Presenter :
Moderator :
Dr Norlida Binti Suhaimi
Dr Wan Rohaidah

Intravenous Paracetamol

PCA Oxynorm

Bupenorphine patch

Perioperative lignocaine infusion
“A Fatal Accident Inquiry in Scotland in 2011 concluded that
a young adult died from liver failure due to an overdose
of paracetamol. The Sheriff found ‘there was, at the time of
the death, a prevailing culture of assumed familiarity with
the administration of IV paracetamol, a familiarity derived
from the common use of oral paracetamol’. The patient,
who weighed 35kg, died nine days after receiving
paracetamol 1g IV on a sustained and regular basis.”

IV paracetamol was licensed in the UK in 2004 and
is used routinely in anaesthetic practice.

Paracetamol is frequently used for perioperative
analgesia, alone or in combination with an opioid.

Clinical studies have shown that paracetamol has
potent analgesics and reduce opioid consumption.

for the short-term treatment of moderate pain especially following surgery

for the short-term treatment of fever

when administration by IV route is clinically justified by
an urgent need to treat pain or hyperthermia and/or
when other routes of administration are not possible.

in patients with hypersensitivity to
paracetamol

in cases of severe hepatocellular
insufficiency.

Precautions for use:
IV Paracetamol should be used with caution in cases of:

hepatocellular insufficiency

severe renal insufficiency (creatinine clearance ≤ 30
mL/min)

chronic alcoholism

chronic malnutrition (low reserves of hepatic
gluthatione)

Paracetamol has essentially no effect on cyclooxygenase in vitro – but it has been classified as a
NSAID because of its moderate analgesic and
antipyretic properties.

The drug is not associated with the increased
incidence of platelet dysfunction, gastritis, and
renal toxicity that are sometimes associated with
NSAIDs

MOA

Unclear

it is thought to exert its analgesic activity by
inhibiting the synthesis of prostaglandins in the
CNS (central acting) and peripherally blocking pain
impulse generation.

In addition, it has been proposed that
acetaminophen has a serotonergic (5-HT)
mechanism and a cannabinoid agonism
mechanism, which may contribute to its analgesic
effect.

It has been proposed that its antipyretic actions are
due to :
- inhibition of the hypothalamic heatregulating center,
- inhibition of prostaglandin synthesis within
the central nervous system , by inhibition of
COX-3 (a COX – 1 ) variant.
- cannabinoid agonism.

The pharmacokinetics of intravenous
acetaminophen have been described in several
studies, and the serum therapeutic level required
to produce an analgesic effect is 16 mcg/mL in
adults and 10 mcg/mL in children.

IV PCM has a
faster onset and
results in more
predictable
pharmacokinetic
than oral or
rectal PCM
formulations
Blood
concentration
Intravenous
Intramuscular
Effervescent tablet
Suppository

provides onset
of pain relief
within five to 10
minutes after
administration.
Effective
concentration
Tablet
1 hour
2 hours

mean IV C
max
(maximum plasma concentration of drug)
was nearly twice that observed with oral administration
and nearly four times that observed with rectal
administration.

The lag time after oral administration is 20-30 min

The lag time after rectal administration often exceeds 1
hour

A major benefit is that IV PCM may be administered
before or during surgery, permitting the initiation of
effective analgesic therapy in the early phase of the
postoperative period.

When patients are able to tolerate oral intake, they
may be switched from IV to oral PCM to maintain the
predictable analgesia established by the IV route.
Distribution:

The volume of distribution of paracetamol is
approximately 1 L/kg.

Oral bioavailability 80%

Paracetamol is not extensively bound to plasma
proteins (10%)

Following infusion of 1 g paracetamol, significant
concentrations of paracetamol (about 1.5 μg/mL)
were observed in the Cerebro Spinal Fluid as and
from the 20th minute following infusion.

Paracetamol metabolized by the liver mainly to
glucuronide conjugates but also sulphate and cysteine
conjugates

These are actively excreted in the urine, only small fraction
being excreted unchanged.

N- acetyl-p-amino-benzoquinoneimine is a highly toxic
metabolite of paracetamol that produced in small amount
in therapeutic doses.

It is rapidly conjugated with hepatic glutathione to render
it harmless

Following toxic dose – gluthatione is exhausted, NAPQI
accumulates – then free to form covalent bonds with
sulphydryl groups on hepatocytes resulting cell death and
centrilobular hepatic necrosis

Treatment:
- with oral methionine(enhances gluthatione
synthesis) and/or oral or IV acetylcysteine which is
hydrolysed to a precursor of glutathione
Composition:
 One
ml contains 10mg paracetamol
 One
50 ml vial contains 500mg paracetamol
 One
100 ml vial contains 1000mg
paracetamol

The 100 ml vial or 100 ml bag is restricted to
adults, adolescents and children weighing more
than 33 kg.

The 50 ml vial is adapted to infants, toddlers and
children weighing less than 33 kg.

IV Paracetamol should be given by infusion over 15
minutes

minimum dose interval should not be less than
four hours (six hours in patients with renal
impairment).

Once the vacuum seal of the glass vial has been
penetrated, the dose of IV must be administered
within 6 hours.

IV Paracetamol is a single-use vial, and the unused
portion must be discarded.

To prevent the possibility of an air embolism, it is
important to observe the end of the infusion

can also be diluted in a 0.9% sodium chloride
solution or 5% glucose solution

Use the diluted solution within the hour following
its preparation (infusion time included).
NON–WEIGHT-BASED DOSING:

For 1000 mg (10 mg/mL) doses, deliver from the
bottle
Use aseptic technique to
prepare the vial and IV line
Insert a vented IV set into
upright vial; open vent
Hang bottle; adjust flow for
15-minute infusion
 Monitor the end of the
infusion in order to
prevent the possibility of
an air embolism

WEIGHT-BASED DOSING:
For extracted doses <1000 mg (10 mg/mL), deliver
from separate container
For small-volume pediatric doses up to 60 mL
Using aseptic technique, withdraw appropriate
dose from vial and into a syringe as above
Administer over 15 minutes using a syringe
pump

Since introduction, there have been concerns about
accidental overdose of IV paracetamol due to errors
in drug prescription and administration,
particularly in children, small adults, the elderly,
alcoholics and those with pre-existing
hepatocellular insufficiency.

Reported errors include:
- incorrect dose in adults with high or low body mass index;
- accidental overdose in children associated with use of 100mlvials;
- 10-fold drug calculation errors;
- confusion between dose volume in millilitres and dose of
drug in milligrams;
- errors when setting up infusion pumps;
- and duplication of doses between the ward and
the operating theatre or recovery.

IV paracetamol should be prescribed carefully, according
to the weight, age and co-morbidities of the patient.
The upper dose limit for each single dose and in each
24-hour period should not be exceeded.

50ml vials of IV paracetamol should be used for patients
less than 33kg. In infants and small children, doses
should be measured accurately using a syringe.

Enquiry about recent paracetamol ingestion should
form part of routine pre-operative assessment.

All doses of paracetamol administered in the
operating theatre should be recorded on the drug
administration chart and in the anaesthetic record.




Advice should be sought from the local poisons
information service in all cases of overdose of
intravenous paracetamol.
Treatment with acetylcysteine is suggested
following a single dose greater than 60mg/kg.
IV paracetamol remains under intensive monitoring
by the MHRA.
All suspected adverse reactions to IV paracetamol
should be reported to the Yellow Card Scheme and
discussed with the local poisons information
service.

Oxycodone is a semi-synthetic derivatives, full
opioid agonist with no antagonist properties.

It has an affinity for kappa, mu and delta opiate
receptors in the brain and spinal cord.

Oxycodone is similar to morphine in its action.
- The therapeutic effect is mainly
analgesic, anxiolytic and sedative.
Oxynorm…

belongs to a group of medicines called strong
analgesics

Indication:
* commonly used as an analgesic in moderate
to severe acute pain
* also used in moderate to severe cancer pain,
and sometimes in chronic non-cancer pain
Reseptor type
Location
Action when
stimulated
µ receptor
*brain especially
areas involved
with sensory &
motor perception
and integration
- Abundant in
preaqueductal grey.
*Spinal cord
- analgesia
- physical
dependence
- resp depression
- reduced peristalsis
- euphoria
- meiosis
δ receptor
* brain
- Analgesia
- anti depressant
- physical
dependence
Reseptor type
Location
Action when
stimulated
Ƙ receptor
* Brain
* Spinal cord
- Spinal analgesia
- Sedation
- Meiosis
NOP receptor
( nociceptin
Orphanin FQ
Peptide receptor
- Most recently
identified
* Brain
* spinal cord
- Anxiety
- Depression
- Affect learning
and memory
- involved in
tolerance
Other pharmacological effects of oxycodone :
- respiratory depression, antitussive,
bronchospasm
- smooth muscle (constipation, reduction in
gastric, biliary and pancreatic secretions,
spasm of sphincter of Oddi and transient
elevations in serum amylase)
- nausea and vomiting : CTZ stimulation via 5HT3 and dopamine receptors
- cardiovascular system (release of histamine
and/or peripheral vasodilatation, possibly
causing pruritus, flushing, sweating and/or
orthostatic hypotension).

Opioids may influence the hypothalamic-pituitaryadrenal or –gonadal axes.
- Some changes that can be seen include an
increase in serum prolactin, and decreases in
plasma cortisol and testosterone.
Clinical symptoms may be manifest from
these hormonal changes.

Absorption
- 40% to 85% bioavailability after oral
administration
- presence of methoxy group at C3
position of the phenanthrene structure
protects drug against glucuronide
conjugation, and hence first pass effect
-100% bioavailability after iv
administration
Distribution:

Distributed to skeletal muscle, liver, intestinal tract,
lungs, spleen and brain.
- tissues with mu, kappa and delta opiod
receptors

Pka 8.5. at pH 7.4, 7.4% unionized
Vd 2-6 L/kg
45% protein binding
Metabolism & Elimination:

Oxycodone has an elimination half-life of approximately 3 hours

metabolised principally in the liver to noroxycodone and
oxymorphone.

Oxymorphone has some analgesic activity but present in plasma in
low concentrations and is not considered to contribute to
oxycodone’s pharmacological effect.

CYP3A4 and CYP2D6 are involved in the formation of noroxycodone
and oxymorphone, respectively.

Metabolites mainly excreted in urine and sweat, accumulates in
patients with renal impairement.

Concentration: Oxycodone hydrochloride 10 mg/ml

Dilute to 1 mg/ml in 0.9% saline, 5% dextrose or
water for injections.

Setting:
* Bolus doses : 0.03 mg/kg (e.g. 1-2mg per 70 kg)
* lock-out time : minimum 5 minutes.
* Background infusion : nil
* Four hour dose limit : 30 mg
Discontinuation of PCA...

PCA should be discontinued when minimal use is
required and the patient is able to tolerate oral
analgesia

Full explanation and reassurance must be given to the
patient.

Ensure that adequate analgesia is prescribed.

Continue regular pain assessment after the pain control
system has been discontinued and act accordingly.
Transferring patients between oral and parenteral
oxycodone…

The dose should be based on the following ratio: 2 mg
of oral oxycodone is equivalent to 1 mg of parenteral
oxycodone.

It must be emphasized that this is a guide to the dose
required.

Inter-patient variability requires that each patient is
carefully titrated to the appropriate dose.

is a semisynthetic, highly lipophilic derivative of the opium alkaloid
thebain

approximately 25-50 times as potent as morphine, usual dose ~
0.3-0.6 mg

Buprenorphine is a partial agonist .has high affinity for, but low
intrinsic activity at, mu receptors.

however, its maximal opioid effects are less than that of full
agonists, and reach a ceiling where higher doses do not result in
increasing effect.

produces analgesia and other effects similar to morphine, including
CVS

peak blood concentration appear at 5 min/i.m., and at 2
hrs/s.l. or oral

plasma protein binding is ~ 96%

plasma half-life is ~ 3 hrs, however, the duration of
action is longer, sometimes up to 6 hrs,

probably due to tissue binding

both N-dealkylation and conjugation occur in the liver,
however most of the drug is excreted unchanged in the
faeces

Transdermal buprenorphine may be used in chronic severe
pain when lower doses of strong opioids are indicated;
especially in patients who need continuous, around-the-clock
narcotic pain relief for an extended period of time.

However, the place of transdermal buprenorphine in pain
management is not well established.

The 7-day patch formulation may have a particular role for
patients who are vomiting or have swallowing difficulties.

Transdermal buprenorphine is not suitable for the
management of acute pain because it has a slow
onset and extended duration of action.
transdermal buprenorphine

5 mg (releasing buprenorphine 5
micrograms per hour) every 7 days


10 mg (10 micrograms per hour) every 7 days
20 mg (20 micrograms per hour)every 7 days

Transdermal buprenorphine patches deliver
buprenorphine at a constant rate over 7 days.

The dose equivalence of transdermal
buprenorphine and oral morphine is not
established.

The manufacturer suggests that the dose range
covered by the three patch strengths may be
equivalent to oral morphine up to 90 mg/day.

Other literature and the dose relativities suggested
that the buprenorphine 20-microgram-per-hour
patch might be equivalent to oral morphine up to
36 mg/day or 53 mg/day
Buprenorphine: a partial agonist

Buprenorphine is a partial agonist so there is a ceiling dose to
its analgesic effect — that is, above a certain dose there is no
further analgesic effect.

The dose at which this occurs in humans is not established
but it is unlikely at the doses in the transdermal patches.

Buprenorphine may trigger opioid withdrawal symptoms in
people who have developed physical dependence on other
opioids.

Buprenorphine has high affinity for mu opioid
receptors and is not easily displaced by opioid
antagonists.

Consequently, the effects of buprenorphine in
overdose are only partially reversed by naloxone

Buprenorphine produces typical opioid adverse
effects (such as constipation, headache, nausea,
vomiting, dizziness).

Local irritation may occur at the application site.

Buprenorphine has a long half-life, so plasma
concentrations fall slowly after the patch is
removed.

Another opioid should not be started within 24 hours
of removing a patch
Dependence and abuse potential

Physical dependence may develop with chronic use of
buprenorphine.

If a withdrawal syndrome does occur when
buprenorphine is discontinued, it is usually of mild to
moderate intensity, occurs within 2 days and resolves
within 2 weeks.

Avoid prescribing buprenorphine to people who
may be dependent on other opioids because it can
precipitate withdrawal symptoms, including pain.

Transdermal buprenorphine may have lower abuse
potential than other buprenorphine dosage forms
because of the relatively low plasma concentrations
achieved, the slow onset of effect and because it is
likely to be difficult to extract the drug from the
matrix design.

Misuse could take the form of using excessive
amounts of the intact patch or applying it to sites
that would enhance systemic absorption.

It should be used with caution in people with a past
history of dependence on alcohol or other drugs.

In overdose the effects of buprenorphine are only
partially reversed by naloxone.

The manufacturer states that the dose of naloxone
should start in the usual range but that naloxone 5–12
mg intravenously may be required.

Repeated naloxone doses may be needed because
naloxone has a shorter duration of action than
buprenorphine.

Management of overdose should focus on maintaining
adequate ventilation.

the effect of buprenorphine on respiratory
depression reaches a ceiling, with higher doses not
increasing respiratory depression to a significant
degree.

However, if buprenorphine is used in combination
with other central nervous system depressants,
such as benzodiazepines, the combined effect on
respiration can be life threatening.

Opioid-naïve patients should start at the lowest
strength.

Supplemental analgesics should be continued as needed
during titration because buprenorphine concentrations
rise slowly.

Patients converting from other opioids (up to the
equivalent of oral morphine 90 mg/day) can also begin
on a low strength of buprenorphine and should
continue with their previous regimen during titration.



The dose should be titrated to effect and should
not be increased at intervals of less than 3 days.
To increase the dose, remove the current patch and
apply a higher strength patch or a combination of 2
patches.
No more than two 20-microgram-per-hour
patches should be used at once.

Apply Buprenorphine patch to a hairless or nearly
hairless skin site at the upper outer arm, upper
chest, upper back or the side of the chest.

These 4 sites (each present on both sides of the
body) provide 8 possible application sites.

Rotate Buprenorphine patch among the 8 described
skin sites.

New patches should always be applied to a
different site from the previous one.

Any site should not be re-used for 3–4 weeks to
minimize the risk of local skin irritation

immediately re-using a site can increase the rate of
absorption of buprenorphine.

Discuss the potential adverse effects of
buprenorphine.

Most adverse effects reduce with time.

Constipation may persist; advise patients to drink
adequate amounts of water, increase their fibre
intake and remain as mobile as possible.

Regular laxatives such as lactulose should be
started when buprenorphine is initiated and
continued for long as buprenorphine is used.

Intravenous infusion of lidocaine decreases
postoperative pain and speeds the return of bowel
function.

tested the hypothesis that perioperative lidocaine
infusion facilitates acute rehabilitation protocol in
patients undergoing laparoscopic colectomy.

the concept of fast-track surgery has been developed to
reduce postoperative morbidity and duration of
hospitalization, and to accelerate postoperative recovery and
convalescence.

Acute rehabilitation programs combine preoperative
optimization of patients’ physical and psychological status,
attenuation of surgical stress, dynamic pain relief, enforced
mobilization, and early oral (enteral) nutrition, as well as
changes in surgical care de-emphasizing tubes and drains.

Effective postoperative analgesia is key to acute rehabilitation.

An alternative approach to accelerate postoperative recovery
after colon surgery is administration of intravenous
lidocaine, which has analgesic, antihyperalgesic,
and antiinflammatory properties and has been reported
to speed the return of bowel function after surgery.

In a case series, acute rehabilitation after laparoscopic colectomy
using intravenous lidocaine yielded outcomes similar
to those reported using epidural.

Furthermore,nontoxic plasma lidocaine
concentrations reduce requirements for various
volatile anesthetics in several animal species
although the benefits in humans remain unclear.

intravenous lidocaine is inexpensive, easy to
administer, and relatively safe.

enrolled 45 ASA status I–III patients scheduled to undergo elective
laparoscopic colectomy for nonmalignant disease at
the Centre Hospitalier Universitaire de Lie`ge. (Lie`ge, Belgium)

Patients were enrolled from January 2003 until December 2004.

Exclusion criteria :
- age greater than 70 yr,
- history of gastroduodenal peptic ulcer or renal failure
hepatic insufficiency,
- psychiatric disorder
- steroid treatment
- chronic treatment with opioid.
-
Protocol

Patients fasted at least 6 h and were orally
premedicated with 50 mg hydroxyzine and 0.5 mg
alprazolam 2 h before surgery.

Lactated Ringer’s solution (8 ml/kg/h) was infused
throughout surgery.
Anesthesia

Patients were randomly allocated to two groups

double blinded study.

Just before induction of anesthesia, patients
assigned to receive lidocaine (n " 22) :
- given an intravenous bolus injection of 1.5 mg/kg
lidocaine followed by a continuous infusion of
2 mg/kg/h.
- The lidocaine infusion was continued at a rate of 1.33
mg/kg/h for 24 h postoperatively.

Patients assigned to the control group (n " 23) were given
equal volumes of saline

General anesthesia was induced with 0.15 ug/kg
sufentanil and 2 mg/kg propofol.

Orotracheal intubation was facilitated with
cis-atracurium,

cis-atracurium was also used for intraoperative
muscle relaxation full muscle relaxation during
surgery

Anesthesia was maintained with sevoflurane in a
mixture of oxygen and air with 2 l/min fresh gas flow.

Sevoflurane concentration was adjusted to maintain
mean arterial pressure within 15% of the preinduction
value.

The use of opioid was restricted during surgery:

Sufentanil, 5 ug, was injected only if mean arterial
pressure increased more than 15% or if heart rate was
greater than 100 beats/min despite the administration
of sevoflurane to an end-tidal concentration of 3.5%.

BIS was monitored

allowed increases in inspired sevoflurane concentration
if BIS exceeded 50.

Core temperature was kept above 36.0°C using a
forced-air warming system.

All patients were given 0.625 mg droperidol and 2 mg
tropisetron, a 5-hydroxytryptamine type 3 antagonist,
as prophylaxis against postoperative nausea and
vomiting 1h before the end of surgery.
Surgical Procedure

Two experienced laparoscopic surgeons (B.J.D.,
S.R.L.) performed procedures using a standard four- or fivetrocar technique.

For right colectomy, after intracorporeal dissection of the
ascending colon and the Bauhin valve, the specimen was
exteriorized through a 5- to 6-cm minilaparotomy in the right
lower abdomen.

After resection of the pathologic colon, the anastomosis was
hand-sewn and returned to the abdominal cavity.

The minilaparotomy was then closed.

In laparoscopic sigmoid colectomy, the sigmoid colon
was first mobilized intracorporeally up to the
rectosigmoid junction.

The rectosigmoid junction was cut using a stapler.

The sigmoid colon was retrieved through a 5- to 6-
cm minilaparotomy in the left lower abdomen and
then resected.

The surgeons were unaware of the patient’s group
assignment.
Postoperative Analgesia

Postoperative analgesia was provided in both groups by
the combination of the paracetamol (acetaminophen)

precursor propacetamol - 2 g propacetamol= 1 g
paracetamol),

2 g intravenously 30 min before the end of surgery and
then every 6 h,

and ketorolac, 30 mg intravenously every 8 h.

Patient-controlled analgesia with piritramide
was used as rescue medication (bolus=1
mg, lockout interval =5 min, no basal infusion).

Twenty-four hours after the end of surgery, the
intravenous infusion of lidocaine or placebo was
stopped

analgesia was provided with oral paracetamol, 1 g
every 6 h;
-
diclofenac 75 mg twice daily;
-
and 100 mg tramadol, if necessary.








An abdominal drain was left in contact with the anastomosis for 24
h.
The bladder catheter was removed on the first postoperative
morning.
An intravenous infusion of 5% glucose was started after
surgery at a rate of 80 ml/h.
Patients were allowed to drink water 6 h after surgery.
If patients did not report nausea or vomiting, they were given 200
ml of nutritive supplement without residue (Clinutren® 1.5 kcal/ml;
Nestle 1 h later.
On the first postoperative day, patients had a light breakfast and
lunch.
If this food was tolerated, the intravenous infusion was stopped and
a normal diet was resumed.
Patients were asked to drink three 200-ml cartons of nutritive
supplement each day.

Active mobilization was started in bed 4 h after
surgery.

Assisted ambulation was enforced on the
subsequent days: 20 m in the morning and 50 m in
the afternoon on postoperative day 1, then 100 m
in the morning and the afternoon on day 2.

Defecation and tolerance of normal diet were
required before discharge.

Arterial pressure, heart rate, and end-tidal sevoflurane
concentrations were measured on a Datex-Ohmeda S/5
monitor every 15 min during anesthesia.

BIS scores were also recorded at 15-min intervals.

After surgery, piritramide consumption was recorded every 4
h.

Pain scores were obtained on a visual analog scale at rest,
during mobilization from the supine to the sitting position,
and during coughing at 2 and 6 h postoperatively and at 9:00
AM, 1:00 PM, and 5:00 PM on postoperative days 1 and 2.

Postoperative fatigue scores and gastrointestinal
discomfort (colic, abdominal fullness, internal
discomfort) were also assessed on a visual analog
scale at the same times.

Times to first flatus, defecation, and hospital
discharge were recorded.

Episodes of postoperative nausea and vomiting
were noted.

Immediately after induction of anesthesia, the bladder

was catheterized and emptied.

In the first 30 patients (n " 15 in each group), urine was then
collected to measure urinary secretion of cortisol,
epinephrine, and norepinephrine to assess the stress
response during anesthesia and surgery.

Blood samples were drawn in the same patients before
surgery and after surgery at 2, 6, 24, and 48 h.

Plasma concentrations of glucose, C-reactive
protein, cortisol, catecholamines, and leukocyte counts were
measured.

Blood samples were drawn at 5, 15, and 60 min
after anesthetic induction, at the end of surgery,
and 24 h after the end of surgery to measure
plasma lidocaine concentrations
A previous study at same institution using a similar
protocol indicated that18 patients per group
allowed detecting a 12-h difference
in the recovery of bowel function between the
groups, at an alpha level of 0.05 and with 80%
power.


therefore enrolled patients until 40 patients (n " 20
in each group) completed the study.

Continuous variables are presented as mean ± SD; they were
compared using analysis of variance for repeated measures for
two criteria (time and treatment)
followed by the Scheffe´ test for multiple comparisons or
the Student t test, as appropriate.

If the Kolmogorov-Smirnov normality test did not demonstrate
gaussian distributions, the Mann–Whitney test was used;

data are then presented as median [25–75% interquartile range].

Categorical data were analyzed with chi-square tests.

P ≤0.05 was considered significant.

Three patients in the control group, but none in the
lidocaine group, requested tramadol after the
interruption of piritramide patient-controlled
analgesia between the 24th and 48th postoperative
hours:

These patients were given 100, 200, and 400 mg.

patients in the lidocaine group tolerated a normal diet the day
after surgery and had their intravenous infusion interrupted
24 h after surgery,

whereas three patients in the control group required
prolongation of postoperative fasting and intravenous
infusion (31, 54, and 72 h) (P " 0.22).

Four patients in the saline group but only one in the lidocaine
group experienced nausea (P =0.17).

Vomiting occurred in two patients in the saline group and
none in the lidocaine group (P =0.23)

Lidocaine plasma concentrations were measured in 15
patients and were 1.6 ±0.9 ug/ml at 5 min, 1.3 ± 0.4
ug/ml at 15 min, and 1.8 ±0.5 ug/ml at 60 min after the
bolus injection of lidocaine;

2.4 ±0.6 ug/ml at the end of surgery

2.7 ±1.1 ug/ml at the end of the 24-h infusion.

The highest plasma concentrations of lidocaine measured
at each of these time points were 3.5, 2.1, 2.6, 4.0, and
4.6 ug/ml, respectively.

This study demonstrated that perioperative intravenous
infusion of nontoxic doses of lidocaine improved:
- postoperative analgesia,
- reduced postoperative opioid requirements,
- accelerated postoperative recovery of bowel
function,
- attenuated postoperative fatigue,
- reduced the duration of hospitalization,
- facilitated acute rehabilitation
in patients undergoing laparoscopic abdominal surgery.

results further indicated that moderate plasma lidocaine concentrations
reduced sevoflurane requirements necessary for maintaining
intraoperative hemodynamic stability and anesthetic depth.

Intravenous lidocaine is analgesic, antihyperalgesic,
and antiinflammatory.

These properties are mediated by a variety of
mechanisms, including sodium channel blockade,
as well as inhibition of G protein–coupled receptors
and N-methyl-D-aspartate receptors.

In this study, intravenous lidocaine reduced
postoperative opioid consumption, as well as pain
scores during activity.

the analgesic effect persisted after the lidocaine
infusion was discontinued, which suggests a
prevention of
spinal or peripheral hypersensitivity or both.

Inhibition of N-methyl-D-aspartate receptors which play a
major role in postoperative hyperalgesia

Abdominal discomfort was significantly reduced by lidocaine,
which is consistent with the ability of lidocaine to alleviate
visceral pain in animal models.

Systemic lidocaine also improved postoperative bowel
function.

Defecation occurred almost 1 day earlier in the lidocaine
group.

The reduction in ileus duration by intravenous lidocaine may
be mediated by the reduction of postoperative opioid
consumption, the antiinflammatory properties of lidocaine,
and/or a direct inhibition of the sympathetic myenteric
plexus.

In summary, this study demonstrated that perioperative
administration of low doses of intravenous lidocaine
reduces intraoperative anesthetic requirements and has
a clinically relevant beneficial effect on postoperative
recovery after colectomy.

These data suggest that intravenous local anesthetics
can contribute to postoperative acute rehabilitation
programs.