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Role of Ketamine in Acute Postoperative Pain Management: A Narrative Review

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BioMed Research International
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Objectives . The objective of this narrative review was to examine the usage of ketamine as a postoperative analgesic agent across a wide variety of surgeries. Design . A literature search was performed using the phrases “ketamine” and “postoperative pain.” The authors analyzed the studies that involved testing ketamine’s effectiveness at controlling postoperative pain. Effectiveness was assessed through various outcomes such as the amount of opiate consumption, visual analog scale (VAS) pain scores, and persistent postoperative pain at long-term follow-up. Results . While many different administration protocols were evaluated, delivering ketamine both as a pre- or perioperative bolus and postoperative infusion for up to 48 hours appeared to be the most effective. These effects are dose-dependent. However, a number of studies analyzed showed no benefit in using ketamine versus placebo for controlling postoperative pain. While ketamine is a safe and well-tolerated drug, it does have adverse effects, and there are concerns for possible neurotoxicity and effects on memory. Conclusions . In a number of limited situations, ketamine has shown some efficacy in controlling postoperative pain and decreasing opioid consumption. More randomized controlled trials are necessary to determine the surgical procedures and administrations (i.e., intravenous, epidural) that ketamine is best suited for.
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Review Article
Role of Ketamine in Acute Postoperative Pain Management:
A Narrative Review
Brian M. Radvansky, Khushbu Shah, Anant Parikh, Anthony N. Sifonios,
Vanny Le, and Jean D. Eloy
Department of Anesthesiology and Peri-Operative Medicine, Rutgers-New Jersey Medical School, 185 South Orange Avenue,
SouthOrange,Newark,NJ07103,USA
Correspondence should be addressed to Jean D. Eloy; eloyje@njms.rutgers.edu
Received  December ; Accepted  March 
Academic Editor: Kok Eng Khor
Copyright ©  Brian M. Radvansky et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Objectives. e objective of this narrative review was to examine the usage of ketamine as a postoperative analgesic agent across
a wide variety of surgeries. Design. A literature search was performed using the phrases “ketamine” and “postoperative pain.
e authors analyzed the studies that involved testing ketamines eectiveness at controlling postoperative pain. Eectiveness was
assessed through various outcomes such as the amount of opiate consumption, visual analog scale (VAS) pain scores, and persistent
postoperative pain at long-term follow-up. Results. While many dierent administration protocols were evaluated, delivering
ketamine both as a pre- or perioperative bolus and postoperative infusion for up to  hours appeared to be the most eective.
ese eects are dose-dependent. However, a number of studies analyzed showed no benet in using ketamine versus placebo for
controlling postoperative pain. While ketamine is asafe and well-tolerated drug, it does have adverse eects, and there are concerns
for possible neurotoxicity and eects on memory. Conclusions. In a number of limited situations, ketamine has shown some
ecacy in controlling postoperative pain and decreasing opioid consumption. More randomized controlled trials are necessary
to determine the surgical procedures and administrations (i.e., intravenous, epidural) that ketamine is best suited for.
1. Introduction
Postoperative pain is one of the most undesirable experiences
for a patient undergoing surgery. Deliberate action should be
taken to prophylactically treat the pain. If postoperative pain
does develop, it should be managed early and aggressively,
becauseseverepainnotonlyinducesadelayindischargeand
poorer patient satisfaction, but also can create a hyperalgesic
condition known as persistent postoperative pain (PPP). is
strainsnotonlythepatient,butalsothehealthcaresystem
as a whole. Recent studies show that PPP has an incidence
as high as %. Furthermore, .% of patients report that
this pain is moderate to severe []. erefore, it is in the
anesthesiologist’s best interest to be aware of the severity of
this problem and of all the pharmacological agents used to
prevent and treat postoperative pain. To date, the mainstay of
treatment has been the administration of exogenous opioids
such as morphine or fentanyl. However, pain is not always
fullyrelievedbysuchagents,andoenpatientsdevelop
tolerance to them. e ever-increasing doses of opioids are
clearly not without their adverse eects. In addition to that,
many patients and even some clinicians wrongly believe that
addiction can be inevitable aer administration of opioids
[].
Recently, interest has focused on the use of N-methyl-D-
aspartate (NMDA) receptor antagonists for the management
of postoperative pain. In particular, ketamine has been thrust
into the limelight both as a standalone drug and as an
adjuvant to other analgesics (e.g., morphine, fentanyl, and
tramadol) []. Ketamine exerts its main analgesic eect by
antagonism of NMDA receptors []. In doing so, ketamine
modulatescentralsensoryprocessingofpain.Inbothanimal
and human studies, ketamine has shown itself to be a potent
antihyperalgesic agent. It can counteract opioid-induced
hyperalgesia and prevent the development of opioid tolerance
[].
Ketamine was rst described in the literature in 
[]andFDA-approvedin[]. e drug was originally
Hindawi Publishing Corporation
BioMed Research International
Volume 2015, Article ID 749837, 10 pages
http://dx.doi.org/10.1155/2015/749837
BioMed Research International
noticed to have anesthetic eects, much like its close relative,
phencyclidine, and only later, its analgesic properties did
become coveted []. Various studies mentioned throughout
this review speak of its use for postoperative analgesia.
Ketaminehasalsobeenusedtotreatdepression[,],
complex regional pain syndrome [], cancer pain [,],
alcohol addiction [], heroin addiction [,], asthma
exacerbations [], wheezing [], and pain during propofol
injection []. Adverse eects can include irritability, night-
mares, dissociation, headaches, impaired memory, transient
elevations in blood pressure and heart rate, urinary tract
symptoms, and hepatotoxicity [].
isreviewwilldescribethepharmacologyofketamine,
examine its usage as a postoperative analgesic, and discuss its
adverse eects and safety prole.
2. Chemical and Structural Characteristics
e word “ketamine” is a portmanteau of the words “ketone”
and “amine,” speaking of its chemical structure. It is a
hydrochloride salt, available in both powdered and aque-
ous forms, with the molecular formula C13H16ClNO and
a molecular mass of . g/mol. It is composed of a
chlorophenyl ring structure that is bonded to a cyclohex-
anone ring. Ketamine has a chiral center at the carbon-
atom of its cyclohexanone ring and therefore it exists as the
optical stereoisomers S(+) and R()ketamine. Ketamine was
previously only available as a racemic mixture but now comes
in its two stereoisomer varieties. S(+)ketamine binds NMDA
receptors with anity that is four times greater than that of
R()ketamine. While the duration of S(+)ketamine is shorter
than that of R()ketamine, S(+)ketamine has been shown
to have an analgesic potency twice as great as the racemic
mixture and four times as great as R()ketamine [].
3. Pharmacodynamics
e diverse eects and multifaceted mechanisms of action of
ketamine have given it the title “nightmare of the pharmacol-
ogist” []. As there are many high-quality reviews that focus
solelyonthepharmacologyofketamine[,], we will
only touch upon the most salient and novel points. Ketamines
predominant eect is NMDA receptor antagonism. It binds
noncompetitively to the phencyclidine binding site of NMDA
receptors and modies receptors via allosteric mechanisms.
e NMDA receptor is noteworthy in anesthesia because of
its role in central sensitization. is complex process involves
a nociceptive signal that is potentiated in the peripheral
nervous system, causing hyperexcitability in the spinal cord.
It can evoke chronic pain and allodynia at surgical incision
sites, as well as at sites surrounding incisions. e blunting
of central sensitization has played an important role in
the prevention and treatment of both postoperative pain
and chronic pain []. Ketamine has also been used in
IV regional anesthesia, further speaking of its peripheral
analgesic eects. However, when used as an eective IV re-
gional agent, the concentrations of ketamine were more
than -fold greater than when used systemically, decreasing
the likelihood that systemic administration provides a strong
eect on peripheral receptors [].
Ketamine causes the central eect of anesthesia when it
interacts with NMDA receptors in the brain. Brain concen-
trations of ketamine were directly related to analgesia using
an ischemic pain model. Pain activation in the secondary
somatosensory cortex, insula, thalamus, and anterior cin-
gulate cortex was all decreased. Functional magnetic reso-
nance imaging (fMRI) studies demonstrated that both pain
and ketamine changed brain connectivity in areas involved
in endogenous pain modulation. e studies showed that
ketamine was responsible for a decrease in connectivity in
the brain regions responsible for pain sensing and aective
processing [,].
e analgesic eects of ketamine do not end with NMDA
receptors. It has been shown to interact with opioid receptors
𝜇preferentially in rats []. Studies in guinea pig ileum
pointed to possible activation of the 𝜅-opioid receptor as the
site of analgesia []. However, subsequent tests performed
with naloxone failed to aect the analgesia attributed to
the ketamine, and interaction with any opiate receptor was
questioned []. Other studies showed the reduction in e-
cacy of ketamine as an anesthetic induction agent in the
presence of naloxone, again implying an interaction with the
opiate receptor []. A  study by Pacheco et al. which
used specic opioid receptor blocking agents suggests that
interaction with 𝜇-and𝛿-opioid receptors is responsible for
the central antinociceptive eects of ketamine [].
Studies show that prevention of opioid tolerance may
be another mechanism of pain prevention by ketamine. It
has been reported that 𝜇-receptor activation by opioids leads
to a sustained increase in glutamate synaptic eectiveness
at the level of NMDA receptors. Although the mechanisms
that allow ketamine to be an analgesic and opiate-sparing
agent aer opiate exposure remain poorly understood; an
important concept that is worth mentioning is being studied
in rat models. Rat studies in brain ischemia have found a
role of postsynaptic density (PSD), proteins, specically PSD-
, in potentiating NMDA function and signaling to nitric
oxide synthase resulting in chronic and neuropathic pain.
Studies show that ketamine may decrease injury-triggered
increases in interactions between the NMDA receptor, post-
synaptic density protein  (PSD), and protein kinases,
thereby reducing nitric oxide-related neuronal injury [].
is concept may represent a mechanism underlying reduced
pain sensitization and opiate tolerance phenomena. Cancer
patients who receive chronic opioids oen have developed a
high level of tolerance, and, in this situation, ketamine can be
a useful adjuvant in analgesia [,].
Many other receptors have been shown to play role in ket-
amine analgesia; however, their mechanisms remain unclear.
Once thought to be an opioid receptor, the sigma-receptor
hasbeenimplicatedasabindingsiteforketamine.erole
of sigma receptors is uncertain; they may modify other recep-
tors such as NMDA receptors.
Needless to say, the eects of ketamine on the human
body, both within the realm of analgesia and without, are
incredibly complex. Further study is encouraged to fully
BioMed Research International
elucidate the eects of this multifaceted drug on the body’s
various receptors.
4. Applications in Acute Pain Management
4.1. Otolaryngologic Surgery. AstudybyJhaetal.[]
(Table ) evaluated the ecacy of ketamine in postoperative
analgesia aer surgical site inltration for pediatric patients
undergoing cle palate surgery. Surgical sites were inltrated
with either  mg/kg of bupivacaine or .mg/kg of ketamine.
Although pain scores were similar between groups at the
 h mark, pain scores were lower with ketamine at the  h
mark. Only % of children in the ketamine group required
rescue analgesia, compared to % in the bupivacaine group.
Administration of ketamine also led to statistically signicant
decreases in sleep disturbances and dysphagia when com-
pared to the bupivacaine group. is allowed for an earlier
resumption of feeding with ketamine inltration.
Eghbal et al. [] examined the eects of ketamine
on postoperative pain and emergence agitation in children
undergoing adenotonsillectomy. is randomized clinical
trial (RCT) divided children into a placebo (normal saline)
group and a ketamine (. mg/kg IV) group. Emergence agi-
tation scores, acetaminophen requirements, and pain scores
at all hours were signicantly lower in the ketamine group.
A  meta-analysis by Cho et al. []reportsthat,
in tonsillectomy in children, preoperative administration of
ketamine, either systemically or locally, resulted in signi-
cantly decreased pain at  hours and decreased analgesic need
over  hours.
4.2. Spinal Surgery. Nitta et al. [] tested the ecacy of mor-
phine alone, morphine and ketamine, morphine and clon-
idine, and morphine/ketamine/clonidine in reducing the
need for patient-controlled analgesia (PCA) following cer-
vical and lumbar spinal surgery. When used, ketamine was
delivered as a high-dose infusion at . mg/kg/hour. e
study demonstrated that oral premedication with clonidine
combined with intraoperative administration of ketamine
potentiated the analgesic eect of postoperative IV morphine.
ere was a signicant reduction in the amount of PCA
requests and in the amount of cumulative morphine delivered
viaPCAat,,,andhours.isdemonstrates
ketamine’s adjunctive eect when added to other analgesics,
synergistically decreasing overall administration of opioids.
Hadi et al. []usedlow-doseIVketamineasanadjunct
to therapy during and aer lumbar microdiscectomy surgery.
Patients were divided into a control group, a group receiv-
ing 𝜇g/kg/min perioperatively and a group receiving both
𝜇g/kg/min perioperatively and  𝜇g/kg/min postoperatively.
e patients in the control group required rst analgesic
demand dose earlier than the ketamine groups. Total mor-
phine consumption, visual analog scale (VAS) pain scores,
and rates of nausea and vomiting were signicantly lower in
the group receiving both peri- and postoperative ketamine
versus the control group.
Kimetal.[] report similar results in lumbar spinal
fusion patients: a ketamine  𝜇g/kg/min infusion following
a bolus dose of . mg/kg resulted in patients requiring
signicantly less fentanyl in the postoperative period with no
increase in adverse eects [].
Pestieau et al. [] evaluated a low-dose perioperative
infusion of ketamine in pediatric patients undergoing scol-
iosis surgery, a procedure in which opioid analgesic require-
ments are routinely high. e study was a double-blinded
controlled trial with one group receiving ketamine and
the other receiving a placebo. Patients were given a bolus
of . mg/kg ketamine prior to incision, an intraoperative
infusion of . mg/kg/h, and a postoperative infusion of
. mg/kg/h. Postoperative opioid usage was similar between
thetwogroupsaswerethereportedpainscores.
4.3. Orthopedic Surgery. Cengiz et al. []performeda
randomized double-blinded study to evaluate the eect
of low-dose ( 𝜇g/kg/minute) intraoperative ketamine on
postoperative pain aer total knee replacement surgery. e
control group received a placebo. ere was a prolonged
time to rst analgesic request in the ketamine group and a
reductionincumulativemorphineconsumptionat,,,,
and  hours aer surgery. VAS scores were also signicantly
lowerinthegroupreceivingketamineinsteadofplacebo.
AstudyperformedbyGuar
´
aSobrinhoetal.[]assessed
ketamine’s eectiveness as an analgesic agent when deliv-
ered intra-articularly during total knee replacement surgery.
Authors did not nd a signicant dierence between groups
using . mg/kg S(+)ketamine, .mg/kg S(+)ketamine and
control groups in terms of postoperative pain scores.
4.4. oracic Surgery. D’Alonzo et al. []testedasingle
. mg/kg bolus of ketamine delivered intravenously prior
to chest wall incision versus placebo. Levels of IL- and
C-reactive protein (CRP) were compared before and aer
surgery between the two groups and reported pain scores
at  and  hours postoperatively. IL- levels, CRP levels,
and postoperative pain scores at both of these times did not
vary signicantly between the two groups, suggesting that
this dosing schedule of ketamine does not have a measurable
eect on postoperative pain in thoracic surgery.
Nesher et al.’s  study [] examined thoracic surgery
patients who received PCA boluses of morphine combined
with ketamine versus morphine alone. Fiy-eight patients
were divided into two groups, one group receiving .mg
IV bolus morphine upon request and the other receiving
. mg morphine and  mg ketamine IV bolus upon request.
e group receiving the ketamine/morphine combination
required only half the amount of morphine as the morphine-
only group. At the -hour time-point,  of the morphine-
only patients still required PCA compared to  patients in
the morphine/ketamine group. Pain scores and postoperative
nausea and vomiting (PONV) were also decreased in the
ketamine/morphine group.
4.5. Ophthalmological Surgery. Abdolahi et al. [] utilized
low-dose ketamine (. mg/kg) during painful ophthalmo-
logic surgeries (i.e., retinal detachments, strabismus, and
keratoplasty). Ketamine was administered during anesthetic
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T : Studies in which ketamine usage has signicant benet.
Author Year Surgical setting Dosing Timing Outcomes
Single studies
Jha et al. []
Cle palette repair . mg/kg inltration of surgical site Lower pain score than bupivacaine ( mg/kg)
at  h, less rescue analgesia required
Eghbal et al. []
Adenot onsillec tomy . m g/kg IV bolus Decreased emergence agitation,
acetaminophen requirements, and pain scores
Nitta et al. []
Cervical and lumbar spinal surger y . mg/kg/h IV Bolus given for  h periop. (total of
 mg/kg total)
Reduction in PCA requests and total morphine
distributedat,,,andhours
Hadi et al. []
Lumbar microdiscectomy 𝜇g/kg/min IV Peri- and pos top. for a tot al of  h Decreased total morphine consumption, pain
scores, and PONV
Kim et al. []
Lumbar spinal fusion . mg/kg bolus, 𝜇g/kg/min IV
infusion Infusion for  h postop. Less fentanyl requirement postop.
Cengiz et al. []
Tot al k nee r e p l a c e m e n t 𝜇g/kg/min IV Periop. only Reduction in morphine consumption at , , ,
, and  h, lower pain scores
Nesher et al. []
oracic surgery  mg morphine and  mg ketamine
IV-PCA
Morphine consumption and patients requiring
PCA at  h reduced by %; decreased pain
scores and PONV
Suppa et al. []
Cesarean section . mg/kg bolus, 𝜇g/kg/min IV
infusion
Bolus @  min p ostop. then infusion for
 h Reduced pain sensitivity at T- dermatome
Zakine et al. []
Major abdominal surgery . mg/kg bolus, 𝜇g/kg/min IV
infusion Periop. bolus, infusion for  h Decreased morphine consumption, pain
scores, and PONV
de Kock et al. []
Rectal adenocarcinoma resection . mg/kg bolus, . mg/kg/h IV
infusion Periop. infusion only
Lower morphine requirements, smaller
hyperalgesic areas, and less pain at months of
follow-up
Systematic reviews and meta-analyses
Cho et al. []
Tonsillectomy Various Preop. dosing Decreased pain at  h, decreased analgesic
need at  h
Laskowski et al. []
Var io u s Va r i o u s Var i o u s % of ketamine groups required less postop.
opioids, % reported less postop. pain
Elia and Tram`
er []
Var io u s Va r i o u s Var i o u s
Decrease in morphine consumption, longer
time to rst analgesic request, less pain at
months offollow-up
Subramaniam et al. []Var i o u s Va r i o u s Var i o u s
Single bolus-less opioid consumption in %
of trials; continuous infusion-less opioid
consumption in % of trials; epidural
infusion-benecial in % of trials
McCartney et al. []
Various .–. mg/kg, various routes Various Decreased postop. pain and/or decreased
analgesic consumption in % of trials’
PONV: postoperative nausea and vomiting.
BioMed Research International
induction. Recovery time, postoperative pain scores, anes-
thetic consumption, analgesic requirements, and perioper-
ative additional analgesic were measured across the two
groups. ere were no dierences in any of these variables
between the two groups.
4.6. Gynecological Surgery. omas et al. []studiedthe
usage of a single preoperative dose of ketamine before elect-
ive gynecological procedures. is prospective study divided
patients into a control group, which received normal saline
andaketaminegroup,whichreceived.mg/kgofketamine
just before anesthetic induction. Although the ketamine
group required slightly less cumulative morphine for post-
operative analgesia, this result was not signicant. ere was
also no signicant dierence in the reporting of pain on
the VAS between the two groups. Although there was no
dierence in the length of postoperative stays, the group
receiving ketamine reported signicantly greater satisfaction
with their pain management.
Bilgen et al.’s  study [] utilized three dierent doses
of ketamine (., ., and  mg/kg) and a placebo to test the
eects on postoperative morphine requirements and pain in
women undergoing elective Cesarean sections. e primary
outcome assessed was cumulative postoperative morphine
consumption at  hours. is variable, acute pain score and
prolonged postoperative pain measured at  weeks,  month,
 months, and  year were all similar between all groups.
Ketamine did not have a signicant eect on any of these
outcomes.
Suppa et al. [] performed a similar study in women
undergoing elective Cesarean sections, using a . mg/kg
ketamine bolus  minutes aer birth in addition to a
𝜇g/kg/min IV ketamine infusion for  hours thereaer.
Usage of ketamine reduced morphine requirements at the
–, –, and –-hour time points. e patients in
the ketamine group showed reduced pain sensitivity at the
T- dermatome, suggesting an antihyperalgesic eect. At
three years aer surgery, patients reported no dierences in
residual pain or dysesthetic symptoms.
4.7. Major Abdominal Surgery. Zakine et al. []performed
a double-blinded study comparing the eectiveness of keta-
mine administration in two dierent settings with one control
group which received placebo. e rst ketamine group
received a . mg/kg bolus perioperatively and a 𝜇g/kg/min
infusion thereaer for  hours; the second ketamine group
received a . mg/kg bolus perioperatively and a 𝜇g/kg/min
infusion only for the duration of the surgical procedure. All
of the patients were given morphine PCA. e authors found
that cumulative morphine consumption was signicantly
lower in the group receiving the -hour infusion when
comparedtotheshorterinfusionandcontrolgroups.VAS
scores were measured postoperatively and were signicantly
lower in the ketamine groups when compared to the control
group. As an added eect, while all patients in the study
received hydroxyzine preoperatively, the -hour infusion
group experienced signicantly less nausea than the control
group (% versus %, 𝑃 = 0.005). It is worth nothing that
there were no side eects of the ketamine, psychotomimetic,
or otherwise.
Katz et al. [] analyzed ketamine as a postoperative anal-
gesic in men undergoing radical prostatectomy. Men were
double-blinded into  dierent groups, all of which received
fentanyl. In addition, group  received a preincisional intra-
venous bolus (. mg/kg) and infusion (. mL/kg/min)
of ketamine, group  received the same dosages  minutes
aer incision, and group  received no ketamine. e authors
found that pain scores did not dier signicantly among the
groups and follow-up at two weeks and again at six months
they showed no signicant dierences in pain incidence or
intensity.
de Kock et al. [] studied ketamine given both systemi-
cally and epidurally to patients undergoing rectal adenocar-
cinoma resection. All patients received a preoperative epidu-
ral bolus and continuous infusion of bupivacaine/ sufen-
tanil/clonidine. A control group received no ketamine, and
other groups received ketamine at dierent dosages, admin-
isteredeitherepidurallyorintravenously.egroupthat
received a ketamine bolus of .mg/kg and continuous infu-
sion of . mg/kg/h had signicantly lower PCA require-
ments, smaller hyperalgesic areas, and less residual pain
through six months of follow-up.
4.8. Systematic Reviews. AreviewbyLaskowskietal.
[] found a reduction in total opioid consumption and
an increase in time to rst analgesic request in groups
receiving ketamine. % of the ketamine treatment groups
required less postoperative opioid analgesia and reported less
postoperative pain.
AsecondreviewbyEliaandTram
`
er [] shows signif-
icant decreases in pain intensity at rest when ketamine is
comparedwithacontrolath,h,h,andhours
postoperatively. All trials except one within the review
report a signicant decrease in morphine consumption when
ketamine is used intraoperatively. Average time to rst
analgesic request had an average improvement of  minutes.
Regarding long-term follow-up, signicantly fewer patients
who had received high-dose IV ketamine (bolus . mg/kg,
infusion . mg/kg/h during surgery) suered from residual
pain at the -month mark.
Subramaniam et al.’s  systematic review [], includ-
ing  studies and  patients, addressed ketamines eec-
tiveness in reducing opioid consumption for postoperative
analgesia. ey divided subjects into  subgroups based on
therouteandmethodofketamineadministration:ketamine
as single dose, continuous infusion, PCA, and epidural
ketamine with opioids. Low-dose ketamine was found to be
safe, and no increase in side eects was suggested. A single
bolus dose of ketamine decreased opioid requirements in
 of  studies. Continuous infusion of ketamine decreased
IV and epidural opioid requirements in  out of  studies.
Adding ketamine to PCA morphine was not found to be
useful. Epidural ketamine showed benecial eects in  out of
 studies. Among the various methods of IV ketamine admin-
istration, continuous IV infusion of ketamine was the most
helpful in major surgeries requiring increased postoperative
BioMed Research International
opiate use such as major abdominal surgical procedures and
thoracic procedures.
McCartney et al. []performedasystematicreviewthat
looked at the eects of various NMDA receptor antagonists,
including ketamine, on postoperative pain and analgesic
consumption. Twenty-four ketamine-based studies met their
inclusion criteria;  of  (%) demonstrated a positive
eect in lowering postoperative pain and/or decreasing anal-
gesic consumption. Dosages used in the analyzed studies
ranged from . to mg/kg.
5. Adverse Effects
Ketaminehasbeenreportedtobeasafeandwell-tolerated
drug [,]. Despite the benets and the increase in pop-
ularity of using ketamine as both an anesthetic and an anal-
gesic, there are some troubling adverse eects associated with
its use. ese eects are usually temporary; however, they
can be signicantly distressing for patients. erefore, it is
paramount to discuss these eects. Common adverse eects
include feelings of inebriation, nausea, psychotomimetic
eects, and headaches with long-term use, possibly resulting
in impaired cognition, memory, and mood [].
e most common concerns about ketamine as an anal-
gesic agent are related to its mind-altering eects. Katalinic’s
team addressed these concerns and their review showed that
most of the research conducted using subanesthetic doses
of ketamine has shown transient increases in the following
psychiatric symptoms: positive and negative symptoms of
schizophrenia, dissociative symptoms, and manic symptoms.
Fortuitously, these symptoms are only present at times of
administration and usually disappear within  minutes of
administration []. Quiet, relaxed surroundings contribute
to a reduced incidence of these side eects and when
ketamine is administered alone, the prophylactic use of
asedativeagentsuchas..mgoralmidazolamhas
generally decreased their incidence and severity [].
Other psychotomimetic eects of ketamine use include
feelings of intoxication, increased confusion, lowered inhibi-
tion, and perceptual disturbances. In addition, research
shows that chronic use of ketamine may impair several mem-
ory systems including episodic and working memory. None-
theless, these eects have been restricted to time of adminis-
tration and are transient in nature. Additionally, implications
of these eects have not been found to be dependent on dose
or route of administration [].
No severe physical symptoms have been reported with
the use of low-dose ketamine; however, studies have reported
benign eects of lightheadedness, headache, nausea, diplopia,
drowsiness, and dizziness. ese eects, unlike the psychot-
omimetic eects, tend to be dose-dependent. ey are also
limited to time of administration and a short time thereaer
[].
Ketamine can also induce various CNS side eects (e.g.,
dizziness, diplopia, dysphoria, dreams, hallucinations, disori-
entation, strange sensations, lightheadedness, sleep dicul-
ties, and confusion). One systematic review found incidences
of these CNS eects were %, %, %, and .% with
IV PCA, IV infusion, IV single dose, and epidural groups,
respectively. No signicant increase in these eects was seen
compared to patients who did not receive ketamine [].
Almost  cases of ketamine-induced uropathy have
been reported in the literature, mostly in the context of
chronic abuse, but ve within medical analgesic use [].
Case series demonstrate a temporal link between ketamine
abuse and urological symptoms, urinary tract damage, and
renalimpairment,withsomebutnotallsymptomsimproving
upon cessation of ketamine. Chu et al. reported lower uri-
nary tract symptoms of ketamine-induced cystitis, dysuria,
urgency, frequency, incontinence, macroscopic hematuria,
and suprapubic pain. Investigations showed negative urine
cultures in % and cystoscopy showed epithelial damage in
% [].
Hepatotoxicity has been reported at anesthetic doses
( mg/kg) and patients receiving low-dose continuous infu-
sion. Noppers et al. present data on the occurrence of
ketamine-induced liver injury during repeated administra-
tions of S(+)ketamine for the treatment of chronic pain.
Six patients received  continuous intravenous -hour
S(+)ketamine infusions, – mg/h, separated by  days.
ree of these patients developed hepatotoxicity evident
through elevated transaminases. Ketamine infusion was
promptly terminated and the liver enzymes slowly returned
to reference values within  months, suggesting an increased
risk for development of ketamine-induced liver injury when
theinfusionisprolongedand/orrepeatedwithinashorttime
frame []. Trials using single doses of ketamine < mg/kg
report no changes in liver function tests [].
It has been described in the literature that ketamine
use can lead to neuronal cell apoptosis. is is triggered
by the direct blockade of NMDA receptors. e eect was
demonstrated in rats at repeated doses of  mg/kg [].
However, an eect was not seen aer a single bolus at this
dose [].isisespeciallyconcerninginthedeveloping
brain, where ketamine can interfere with both neuronal
proliferation and dierentiation []. Recent studies have
already indicated that ketamine can result in long-lasting
cognitive decits in a primate model. Paule et al. tested this
eect with rhesus monkeys who received enough ketamine
to maintain anesthesia for a  hour surgery during their
rst week of life. At approximately  months of age, control
monkeys began to outperform the ketamine-dosed monkeys
at a battery of tests. At three-and-one-half years of age, the
ketamine monkeys still performed worse than the controls
[].
Chang et al. [] reported a marked and sudden
increase in intracranial pressure (ICP) during induction
with ketamine in a patient with traumatic brain injury. It
should be noted, however, that this patient’s ICP was quite
elevated even before induction. e ICP fell rapidly when
mechanical ventilation began. Administration of ketamine
for sedations has been shown to result in higher opening
pressures during lumbar puncture in children, but this eect,
like the psychotomimetic eects, can be tempered with
midazolam [].
In a study conducted to evaluate the safety and ecacy
of ketamine for the treatment of refractory status epilepticus,
BioMed Research International
it was found that the drug’s administration caused possible
adverse events in  out of  study patients. ese included
a life-threatening severe acidosis, a syndrome similar to
propofol-related infusion syndrome, supraventricular tachy-
cardia, and atrial brillation [].
Ketamine is not FDA-approved for epidural use as it car-
ries a risk of neurotoxicity. Furthermore, there is no safety
or ecacy data on the neuraxial administration of ketamine.
Becauseofthis,theepiduraland/orintrathecaladminis-
tration of ketamine are discouraged outside of the preclin-
ical research setting. Spinal neurotoxicity aer continuous
intrathecal ketamine infusion of mg/day over  weeks
has been reported [].However,thedrugusedinthis
case was not preservative-free, and chemical cytotoxicity
has oen implicated the preservatives used rather than the
active compound. erefore, only preservative-free ketamine
should be used for intrathecal infusion. is eect was also
described aer a -week continuous infusion, a situation that
we are unlikely to see in patients that are given ketamine with
the short-term goal of postoperative analgesia.
Potential dependence through chronic or repetitive keta-
mine use is concerning. Studies of recreation ketamine-
using populations report cravings for the drug, physiolog-
ical tolerance, and possible withdrawal symptoms on drug
cessation. Physiological tolerance is of particular relevance
as it has been suggested for individuals having undergone
repeated procedures requiring anesthesia with ketamine [].
Tolerance development with ketamine used as analgesia is
less certain. Perry et al. []followedhealthysubjectsgiven
subanesthetic doses of ketamine for up to  months. Results
showed no reports of cravings or abuse outside of the study,
suggesting that ketamine in low doses is less likely to produce
dependence.
6. Conclusion
Although it was rst used purely as an anesthetic, ketamine is
making a certain resurgence in the management of postoper-
ative pain. Many of the aforementioned studies have demon-
strated signicant eectiveness in controlling postoperative
pain, increasing time to rst analgesic request, and decreasing
overall opioids required, as well as demonstrating fewer of the
opioid-related side eects like PONV. ese eects have been
demonstrated across many realms of surgery, including oto-
laryngology, abdominal surgery, orthopedic surgery, spinal
surgery, and gynecological surgery. While all of the exact
mechanisms have not been entirely agreed upon, the primary
eect of the drug is related to its NMDA receptor antagonism.
An intravenous bolus given prior to incision followed by a
continuous infusion appears to be the most eective modal-
ity for postoperative pain control. If the infusion is given
over a protracted time course ( h) for more invasive and
routinely painful procedures, patients can have a decreased
risk of developing persistent postoperative pain in months
thatfollow.isinfusioncanalsobecombinedwithPCA
for excellent control of acute postoperative pain. Ketamine
may not provide a clear benet for patients undergoing
smaller procedures, as analgesia with low dosages of opioids,
NSAIDs, and local anesthetic inltration can usually provide
adequate pain relief. e oen feared psychotomimetic eects
can be blunted by administering general anesthesia or the
less eective benzodiazepine. While animal models show
some degree of neurotoxicity in high-dose applications and
possible induction of neuronal apoptosis, these eects have
not been demonstrated and are not of concern at the dosages
and durations employed for postoperative analgesia. e
other conclusion that can be drawn from the aforementioned
studies is that although ketamine was eective in many of
thetrials,othertrialsshowedthatitprovidednobenet
when compared to a placebo. While ketamine holds a place
in the prevention and treatment of postoperative pain, more
large, high-quality controlled studies are necessary in order to
determine which procedures it is best suited for and at what
dosages and frequencies it should be administered.
Conflict of Interests
e authors declare no competing nancial interests.
Acknowledgment
All research performed by Department of Anesthesiology,
Rutgers New Jersey Medical School.
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... Understanding the mechanisms by which ketamine reduces pain and opioid requirements is crucial for optimizing its use in gynecological surgery, Radvansky et al. (2015) provided a narrative review on the role of ketamine in acute postoperative pain management [6]. They discussed ketamine's action as an N-methyl-D-aspartate (NMDA) receptor antagonist, which is thought to be the primary mechanism for its analgesic effects. ...
... The primary mechanism by which ketamine exerts its analgesic and opioid-sparing effects is through its action as an N-methyl-D-aspartate (NMDA) receptor antagonist. Radvansky et al. (2015) [6] provide a comprehensive overview of this mechanism in their narrative review. By blocking NMDA receptors, ketamine inhibits central sensitization and wind-up phenomena, which are key processes in the development of chronic pain. ...
... The narrative review by Radvansky et al. (2015) [6] on the role of ketamine in acute postoperative pain management provides a comprehensive overview of ketamine's mechanisms of action and clinical applications: a) Pharmacology: The review details ketamine's complex pharmacology, including its interactions with NMDA receptors and other neurotransmitter systems. b) Dosing Regimens: Various dosing strategies are discussed, including pre-incisional bolus, intraoperative infusion, and postoperative administration. ...
Article
Full-text available
This analysis aimed to evaluate the efficacy of ketamine infusion for reducing post-operative pain and opioid use in gynecological surgeries. A comprehensive review of recent studies revealed that ketamine consistently demonstrates significant pain-reducing and opioid-sparing effects across various surgical contexts, including gynecological procedures. Sub-anesthetic doses of ketamine were found to be effective and well-tolerated. However, optimal dosing regimens and timing of administration specific to gynecological surgeries require further investigation. The analysis recommends conducting large-scale, procedure-specific trials to establish tailored protocols for different gynecological surgeries. Additionally, long-term follow-up studies are needed to assess the impact on chronic pain development and persistent opioid use. This analysis is significant for refining pain management strategies in gynecological surgeries, potentially improving patient outcomes and addressing opioid-related concerns. It underscores the need for more flexible regulations to facilitate ketamine's clinical use in this context.
... Recent studies have shown a variety of postoperative pain management strategies, including but not limited to epidural analgesia, transverse abdominis plane (TAP) block, quadratus lumborum block, and wound infiltrations [6,12,16,17] . Wound infiltration procedures with ketamine, on the other hand, are gaining popularity because of its novelty, simplicity, and minimal complication profiles [18][19][20][21] . ...
... Postoperative wound infiltration techniques have recently gained popularity due to their ease of use and affordability in terms of administration strategies and side effects [6,12,16,17] . Recent studies comparing ketamine wound infiltration [6,21,22] with local anesthetics, glucocorticoids, opioids [22][23][24] , nonsteroidal anti-inflammatory agents [25] , and alpha-2 agonists [26,27] are released. The effectiveness and safety of low-dose preemptive and perioperative intravenous ketamine for postoperative pain is well established [20,21,28] . ...
... Recent studies comparing ketamine wound infiltration [6,21,22] with local anesthetics, glucocorticoids, opioids [22][23][24] , nonsteroidal anti-inflammatory agents [25] , and alpha-2 agonists [26,27] are released. The effectiveness and safety of low-dose preemptive and perioperative intravenous ketamine for postoperative pain is well established [20,21,28] . However, the efficacy and safety of subcutaneous infiltration of ketamine compared to local anesthetics and other adjuvants is still uncertain and a topic of debate. ...
Article
Full-text available
Background Postoperative pain has a huge impact to the patients, families, healthcare practitioners, and healthcare delivery. Pain management with opioid-based analgesics and blind techniques have certain limitations, and ultrasound-based regional analgesia necessitates resources and experience, but ketamine wound infiltration is innovative with few side effects. However, its effectiveness is still uncertain. Methods A thorough search was carried out across various databases including PubMed/Medline, Cochrane, Science Direct, CINHAL, and LILACS, with no limitations on date or language. Only randomized trials comparing the effectiveness of ketamine wound infiltration for managing postoperative pain were considered for inclusion. Two authors independently conducted data extraction, and the quality of evidence was assessed using GRADEpro software. Trial sequential analysis was utilized to ascertain the conclusiveness of the findings. Results The review showed that the first analgesic request was higher in control group as compared to Ketamine SMD=1.68 (95% CI: 0.95 to 2.41). The TSA revealed that the cumulative Z-curve crosses both alpha-spending boundaries and reaches the required information size threshold, revealing strong power for current evidence. However, the quality of evidence was moderate. Conclusion Despite available evidences, provision of firm conclusion is less optimal with current evidence as the included studies were unpowered with low to very low quality of evidences. Registration: This systematic review protocol was registered in Prospero (CRD42021268774).
... For patients managed with GA, the dosage of anesthetic drugs (converted into dose/weight) was collected. We analyzed the intraoperative drugs most likely to cause delirium: morphine, ketamine [31][32][33], and analgesics such as nefopam and tramadol [34]. ...
Article
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Background: Postoperative delirium (POD) is a common surgical complication that increases hospital stay duration, hospitalization costs, readmission rates and mortality. This study aims to describe the incidence of POD in an elderly patient population and to investigate pain assessment as a risk factor for postoperative confusion. Additionally, we aim to determine a predictive model for POD. Methods: We conducted a retrospective, observational, single-center study at La Timone Hospital between September 2020 and September 2021. We included patients aged 65 or older, admitted for scheduled or emergency surgical care, with an expected postoperative stay of three days or more and no history of dementia. Data were collected in three stages of hospitalization: preoperative, perioperative, and postoperative. Preoperative data included medical history and lifestyle; perioperative data included surgical and anesthesia characteristics, and postoperative data were collected. Results: Of the 531 patients admitted for surgical care, we analyzed 109 patients. Among these, 24 (22%) experienced a POD episode within the first three postoperative days. Age, preoperative cognitive impairments, preoperative sensory deficits, and long-term benzodiazepine use were identified as risk factors for POD. A significant difference in pain levels was also observed for all NRS scores during the first three postoperative days. After multivariate analysis, we retained two predictive models for POD. Conclusions: This study identified risk factors for POD and proposed predictive models based on these factors. Two models were particularly notable for their potential use in anesthesia consultations and patient follow-up services to quickly detect patients at risk of POD.
... ketamine has a non-GABAergic mechanism of action [24]. It produces analgesia and rapid sedation by dual mechanisms mediated by inhibition of the N-methyl-D-aspartate receptor and activation of the opioid μ-and κ-receptors [25]. Additionally, ketamine provides bronchodilation, preservation of cardiac output, increase in blood pressure, and maintenance of respiratory drive and airway reflexes while actively weaning from MV [26]. ...
Article
Background: Opioid-sparing sedoanalgesia relies on non-opioid multimodal analgesic and sedative agents. It is being developed to decrease or eliminate opioid use for the management of acute postoperative pain to avoid opioid complications. This study aimed to compare ketamine and dexmedetomidine for their efficiency and safety in inducing opioid-sparing sedoanalgesia in patients following open heart surgery. Methods: Ninety adult cardiac patients who underwent open heart surgery were enrolled. They were randomly divided into three groups. Group D received a dexmedetomidine infusion of 0.1– 0.2 μg/kg/hour, group K received a ketamine infusion of 1–2 μg/kg/min while group C received a placebo as a control group. Drugs were given after the operation in the surgical intensive care unit. Total postoperative opioid consumption was the primary outcome. Richmond agitation sedation scale, visual analog pain scale, time to first analgesic request, patient satisfaction, and incidence of any complications were recorded. Results: In this study, we found that the median (interquartile range) postoperative opioid consumption was significantly lower in groups D and K than in group C (156 (40), 140 (83), 185 (110); p < 0.001). Richmond agitation sedation scale was statistically significant until 6 hours postoperative (p-value: < 0.05). Patient satisfaction score was higher in groups D and K than in group C (p-value: 0.005). On the other side, there is no statistically significant difference between the three study groups regarding time to first analgesic request (minutes) (p-value: 0.064) or visual analog pain scale (p-value: > 0.05). Incidence of complications was highly significant between the study groups (p-value: < 0.001). Conclusions: To decrease postoperative opioid use with their multiple side effects and improve patient satisfaction scores in patients undergoing open heart surgery under general anesthesia, the use of either ketamine or dexmedetomidine is recommended in the postoperative period as an adjuvant modality and a good idea with observation of possibility of some preventable side effects.
... Information sharing, psychological strategies including diversion, relaxation, and cognitive behavioral treatments, transcutaneous electrical nerve stimulation (TENS), acupuncture, manual therapies, hydrotherapy, and physiotherapy are a few of them [12] . • Pharmacological agents [13] 1. Non-opioid analgesics [14] ▪ Paracetamol ▪ NSAIDs 2. Opioid treatments: Opioid receptor-specific binding and activation occur in the central and peripheral nervous systems when opioid analgesics bind to and activate certain receptor sites. By several methods, these receptors block the transmission of pain when they are triggered, resulting in analgesia [15] . ...
... This can be a breath of fresh air in the future, bearing in mind that the use of opioids is expected to decrease; in fact, it is still not new to science outside of anesthesiology and intensive care therapy, so the cost of using opioids can be reduced, even replaced, by ketamine which is also more easily found in type C hospitals in remote areas. [16][17][18][19] In a study by Jehosua et al., it was found that in the group that did not use a CONOX-type EEG monitoring tool, there were more side effects of anesthesia, such as higher intraoperative hemodynamic turmoil, postoperative cognitive disorder, intraoperative awakening, PONV, to moderate to severe pain while in the recovery room. 5 Ren et al.'s study showed that the anxiety score (HAD-A) and depression score (HAD-D) in the postoperative group with colorectal cancer who were given subdose ketamine 5 minutes before a single bolus operation also had a higher Quality of Recovery-40 (QoR-40) level, as well as levels of anxiety and depression and IL-6, IL-8, and TNF-α, being lower. ...
Article
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Aims and background In postoperative patients in the intensive care units (ICUs), not only analgesics are needed but also sedation so that the patient can remain calm during treatment, especially patients with mechanical ventilation. By using the measurement parameters of the quantum consciousness index (qCON) and quantum noxious index (qNOX) in measuring the depth of sedation and adequacy of analgesics, the use of subdose ketamine instead of fentanyl and midazolam as sedative, analgesic agents can be performed as a new alternative to nociceptive monitoring methods with more objective results. This study aims to obtain results of comparing qCON and qNOX in postoperative patients by administering subdose ketamine compared with a combination of fentanyl and midazolam in RSUP Haji Adam Malik Medan. Materials and methods A randomized clinical trial with a double-blind approach has been used in this study. A total of 44 experimental samples were gathered and randomly split into two groups after meeting the criteria for inclusion. Group A administered a ketamine subdose, whereas Group B administered a mixture of fentanyl and midazolam. The research data obtained were tested using Statistical Product and Science Service (SPSS). Results There were differences in the median, minimum, and maximum values of qCON and qNOX in the groups given subdose ketamine and fentanyl and midazolam, but these were not statistically significant (p > 0.05) at T0, T1, and T2. Conclusion Administering a subdose of ketamine can provide sedation and analgesia comparable to fentanyl and midazolam. How to cite this article Masharto AR, Lubis AP, Bangun CG, Wahyuni AS. Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study. Indian J Crit Care Med 2024;28(6):581–586.
Chapter
Renal cell carcinoma is the most common urological malignancy which can be managed surgically in the advance stage to improve the quality of life. Preoperatively recent imaging studies are recommended because of the nature of renal cell carcinoma to extend through venous invasion, a 2D ECHO and lower limb Doppler will be done prophylactically in high-risk patients. General anesthesia with endotracheal intubation and epidural analgesia is the preferred anesthesia technique. The surgery is done under the vicinity of major vessels and intraoperatively bleeding is expected so good intravenous access should be taken and invasive monitoring should be done in selected high-risk patients. Team must be cautious during the positioning of the patient to avoid any nerve and organ injury. Preoperative hypovolemic state should be avoided and target urine output kept above 1 mL/kg body weight. Laparoscopic radical nephrectomy patients may complain mild to moderate pain in the immediate postoperative period, they also complain of shoulder pain which is due to irritation of peritoneum, diaphragm, and neuroprexia, which can be managed successfully with intraoperative and postoperative intravenous opioids and paracetamol. Neuraxial or regional analgesia technique provide good perioperative pain relief, decrease the requirement of opioids, and the patient can mobilize early.
Chapter
In this chapter, we delve into a comprehensive exploration of both pharmacological and surgical interventions for pain relief. These approaches are firmly rooted in our understanding of nociception pathways, which we thoroughly explored previously. The pharmacological section of this chapter takes us through a diverse landscape of pain relief strategies. It encompasses essential treatments such as Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), pivotal for addressing the inflammatory components of pain, and anticonvulsants acting on ion channels. Moreover, we navigate through the intriguing realm of psychotropic medications, opioids, cannabinoids, anti-NMDA agents, and even psychedelics. Each of these approaches is meticulously examined, shedding light on their mechanisms of action, potential adverse effects, and considerations regarding tolerance and dependence. The effective utilization of these pharmacological tools relies on a nuanced understanding of factors such as medication selection and dosage. We emphasize the multifactorial considerations that underpin the art of effective pharmacotherapy for pain relief. Complementing our exploration of pharmacology, we venture into the domain of surgical interventions aimed at modulating nociceptive pathways within the central nervous system. Neurostimulation has emerged as a frequently employed technique for managing pain perception. This involves precise stimulation at various trigger points along pain pathways, including the spinal cord’s posterior column, somatosensory thalamus, and motor cortex. Additionally, we delve into the intriguing field of psychosurgery, which targets both the sensory and affective components of pain perception. This chapter serves as an in-depth examination of the fundamental techniques that drive pain alleviation in clinical practice. It offers a comprehensive overview of the latest therapeutic approaches used in the clinic, reflecting the ongoing evolution of pain management strategies. Our ultimate goal is to provide insights into the most current and effective methods for pain alleviation, equipping clinicians with the knowledge they need to optimize patient care.
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Background and objectives The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children. Subjects and Methods Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0–24 hours after leaving the operation room were included in the analysis. Results The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics. Conclusion Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.
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Objective: To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. Study design: A randomized, double-blind comparative study. Place and duration of study: Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Methodology: Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Results: Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Conclusion: Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.
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