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RE: Ketamine abstracts
Immediately below is a brief extraction from the pages of abstracts; the complete
abstracts listed below that start on p 3.
4 mg/kg po after an i.m. test-dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg
midazolam.
After a 'baseline' week, oral ketamine was taken once a day for 1 week. The dose of
20 mg was increased each day until an analgesic effect was noticed or adverse effects
occurred, or until a maximum of 100 mg was reached. adverse effects (dizziness,
drowsiness
oral ketamine starting at a divided dose of 100 mg/day and titrating upwards by 40
mg/day until efficacy was reached, or until side effects became limiting.. Nine
patients discontinued ketamine because of intolerable side effects, four patients
experienced few or no side effects but had no discernible benefit, four others had
equivocal responses. Four patients have continued oral ketamine for long periods.
One patient has had no significant benefit or side effects but continues to use
ketamine 500 mg/day and three people have used doses ranging from 100-240 mg/
day for over 1 year duration and have reported improvements in pain and
decreased use of analgesics.
a 5-mg nitroglycerin patch daily; the ketamine 0.5 mg/kg oral ketamine at 12-h
intervals in cancer pts on morphine
ketamine 50 mg x 4 per day dissolved in juice.
See below on topical: One to 2 weeks later, we observed improvement of the report
of pain intensity, measured by the visual analog scale, in 4 patients with acute early
dystrophic stage of CRPS I. Swelling of the affected limbs subsided as well.
See below article Preparation of ketamine tablets
oral ketamine with titration to 50mg three times a day was beneficial in decreasing
allodynia and hyperalgesia, as well as improving functional capabilities. Known side
1
RE: Ketamine abstracts
effects including dysphoria, hallucinations, and paranoid feelings were attenuated
with benzodiazepines. 68 yo w post stroke central pain
oral transmucosal ketamine (5-6 mg.kg-1) for premedication in 25 children and
compared it with intranasal ketamine (5-6 mg.kg-1), placebo and intramuscular
ketamine (5-6 mg.kg-1). Transmucosal provided effective sedation, facilitated i.v. line
insertion and was accepted with pleasure by the patients (as lollipops).
I.V. initial dose of 100 mg/24 hr was escalated if required to 300 mg/24 hr and then
to a maximum dose of 500 mg/24hr. The overall response rate was 29/43 (67%).
controlled delivery transdermal patch containing ketamine (25 mg/24 h)
Magnesium is known to block the NMDA receptor. It reduces the neuropathic pain
response in animals, and attenuates postoperative pain and migraine in humans. two
intravenous doses of magnesium sulfate in 12 patients with neuropathic pain due to
malignant infiltration of the brachial or lumbosacral plexus. The first six patients
received 500 mg, the remainder 1 g. were well tolerated. 500 mg, three patients
experienced complete pain relief – seems better than 1 gm results
plasma ketamine concentration associated with analgesia was 150 ng ml-1
following the i.m. dose, but only 40 ng ml-1 after the oral dose. Oral
administration was, however, associated with much greater concentrations of
the metabolite norketamine, which may have contributed to the analgesic
effect.
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RE: Ketamine abstracts
Ketamine in chronic pain management: an evidence-based review.
Author
Hocking G., Cousins M. et al.
Source
Anesth Analg, 2003 Dec;97(6):1730 - 1739
Document
Ketamine has diverse effects that may be of relevance to chronic pain including:
N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated
Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been
in clinical practice for over 30 yr; however, there has been little formal research
on the effectiveness of ketamine for chronic pain management. In this review we
evaluate the available clinical data as a basis for defining the potential use of
ketamine for chronic pain. Literature referenced in this review was obtained from
a computer search of EMBASE and MEDLINE from 1966 through August, 2002.
Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia.
Abstracts were screened for relevance and publications relating to chronic pain
use were obtained. Levels of evidence were stratified according to accepted
guidelines (level I-IV). For central pain, there is level II and level IV evidence of
efficacy for parenteral and oral ketamine. For complex regional pain syndromes,
there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia,
there is level II evidence of pain relief, reduced tenderness at trigger points, and
increased endurance. For ischemic pain, a level II study reported a potent dosedependent analgesic effect, but with a narrow therapeutic window. For
nonspecific neuropathic pain, level II and level IV studies reported divergent
results with questionable long-term effects on pain. For phantom limb pain and
postherpetic neuralgia, level II and level II studies provided objective evidence of
reduced hyperpathia and pain relief was usually substantial either after parenteral
or oral ketamine. Acute on chronic episodes of severe neuropathic pain
represented the most frequent use of ketamine as a "third line analgesic," often by
IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of
ketamine for treatment of chronic pain is moderate to weak. However, in
situations where standard analgesic options have failed ketamine is a reasonable
"third line" option. Further controlled studies are needed.
Drugs. 2003;63(1):17-32.
Related Articles, Links
Responsible prescribing of opioids for the management of chronic
pain.
Nicholson B.
Lehigh Valley Hospital Pain Center, Allentown, Pennsylvania, USA.
3
RE: Ketamine abstracts
[email protected]
The management of patients with chronic pain is a common clinical challenge.
Indeed, chronic pain is often inadequately controlled in patients with cancer and
in those with non-cancer chronic pain. Because of the complex nature of chronic
pain, successful long-term treatment is more difficult than for acute pain. Most
often acute pain is nociceptive, whereas chronic pain can be nociceptive (i.e., in
response to noxious stimuli), neuropathic (i.e., initiated by a primary lesion or
dysfunction in the nervous system) or mixed in origin. Opioids are the current
standard of care for the treatment of moderate or severe nociceptive pain. Opioids
mediate their actions by binding and activating receptors both in the peripheral
nervous system and those that are found in inhibitory pain circuits that descend
from the midbrain to the spinal cord dorsal horn. Opioid agonists exert a number
of physiological responses including analgesia, which increases with increasing
doses. The use of opioids to manage pain in patients with cancer is well accepted.
The WHO step-wise algorithm for analgesic therapy based on pain severity
reserves the use of opioid therapy for moderate and severe pain. The WHO
algorithm has proven to be highly effective for the management of cancer pain.
However, the use of opioids to treat patients with chronic non-cancer pain is
controversial because of concerns about efficacy and safety, and the
possibility of addiction or abuse. The results of clinical surveys and
retrospective case series involving patients with non-cancer chronic pain
have been inconsistent in regard to resolving these controversial issues. The
oral route of drug administration is most appropriate for patients receiving
opioids; although rectal, transdermal and parenteral routes of administration are
used in specific situations. For continuous chronic pain, opioids should be
administered around-the-clock and several long-acting formulations are available
that require administration only once or twice daily. Opioid doses should be
titrated according to agent-specific schedules to maximise pain relief and maintain
tolerability. Adverse effects include constipation, nausea and vomiting, sedation,
cognitive impairment and respiratory depression. Tolerance to the analgesic and
adverse effects as well as physical dependence, which causes withdrawal
symptoms upon discontinuance, may occur with opioid use. Estimates of
addiction rates among patients with chronic non-cancer pain range from 3.2
to 18.9%. Successful pain treatment and symptom management is an attainable
goal for the majority of patients with chronic pain. Further controlled clinical
trials are needed to define the role of opioid therapy in chronic non-cancer pain,
and to establish criteria for patient selection and specific treatment algorithms.
Publication Types:


Review
Review, Tutorial
PMID: 12487620 [PubMed - indexed for MEDLINE]
4
RE: Ketamine abstracts
Anesth Analg. 2003 Dec;97(6):1730-9.
Related Articles, Links
Ketamine in chronic pain management: an evidence-based review.
Hocking G, Cousins MJ.
Pain Management and Research Centre, University of Sydney, Royal North Shore
Hospital, St Leonards, Sydney, NSW 2065, Australia.
Ketamine has diverse effects that may be of relevance to chronic pain including:
N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors;
inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine
re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there
has been little formal research on the effectiveness of ketamine for chronic pain
management. In this review we evaluate the available clinical data as a basis for
defining the potential use of ketamine for chronic pain. Literature referenced in
this review was obtained from a computer search of EMBASE and MEDLINE
from 1966 through August, 2002. Search terms included ketamine, ketalar, pain,
painful, analgesic, and analgesia. Abstracts were screened for relevance and
publications relating to chronic pain use were obtained. Levels of evidence were
stratified according to accepted guidelines (level I-IV). For central pain, there is
level II and level IV evidence of efficacy for parenteral and oral ketamine.
For complex regional pain syndromes, there is only level IV evidence of
efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of
pain relief, reduced tenderness at trigger points, and increased endurance.
For ischemic pain, a level II study reported a potent dose-dependent
analgesic effect, but with a narrow therapeutic window. For nonspecific
neuropathic pain, level II and level IV studies reported divergent results with
questionable long-term effects on pain. For phantom limb pain and
postherpetic neuralgia, level II and level II studies provided objective
evidence of reduced hyperpathia and pain relief was usually substantial
either after parenteral or oral ketamine. Acute on chronic episodes of severe
neuropathic pain represented the most frequent use of ketamine as a "third line
analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the
evidence for efficacy of ketamine for treatment of chronic pain is moderate to
weak. However, in situations where standard analgesic options have failed
ketamine is a reasonable "third line" option. Further controlled studies are needed.
5
RE: Ketamine abstracts
Publication Types:


Review
Review, Tutorial
PMID: 14633551 [PubMed - indexed for MEDLINE]
Pain. 2001 May;92(1-2):311-3.
Related Articles, Links
Comment in:

Pain. 2002 Feb;95(3):288-9; author reply 289.
Treatment of central post-stroke pain with oral ketamine.
Vick PG, Lamer TJ.
Department of Anesthesiology, University of North Carolina at Chapel Hill,
Campus Box # 7010, Chapel Hill, NC 27599-7010, USA. [email protected]
Case report of 68 year old female with central post-stroke pain successfully
treated with oral ketamine. The patient's pain was refractory to conventional pain
treatments and she had persistent right hemi-body neuropathic pain with allodynia
and hyperalgesia. An intravenous ketamine trial, followed by oral ketamine with
titration to 50mg three times a day was beneficial in decreasing allodynia and
hyperalgesia, as well as improving functional capabilities. Known side effects
including dysphoria, hallucinations, and paranoid feelings were attenuated
with benzodiazepines.
Publication Types:

Case Reports
PMID: 11323153 [PubMed - indexed for MEDLINE]
J Pain Palliat Care Pharmacother. 2002;16(3):27-35.
Related Articles, Links
6
RE: Ketamine abstracts
Ketamine as an analgesic: parenteral, oral, rectal, subcutaneous,
transdermal and intranasal administration.
Kronenberg RH.
Thunderbird Samaritan Medical Center, Glendale, AZ 85306, USA.
[email protected]
Ketamine is a parenteral anesthetic agent that provides analgesic activity at subanesthetic doses. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with
opioid receptor activity. Controlled studies and case reports on ketamine
demonstrate efficacy in neuropathic and nociceptive pain. Because ketamine is a
phencyclidine analogue, it has some of the psychological adverse effects found
with that hallucinogen, especially in adults. Therefore, ketamine is not routinely
used as an anesthetic in adult patients. It is a frequently used veterinary anesthetic,
and is used more frequently in children than in adults. The psychotomimetic
effects have prompted the DEA to classify ketamine as a Schedule III Controlled
Substance. A review of the literature documents the analgesic use of ketamine by
anesthesiologists and pain specialists in patients who have been refractory to
standard analgesic medication regimens. Most reports demonstrate no or mild
psychotomimetic effects when ketamine is dosed at sub-anesthetic doses.
Patients who respond to ketamine tend to demonstrate dramatic pain relief
that obviates the desire to stop treatment due to psychotomimetic effects
(including hallucinations and extracorporeal experiences). Ketamine is
approved by the FDA for intravenous and intramuscular administration. Use of
this drug by the oral, intranasal, transdermal, rectal, and subcutaneous routes has
been reported with analgesic efficacy in treating nociceptive and neuropathic
pain. Ketamine also has been reported to produce opioid dose sparing and
good patient acceptance. A transdermal formulation is currently under patent
review in Brazil and an intranasal formulation is currently undergoing phase I/II
clinical trials.
Publication Types:


Review
Review, Tutorial
PMID: 14640353 [PubMed - indexed for MEDLINE]
Palliat Med. 1996 Jul;10(3):247-50.
Related Articles, Links
Ketamine injection used orally.
Broadley KE, Kurowska A, Tookman A.
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RE: Ketamine abstracts
Edenhall Marie Curie Centre, London, UK.
Ketamine has been used parenterally for pain unresponsive to opioids, including
neuropathic pain, and has also been used as an alternative analgesic agent after
surgery. Although oral administration of ketamine has been used for some time as
a single dose, it has not been given by this route on a regular basis. The use of
ketamine administered orally is described for two patients with severe
neuropathic pain who were intolerant of, or whose pain was unrelieved by, more
commonly used agents. Pain relief was achieved without significant side
effects.
Publication Types:

Case Reports
PMID: 8817596 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 2002 Feb;23(2):165-70.
Related Articles, Links
Low dose ketamine as an analgesic adjuvant in difficult pain
syndromes: a strategy for conversion from parenteral to oral
ketamine.
Fitzgibbon EJ, Hall P, Schroder C, Seely J, Viola R.
University of Ottawa Institute of Palliative Care, Ottawa, Ontario, Canada.
Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor
antagonist with analgesic and dissociative anesthetic properties. Low dose or subanesthetic doses of ketamine have been used effectively as either a primary
analgesic or analgesic adjuvant in a variety of pain syndromes. In this paper, three
patients with difficult to treat, predominantly neuropathic pain syndromes will be
described. Their pain syndromes were initially managed successfully with the
addition of low dose parenteral ketamine as an analgesic adjuvant. The
strategy of concurrently starting ketamine at a low dose, i.e., 40-60 mg over
24 hours, with a benzodiazepine proved effective in preventing
psychotomimetic side effects. An unavoidable shortage of ketamine
prompted a literature search, which suggested that the equianalgesic dose of
oral ketamine could be lower than the parenteral dose. Subsequently the
patients were converted to oral ketamine at doses 30 to 40% of the previous
parenteral dose. Their pain syndromes remained controlled on the lower dose of
8
RE: Ketamine abstracts
oral ketamine with remarkably few side effects. The implications of this warrant
further discussion and study.
1: Pain. 1999 Nov;83(2):283-7.
Related Articles, Links
N of 1 randomised controlled trials of oral ketamine in patients with
chronic pain.
Haines DR, Gaines SP.
Department of Anaesthesia, Royal Hull Hospitals NHS Trust, Hull Royal
Infirmary, Anlaby Road, Kingston on, Hull, UK. [email protected]
Anecdotal reports suggest that the general anaesthetic drug ketamine, taken orally
in low doses, can give rise to some extra analgesia in patients with refractory
neuropathic pain. This study was designed to determine the proportion of patients
with chronic neuropathic pain responding to oral ketamine, and then to separate
the true treatment effect from non-specific effects by means of an n of 1
randomised controlled trial. Twenty-one patients gave informed consent and
completed daily pain diaries and continued on their usual treatments (drug and
non-drug) for the duration of the study. After a 'baseline' week, oral ketamine
was taken once a day for 1 week. The dose of 20 mg was increased each day
until an analgesic effect was noticed or adverse effects occurred, or until a
maximum of 100 mg was reached. Those patients responding to oral ketamine
were then entered into the n of 1 randomised trial which consisted of three
treatment/placebo week pairs. Twelve patients did not progress to the n of 1 trial
because of no benefit and/or intolerable adverse effects (dizziness, drowsiness
etc.). Nine patients completed the n of 1 trial; there was no difference between the
ketamine and placebo weeks in six patients; one patient demonstrated effective
analgesia with ketamine, but it was of short duration and marred by unpleasant
adverse effects; two patients showed some evidence of a beneficial response to
ketamine, and continued with the oral ketamine after the trial. We conclude that
oral ketamine only gave rise to an extra analgesic response in three out of 21
patients with chronic neuropathic pain (14%). Adverse effects limited the use
of the drug in almost half of the patients. The n of 1 trial was useful in
demonstrating no true therapeutic effect for the ketamine in two thirds of the
patients progressing to that part of the trial.
Publication Types:
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Clinical Trial
Multicenter Study
Randomized Controlled Trial
9
RE: Ketamine abstracts
PMID: 10534600 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 1999 May;17(5):384-6.
Related Articles, Links
Comment in:

J Pain Symptom Manage. 2000 Jan;19(1):3-4.
Clinical experience with oral ketamine.
Enarson MC, Hays H, Woodroffe MA.
Department of Family Medicine, University of Alberta, Edmonton, Canada.
Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist
used recently for analgesia in patients with chronic pain. Twenty one patients
with chronic neuropathic pain were treated with oral ketamine starting at a
divided dose of 100 mg/day and titrating upwards by 40 mg/day until efficacy
was reached, or until side effects became limiting. A retrospective chart review
was conducted to evaluate the analgesic efficacy and side effects of the treatment.
Nine patients discontinued ketamine because of intolerable side effects, four
patients experienced few or no side effects but had no discernible benefit,
four others had equivocal responses. Four patients have continued oral
ketamine for long periods. One patient has had no significant benefit or side
effects but continues to use ketamine 500 mg/day and three people have used
doses ranging from 100-240 mg day for over 1 year duration and have
reported improvements in pain and decreased use of analgesics. The analgesic
benefits of ketamine appeared to be most pronounced in, but not limited to,
patients with pain histories of less than 5 years.
Publication Types:

Clinical Trial
PMID: 10355218 [PubMed - indexed for MEDLINE]
J Pharmacol Exp Ther. 1999 May;289(2):1060-6.
Related Articles, Links
10
RE: Ketamine abstracts
Prolonged analgesic effect of ketamine, an N-methyl-D-aspartate
receptor inhibitor, in patients with chronic pain.
Rabben T, Skjelbred P, Oye I.
Section of Dental Pharmacology and Pharmacotherapeutics, Faculty of Dentistry,
I.O.), University of Oslo, Oslo, Norway.
We examined the role of N-methyl-D-aspartate (NMDA) receptors in chronic
(pathological) pain in humans by using the NMDA receptor antagonist ketamine
as a probe. Thirty patients with neuropathic pain in the trigeminal area were given
an i.m. injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg.
Pethidine 1.0 mg/kg served as a control. Three different response patterns were
observed. Ketamine caused a long-term (6-24 h) analgesic effect partly
dissociated from the mental side effects in 8 of the 26 patients who completed the
study; these patients also had a slight analgesic effect of pethidine. In nine
patients, ketamine caused a short-lasting (<2 h) analgesic effect closely associated
with the mental side effects, whereas pethidine caused little or no analgesia. The
remaining nine patients did not experience any reduction of pain after either drug
in spite of characteristic side effects. One week after the i.m. challenge the
patients received either 4.0 mg/kg ketamine hydrochloride or placebo capsules
to be taken orally as a nightly dose for three consecutive nights. Five of the
eight patients who had a long-term analgesic effect of the i.m. challenge
reported decreased pain on days after ketamine. None of the others reported
an analgesic effect. The phenomenon of long-term depression of pain in a
subgroup of patients was thus confirmed when ketamine was given p.o. These
findings indicate that NMDA receptors are involved in the perception and
maintenance of pathological pain in some patients. In others, pain appears to be
mediated by NMDA receptor-independent mechanisms. We suggest that NMDA
receptor-independent transmission in central pain pathways may contribute to the
reduced efficiency of analgesic drugs often seen in chronic pain states.
Publication Types:
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
Clinical Trial
Randomized Controlled Trial
PMID: 10215688 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 1999 Jul;18(1):61-6.
Related Articles, Links
11
RE: Ketamine abstracts
Analgesic effect of oral ketamine in chronic neuropathic pain of
spinal origin: a case report.
Fisher K, Hagen NA.
Department of Oncology, University of Calgary, Canada.
Ketamine is an injectable anesthetic induction agent that has been reported to
have analgesic activity in pain from a variety of mechanisms, but predominantly
in neuralgic and dysesthetic neuropathic pain. In this case report we illustrate the
effectiveness of ketamine in a patient with neuropathic pain resulting from cauda
equina trauma. Among the issues addressed are the role of pretreatment with
haloperidol to prevent ketamine-induced psychomimetic effects, the potential
for fewer side effects and a need for lower doses when ketamine is
administered orally, and the need for further study regarding appropriate
monitoring parameters during the titration phase. Oral ketamine can be
effective in treatment refractory chronic neuropathic pain of spinal origin.
Publication Types:

Case Reports
PMID: 10439575 [PubMed - indexed for MEDLINE]
Anaesth Intensive Care. 2002 Aug;30(4):487-9.
Related Articles, Links
Successful use of oral methadone after failure of intravenous
morphine and ketamine.
Sartain JB, Mitchell SJ.
Department of Anaesthesia and Intensive Care, Cairns Base Hospital,
Queensland. [email protected]
12
RE: Ketamine abstracts
We describe an opioid-tolerant patient with severe acute pain which was
unrelieved by morphine and ketamine via intravenous patient-controlled
analgesia, but almost totally relieved by methadone. In the previous 24 hours, 509
mg of intravenous morphine and 769 mg of ketamine had been used and this was
replaced by 200 mg of oral methadone. This implies that the success of
methadone in morphine tolerant patients chiefly involves factors other than its
role as an N-methyl-D-aspartate receptor antagonist, and that methadone should
be considered as a replacement for morphine when the N-methyl-D-aspartate
antagonist ketamine has proved ineffective.
Publication Types:

Case Reports
PMID: 12180591 [PubMed - indexed for MEDLINE]
Ann Pharmacother. 2002 Oct;36(10):1614-9.
Related Articles, Links
Erratum in:

Ann Pharmacother. 2003 Sep;37(9):1346.
Adjuvant ketamine analgesia for the management of cancer pain.
McQueen AL, Baroletti SA.
Division of Drug Information, Department of Pharmacy Services, Brigham and
Women's Hospital, Boston, MA 02115, USA.
OBJECTIVE: To review the clinical literature evaluating the utilization of
intravenous ketamine for the management of cancer-related pain, to summarize
the data that suggest ketamine is an appropriate adjuvant method of providing
analgesia and to report a case of successful pain management using ketamine in a
patient with recurrent testicular cancer at our institution. DATA SOURCES:
Primary literature was identified through a MEDLINE search (1966-March
2002), and additional information was obtained through secondary and tertiary
sources. DATA SYNTHESIS: The available data suggest that supplementation of
morphine with ketamine improves analgesia in patients with cancer, and also
provides insight to the controversy regarding the efficacy and adverse effects of
various ketamine doses. At subanesthetic doses, ketamine may be beneficial at
reducing opioid requirements and related adverse effects. CASE SUMMARY: A
34-year-old white man with recurrent testicular cancer was admitted with
13
RE: Ketamine abstracts
radiating neuropathic pain of the legs and lower back. The patient was suspected
to also be experiencing opioid adverse effects; therefore, alternative analgesic
options were warranted. Ketamine was successful in reducing patient-reported
pain and was also well tolerated. CONCLUSIONS: Ketamine is an adjuvant
analgesic for the treatment of cancer-related pain when other agents either fail or
are intolerable. Accordingly, there are several factors that may prevent adequate
pain control with opioid use; therefore, alternative analgesic options should be
considered. Promise exists for ketamine as a contemporary analgesic in the
appropriate patient.
Publication Types:



Case Reports
Review
Review Literature
PMID: 12243612 [PubMed - indexed for MEDLINE]
Eur J Pain. 2001;5(3):233-40.
Related Articles, Links
Interindividual differences in the analgesic response to ketamine in
chronic orofacial pain.
Rabben T, Oye I.
Department of Pharmacology, Oslo University School of Medicine, Box 1057
Blindern, N-0316 Oslo, Norway. [email protected]
The analgesic effect of the N-methyl-D-aspartate (NMDA) receptor blocker
ketamine in 17 patients (13 females and four males, age 32-88 years) who had
suffered neuropathic orofacial pain for time periods ranging from 6 months to 28
years was examined. The patients were given an i.m. test-dose of 0.4 mg/kg
ketamine combined with 0.05 mg/kg midazolam. Four patients did not experience
any analgesic effect of the i.m. test dose. The remaining 13 patients experienced
an analgesic effect which lasted for less than 1 h (transient effect) in seven and for
several hours (long-term effect) in six. One week later they were given 4 mg/kg
ketamine to be taken orally in combination with a hypnotic drug for three
consecutive nights. All patients who reported a long-term analgesic effect after
i.m. ketamine also reported reduced pain intensity on days after taking ketamine
at night. The findings of this open study are in accord with the results from a
previous double-blind randomized investigation. In order to evaluate the role of
age and pain duration for the analgesic effect of ketamine, we pooled the data
from the two studies and performed a correlation analysis of 43 patients. We
14
RE: Ketamine abstracts
found a positive correlation between a long pain-history and lack of analgesic
effect and also between a short pain-history and a long-term analgesic effect
of low-dose ketamine. The apparent relationship between patient age and
ketamine response was, however, not statistically significant. Further, patients
with pain following a nerve lesion and patients without a known lesion of
peripheral nerves were equally distributed between the three response groups.
These results indicate that pain mechanisms are subject to alterations with time
and that these alterations involve transition from NMDA to non-NMDA receptor
mediated transmission in central pain pathways. Copyright 2001 European
Federation of Chapters of the International Association for the Study of Pain.
Publication Types:

Clinical Trial
PMID: 11558979 [PubMed - indexed for MEDLINE]
Palliat Med. 1996 Jul;10(3):225-30.
Related Articles, Links
Ketamine in cancer pain: an update.
Mercadante S.
Department of Anaesthesia and Intensive Care, Buccheri La Ferla Hospital &
Pain Relief and Palliative Care, SAMOT, Palermo, Italy.
Ketamine has been shown to have potent analgesic properties at low dosages.
Bioavailability is high when it is given parenterally, but low after oral or rectal
administration. Active metabolites should account for part of the analgesic
effect of ketamine during long-term oral administration. NMDA receptor
inhibition by ketamine may reflect a wind-down phenomenon, and should
alleviate NMDA-related neuropathic pain, reversing the rightward shift of
the opioid-response curve. A synergistic effect between ketamine and opioids
has been observed in cancer pain patients who have lost an analgesic response to
high doses of morphine. Further studies need to be carried out to confirm the
benefits of ketamine in cancer pain, and to determine the best route of
administration, dosages and the incidence of side effects.
Publication Types:


Review
Review, Tutorial
15
RE: Ketamine abstracts
PMID: 8817593 [PubMed - indexed for MEDLINE]
Acta Anaesthesiol Scand. 1997 Mar;41(3):422-6.
Related Articles, Links
Comment in:

Acta Anaesthesiol Scand. 1997 Mar;41(3):329-31.
Four years' treatment with ketamine and a trial of
dextromethorphan in a patient with severe post-herpetic neuralgia.
Klepstad P, Borchgrevink PC.
Department of Anesthesiology, Regional Hospital, University of Trondheim,
Norway.
N-methyl-D-aspartate (NMDA) receptors are involved in the development of
neuropathic pain. Ketamine, a non-competitive NMDA receptor antagonist, has in
several case reports given pain relief but efficacy in dosages tolerated in longterm ketamine treatment is unknown. Another substance with an antagonist action
at NMDA receptors and which is approved for peroral administration is
dextromethorphan. In a randomized study dextromethorphan was no better than
placebo for neuropathic pain but this does not exclude efficacy in selected
patients. We report a patient with severe post-herpetic pain resistant to
conventional pain treatment which was treated with ketamine for 4 years
with good pain relief. The practical application of long-term treatment in
different administration forms of ketamine is described. The patient also
responded with pain relief in a double-blind trial with oral
dextromethorphan.
Publication Types:

Case Reports
PMID: 9113190 [PubMed - indexed for MEDLINE]
Reg Anesth. 1996 Nov-Dec;21(6):534-41.
Related Articles, Links
16
RE: Ketamine abstracts
Comment in:

Reg Anesth. 1996 Nov-Dec;21(6):508-13.
Ketamine potentiates analgesic effect of morphine in postoperative
epidural pain control.
Wong CS, Liaw WJ, Tung CS, Su YF, Ho ST.
Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan,
Republic of China.
BACKGROUND AND OBJECTIVES: Ketamine is currently the only N-methylD-aspartate receptor channel blocker in clinical use. This study evaluated the
analgesic efficacy of epidurally coadministered ketamine and morphine in
postoperative pain control. METHODS: The patient population consisted of
ASA class I and II patients undergoing major joint replacement. Epidural
lidocaine was used as the primary anesthesia for the surgery. In phase I of the
study, either ketamine (10-30 mg) or morphine (0.5-2 mg) was administered via
epidural catheter immediately after surgery. This was done to evaluate the doseresponse effect of these drugs when used for postoperative pain relief, and the
results were applied to phase II of the study, in which all patients received
ketamine pretreatment (total 30 mg) with each dose of lidocaine administered
before and during surgery. Forty patients were randomly divided into four groups,
each of which received one of three different pain control regimens mixed with 10
ml of saline: group B received 10 mg ketamine, group C 2 mg morphine, and
group D 10 mg ketamine plus 0.5 mg morphine while the control group A
received 10 mL of saline with no additive. The intensity of pain expressed by
patients, as well as the number of intramuscular meperidine (1 mg/kg) injections
administered and any side effects that may have occurred, were recorded.
RESULTS: Ketamine produced no significant pain relief. A 2-mg morphine dose
did produce significant analgesia but was accompanied by a high incidence of
side effects. Co-administration of subanalgesic doses of ketamine, 10 mg and
morphine, 0.5 mg, however, also produced a strong analgesic effect.
CONCLUSIONS: Ketamine, although not itself an epidural analgesic agent,
potentiates the analgesic effect of morphine, especially when administered as a
pretreatment. The resulting lowered dosage of epidural morphine needed for
postoperative pain relief reduces, in turn, the incidence of side effects.
Pretreatment of patients with ketamine epidurally, followed by injections of
combined morphine and ketamine could be a promising new analgesic regimen.
Publication Types:

Clinical Trial
17
RE: Ketamine abstracts



Clinical Trial, Phase I
Clinical Trial, Phase II
Randomized Controlled Trial
PMID: 8956390 [PubMed - indexed for MEDLINE]
Pain. 1994 Jan;56(1):51-7.
Related Articles, Links
Erratum in:

Pain 1994 Sep;58(3):433.
Response of chronic neuropathic pain syndromes to ketamine: a
preliminary study.
Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M.
Department of Neurology, University of Wisconsin Hospital and Clinics,
Madison 53792.
Hyperactivity of N-methyl-D-aspartate (NMDA) receptors may be one of the
factors in the genesis of neuropathic pain. Ketamine is an NMDA-blocking agent
widely used in human medicine. Ketamine (at 250 mcg/kg i.v. slow push) was
administered to 6 patients for control of chronic neuropathic pain syndromes in
double-blind placebo-controlled fashion. All 3 patients with peripheral nervous
system (PNS) disease-related pain, and 2 of 3 patients with central pain and
dysesthesia syndromes responded with a temporary decrease in the rating of
ongoing pain. The allodynia, hyperalgesia and after-sensation present in 5
patients improved after the administration of ketamine. Dose-response
estimation in 2 patients with PNS-related neuropathic pain revealed that ketamine
was effective in dose-related fashion. Continuous subcutaneous infusion of
ketamine administered to 1 patient with PNS-related neuropathic pain caused no
additional improvement in pain control but caused intolerable cognitive and
memory side effects. In contrast, side effects during single-dose injections were
mild and well tolerated. Ketamine affected the evoked pain and associated
after-sensation in chronic neuropathic pain syndromes more than the
ongoing constant pain.
Publication Types:



Case Reports
Clinical Trial
Randomized Controlled Trial
18
RE: Ketamine abstracts
PMID: 8159441 [PubMed - indexed for MEDLINE]
Acta Anaesthesiol Scand. 1997 Mar;41(3):427-9.
Related Articles, Links
Comment in:

Acta Anaesthesiol Scand. 1997 Mar;41(3):329-31.
Oral ketamine therapy in the treatment of postamputation stump
pain.
Nikolajsen L, Hansen PO, Jensen TS.
Department of Neurology, Aarhus University Hospital, Denmark.
BACKGROUND: Hyperactivity of N-methyl-D-aspartate (NMDA) receptors
may be one of the factors in the maintenance of postamputation stump pain.
CASE REPORT: Ketamine-a clinical available NMDA receptor antagonist-was
administered intravenously to a patient with established stump pain in a doubleblind saline-controlled fashion. Following infusion stump pain was alleviated for
31 hours. Ketamine reduced the allodynic area and wind-up-like pain and
increased pressure-pain thresholds. Treatment was started with ketamine 50 mg x
4 per day dissolved in juice. No side effects or development of tolerance were
observed during a 3-month treatment period. CONCLUSION: NMDA receptor
antagonists may have a potential in the treatment of neuropathic pain, including
stump pain.
Publication Types:



Case Reports
Clinical Trial
Controlled Clinical Trial
PMID: 9113191 [PubMed - indexed for MEDLINE]
2: Fitzgibbon EJ, Hall P, Schroder C, Seely J, Viola R.
Related Articles, Links
Low dose ketamine as an analgesic adjuvant in difficult pain syndromes: a
19
RE: Ketamine abstracts
strategy for conversion from parenteral to oral ketamine.
J Pain Symptom Manage. 2002 Feb;23(2):165-70.
PMID: 11844639 [PubMed - indexed for MEDLINE]
Related Articles, Links
3: Mercadante S, Lodi F, Sapio M, Calligara M, Serretta R.
Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain.
J Pain Symptom Manage. 1995 Oct;10(7):564-8.
PMID: 8537699 [PubMed - indexed for MEDLINE]
Related Articles, Links
4: Schmid RL, Sandler AN, Katz J.
Use and efficacy of low-dose ketamine in the management of acute postoperative
pain: a review of current techniques and outcomes.
Pain. 1999 Aug;82(2):111-25. Review.
PMID: 10467917 [PubMed - indexed for MEDLINE]
Related Articles, Links
5: Ripamonti C, Zecca E, De Conno F.
Pharmacological treatment of cancer pain: alternative routes of opioid
administration.
Tumori. 1998 May-Jun;84(3):289-300. Review.
PMID: 9678610 [PubMed - indexed for MEDLINE]
Related Articles, Links
6: Haines DR, Gaines SP.
N of 1 randomised controlled trials of oral ketamine in patients with chronic pain.
Pain. 1999 Nov;83(2):283-7.
PMID: 10534600 [PubMed - indexed for MEDLINE]
7: Enarson MC, Hays H, Woodroffe MA.
Clinical experience with oral ketamine.
Related Articles, Links
J Pain Symptom Manage. 1999 May;17(5):384-6.
PMID: 10355218 [PubMed - indexed for MEDLINE]
Related Articles, Links
8: Kong PE, Snijdelaar DG, Crul BJ.
[Parenteral administration of low dose ketamine for the treatment of neuropathic
pain in cancer patients]
Ned Tijdschr Geneeskd. 2002 Dec 28;146(52):2556-8. Dutch.
PMID: 12532671 [PubMed - indexed for MEDLINE]
9: Reboso Morales JA, Gonzalez Miranda F.
[Ketamine]
Related Articles, Links
Rev Esp Anestesiol Reanim. 1999 Mar;46(3):111-22. Review. Spanish.
PMID: 10228376 [PubMed - indexed for MEDLINE]
Related Articles, Links
10: Sartain JB, Mitchell SJ.
Successful use of oral methadone after failure of intravenous morphine and
ketamine.
Anaesth Intensive Care. 2002 Aug;30(4):487-9.
PMID: 12180591 [PubMed - indexed for MEDLINE]
20
RE: Ketamine abstracts
Related Articles, Links
11: Fisher K, Hagen NA.
Analgesic effect of oral ketamine in chronic neuropathic pain of spinal origin: a
case report.
J Pain Symptom Manage. 1999 Jul;18(1):61-6.
PMID: 10439575 [PubMed - indexed for MEDLINE]
Related Articles, Links
12: Rabben T, Skjelbred P, Oye I.
Prolonged analgesic effect of ketamine, an N-methyl-D-aspartate receptor
inhibitor, in patients with chronic pain.
J Pharmacol Exp Ther. 1999 May;289(2):1060-6.
PMID: 10215688 [PubMed - indexed for MEDLINE]
Related Articles, Links
13: McQueen AL, Baroletti SA.
Adjuvant ketamine analgesia for the management of cancer pain.
Ann Pharmacother. 2002 Oct;36(10):1614-9. Review. Erratum in: Ann Pharmacother. 2003
Sep;37(9):1346.
PMID: 12243612 [PubMed - indexed for MEDLINE]
Related Articles, Links
14: Rabben T, Oye I.
Interindividual differences in the analgesic response to ketamine in chronic
orofacial pain.
Eur J Pain. 2001;5(3):233-40.
PMID: 11558979 [PubMed - indexed for MEDLINE]
15: Mercadante S.
Ketamine in cancer pain: an update.
Related Articles, Links
Palliat Med. 1996 Jul;10(3):225-30. Review.
PMID: 8817593 [PubMed - indexed for MEDLINE]
Related Articles, Links
16: Wong CS, Liaw WJ, Tung CS, Su YF, Ho ST.
Ketamine potentiates analgesic effect of morphine in postoperative epidural pain
control.
Reg Anesth. 1996 Nov-Dec;21(6):534-41.
PMID: 8956390 [PubMed - indexed for MEDLINE]
Related Articles, Links
17: Oye I, Rabben T, Fagerlund TH.
[Analgesic effect of ketamine in a patient with neuropathic pain]
Tidsskr Nor Laegeforen. 1996 Oct 30;116(26):3130-1. Norwegian.
PMID: 8999575 [PubMed - indexed for MEDLINE]
18: Radovanovic D, Pjevic M.
[Ketamine: the past 30 years and its future]
Related Articles, Links
Med Pregl. 2003 Sep-Oct;56(9-10):439-45. Review. Serbian.
PMID: 14740534 [PubMed - indexed for MEDLINE]
Yanagihara Y, Ohtani M, Matsumoto M, Kariya S, Uchino K, Hiraishi T, Related Articles, Links
19: Ashizawa N, Aoyama T, Yamamura Y, Iga T.
21
RE: Ketamine abstracts
[Preparation of ketamine tablets for treatment of patients with neuropathic pain]
Yakugaku Zasshi. 1999 Dec;119(12):980-7. Japanese.
PMID: 10630103 [PubMed - indexed for MEDLINE]
Related Articles, Links
20: Lin SM, Liu K, Tsai SK, Lee TY.
Rectal ketamine versus intranasal ketamine as premedicant in children.
Ma Zui Xue Za Zhi. 1990 Jun;28(2):177-83.
PMID: 2215104 [PubMed - indexed for MEDLINE]
Summary
Show:
20
Sort
Text
J Pain Symptom Manage. 1995 Oct;10(7):564-8.
Related Articles, Links
Long-term ketamine subcutaneous continuous infusion in
neuropathic cancer pain.
Mercadante S, Lodi F, Sapio M, Calligara M, Serretta R.
Department of Anesthesia and Intensive Care, Buccheri La Ferla Hospital,
Fatebenefratelli, Palermo, Italy.
Neuropathic cancer pain may be less responsive to opioids than other pain.
Several studies suggest that N-methyl-D-aspartate (NMDA)-receptor antagonists
could play a role in the treatment of neuropathic pain. Ketamine is an NMDAreceptor antagonist that is used as an anesthetic and has been suggested as a useful
drug for neuropathic pain. Subanesthetic doses of ketamine can yield analgesia
without hypnosis. We describe a patient who developed neuropathic cancer pain
unresponsive to opioid escalation and spinal administration of a combination of
bupivacaine-morphine and was subsequently treated by subcutaneous continuous
ketamine infusion. A starting dose of 150 mg/day provided good pain relief and a
dramatic reduction of the oral morphine dose (from 5 g to 200 mg). A slow and
progressive increase of ketamine and morphine dosage (400 mg and 200 mg by
the subcutaneous route, respectively) continued to provide adequate pain relief
after 13 months of therapy despite signs of progressive disease.
Publication Types:

Case Reports
PMID: 8537699 [PubMed - indexed for MEDLINE]
22
RE: Ketamine abstracts
1: Pain. 1999 Aug;82(2):111-25.
Related Articles, Links
Comment in:

Pain. 2000 Dec 1;88(3):311-2.
Use and efficacy of low-dose ketamine in the management of acute
postoperative pain: a review of current techniques and outcomes.
Schmid RL, Sandler AN, Katz J.
Department of Anaesthesia, The Toronto Hospital, Ontario, Canada.
Ketamine hydrochloride is a well known general anesthetic and short acting
analgesic in use for almost 3 decades. The role of the NMDA receptor in the
processing of nociceptive input has led naturally to renewed clinical interest in Nmethyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper
reviews the use and efficacy of low-dose ketamine in the management of acute
postoperative pain. The literature was obtained from a computer search of the
MEDLINE database from 1966 through December 1998. Studies were included
for review if they were randomized, prospective, controlled, double-blind and
reported pain scores. We evaluate the clinical literature and discuss the efficacy of
low-dose ketamine in the management of acute postoperative pain when
administered alone or in conjunction with other agents via the oral, intramuscular,
subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined
as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1
mg/kg when administered via the intravenous or epidural route. For continuous
i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg
per min. We conclude that ketamine may provide clinicians with a tool to improve
postoperative pain management and to reduce opioid related adverse effects. The
evidence suggests that low-dose ketamine may play an important role in
postoperative pain management when used as an adjunct to local anesthetics,
opioids, or other analgesic agents. Further research is required in the following
areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local
anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)ketamine; (d) the influence of ketamine on long-term outcome such as chronic
pain (e) long-term physical and chemical stability of mixtures containing
ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on
cognitive and memory functioning after surgery.
Publication Types:
23
RE: Ketamine abstracts


Review
Review, Tutorial
PMID: 10467917 [PubMed - indexed for MEDLINE]
Ann N Y Acad Sci. 2003 Nov;1003:176-84.
Related Articles, Links
NMDA receptor antagonism and the ethanol intoxication signal:
from alcoholism risk to pharmacotherapy.
Krystal JH, Petrakis IL, Krupitsky E, Schutz C, Trevisan L, D'Souza DC.
Department of Psychiatry, Yale University School of Medicine, New Haven,
Connecticut 06510, USA. [email protected]
This paper reviews clinical evidence suggesting that antagonism of the N-methylD-aspartate subtype of glutamate receptors by ethanol may convey an important
component of the ethanol intoxication signal, that is, subjective and objective
responses associated with the consumption of a large amount of ethanol. It will
then review recent evidence that two phenotypes associated with increased risk
for heavy alcohol consumption, recovering ethanol-dependent patients, and
healthy individuals with a family history of alcohol dependence, exhibit reduced
sensitivity to the dysphoric consequences of administration of the NMDA
receptor antagonist, ketamine. Each of these groups displays reduced sensitivity to
a potentially important response that might normally trigger the cessation of
ethanol consumption. These data raise the possibility that alterations in NMDA
receptor function that reduce the response to the NMDA antagonist component of
ethanol may increase the risk for heavy drinking. This hypothesis is consistent
with growing evidence that NMDA receptor antagonists may play a role in the
treatment of alcoholism by suppressing alcohol withdrawal, reducing the
development or expression of alcohol tolerance, or preventing or reversing the
sensitiziation to ethanol effects.
Publication Types:


Review
Review, Tutorial
PMID: 14684445 [PubMed - indexed for MEDLINE]
24
RE: Ketamine abstracts
Adv Exp Med Biol. 2003;523:269-77. Related Articles, Links
Ketamine, revival of a versatile intravenous anaesthetic.
Raeder J.
Department of Anaesthesiology, Ullevaal University Hospital, N-0407 Oslo, Norway.
PMID: 15088858 [PubMed - in process]
&&&&&&&&&&&&&
Anaesthesia. 2004 Mar;59(3):222-8. Related Articles, Links
A randomised, controlled study of peri-operative low dose s(+)-ketamine in combination
with postoperative patient-controlled s(+)-ketamine and morphine after radical
prostatectomy.
Snijdelaar DG, Cornelisse HB, Schmid RL, Katz J.
Department of Anesthesiology/Pain Centre, University Medical Centre Nijmegen, PO
Box 9101, 6500 HB Nijmegen, The Netherlands. [email protected]
In a randomised, double-blind prospective study we compared the effects on
postoperative pain and analgesic consumption of intra-operative s(+)-ketamine (100
microg.kg-1 bolus and a continuous infusion of 2 microg.kg-1.min-1) followed by
postoperative patient-controlled analgesia with morphine (1 mg per bolus) plus s(+)ketamine (0.5 mg per bolus), or intra-operative saline followed by postoperative patientcontrolled analgesia morphine (1 mg per bolus) alone. A total of 28 male patients
undergoing radical prostatectomy were studied. Morphine consumption, pain scores,
pressure algometry and adverse effects were recorded for 48 h after surgery.
Cumulative morphine consumption was significantly lower in the
ketamine/morphine group (47.9 +/- 26.2 mg) than in the saline/morphine group
(73.4 +/- 34.8 mg; p = 0.049). Pain scores at rest were significantly lower in the
ketamine/morphine group across the 48-h study period (p = 0.01). No significant
differences were found in pressure algometry measurements or the occurrence of adverse
effects.
Publication Types:
Clinical Trial
Randomized Controlled Trial
25
RE: Ketamine abstracts
PMID: 14984518 [PubMed - indexed for MEDLINE]
&&&&&&&&&&&&&&&&&
Ann N Y Acad Sci. 2003 Nov;1003:119-30.
Related Articles, Links
The NMDA receptor hypofunction model of psychosis.
Farber NB.
Department of Psychiatry, Washington University, St. Louis, Missouri 631101093, USA. [email protected]
Antagonists of the NMDA glutamate receptor, including phencyclidine (PCP),
ketamine, and CGS-19755, produce cognitive and behavioral changes in
humans. In rodents these agents produce a myriad of histopathological and
neurochemical changes. Several lines of evidence suggest that a large number of
these drug-induced effects are dose-dependent manifestations of the same
general disinhibition process in which NMDA antagonists abolish
GABAergic inhibition, resulting in the simultaneous excessive release of
acetylcholine and glutamate. Progressive increases in the severity of NMDA
receptor hypofunction (NRHypo) within the brain produce an increasing range of
effects on brain function. Underexcitation of NMDA receptors, induced by
even relatively low doses of NMDA antagonist drugs, can produce specific
forms of memory dysfunction without clinically evident psychosis. More
severe NRHypo can produce a clinical syndrome very similar to a psychotic
schizophrenic exacerbation. Finally, sustained and severe NRHypo in the adult
brain is associated with a form of neurotoxicity with well-characterized
neuropathological features. In this paper several of these effects of NMDA
antagonists and a likely mechanism responsible for producing them will be
reviewed. In addition the possible role of NRHypo in the pathophysiology of
idiopathic psychotic disorders will be considered.
Publication Types:


Review
Review, Multicase
PMID: 14684440 [PubMed - indexed for MEDLINE]
&&&&&&&&&&&&&&&&&
26
RE: Ketamine abstracts
Reprod Biol. 2002 Mar;2(1):13-24.
Related Articles, Links
Modulation of growth hormone, luteinizing hormone, and
testosterone secretion by excitatory amino acids in boars.
Estienne MJ, Barb CR.
Department of Agriculture, University of Maryland Eastern Shore, Princess Anne,
MD, USA. [email protected]
Ketamine hydrochloride, an n-methyl-d-aspartate (NMDA) receptor antagonist
was used in an experiment that tested the hypothesis that fasting-induced
increases in growth hormone (GH) secretion is mediated by excitatory amino acid
(EAA) neurotransmission in boars. The effects of the drug on circulating
concentrations of luteinizing hormone (LH) and testosterone were also evaluated.
Blood was sampled at 15-min intervals for 8 h from 12 boars fitted with jugular
vein catheters. At Hours 4 and 6, fasted boars (feed was withdrawn 48 h before
the start of blood sampling) received i.m. injections of ketamine (19.9 mg/kg
body weight; n=4) or .9% saline (n=4). Boars allowed feed on an ad libitum basis
(n=4) received i.v. injections of n-methyl-d,l-aspartate (NMA; 2.5 mg/kg body
weight), an NMDA receptor agonist, at Hours 4 and 6. Secretion of GH increased
after NMA injections but was unaffected by treatment with ketamine or saline.
Circulating concentrations of LH and testosterone were increased by injections of
ketamine but were unaffected by injections of NMA or saline. Our results suggest
that NMA is a potent GH secretagogue, but do not support the hypothesis that
EAA neurotransmission drives the increased GH secretion displayed in fasted
boars. Our finding that ketamine increased LH and testosterone release
supports the notion that EAA have inhibitory effects on gonadotropin
secretion in acutely fasted swine.
PMID: 14666159 [PubMed - indexed for MEDLINE]
&&&&&&&&&&
1: J Pain Symptom Manage. 2003 Dec;26(6):1071-2.
Related Articles, Links
Ketamine in the management of chronic pancreatic pain.
Mannion S, O'Brien T.
Publication Types:


Case Reports
Letter
27
RE: Ketamine abstracts
PMID: 14654257 [PubMed - indexed for MEDLINE]
Yakugaku Zasshi. 1999 Dec;119(12):980-7.
Related Articles, Links
[Preparation of ketamine tablets for treatment of patients with
neuropathic pain]
[Article in Japanese]
Yanagihara Y, Ohtani M, Matsumoto M, Kariya S, Uchino K, Hiraishi T,
Ashizawa N, Aoyama T, Yamamura Y, Iga T.
Department of Pharmacy, Tokyo Posts and Telecommunications Hospital, Japan.
Ketamine is known to have distinguished analgesic effects without anesthetic
when administered in a low dose. Since ketamine is not commercially available
except injection forms, we prepared ketamine tablets for the home-care
medication of patients with neuropathic pain. The direct compression or wet
granulation method was employed to form 150 mg of tablets containing 50 mg of
ketamine. The latter method was superior to the former one in terms of content
uniformity, weight variation and disintegration tests of the tablets. Ketamine
contents in the tablet prepared by the wet granulation method were unchanged for
12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH).
The Cmax and AUC0-3 h values for ketamine after administration of the tablet
were slightly smaller than those of the syrup in a healthy volunteer. However,
analgesic effects of the tablet was similar to that of the syrup in a patient with
neuropathic pain. And the tablet was also effective for another four patients with
neuropathic pain. These results indicate that ketamine tablets are useful for the
home-care medication of patients with neuropathic pain.
Publication Types:


Case Reports
Clinical Trial
PMID: 10630103 [PubMed - indexed for MEDLINE]
Reg Anesth Pain Med. 2002 Sep-Oct;27(5):524-8.
Related Articles, Links
Analgesic effects of ketamine ointment in patients with complex
regional pain syndrome type 1.
28
RE: Ketamine abstracts
Ushida T, Tani T, Kanbara T, Zinchuk VS, Kawasaki M, Yamamoto H.
Departments of Orthopedic Surgery, Kochi Medical School, Nankoku, Kochi,
Japan. [email protected]
OBJECTIVE: Ketamine hydrochloride (KET), an agent used for general
anesthesia, has local anesthetic effects and N-methyl-D-aspartate (NMDA)
receptor antagonist action. Because recent studies emphasized the role of
peripherally distributed NMDA receptors in processing the nociceptive
information, we investigated whether peripheral application of the ointment
containing KET is able to attenuate the symptoms of local neuropathic pain.
CASE REPORTS: We applied ointment containing KET (0.25%-1.5%) to the
affected area on limbs in 5 patients with complex regional pain syndrome type I
(CRPS I) and in 2 patients with type II (CRPS II). One to 2 weeks later, we
observed improvement of the report of pain intensity, measured by the visual
analog scale, in 4 patients with acute early dystrophic stage of CRPS I.
Swelling of the affected limbs subsided as well. No apparent changes were
noticed in 1 patient with chronic atrophic stage of CRPS I and in both patients
with CRPS II. CONCLUSION: Topical application of KET appears to be
beneficial for the patients with acute early dystrophic stage of CRPS I because of
either its local anesthetic effect or NMDA receptor antagonist action. Patients
with chronic atrophic stage of CRPS I and CRPS II patients do not appear to
respond to this treatment.
Publication Types:

Case Reports
PMID: 12373705 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 2003 May;25(5):400-2.
Related Articles, Links
A retrospective comparison of the dose ratio between subcutaneous
and oral ketamine.
Benitez-Rosario MA, Feria M, Salinas-Martin A, Martinez-Castillo LP,
Martin-Ortega JJ.
Publication Types:


Case Reports
Letter
29
RE: Ketamine abstracts
PMID: 12727033 [PubMed - indexed for MEDLINE]
J Burn Care Rehabil. 1997 Jan-Feb;18(1 Pt 1):34-6.
Related Articles, Links
Superiority of oral ketamine as an analgesic and sedative for wound
care procedures in the pediatric patient with burns.
Humphries Y, Melson M, Gore D.
Evans Haynes Burn Center, Medical College of Virginia, Richmond 23298-0475,
USA.
The management of pain and anxiety in pediatric patients with burns includes the
challenge of striking a balance between inadequate versus excessive medication.
Ketamine provides effective sedative, analgesic, and amnestic properties for
children and has been used intravenously with good results. With its recent
availability as an elixir, we speculated that ketamine given orally may provide
effective analgesia and sedation during wound care procedures with a wide safety
margin. To test this hypothesis, 19 pediatric patients with burns undergoing a
wound care procedure were randomized to receive either ketamine oral
suspension or 300 mg acetaminophen with codeine phosphate and
diphenhydramine, our prior standard for analgesia and sedation. Intensity of
pain was determined with use of a color slide algometer and demonstrated more
than 400% reduction in pain with the use of ketamine (p < 0.05). The Ramsey
scale was used to quantitate sedation and demonstrated that ketamine improved
sedation by 360% (p < 0.05). These results substantiate improved analgesia and
sedation with oral ketamine as compared to a commonly used narcotic and
sedative in facilitating wound care procedures in pediatric patients with burns.
These findings suggest that expanded use of ketamine oral suspension may be.
Publication Types:


Clinical Trial
Randomized Controlled Trial
PMID: 9063785 [PubMed - indexed for MEDLINE]
Clin Neuropharmacol. 1995 Aug;18(4):360-8.
Related Articles, Links
Intravenous infusion of the NMDA antagonist, ketamine, in chronic
posttraumatic pain with allodynia: a double-blind comparison to
30
RE: Ketamine abstracts
alfentanil and placebo.
Max MB, Byas-Smith MG, Gracely RH, Bennett GJ.
Neurobiology and Anesthesiology Branch, National Institute of Dental Research,
National Institutes of Health, Bethesda, Maryland, USA.
NMDA antagonists and opioids relieve experimentally produced hyperalgesia in
animals and humans, presumably by attenuating a heightened central nervous
system response to afferent input. A few small studies in patients have suggested
that intravenous boluses or rapid infusions of the N-methyl-D-aspartate (NMDA)
antagonist ketamine relieve some neuropathic pains but also produce
disturbances of cognition and mood. In a randomized, double-blind, crossover
trial, we treated eight patients with chronic posttraumatic pain and widespread
mechanical allodynia with 2-h intravenous infusions of the NMDA antagonist
ketamine (mean dose, 58 mg), the opioid mu-receptor agonist alfentanil
(mean dose, 11 mg), and placebo. The patients were selected because extensive
sensory testing suggested that altered central processing contributed to their
symptoms. The slow rate of drug infusion was chosen to see if pain relief would
precede dose-limiting side effects. Means of the peak effect scores achieved
during the 2-h infusion were for pain relief: ketamine, 65%, alfentanil, 46%,
and placebo, 22% (p < 0.01 for ketamine and p = 0.08 for alfentanil, each
compared to placebo); and for relief of allodynia: ketamine, 71%, alfentanil,
57%, and placebo, 21% (p < 0.01 for both ketamine and alfentanil).
Appreciable symptomatic relief developed only after the onset of unpleasant
drug side effects. After the infusion was stopped, pain relief disappeared
before the side effects resolved. We conclude that NMDA antagonists may have
promise for the treatment of neuropathic pain, but strategies are needed to
improve their therapeutic ratio, such as intrathecal administration or systemic
treatment with more selective drugs.
Publication Types:


Clinical Trial
Randomized Controlled Trial
PMID: 8665549 [PubMed - indexed for MEDLINE]
J Pharm Sci. 1982 May;71(5):539-42.
Related Articles, Links
Bioavailability, pharmacokinetics, and analgesic activity of ketamine
in humans.
Clements JA, Nimmo WS, Grant IS.
31
RE: Ketamine abstracts
The pharmacokinetics of ketamine in analgesic doses after intravenous,
intramuscular, and oral administration was investigated in healthy volunteers.
Plasma ketamine concentration-time curves were fitted by a twocompartment open model with a terminal half-life of 186 min. Absorption
after intramuscular injection was rapid and the bioavailability was 93%.
However, only 17% of an oral dose was absorbed because of extensive firstpass metabolism. Simultaneous measurements of the elevation of pain threshold
in an ischemic exercise test showed a marked effect for 15-60 min after
intramuscular injection, but little or no effect after the oral solution. Pain
threshold elevation occurred at plasma ketamine concentrations above 160 ng/ml.
PMID: 7097501 [PubMed - indexed for MEDLINE]
Pain. 2003 Jul;104(1-2):25-34.
Related Articles, Links
Intra-articular (IA) catheter administration of postoperative
analgesics. A new trial design allows evaluation of baseline pain,
demonstrates large variation in need of analgesics, and finds no
analgesic effect of IA ketamine compared with IA saline.
Rosseland LA, Stubhaug A, Sandberg L, Breivik H.
Department of Anaesthesiology, Rikshospitalet University Hospital, N-0027,
Oslo, Norway. [email protected]
All previous studies of intra-articular (IA) analgesic drugs for postarthroscopy
pain have administered test-drugs at the end of the arthroscopic procedure, before
any baseline pain could be assessed. Assay sensitivity has often not been
documented or has been assumed to be present if a placebo control group had
significant pain during the observation period. We present an improved study
design employing an IA catheter for test-drug administration only in patients with
moderate-to-severe baseline pain within 2h postoperatively. Using this technique
we explored the incidence of moderate-to-severe pain and possible predisposing
factors for pain through a close follow-up of all patients. The study incorporated
an explanatory study of IA ketamine. A double-blind, double-dummy technique
was used. Summed pain intensity differences 0-120 min after test medication was
the primary outcome variable. Of 77 patients assessed for inclusion, only 45
had moderate or severe pain. Significantly more women (78%) than men
(45%) had moderate-to-severe pain (P<0.005). Those not included continued to
have no or mild pain and consumed less rescue analgesics than those who had
high baseline pain. Mean baseline pain in the patient group with moderate or
severe pain was 50mm on a 0-100 m visual analogue scale (VAS)
(SD=15.1)(n=45). Mean VAS in the patient group with no or mild pain was
32
RE: Ketamine abstracts
7.5mm (SD=8.7)(n=32).The new method for IA analgesic trials solves the
problem with undesirable inclusion of patients with no or mild pain. We observed
rapid onset and significant pain relief after IA injection of 10 ml saline with
or without ketamine 10mg, but no difference between these two test
medications!!!!!!!!! Intra-muscular ketamine 10mg showed significantly
better early pain relief, global evaluation, and longer time to rescue
analgesic, compared with IA ketamine 10mg.
Publication Types:


Clinical Trial
Randomized Controlled Trial
PMID: 12855311 [PubMed - indexed for MEDLINE]
Anesthesiology. 1999 Jun;90(6):1528-33.
Related Articles, Links
Oral ketamine and transdermal nitroglycerin as analgesic adjuvants
to oral morphine therapy for cancer pain management.
Lauretti GR, Lima IC, Reis MP, Prado WA, Pereira NL.
Department of Surgery, Orthopedics and Traumatology, Center for Pain
Treatment, Hospital das Clinicas, Faculty of Medicine of Ribeirao Preto,
University of Sao Paulo, Brazil. [email protected]
BACKGROUND: Guidelines for cancer pain management include nonsteroidal
antiinflammatory drugs with opioids administered in a time-contingent manner.
This study was designed to evaluate the role of oral ketamine or transdermal
nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in
cancer pain therapy. METHODS: After institutional approval and informed
patient consent were obtained, 60 patients with cancer pain were randomized to
one of four groups (n = 15) and studied prospectively to evaluate analgesia and
any adverse effects. A visual analog scale that consisted of a 10-cm line with 0
representing "no pain at all" and 10 representing "the worst possible pain" was
introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime.
The morphine regimen was adjusted individually to a maximal oral dose of 80-90
mg/day to keep the visual analog scale score less than 4. When patients reported
pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine
daily, the test drug was added as follows: the control group (CG) received an
additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group
(NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG)
received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group
(DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to
33
RE: Ketamine abstracts
manipulate their daily morphine consumption when the test drug was introduced
to keep their visual analog scale score less than 4. RESULTS: The groups were
similar with respect to demographic data and visual analog scale pain scores
before treatment. The visual analog scale scores after the test drug was introduced
were similar among the groups. The daily consumption of oral morphine was as
follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20:
CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG
(P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and
DG groups reported somnolence, but patients in the NG and KG groups did not.
CONCLUSIONS: Low-dose ketamine and transdermal nitroglycerin were
effective coadjuvant analgesics. In conjunction with their opioid tolerancesparing function, joint delivery of ketamine or nitric oxide donors with opiates
may be of significant benefit in cancer pain management.
Publication Types:


Clinical Trial
Randomized Controlled Trial
PMID: 10360847 [PubMed - indexed for MEDLINE]
Best Pract Res Clin Anaesthesiol. 2002 Dec;16(4):475-88.
Related Articles, Links
Pharmacology of systemic analgesics.
Camu F, Vanlersberghe C.
Deportment of Anaesthesiology, Flemish Free University of Brussels Medical
Center, 1090 Brussels, Belgium.
Systemic administration of analgesic drugs is still the most widely used method
for providing pain relief in acute painful situations. Opioids may be selected on
the basis of their physicochemical characteristics and their diffusion index to the
brain. But in clinical practice, their very steep concentration-analgesic effect
relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in
plasma concentrations of opioids may lead to profound fluctuations in analgesic
effect when their plasma and effect-site concentrations are near the minimum
effective analgesic concentration (MEAC). Combining drugs acting on different
mechanisms of nociceptive modulation offers benefits from additive/synergistic
effects and will decrease the incidence of their adverse effects. Evidence-based
reviews showed that effective pain relief using non-opioid analgesics relied on
paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs).
The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires
further evaluation. NSAIDs, CSIs and paracetamol share the property of
morphine sparing in situations of severe (post-operative) pain. CSIs may be
34
RE: Ketamine abstracts
beneficial in patients in whom post-operative bleeding is a major surgical risk as
the effects of NSAIDs on coagulation may last for days. Finally, low-dose
ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic
concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and
exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.
Publication Types:


Review
Review, Tutorial
PMID: 12516886 [PubMed - indexed for MEDLINE]
Clin J Pain. 1994 Sep;10(3):240-2.
Related Articles, Links
Successful treatment of postherpetic neuralgia with oral ketamine.
Hoffmann V, Coppejans H, Vercauteren M, Adriaensen H.
Department of Anesthesia, University Hospital of Antwerpen, Edegem, Belgium.
OBJECTIVE: To demonstrate the possibilities of the use of oral ketamine in the
treatment of postherpetic neuralgia. SETTING: A pain clinic in a university
hospital. PATIENT: A patient with postherpetic neuralgia of the ophthalmic
nerve. INTERVENTION: Subcutaneous and later oral ketamine after classical
treatment had failed. RESULTS: A complete recovery was accomplished
without any sign of side effects. CONCLUSIONS: Oral ketamine may provide an
alternative in the treatment of postherpetic neuralgia. The possible mechanism of
action by its N-methyl-D-aspartate (NMDA) blocking properties is discussed.
Publication Types:

Case Reports
PMID: 7833583 [PubMed - indexed for MEDLINE]
Br J Anaesth. 1981 Aug;53(8):805-10.
Related Articles, Links
Pharmacokinetics and analgesic effects of i.m. and oral ketamine.
Grant IS, Nimmo WS, Clements JA.
The pharmacokinetics and analgesic effects of i.m. and oral ketamine in a dose of
35
RE: Ketamine abstracts
0.5 mg kg-1 were determined in six healthy volunteers. Analgesia was measured
by the submaximal effort tourniquet test. Following both routes of administration,
ketamine prolonged the period of pain-free ischaemic exercise. Pain thresholds
were increased at 15 min and 30 min after i.m. injection and at 30 min after
oral ketamine. The plasma ketamine concentration associated with analgesia
was 150 ng ml-1 following the i.m. dose, but only 40 ng ml-1 after the oral
dose. Oral administration was, however, associated with much greater
concentrations of the metabolite norketamine, which may have contributed
to the analgesic effect.
PMID: 7272143 [PubMed - indexed for MEDLINE]
Cochrane Database Syst Rev. 2003;(1):CD003351.
Related Articles, Links
Ketamine as an adjuvant to opioids for cancer pain.
Bell R, Eccleston C, Kalso E.
Pain Clinic, Haukeland University Hospital, Bergen, Norway, N-5021.
[email protected]
BACKGROUND: Ketamine is a commonly used anaesthetic agent, and in
subanaesthetic doses is also given as an adjuvant to opioids for the treatment of
cancer pain, particularly when opioids alone prove to be ineffective. Ketamine is
known to have hallucinogenic side effects. To date no systematic review of the
benefits and harms of adjuvant ketamine for cancer pain has been undertaken.
OBJECTIVES: To determine the effectiveness and adverse effects of ketamine as
an adjuvant to opioids in the treatment of cancer pain. SEARCH STRATEGY:
Studies were identified from MEDLINE (1966-2001), EMBASE (1980-2001),
CancerLit (1966-2001), the Cochrane Library (Issue 1, 2001); by handsearching
reference lists from review articles, trials, and chapters from standard textbooks
on pain and palliative care. The manufacturer of ketamine (Pfizer Parke-Davis)
provided search results from their in-house database, PARDLARS. SELECTION
CRITERIA: RCTs of adult patients with cancer and pain being treated with an
opioid, and receiving either ketamine (any dose and any route of administration)
or placebo or an active control. DATA COLLECTION AND ANALYSIS: Two
independent reviewers identified four RCTs for possible inclusion in the review,
and 32 case studies/case series reports. Quality and validity assessment was
performed by three independent reviewers, and two RCTs were excluded because
of inappropriate study design. Patient reported pain intensity and pain relief was
assessed using visual analog scales, verbal rating scales or other validated scales,
and adverse effects data were collated. MAIN RESULTS: Two trials were eligible
for inclusion in the review and both concluded that ketamine improves the
effectiveness of morphine in the treatment of cancer pain. However, pooling of
36
RE: Ketamine abstracts
the data was not appropriate because of the small total number of patients (30),
and the presence of clinical heterogeneity. Some patients experienced
hallucinations on both ketamine plus morphine and morphine alone and were
treated successfully with diazepam. No other serious adverse effects were
reported. REVIEWER'S CONCLUSIONS: Current evidence is insufficient to
assess the benefits and harms of ketamine as an adjuvant to opioids for the relief
of cancer pain. More randomized controlled trials are needed.
Publication Types:


Review
Review, Academic
PMID: 12535471 [PubMed - indexed for MEDLINE]
Can J Anaesth. 1989 Mar;36(2):186-97.
Related Articles, Links
Ketamine: an update on the first twenty-five years of clinical
experience.
Reich DL, Silvay G.
Department of Anaesthesiology, Mount Sinai Medical Center, New York, New
York 10029.
In nearly 25 years of clinical experience, the benefits and limitations of ketamine
analgesia and anaesthesia have generally been well-defined. The extensive review
of White et al. and the cardiovascular review of Reves et al. are broad in their
scope and have advanced the understanding of dissociative anaesthesia.
Nevertheless, recent research continues to illuminate different aspects of ketamine
pharmacology, and suggests new clinical uses for this drug. The identification of
the N-methylaspartate receptor gives further support to the concept that
ketamine's analgesic and anaesthetic effects are mediated by separate
mechanisms. The stereospecific binding of (+)ketamine to opiate receptors in
vitro, more rapid emergence from anaesthesia, and the lower incidence of
emergence sequelae, make (+)ketamine a promising drug for future research.
Clinical applications of ketamine that have emerged recently, and are likely to
increase in the future, are the use of oral, rectal, and intranasal preparations
for the purposes of analgesia, sedation, and anaesthetic induction. Ketamine is
now considered a reasonable option for anaesthetic induction in the
hypotensive preterm neonate. The initial experience with epidural and
intrathecal ketamine administration has not been very promising but the data
are only preliminary in this area. The use of ketamine in military and catastrophic
settings is likely to become more common. The clinical availability of midazolam
37
RE: Ketamine abstracts
will complement ketamine anaesthesia in several ways. This rapidly
metabolized benzodiazepine reduces ketamine's cardiovascular stimulation
and emergence phenomena, and does not have active metabolites. It is
dispensed in an aqueous medium, which is usually non-irritating on intravenous
injection, unlike diazepam. The combination of ketamine and midazolam is
expected to achieve high patient acceptance, which never occurred with
ketamine as a sole agent. Finally, it is necessary to point out the potential for
abuse of ketamine. While ketamine is not a controlled substance (in the United
States), the prudent physician should take appropriate precautions against the
unauthorized use of this drug.
Publication Types:


Review
Review, Tutorial
PMID: 2650898 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 1999 Apr;17(4):296-300.
Related Articles, Links
Comment in:


J Pain Symptom Manage. 2000 Jan;19(1):1-3.
J Pain Symptom Manage. 2000 Jan;19(1):3-4.
Low-dose ketamine in the management of opioid nonresponsive
terminal cancer pain.
Fine PG.
University of Utah Health Sciences Center, Department of Anesthesiology, Salt
Lake City, USA.
Two patients with far-advanced cancer, near death, who were experiencing
excruciating and intractable pain that was poorly responsive to rapidly escalating
doses of morphine and hydromorphone were treated with low-dose intravenous
ketamine (0.1-0.2 mg/kg). This intervention eliminated the need for any
further opioid use, providing profound analgesia and a sense of calm during
the last hours and days of these patients' lives. These case reports add to the small
but growing body of clinical literature suggesting that ketamine may have a
significant place in the care of patients with pain that is poorly responsive to
opioids, or who experience dose-limiting adverse effects, near the end of life. This
is an important matter to disseminate in order to reassure the public that we do
have the tools necessary to keep the promise that no one need die with
38
RE: Ketamine abstracts
uncontrolled pain. This therapeutic approach may also serve to reassure
concerned physicians that their efforts to assure pain relief may not be
misconstrued as hastening death.
Publication Types:

Case Reports
PMID: 10203883 [PubMed - indexed for MEDLINE]
Paediatr Anaesth. 1996;6(5):361-5.
Related Articles, Links
Oral transmucosal ketamine: an effective premedication in children.
Cioaca R, Canavea I.
Department of Anaesthesiology, Oral and Maxillo-facial Surgery, University of
Medicine, Bucharest, Romania.
The oral cavity offers a simple, painless way of drug administration. For this
reason, we used oral transmucosal ketamine (5-6 mg.kg-1) for premedication
in 25 children and compared it with intranasal ketamine (5-6 mg.kg-1),
placebo and intramuscular ketamine (5-6 mg.kg-1). Oral transmucosal
ketamine (OTK) provided effective sedation, facilitated i.v. line insertion and was
accepted with pleasure by the patients (as lollipops). The lollipops produced a
slight increase in gastric volumes but did not affect gastric pH. In conclusion
OTK has been shown to be an effective, harmless preoperative medication in
paediatric patients.
Publication Types:


Clinical Trial
Randomized Controlled Trial
PMID: 8880815 [PubMed - indexed for MEDLINE]
Anesth Analg. 2000 Dec;91(6):1479-82.
Related Articles, Links
Transdermal ketamine as an adjuvant for postoperative analgesia
39
RE: Ketamine abstracts
after abdominal gynecological surgery using lidocaine epidural
blockade.
Azevedo VM, Lauretti GR, Pereira NL, Reis MP.
Faculty of Medicine of Ribeirao Preto-University of Sao Paulo, Sao Paulo, Brazil.
We examined the postoperative analgesia of a controlled delivery ketamine
transdermal patch after minor abdominal gynecological surgery using lidocaine
epidural blockade. Fifty-two patients were randomized to one of two groups.
Epidural anesthesia was performed with 25 mL 2% plain lidocaine. At the end of
the surgical procedure, a controlled delivery transdermal patch containing
either ketamine (25 mg/24 h) (Ketamine group) or placebo (Placebo group)
was applied. Pain and adverse effects were assessed hourly postoperatively for 24
h. IM dipyrone was available at patient request. The two groups were
demographically similar. The time to first rescue analgesic was longer in the
Ketamine group (230+/-112 min) compared with the Placebo group (94+/-54
min); (P<0.00001). There were more dipyrone dose injections in 24 h in the
Placebo group compared with the Ketamine group (P<0.0001). The incidence of
adverse effects was similar between groups. We conclude that the transdermalcontrolled delivery of ketamine prolonged the duration of analgesia after minor
gynecological procedures. Implications: Transdermal delivery of ketamine was an
useful adjuvant to postoperative analgesia after epidural lidocaine blockade in the
population studied.
Publication Types:


Clinical Trial
Randomized Controlled Trial
PMID: 11094004 [PubMed - indexed for MEDLINE]
J Pediatr Hematol Oncol. 2001 Dec;23(9):616-9.
Related Articles, Links
Long-term treatment with ketamine in a 12-year-old girl with severe
neuropathic pain caused by a cervical spinal tumor.
Klepstad P, Borchgrevink P, Hval B, Flaat S, Kaasa S.
Pain Clinic, Department of Anesthesiology, University Hospital, Trondheim,
Norway. [email protected]
40
RE: Ketamine abstracts
A 12-year-old girl presented with head and neck pain, myoclonic movements, and
decreased strength in all extremities caused by a cervical spinal tumor
(glioblastoma multiforme). A partial resection of the tumor was performed. Three
weeks later, she had superficial pain distributed in all dermatomes below her
cervical medullary lesion. Touch (e.g., gentle hugs from relatives) and movements
elicited paroxysm of intense pain. The pain was not relieved by increased doses of
morphine. A test dose of ketamine (7.5 mg intravenous) provided an abrupt
decrease in pain intensity, and continuous infusions of subcutaneous morphine
and intravenous ketamine were started. Benzodiazepines were administered to
avoid psychotomimetic effects from ketamine and to diminish myoclonic
movements. The doses of analgesics and benzodiazepines were increasingly
titrated (subcutaneous morphine 163-750 mg/24 hr, intravenous ketamine
36-410 mg/24 hr, subcutaneous midazolam 5-20 mg/24 hr, and intravenous
diazepam 11.5-122.5 mg/24 hr) until her death 67 days after start of
ketamine. She remained awake until the last day before her death. For the last
29 days of life, the pain treatment regimen was successfully continued in her
home (400-km distance from the hospital). In conclusion, this case demonstrates
that ketamine treatment may be effective in children with severe neuropathic pain
not responsive to other analgesics. This patient also demonstrates the feasibility of
long-term ketamine treatment in pediatric oncology and that such treatment can
be administered in a home care setting.
Publication Types:

Case Reports
PMID: 11902308 [PubMed - indexed for MEDLINE]
Biopharm Drug Dispos. 2003 Jan;24(1):37-43.
Related Articles, Links
Plasma concentration profiles of ketamine and norketamine after
administration of various ketamine preparations to healthy
Japanese volunteers.
Yanagihara Y, Ohtani M, Kariya S, Uchino K, Hiraishi T, Ashizawa N,
Aoyama T, Yamamura Y, Yamada Y, Iga T.
Department of Pharmacy, Faculty of Medicine, The University of Tokyo
Hospital, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655,
Japan.
Ketamine is known to provide analgesic effects without an anesthetic when
administered in a low dose. We previously reported that a tablet containing
41
RE: Ketamine abstracts
ketamine had analgesic effects in patients with neuropathic pain. In the present
study, we compared the plasma concentration profiles of the enantiomers of
ketamine and its active metabolite, norketamine, up to 8 h after the
administration of 20 mg of ketamine by injection, after the administration of
two tablets containing 25 mg of ketamine, after the administration of two
sublingual tablets containing 25 mg of ketamine, after the insertion of a
suppository containing 50 mg of ketamine, and after the application of a
nasal spray containing 25 mg of ketamine to three healthy volunteers. The
plasma concentration of ketamine biexponentially declined after the
administration by injection; the value of T(1/2beta) for ketamine was
approximately 120 min. The bioavailability of the tablet was estimated to be
approximately 20%; the area under the plasma concentration-time curve,
(AUC)(0-->8 h), of norketamine was approximately 500 ng h/ml in both
enantiomers. The bioavailabilities of the sublingual tablet and the suppository
were estimated to both be approximately 30%; the AUC(0-->8 h) of
norketamine was 280-460 ng h/ml in both enantiomers. The plasma
concentration profiles of the sublingual tablet and the suppository were
almost similar to that of the tablet. The bioavailability of the nasal spray was
estimated to be approximately 45%, which was the highest value among the
preparations tested, and the AUC(0-->6 h) of norketamine was low
(approximately 100 ng h/ml) in both enantiomers. These pharmacokinetic
findings suggested that all of the ketamine preparations tested in this study may
be useful for the alleviation of neuropathic pain. We propose that the type of
ketamine preparation should be selected in accordance with the patient's disease
condition and the required dosage amount of ketamine. Copyright 2002 John
Wiley & Sons, Ltd.
PMID: 12516077 [PubMed - indexed for MEDLINE]
Anesth Analg. 2002 May;94(5):1263-9, table of contents.
Related Articles, Links
The role of ketamine in preventing fentanyl-induced hyperalgesia
and subsequent acute morphine tolerance.
Laulin JP, Maurette P, Corcuff JB, Rivat C, Chauvin M, Simonnet G.
Universite Bordeaux 1, France.
Perioperative opioids increase postoperative pain and morphine
requirement, suggesting acute opioid tolerance.[in RATS] Furthermore,
opioids elicit N-methyl-D-aspartate (NMDA)-dependent pain
hypersensitivity. We investigated postfentanyl morphine analgesic effects and
the consequences of NMDA-receptor antagonist (ketamine) pretreatment. The
rat nociceptive threshold was measured by the paw-pressure vocalization test.
Four fentanyl boluses (every 15 min) elicited a dose-dependent (a) increase
42
RE: Ketamine abstracts
followed by an immediate decrease of the nociceptive threshold and (b) reduction
of the analgesic effect of a subsequent morphine administration (5 mg/kg): 15.8%, -46.6%, -85.1% (4 x 20, 4 x 60, 4 x 100 microg/kg of fentanyl,
respectively). Ketamine pretreatment (10 mg/kg) increased the fentanyl analgesic
effect (4 x 60 microg/kg), suppressed the immediate hyperalgesic phase, and
restored the full effect of a subsequent morphine injection. Fentanyl also elicited a
delayed dose-dependent long-lasting decrease of the nociceptive threshold (days)
that was prevented by a single ketamine pretreatment before fentanyl. However, a
morphine administration at the end of the fentanyl effects restored the long-lasting
hyperalgesia. Repeated ketamine administrations were required to obtain a
complete preventive effect. Although ketamine had no analgesic effect per se at
the dose used herein, our results indicate that sustained NMDA-receptor blocking
could be a fruitful therapy for improving postoperative morphine effectiveness.
IMPLICATIONS: Fentanyl-induced analgesia is followed by early hyperalgesia
(hours), acute tolerance to the analgesic effects of morphine, and long-lasting
hyperalgesia (days). All these phenomena are totally prevented by repeated
administrations of the NMDA-receptor antagonist, ketamine, simultaneously with
fentanyl and morphine administration.
PMID: 11973202 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 2000 Jan;19(1):35-9.
Related Articles, Links
Comment in:

J Pain Symptom Manage. 2000 Jul;20(1):1-2.
The safety and efficacy of a single dose (500 mg or 1 g) of
intravenous magnesium sulfate in neuropathic pain poorly
responsive to strong opioid analgesics in patients with cancer.
Crosby V, Wilcock A, Corcoran R.
Macmillan Specialist Palliative Care Unit, Nottingham City Hospital NHS Trust,
United Kingdom.
43
RE: Ketamine abstracts
Neuropathic pain may respond poorly to morphine and is often difficult to relieve.
Recent attention has been drawn to the role of the N-methyl-D-aspartate (NMDA)
receptor in the potentiation of neuropathic pain. Magnesium is known to block
the NMDA receptor. It reduces the neuropathic pain response in animals, and
attenuates postoperative pain and migraine in humans. We have examined the
safety, tolerability, and efficacy of two intravenous doses of magnesium sulfate
in 12 patients with neuropathic pain due to malignant infiltration of the
brachial or lumbosacral plexus. The first six patients received 500 mg, the
remainder 1 g. Apart from a mild feeling of warmth at the time of the injection,
both doses were well tolerated. After receiving 500 mg, three patients
experienced complete pain relief and two experienced partial pain relief
for up to 4 hours duration; pain was unchanged in one patient. After
receiving 1 g, one patient experienced complete relief and four experienced
partial pain relief of similar duration; pain was unchanged in one patient.
Intravenous magnesium sulfate in these doses appears to be safe and well
tolerated. A useful analgesic effect may be obtained in some patients and further
evaluation is warranted.
Publication Types:

Clinical Trial
PMID: 10687324 [PubMed - indexed for MEDLINE]
J Pain Symptom Manage. 2001 Oct;22(4):834-42.
Related Articles, Links
"Burst" ketamine for refractory cancer pain: an open-label audit of
39 patients.
Jackson K, Ashby M, Martin P, Pisasale M, Brumley D, Hayes B.
McCulloch House, Monash Medical Center, Clayton, Victoria, Australia.
The results of a novel approach to the use of ketamine in refractory cancer pain
are reported. In this prospective, multicenter, unblinded, open-label audit, 39
patients (with a total of 43 pains) received a short duration (3 to 5 days) ketamine
infusion. The initial dose of 100 mg/24 hr was escalated if required to 300
mg/24 hr and then to a maximum dose of 500 mg/24hr. The overall response
rate was 29/43 (67%). Analysis of results according to pain mechanisms showed
that 15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who
appeared to respond, it is possible that another concurrent intervention may have
44
RE: Ketamine abstracts
contributed in whole or part for the pain relief observed. After cessation of
ketamine, 24/29 maintained good pain control, with a maximum documented
duration of eight weeks. However, 5 of the initial 29 responders experienced a
recurrence of pain within 24 hours, and ketamine was recommenced. Of these, 2
underwent another intervention for pain control while 3 continued on ketamine
until their deaths between two and four weeks later. Twelve patients reported
adverse psychomimetic effects, with the incidence rising with increasing dose.
Four of these were non-responders and the ketamine was stopped. Eight were
responders, and in 3 the adverse effects were rendered acceptable with dose
reduction; the other 5 rejected a dose reduction. The results reported suggest
the need for further investigation of the place of ketamine in cancer pain
management.
Publication Types:

Multicenter Study
PMID: 11576800 [PubMed - indexed for MEDLINE]
J Pain. 2001 Feb;2(1):75-6.
Related Articles, Links
Oral ketamine for opioid-resistant acute pain.
Friedman R, Jallo J, Young WF.
Department of Anesthesiology, Temple University, and the Temple Neurospine
Program, Temple University Hospital, Philadelphia, PA 19140, USA.
[email protected]
We report successful treatment of opioid-resistant postoperative pain in this case
report. Oral ketamine reduced the doses of opioids needed for pain control.
Opioid/N-methyl-D-aspartate receptor antagonist combinations should be studied
further for acute pain treatment.
PMID: 14622788 [PubMed]
Support Care Cancer. 2004 Apr 9 [Epub ahead of print]
Related Articles, Links
Dialogues on complex analgesic strategies for difficult pain
syndromes.
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RE: Ketamine abstracts
Mercadante S, Villari P, Ferrera P.
Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Via S.Lorenzo
312, 90146, Palermo, Italy.
Although the use of oral analgesics for the control of cancer pain has been
demonstrated to be successful in most patients, some patients will fail to respond
to pharmacological therapy or will suffer unacceptable adverse effects.
Experience is accumulating that when adverse effects prevail with oral opioid
administration, the analgesic response may be improved by changing the drug
and/or the route of administration. Switching to an alternative opioid may further
improve the balance between analgesia and adverse effects Despite optimal
systemic opioid treatment, in some complicated circumstances it is necessary to
find different solutions, including the neuraxial administration of multiple drugs
with different characteristics, which are difficult to manage. Three case reports
illustrate how complex could be the analgesic approach using multiple analgesic
regimens and different routes of administration to effectively manage complex
pain syndromes commonly defined as unresponsive.
PMID: 15083354 [PubMed - as supplied by publisher]
------------------------------------------------------------------------Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative
systematic review.
Author(s): Subramaniam K; Subramaniam B; Steinbrook R;
Animal studies on ketamine and opioid tolerance have shown promising results.
Clinical trials have been contradictory. We performed a systematic review
of randomized, double-blind clinical trials of ketamine added to opioid
analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients
were included. Studies were divided into 5 subgroups: IV ketamine as single
dose (n = 11), continuous infusion (n = 11), patient-controlled analgesia
(PCA) (n = 6), epidural ketamine with opioids (n = 8), and studies in
children (n = 4). Outcome measures included pain scores, time to first
request for analgesia, supplemental analgesics, and adverse events. Efficacy
was estimated by statistical significance (P < 0.05) of outcome measures
as reported in studies and also by calculation of weighted mean difference
for pain scores during the first 24 h after surgery. As compared to morphine
alone, IV PCA with ketamine and morphine did not improve analgesia.
Intravenous
infusion of ketamine decreased IV and epidural opioid requirements in
6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements
in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial
46
RE: Ketamine abstracts
effects. Adverse effects were not increased with small dose ketamine.
We conclude that small dose ketamine is a safe and useful adjuvant to
standard practice opioid-analgesia.
Anesthesia and analgesia.; 2004 Aug;99(2) p482 - 495
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