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At least 793 records · Page 44Linked to original sources
PubMed1996

A case of uncommon withdrawal symptoms after a short period of spinal morphine administration.

A 54-year-old female with chronic failed back surgery syndrome and pain in the back and the right leg was treated by chronic spinal morphine administration by an external pump. After a positive test instillation over a 3-week period the spinal catheter was removed. Within 24 h the patient developed fever, leucocytosis, impaired sense of smell and allodynia and hyperpathia in all 4 limbs. Infection was excluded as a possible cause and a withdrawal after a second test period some weeks later reinitiated the symptoms. The symptoms vanished after restarting the morphine administration. Finally, an internal Medtronic pump was implanted because the patient obtained good pain relief with the test instillation. Good pain relief could be obtained with the daily instillation of 5 mg morphine intrathecally. Fever, leucocytosis, impaired sense of smell, allodynia and hyperpathia in the limbs reappeared a few weeks later. Evaluation showed catheter migration out of the spinal canal.

Analgesics, Opioid↗
PubMed2006

The site of action of epidurally administered opioids and its relevance to postoperative pain management.

The use of epidurally administered opioids to control postoperative pain is a well established and widely accepted technique. However, despite this longstanding use, there is still an ongoing debate concerning the site of action of the opioids used. Some argue that analgesia is mediated by a spinal mechanism and others that a supraspinal mechanism is responsible. On close inspection of the evidence it becomes apparent that epidural opioids act predominantly spinally when administered as a bolus, and predominantly supraspinally when administered as a continuous infusion. A concentration of 10 microg x ml(-1) appears to be the threshold at which epidurally administered fentanyl can elicit segmental analgesia, a value which may have significant clinical applications. The evidence supporting a synergistic relationship between epidural opioids and local anaesthetics is weak and unsupported by a plausible physiological mechanism. Thus the 'threshold concentration' of approximately 10 microg x ml(-1) is unlikely to be lowered by co-administering opioids with local anaesthetics.

Analgesia, Epidural↗
PubMed1993

Monitoring of intraoperative motor-evoked potentials under conditions of controlled neuromuscular blockade.

Motor-evoked potentials were recorded after electrical spinal cord stimulation in 19 patients undergoing neurosurgical or orthopedic procedures. Anesthesia was maintained with nitrous oxide, opioids, and inhaled anesthetics. Vecuronium was infused sufficient to eliminate 90% of twitch tension. The spinal cord was stimulated using either epidural or subarachnoid electrodes. Compound muscle action potentials were recorded from quadriceps and tibialis anterior muscles. Well-formed, stable motor-evoked potentials were recorded in all but one patient, in whom a preexisting myelopathy was felt to preclude recording. Intraoperative deterioration of motor-evoked potentials occurred in one patient who had a postoperative neurologic deficit. This study demonstrates the feasibility and utility of intraoperative motor tract monitoring using direct spinal cord stimulation. Controlled neuromuscular blockade permits recording of compound muscle action potentials while eliminating patient motor activity that could interfere with surgery.

Action Potentials↗
PubMed1991

Continuous intrathecal fentanyl infusion for postoperative analgesia.

Following inadvertent dural puncture during epidural catheter placement, a 20 gauge polyethylene catheter was placed in the intrathecal space, and continuous spinal anesthesia with hyperbaric bupivacaine was administered intraoperatively to supplement general anesthesia. Following surgery, a continuous intrathecal fentanyl infusion (0.2 mcg/kg/hr) was administered to provide postoperative analgesia. The child was awake and comfortable throughout this time and required no supplemental analgesic agents. Although epidural catheters are still our preferred method of analgesia, intrathecal fentanyl infusion is one alternative when inadvertent dural puncture occurs.

Fentanyl↗
PubMed1995

Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat.

We evaluated the pharmacokinetics and regional distribution of propofol in the brain and spinal cord during propofol anesthesia in Sprague-Dawley rats, using high-performance liquid chromatographic determination of propofol concentration in brain, whole blood and plasma. We found that the concentration of propofol in the brain increased and decreased expeditiously during and after a 15-min and 30-min period of i.v. infusion of an anesthetic dose (60 mg/kg per h) of propofol. Furthermore, propofol was evenly distributed in the brain and spinal cord during infusion, with a significant inter-individual variation. Upon the establishment of anesthesia 15 and 30 min following intravenous infusion of propofol, the concentration of propofol in the brain, whole blood and plasma was respectively 15.7 +/- 1.9 and 39.4 +/- 2.7 micrograms/g, 4.5 +/- 1.2 and 13.6 +/- 1.3 micrograms/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 micrograms/ml (mean +/- SEM, n = 6 or 7). These high brain/blood and brain/plasma ratios during anesthesia suggest that propofol manifests a pharmacokinetic profile that is different from at least thiopental.

Anesthesia↗
PubMed2005

[The antiemetic effect of dexamethasone during continuous subcutaneous infusion of morphine for postoperative pain relief].

BACKGROUND: Dexamethasone is known to reduce the incidence of postoperative nausea and vomiting, associated with perioperative intrathecal, epidural, or intravenous morphine. However, the effect of dexamethasone on subcutaneous morphine is unclear. Therefore, we evaluated the antiemetic effect of intravenous dexamethasone during continuous subcutaneous infusion of morphine for postoperative pain relief. METHODS: Twenty patients scheduled for spinal surgery under general anesthesia were enrolled in this randomized, double-blind, and placebo-controlled study. The dexamethasone group (n=10) received dexamethasone 8 mg and the saline group (n=10) received the same amount of saline before the induction of anesthesia. Anesthesia was maintained with propofol and fentanyl. Postoperative pain was treated with continuous subcutaneous morphine via a patient-controlled analgesia device. Postoperatively patients were assessed during 48 hours for nausea and vomiting. RESULTS: Nausea or vomiting ascribable to the subcutaneous morphine developed in 40% of the patients in each group (P:NS). CONCLUSIONS: Our results suggest that the single dose of dexamethasone (8 mg) does not reduce postoperative nausea and vomiting associated with continuous subcutaneous infusion of morphine after spinal surgery.

Adult↗
PubMed1990

Spinal opioids: a nursing perspective.

Nursing care of the patient receiving spinal opioids for pain control is reviewed in a comprehensive manner. Selection of patients, nursing management and patient outcomes are discussed. Three pain control techniques are described: epidural opioid injection for cancer pain, epidural opioid infusion for acute postoperative pain, and single dose spinal opioids for postcesarean section pain. Monitoring and pharmacologic aspects common to all three forms of spinal opioid treatment are given, and specific nursing interventions for each therapy are delineated.

Analgesia, Epidural↗
PubMed2004

Production of paradoxical sensory hypersensitivity by alpha 2-adrenoreceptor agonists.

BACKGROUND: Administration of opioid receptor agonists is followed by paradoxical sensory hypersensitivity. This hypersensitivity has been suggested to contribute to the antinociceptive tolerance observed with opioids. The authors hypothesized that alpha 2-adrenoreceptor agonists, which also produce antinociceptive tolerance, would produce sensory hypersensitivity. METHODS: alpha 2-Adrenoreceptor agonists were administered to male Sprague-Dawley rats as a single subcutaneous injection, a continuous subcutaneous infusion, a single intrathecal injection, or a continuous intrathecal infusion. Thermal sensitivity was determined using latency to withdrawal of the hind paw from radiant heat. Tactile sensitivity was determined using withdrawal threshold to von Frey filaments. Spinal dynorphin content was measured by enzyme immunoassay. RESULTS: Single systemic or intrathecal injections of clonidine or dexmedetomidine produced antinociception followed by delayed thermal and tactile hypersensitivity. Six-day systemic or intrathecal infusion of clonidine produced tactile and thermal hypersensitivity observed even during clonidine infusion. Sensory hypersensitivity was prevented by coadministration of the alpha 2-adrenoreceptor-selective antagonist idazoxan or the N-methyl-D-aspartate receptor-selective antagonist MK-801. Six-day infusion of intrathecal clonidine increased dynorphin content in dorsal lumbar spinal cord. MK-801 and dynorphin antiserum reversed clonidine-induced sensory hypersensitivity. CONCLUSIONS: alpha 2-Adrenoreceptor agonists produce sensory hypersensitivity that may be analogous to that produced by opioids. Sensory hypersensitivity was prevented by idazoxan, demonstrating that it is mediated by alpha 2 receptors. Clonidine infusion increased spinal dynorphin content. Sensory hypersensitivity was prevented or reversed by MK-801 and dynorphin antiserum, implicating N-methyl-D-aspartate receptors and spinal dynorphin in its production. Clinicians should be mindful of the possibility of drug-induced hyperalgesia in patients treated with alpha 2-adrenoreceptor agonists.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1998

Direct convective delivery of macromolecules to the spinal cord.

OBJECT: Because of the limited penetration of macromolecules across the blood-spinal cord barrier, numerous therapeutic compounds with potential for treating spinal cord disorders cannot be used effectively. The authors have developed a technique to deliver and distribute macromolecules regionally in the spinal cord by using convection in the interstitial space. METHODS: The authors designed a delivery system connected to a "floating" silica cannula (inner diameter 100 microm, outer diameter 170 microm) that provides for constant volumetric inflow to the spinal cord. A solution containing albumin that was either unlabeled or labeled with carbon-14 or gadolinium was infused at various volumes (3, 6, 10, 20, 40, or 50 microl) at a rate of 0.1 microl/minute into the spinal cord dorsal columns of nine swine and into the lateral columns of three primates (Macaca mulatta). Volume of distribution (Vd), concentration homogeneity, and percentage of recovery were determined using scintillation analysis, kurtosis calculation (K), and quantitative autoradiography (six swine), magnetic resonance imaging (one swine and three primates), and histological analysis (all animals). Neurological function was observed for up to 3 days in four of the swine and up to 16 weeks in the three primates. The Vd of 14C-albumin was linearly proportional (R2=0.97) to the volume of infusion (Vi) (Vd/Vi=4.4+/-0.5; [mean+/-standard deviation). The increases in Vd resulting from increases in Vi were primarily in the longitudinal dimension (R2=0.83 in swine; R2=0.98 in primates), allowing large segments of spinal cord (up to 4.3 cm; Vi 50 microl) to be perfused with the macromolecule. The concentration across the area of distribution was homogeneous (K=-1.1). The mean recovery of infused albumin from the spinal cord was 85.5+/-5.6%. Magnetic resonance imaging and histological analysis combined with quantitative autoradiography revealed the albumin infusate to be preferentially distributed along the white matter tracts. No animal exhibited a neurological deficit as a result of the infusion. CONCLUSIONS: Regional convective delivery provides reproducible, safe, region-specific, and homogeneous distribution of macromolecules over large longitudinal segments of the spinal cord. This delivery method overcomes many of the obstacles associated with current delivery techniques and provides for research into new treatments of various conditions of the spinal cord.

Animals↗
PubMed2000

The treatment of tetanus with intrathecal baclofen.

The treatment of severe tetanus generally requires prolonged mechanical ventilation. We describe two cases managed with continuous intrathecal infusion of baclofen via a subcutaneous tunnelled spinal catheter and an abdominal injection port. Baclofen, by diminishing spasms and spasticity, allowed reduced sedation and paralysis requirements. This potentially decreases the time and resources required for intensive care management. Complications include sedation, hypotension and CSF infection. After appropriate dose adjustment, baclofen improves the management of severe tetanus.

Aged↗
PubMed1989

Insulin pump treatment of type I diabetes mellitus in a patient with C6 quadriplegia.

A 40-year-old patient with insulin-dependent (Type I) diabetes mellitus since childhood suffered a C6 spinal transection. Recurrent episodes of hypoglycemia resolved after the patient was placed on an insulin pump. The patient is able to set the insulin delivery rate and maintain the pump without assistance. Spinal cord injured patients may lack both the clinical symptoms of, and the ability to respond to, hypoglycemia. The mixing of NPH insulin and regular insulin requires fine motor skills; even with prefilled syringes, the quadriplegic person may have difficulty with subcutaneous injection. The use of an "open loop" insulin pump averts these problems and may provide better glucose control for selected spinal cord injury patients with Type I diabetes.

Adult↗
PubMed1990

Maternal paraparesis after epidural anesthesia and cesarean section.

Continuous epidural infusion of local anesthetics containing epinephrine has become increasingly popular. This technique has been associated with few, if any, complications. We have presented a case of anterior spinal artery syndrome with paraparesis after continuous lumbar epidural infusion of an anesthetic during labor and subsequent emergency cesarean section.

Adult↗
PubMed2006

Neuraxial drug administration: a review of treatment options for anaesthesia and analgesia.

Neuraxial drug administration describes techniques that deliver drugs in close proximity to the spinal cord, i.e. intrathecally into the CSF or epidurally into the fatty tissues surrounding the dura, by injection or infusion. This approach was initially developed in the form of spinal anaesthesia over 100 years ago. Since then, neuraxial drug administration has evolved and now includes a wide range of techniques to administer a large number of different drugs to provide anaesthesia, but also analgesia and treatment of spasticity in a variety of acute and chronic settings. This review concentrates on the pharmacological agents used and the clinical basis behind currently utilised approaches to neuraxial drug administration. With regard to local anaesthetics, the main focus is on the development of the enantiomer-specific compounds ropivacaine and levobupivacaine, which provide similar efficacy to bupivacaine with a reduced risk of severe cardiotoxicity. Opioids are the other group of drugs widely used neuraxially, in particular to provide analgesia alone or more commonly in combination with other agents. The physicochemical properties of the various opioids explain the main differences in efficacy and safety between these drugs when used intrathecally, of which morphine, fentanyl and sufentanil are most commonly used. Another group of drugs including clonidine, dexmedetomidine and epinephrine (adrenaline) provide neuraxial analgesia via alpha-adrenergic receptors and are used mainly as adjuvants to local anaesthetics and opioids. Furthermore, intrathecal baclofen is in routine clinical use to treat spasticity in a number of neurological conditions. Beside these established approaches, a wide range of other drugs have been assessed for neuraxial administration to provide analgesia; however, most are in various early stages of investigation and are not used routinely. These drugs include neostigmine, ketamine, midazolam and adenosine, and the conotoxin ziconotide. The latter is possibly the most unusual compound here; it has recently gained registration for intrathecal use in specific chronic pain conditions.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2005

Continuous opioid agonist treatment dose-dependently regulates mu-opioid receptors and dynamin-2 in mouse spinal cord.

Continuous opioid agonist treatment produces tolerance and in some cases mu opioid receptor (muOR) down-regulation. Previous studies indicate that down-regulation of muOR is more likely with high-efficacy opioid agonists (e.g., etorphine), whereas lower efficacy agonists (e.g., morphine) do not regulate muOR density. It has been suggested that muOR down-regulation may depend upon increases in Dynamin-2 (DYN-2) proteins. Therefore, the present study examined the effect of various infusion doses of etorphine on muOR density, DYN-2 protein, and DYN-2 mRNA abundance in mouse spinal cord. Mice were implanted sc with an osmotic pump that infused etorphine (50-250 microg/kg/day). Controls were implanted with inert placebo pellets. At the end of 7 days, mice were sacrificed, spinal cord removed and processed for radioligand binding, quantitative Western blotting, or RT-PCR assay. Results indicate that etorphine induced dose-dependent regulation of muOR density, DYN-2 proteins, and mRNA abundance in mouse spinal cord. Higher infusion doses significantly down-regulated muOR density, increased DYN-2 protein abundance, and decreased DYN-2 mRNA. Analysis of these results indicated a significant correlation between muOR down-regulation and DYN-2 abundance in mouse spinal cord. Taken together, muOR regulation may depend on changes in DYN-2 abundance induced by high-efficacy opioid agonists in mouse spinal cord.

Analgesics, Opioid↗
PubMed2004

High-efficacy 5-HT1A receptor activation causes a curative-like action on allodynia in rats with spinal cord injury.

The selective, high-efficacy 5-HT(1A) receptor agonist, (3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl]piperidin-1-yl]-methanone (F 13640) has been reported to produce long-term analgesia in rodent models of chronic nociceptive and neuropathic pain; it also preempts allodynia following spinal cord injury. Here, rats underwent spinal cord injury, fully developed allodynia, and were infused with saline or 0.63 mg/day of F 13640 for 56 days. Infusion was then discontinued, and further assessments of allodynia (vocalization threshold to von Frey filament stimulation, responses to brush and cold) were conducted for another 70 days. F 13640-induced analgesia persisted during this post-treatment period. The data offer initial evidence that high-efficacy 5-HT(1A) receptor activation produces an unprecedented curative-like action on pathological pain.

Analgesics↗
PubMed2006

Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review.

Worldwide a large number of patients suffer from severe chronic pain even after treatment with opioids following the 3-step analgesic ladder developed by the WHO. Intraspinal agents, including morphine, have been tried as a fourth step. However, approximately 20% of cases remain refractory. Ziconotide, an intrathecal analgesic with orphan drug status, is a novel alternative for the management of chronic intractable pain. Ziconotide is a synthetic peptide based on the toxin of the fish-hunting marine snail, Conus magus. It is the first therapeutic agent in a new pharmacological class of "topically" active analgesics that selectively target neuron-specific (N-type), voltage-gated calcium channels. Ziconotide produces potent analgesia by interruption of Ca-dependent primary afferent transmission of pain signals in the spinal cord. Ziconotide was significantly more effective than placebo in the treatment of chronic malignant (p < 0.001) and non-malignant pain (p < 0.001). In several clinical studies morphine dosages could be substituted by ziconotide. The drug has a lag-time for the onset and offset of analgesia and adverse effects. Initial doses should therefore be low (2.4 microg/day) and titrated slowly (increasing up to a maximum of 21.6 microg/day in increases of 2.4 microg/day no more than twice weekly). The gradual increase in dose helps to reduce the incidence and severity of adverse events which affect primarily the central nervous system (e.g. dizziness, nausea, confusion). Ziconotide maintains its analgesic efficacy over months and does not cause tolerance, dependence or respiratory depression. Following intrathecal infusion ziconotide is distributed within the cerebral spinal fluid (CSF) where its clearance (0.38 ml/min) corresponds to the rate of turnover of the CSF. Negligible amounts of ziconotide are present in the systemic circulation where it is rapidly degraded by proteolysis. In conclusion, ziconotide is a new and valuable alternative analgesic for the acute and long-term treatment of severe pain, especially in patients refractory to opioids.

Analgesics, Non-Narcotic↗