Intrathecal Ketamine Research Articles

264: Comparison of Addition of Intrathecal Ketamine to Intrathecal Levobupivacaine and Bupivacaine Hydrochlorur in Lower Extremity Surgeries With Spinal Block

264: Comparison of Addition of Intrathecal Ketamine to Intrathecal Levobupivacaine and Bupivacaine Hydrochlorur in Lower Extremity Surgeries With Spinal Block

Comparison of Addition of Intrathecal Ketamine to Intrathecal Levobupivacaine and Bupivacaine Hydrochlorur in Lower Extremity Surgeries With Spinal Block

Comparison of Addition of Intrathecal Ketamine to Intrathecal Levobupivacaine and Bupivacaine Hydrochlorur in Lower Extremity Surgeries With Spinal Block

Spinal (Intrathecal) Ketamine Anaesthesia for Upper Abdominal Surgery – Case Report.

Intravenous ketamine is usually administered for the induction of general anaesthesia. Spinal ketamine for lower abdominal and lower limb surgery is sporadically reported in the literature. However, the use of spinal ketamine for upper body surgery is rare. We describe the case of a 35-year old man, with a retroperitoneal tumour and severe intercurrent cardiovascular morbidity, that had exploratory laparotomy and tumour biopsy with Intrathecal ketamine administered through the L4/L5 interspace. The patient had good surgical analgesia, with stable vital signs throughout the surgery. After surgery, the spinal catheter was left in place, and withdrawn 48 hours later. The patient did well in the immediate postoperative period, although he gradually succumbed to the primary illness (malignant retroperitoneal cancer) on the 15th postoperative day. Keywords: Spinal, intrathecal, ketamine, anaesthesia.Nigerian Journal of Surgical Sciences Vol. 17 (2) 2007: pp. 129-132

Combination of low doses of intrathecal ketamine and midazolam with bupivacaine improves postoperative analgesia in orthopaedic surgery

Intrathecal ketamine produces a short period of analgesia with stable haemodynamics. Midazolam with bupivacaine prolongs the duration of analgesia when administered intrathecally but does not prevent hypotension. The objective of this study was to assess the effect of a combination of intrathecal bupivacaine, ketamine and midazolam on the duration of analgesia and haemodynamic parameters. A prospective, randomized, double-blind study was carried out in 60 ASA I and II patients undergoing lower limb surgery under spinal anaesthesia. Patients were divided into three groups of 20 each. Patients in all the three groups received 3 mL of hyperbaric bupivacaine (0.5%) intrathecally. In addition, patients in Groups II and III received intrathecal ketamine (0.1 mg kg-1) and the same dose of ketamine along with midazolam (0.02 mg kg-1), respectively. All patients were evaluated for block characteristics, duration of pain-free period, total rescue analgesic requirement in the 24-h postoperative period, total dose of mephenteramine to treat hypotension and any central or neurological complication. No patients in Group II required mephenteramine while 40% of patients in Group I and 10% in Group III required mephenteramine to maintain blood pressure after spinal anaesthesia. The mean +/- standard deviation duration of pain-free period was 331.5 +/- 89.9, 369.7 +/- 124.2 and 730.5 +/- 81.5 min in Group I, II and III, respectively. The pain-free interval was significantly greater in Group III compared to Groups I and II (P < 0.001). No patient had any complications. A low dose of midazolam and ketamine with bupivacaine intrathecally results in prolonged analgesia and less haemodynamic fluctuations. However, the safety of this combination needs to be proved before its use in clinical practice.

49. The effects of intrathecal ketamine in rats as an analgesic and the histopatologic changes in medulla spinalis

49. The effects of intrathecal ketamine in rats as an analgesic and the histopatologic changes in medulla spinalis

The effects of intrathecal ketamine in rats as an analgesic and the histopatologic changes in medulla spinalis

The effects of intrathecal ketamine in rats as an analgesic and the histopatologic changes in medulla spinalis

Effects of intrathecal ketamine on formalin-induced c-fos expressionin the spinal dorsal horn: Differences in laminae

Effects of intrathecal ketamine on formalin-induced c-fos expressionin the spinal dorsal horn: Differences in laminae

Effects of intrathecal ketamine on formalin-induced c-fos expressionin the spinal dorsal horn: differences in laminae

Effects of intrathecal ketamine on formalin-induced c-fos expressionin the spinal dorsal horn: differences in laminae

The fatty acid content and composition of spinal cord and brain of rabbits receiving intrathecal ketamine

AbstractThe present study investigates the effects of intrathecal ketamine on the concentration and composition of fatty acids in blood-brain barrier (BBB) tissues of New Zealand male rabbits. Ketamine is a drug that produces analgesia following intrathecal injection. It is very well known that fatty acids (FAs) play an important role in membrane fluidity of BBB tissues, which control the transportation of substances into brain. The total cellular fatty acids in brain and three spinal cord sections (cervical, thoracic, lumbar) of rabbits with or without drug administration were determined by gas chromatography using the Sherlock software (Microbial ID, Newark, DE) with the eukary database of fatty acid methyl ester (FAME) profiles for eukaryotic cells (Sherlock version 4.0). The fatty acid profiles of three different spinal cord sections were quite similar, but different than those of brain tissues. There were 23–25 fatty acids in spinal cord sections and 11 in the brain tissues of control animals compare...

Comparison of Antinociceptive Effect and c-fos Expression of Pre- Versus Posttreatment with Intrathecal Ketamine

Comparison of Antinociceptive Effect and c-fos Expression of Pre- Versus Posttreatment with Intrathecal Ketamine

Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems

Ketamine has been found to exert antinociceptive effects in animals and to be analgesic at subanaesthetic doses in humans. This study was designed to investigate the involvement of spinal cord mechanisms in the potentiation of opioid analgesia by parenteral non-spinal administration of ketamine. Thresholds for nociception were measured in an acute pain model in rats that allowed identification of antinociceptive effects due to drug action in the spinal cord. Dose-response curves for the antinociceptive effects of ketamine alone and ketamine in conjunction with the mu opioid fentanyl were constructed. Intraperitoneal ketamine up to 3.75 mg kg(-1) caused no sedative or antinociceptive effects and intrathecal ketamine caused dose-dependent, spinally mediated antinociceptive effects. Injections of ketamine doses that caused no antinociceptive effects when given alone (intrathecal 25 microg and intraperitoneal 3.75 mg/kg) significantly increased spinally mediated antinociception produced by intrathecal fentanyl injections when assessed using noxious heat (tail-flick test) but not when assessed by noxious electrical current (electrical current threshold test). We conclude that ketamine can potentiate the effects of fentanyl by an interaction at the level of the spinal cord even when ketamine is given via a non-spinal route of administration.

Comparison of Antinociceptive Effect of Pre- versus Post-treatment with Intrathecal Ketamine on the Formalin Test in Rats

Background: N-methyl-D-aspartate (NMDA) antagonists can be useful as preemptive analgesic agents and effective in reducing established central sensitization. The purpose of this study was to evaluate the preemptive effect of intrathecal ketamine and compare the behavioral antinociceptive responses between pre- versus post-formalin ketamine administration in a rat pain model. Methods: Sprague-Dawley rats (250-300 g) were prepared with a PE 10 indwelling intrathecal catheter to receive either saline (control) or ketamine. Rats received ketamine 100 intrathecally through a catheter either 7 min before or 5 min after formalin. The formalin test was performed with 5% formalin 100l. The control (n = 8), pre-treatment (n = 7), and post-treatment (n = 7) groups were studied. Pain related behaviors were quantified by counting the incidences of flinching of the formalin injected paw for 60 minutes. Results: Intraplantar formalin injection produced a biphasic (phase 1, 0-10 minutes; phase 2, 10-60 minutes after formalin injection) response of flinching behavior in control, pre-treatment, and post-treatment groups. The post-treatment group showed less frequent phase 2 flinching than the control group (P was effective on inhibition of phase 2 nociceptive behaviors following the formalin injection. These results suggested that intrathecal ketamine shows an analgesic effect when administered as a post-treatment.

Systemic, but not intrathecal, ketamine produces preemptive analgesia in the rat formalin model.

We investigated the antinociceptive effects of pre- or posttreatment of intrathecal or intravenous ketamine on formalin-induced pain behaviors. Rats were divided into 4 groups of 7 rats each and 2 control groups (saline). Rats received ketamine 1 mg/kg intrathecally (i.t.) through a catheter either 15 min before or 5 min after formalin. In the other groups, they received ketamine 1 mg/kg intravenously (i.v.) through a catheter either 1 min before or 5 min after the formalin. Pain related behavior was quantified by counting the incidence of flinching of the injected paw for 60 min. Formalin induced a biphasic fliching (phase 1, 0-5 min; phase 2, 10-60 min after formalin injection) of injected paw. The inter-group (control, pre, and posttreatment groups) comparisons were performed separately for route of administration (i.t. or i.v.) and phase 1 and 2 using one-way ANOVA and Tukey test. Flinches of phase 1 were not different among the three i.t. groups. The total flinches of phase 2 were reduced by posttreatment with i.t. ketamine (P < 0.05); In contrast, i.v. ketamine was effective only when given as a pretreatment. Flinches of phase 1 and 2 were reduced by pretreatment with i.v. ketamine (P < 0.05). Intrathecal ketamine was an analgesic even when administered as a posttreatment, whereas intravenous ketamine produced effective preemption only when given as a pretreatment.

Effect of ketamine on spinal cord nociceptive transmission in normal and monoarthritic rats.

The effects of systemically and intrathecally administered ketamine on spinal wind-up of normal and monoarthritic rats were studied by using C-fiber reflex responses evoked by repetitive (0.6 Hz) electric stimulation. Both systemic and intrathecal ketamine induced dose-dependent depression of wind-up activity in normal rats, as revealed by the dose-related inhibitory effects of the drug. At the same intraperitoneal doses, ketamine produced a greater inhibitory effect on wind-up activity of monoarthritic rats, compared to normal animals. The intrathecal administration of ketamine also produced wind-up inhibition, the efficacy being higher in the monoarthritic rats. Results indicate that ketamine depresses spinal wind-up, specially in rats submitted to chronic pain, probably due to its antagonistic properties on dorsal horn NMDA receptors, which play a crucial role in the maintenance of chronic pain.

Basic Science (28)

Analgesic mechanisms of ketamine in the presence and absence of peripheral. (Sapporo Medical University School of Medicine, Sapporo, Japan) Anesthesiology 2000;93:520–528.In this study, the authors investigated the contribution of the supraspinal monoaminergic descending inhibitory system to ketamine analgesia for acute nociception and inflammation‐induced hyperalgesia. Male Sprague‐Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive threshold. The analgesic effects of intrathecal or intraperitoneal ketamine were examined in the rats that received unilateral intraplantar carrageenan and in those that were untreated. In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine. Using an intrathecal microdialysis method, noradrenaline and 5‐hydroxytryptamine concentrations in lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both saline‐ and carrageenan‐treated rats. In the untreated rats, intraperitoneal but not intrathecal ketamine produced antinociceptive effects in a dose‐dependent manner. Pretreatment with intrathecal yohimbine or methysergide inhibited these antinociceptive effects. Intraplantar carrageenan significantly reduced paw withdrawal latencies on the injected paw, but not on the contralateral paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw withdrawal latencies on the injected side in a dose‐dependent manner without any effects on the contralateral side. Neither yohimbine nor methysergide inhibited these antihyperalgesic effects. In analyses of monoamines, the magnitiute of increase in monoamines after intraperitoneal ketamine was significantly smaller in the carrageenan‐treated rats than in the saline‐treated rats. Conclude that these results demonstrated that ketamine produced antinociceptive effects through an activation of the monoaminergic descending inhibitory system, whereas, in a unilateral peripheral inflammation‐induced hyperalgesic state, the monoaminergic system did not contribute to the antihyperalgesic effects of ketamine. The mechanisms of the antinociceptive and antihyperalgesic properties of ketamine are different.

Analgesic mechanisms of ketamine in the presence and absence of peripheral inflammation.

The studies on the mechanisms of ketamine antinociception have led to conflicting results. In this study, the authors investigated the contribution of supraspinal monoaminergic descending inhibitory system to ketamine analgesia for acute nociception and inflammation-induced hyperalgesia. Male Sprague-Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive threshold. The analgesic effects of intrathecal or intraperitoneal ketamine were examined in the rats that received unilateral intraplantar carrageenan and in those that were untreated. In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine. Using an intrathecal microdialysis method, noradrenaline and 5-hydroxytryptamine concentrations in lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both saline- and carrageenan-treated rats. In the untreated rats, intraperitoneal but not intrathecal ketamine produced antinociceptive effects in a dose-dependent manner. Pretreatment with intrathecal yohimbine or methysergide inhibited these antinociceptive effects. Intraplantar carrageenan significantly reduced paw withdrawal latencies on the injected paw but not on the contralateral paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw withdrawal latencies on the injected side in a dose-dependent manner without any effects on the contralateral side. Neither yohimbine nor methysergide inhibited these antihyperalgesic effects. In analyses of monoamines, the magnitude of increase in monoamines after intraperitoneal ketamine was significantly smaller in the carrageenan-treated rats than in the saline-treated rats. These results demonstrated that ketamine produced antinociceptive effects through an activation of the monoaminergic descending inhibitory system, whereas, in a unilateral peripheral inflammation-induced hyperalgesic state, the monoaminergic system did not contribute to the antihyperalgesic effects of ketamine. The mechanisms of the antinociceptive and antihyperalgesic properties of ketamine are different.

Intrathecal drug therapy for chronic pain: from basic science to clinical practice.

Intrathecal drug therapy for chronic pain: from basic science to clinical practice.

Histological Findings After Long-Term Infusion of Intrathecal Ketamine for Chronic Pain: A Case Report

Ketamine, a selective, noncompetitive N-methyl- d-aspartate (NMDA)-receptor antagonist, is able to alter pain perception at the spinal level. Little clinical data exist on the intrathecal and epidural use of ketamine in chronic pain. Histopathologic findings after intrathecal injection of ketamine with and without preservatives are rarely reported. This outcome was evaluated in a 72-year-old woman with abdominal pain due to cancer who was treated with the intrathecal application of bupivacaine, clonidine, and morphine. We reached satisfactory pain relief with the addition of ketamine to the mixture for 7 days. On postmortem, focal lymphocytic vasculitis close to the catheter injection site was found. This finding has not been described previously after long-term application of ketamine intrathecally. The intrathecal infusion of ketamine with preservative, or the mixture of ketamine, clonidine, morphine, and bupivacaine resulted in isolated lymphocytic vasculitis of the spinal cord and leptomeninges without any clinical signs of neurological deficit.

Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model

Background and Objectives. Ketamine is an N-Methyl-D-Aspartate (NMDA) receptor antagonist, which has been found to effectively treat somatic and neuropathic pain. This study examines the effect (on neuropathic pain) of preemptive ketamine using different routes of administration (intrathecal versus intraperitoneal). Methods. The Institutional Animal Care and Use Committee approved the study. Thirty male Sprague-Dawley rats (250–275 g) were divided into three treatment groups [intrathecal saline/intraperitoneal saline or Control (CTL), intrathecal ketamine/intraperitoneal saline (ITK), and intrathecal saline/intraperitoneal ketamine (IPK)] prior to undergoing surgery to induce neuropathic pain by tight ligation of the left L5 and L6 spinal nerves. All drugs were given 15 minutes before nerve ligation. The ITK group received intrathecal ketamine (0.5% solution, 1 mg/kg), the IPK group received intraperitoneal ketamine (0.5% solution, 1 mg/kg), saline was given in equal volume (approximately 0.05 mL). Mechanical allodynia, cold allodynia, and ongoing pain behaviors indicative of neuropathic pain were assessed on postoperative days 1, 3, 7, and 14 using validated methods. Results. Compared with the CTL group, the ITK group showed a state of decreased mechanical allodynia, cold allodynia, and ongoing pain as revealed by the von Frey hair, acetone, and cold plate testing respectively. Further this decrease was sustained for at least 2 weeks. The IPK group showed intermediate results between the CTL and ITK. Conclusions. Neuropathic pain behaviors were significantly reduced for at least 2 weeks after intrathecal ketamine was preemptively administered to animals undergoing surgery to induce neuropathic pain. The mechanism of action is thought to be prevention of spinal cord sensitization.

Preemptive Intrathecal Ketamine Injection Produces a Long-lasting Decrease in Neuropathic Pain Behaviors in a Rat Model

Preemptive Intrathecal Ketamine Injection Produces a Long-lasting Decrease in Neuropathic Pain Behaviors in a Rat Model