catatonia. Conversely studies
looking at the effect of sub-anaesthetic doses of ketamine have found
that not only does perioperative use not increase the level of sedation, it
may actually decrease sedation possibly secondary to its opioid-sparing
10
effects.
Gabapentinoids
Although the two clinically used gabapentinoids (gabapentin and
pregabalin) are currently only licensed for chronic neuropathic pain,
epilepsy and anxiety, they are being used more and more as an adjuvant
for perioperative analgesia. Gabapentinoids mainly
act on the a-2-d-1 subunit of pre-synaptic calcium channels and inhibit
the neuronal calcium influx. This reduces the release of excitatory
neurotransmitters and therefore suppresses neuronal excitability. They
are thought to contribute to better post-operative pain control, both by
enhancing opioid analgesia and preventing opioid tolerance along with
anxiolytic and sleep-modulating properties. Gabapentionoids are
generally well tolerated. Commonly reported adverse effects include
sedation, dizziness or headache, visual disturbances and peripheral
oedema. It appears that perioperative gabapentin reduces the likelihood
of postoperative delirium, and pregabalin reduces PONV. These effects
may be linked to a reduction in opioid use.
Of the two, pregabalin has a greater analgesic potency and a more
favourable pharmacokinetic profile as it is more rapidly absorbed, has a
more predictable oral bioavailability and is longer acting. Gabapentin
has very similar benefits and being an older drug there is more evidence
surrounding its use. It has been shown to improve analgesia both at rest
and with movement and improves postoperative functional recovery
including improved pulmonary function.
When choosing between gabapentin and pregabalin it appears that
either works well and larger studies would be needed to determine if
one is more efficacious than the other. The choice may come down to
cost as gabapentin is available in generic form while pregabalin is still
patent-protected.
a-2 Agonists
a-2 Adrenergic receptors are found in neurones in the central and
peripheral nervous system and when stimulated they inhibit nociceptive
neurones. The two commonly used a-2 agonists are clonidine and
dexmedetomidine. It is well known that epidural or intrathecal
administration of a-2 agonists result in prolongation of the block and
are useful adjuvants for treating neuropathic pain, cancer related pain
and postoperative pain. They also have an opioid-sparing effect and
extra analgesic benefits such as sedation, anxiolysis, reduction in
postoperative shivering,

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 INTESTINAL SURGERY e II

Pitfalls in analgesia
Epidural Intrathecal opioids Rectus sheath/TAP blocks Opioid PCA

C Fluid control: Fluid overload
may still result even with
goal directed fluid therapy
C Mobilization may be delayed
C Early removal of urinary
catheters may be delayed
C Risk delayed respiratory
depression
C Require closer post-
operative monitoring
C Small risk pruritus
C Failure or incomplete block
C Inadvertent intravascular or
intraperitoneal injection
C If catheters used e boluses
needed to maintain
adequate block
C Nausea and vomiting
C Ileus
C May require nasogastric
tube
C Early removal of urinary
catheters may be delayed

Table 2

agitation, shortening of postoperative ileus, a reduction in the stress
response to surgery and an anaesthetic sparing effect.
However, they can be associated with significant hypotension and
bradycardia. It was thought that blunting of the sympathetic outflow by
low-dose clonidine may prevent perioperative myocardial infarction
and death without inducing haemody-namic instability. This formed the
basis of the Perioperative Ischaemic Evaluation 2 (POISE-2) trial. This
international ran-domized controlled trial concluded that low-dose
clonidine did not reduce the rate of death or non-fatal MI and also that it
increased the risk of clinically significant hypotension and non-fatal
12
cardiac arrest. Dexmedetomidine is approximately eight times more
specific at the a-2 receptors but as yet there is no study comparing
dexmedetomidine versus clonidine.
Magnesium
particularly in hypertensive patients receiving anti-hypertensive
medication and they have been associated with a higher rate of serious
cardiovascular (CV) thrombotic events. In laparoscopic colonic surgery,
NSAID’s have been associated with a higher rate of anastomotic
14
breakdown compared to opioid analgesia.
However, information relating to the CV risks associated with the
use of NSAIDs and COX-2 inhibitors is derived from long-term
treatment data and may not reflect the risk of short-term use in the acute
pain setting. The US FDA (Food and Drug Administration) concluded
that ‘Short-term use of NSAIDs to relieve acute pain, particularly at low
doses, does not appear to confer an increased risk of serious adverse CV
15
events.
Although excellent analgesia is important, it is not the only
postoperative consideration. Side-effects from analgesia may
compromise other aspects of the enhanced recovery protocol (Table 2).

Magnesium has been used for many years as an anticonvulsant drug and
antiarrhythmic drug. The mechanism of its action in providing analgesia
Additional anaesthetic considerations
is unclear but is thought to be related to its interaction with calcium
channels and NMDA receptors. It has been suggested that it may have a Appropriate antibiotics should be given according to local guidelines
role in reducing catechol-amine release and sympathetic stimulation, allowing enough time between administration and skin incision. This
thereby decreasing peripheral nociception and the stress response to also provides cover prior to central neuraxial block being administered.
surgery. Systematic reviews of perioperative magnesium have failed to PONV can have a significant negative
find convincing evidence of improved analgesia although there are
multiple papers with data that illustrates that magnesium can affect pain
13
threshold and reduce pain perception even at low doses. It has
Anaesthetic goals of enhanced recovery
however been shown to be opioid-sparing and reduce postoperative
pain both when given as a bolus or

13 Anaesthetic
as an infusion intraoperatively or when added to morphine for PCA. goals

• Early mobility
Non-steroidal anti-inflammatory drugs (NSAIDs) • Early return of gut function
Aims • Modulation of stress response
NSAIDs have proven analgesic efficacy and have been shown to reduce
morphine consumption following abdominal surgery. COX-2-selective
inhibitors have been shown to provide equi-potent postoperative • Reduced complications
analgesic efficacy relative to conventional NSAIDs. There are also • Improved healing
Expected • Reduced length of hospital stay
some significant side-effects associated with NSAIDs. Short-term use outcomes
increases the risk of renal impairment especially in high-risk patients or
those with pre-existing renal dysfunction. They may elevate blood
pressure, Figure 2

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 INTESTINAL SURGERY e II
impact on recovery. Prophylactic administration of 5HT3 recep-tor
antagonists (ondansetron) and dexamethasone should be given as first
line antiemetics. The use of total intravenous anaesthesia (propofol and
remifentanil infusions) also reduces the incidence of PONV. The timing
of administration of antith-rombotic and antiplatelet medication is an
important consider-ation before performing a regional anaesthetic
technique. Non-invasive cardiac output monitoring should be used to
aid peri-operative fluid management aiming to avoid the ‘liberal’ fluid
administration that could threaten healing of the surgical anas-tomosis
site.
Summary
Colorectal surgery has changed immensely following the intro-duction
of laparoscopic techniques. This is evident from improved short-term
outcomes such as ‘length of stay’ and pain scores. Anaesthetic
techniques have also evolved around it. Intrathecal analgesia being
more commonly used instead of epidural analgesia and the use of non-
invasive cardiac output monitors for precise fluid administration. In an
ideal world even if one can provide a complete blockade of afferent
neural stimuli; this will only reduce endocrine-metabolic responses but
not inflammation. By contrast, opioids and NSAIDs have little or no
stress-reducing effect when used in recommended doses. How-ever, the
effects of continuous epidural analgesia as a single intervention in
2 8 Ventham NT, O’Neill S, Johns N, Brady RR, Fearon KCH. Evalu-
major operations to reduce the stress response are still uncertain.
Though there is currently no evidence, it is only reasonable to
extrapolate the effects of a dense blockade pro-vided by intrathecal
opioids, which modulates the stress response and contributes to a rapid
recovery. This blockade of nociceptive inputs can be complimented and
prolonged by the use of supplementary abdominal wall nerve blocks
and local anaesthetic infusions.
Further adoption of the ERAS principles of ‘aggregation of marginal
gains’ in the form of a multimodal analgesic plans ap-pears the future of
analgesia following colorectal procedure. Intrathecal opiates along with
regional local anaesthetic blocks and non-opioid adjuvant analgesics
have shown favourable re-sults in terms of reducing the ‘stress
response’ to surgery. On the other hand, goal directed fluid therapy has
improved gut mobility and possibly enhanced anastomotic healing.
Implementing all the possible components of ERAS and using a
multimodal approach to pain management is key to improving
outcomes in colorectal surgery.
Anaesthetists rightly champion this aspect of care. The anaesthetic
goals of enhanced recovery are shown in Figure 2.A
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