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PubMed2006

Level of consciousness affects the excitability of spinal motor neurones during propofol sedation in humans.

BACKGROUND: To investigate the relationship between the depression of spinal motor neuronal excitability and the sedative level induced by propofol infusion, we simultaneously analysed the suppressive effect of propofol on the F wave and the sedative level during propofol infusion. METHODS: After spinal anaesthesia, sedation was achieved using a propofol target-controlled infusion (TCI) system to achieve a score of 4 on the Wilson sedation scale. The excitability of spinal motor neurones was determined by measuring the left median nerve F wave. F-wave persistence and the F/M ratio were recorded at pre-sedation as the control, during sedation, at arousal by mild physical stimulation and at post-sedation. RESULTS: Wilson sedation scores increased significantly corresponding to the increase in the target propofol concentration (Cpt), and a Cpt-producing Wilson sedation scale 4 ranged between 1.2 and 1.8 microg ml(-1). The F-wave persistence and F/M ratio before propofol infusion were 80.7 (8.6)% and 9.5 (3.9)%, respectively. At Wilson sedation scale 4, F-wave persistence and F/M ratio were 17.6 (12.8)% (0-37.5%) and 4.3 (4.1)%, and, at return of consciousness by mild physical stimulation, significantly increased to 71.3 (7.9)% and 10.0 (5.0)%, respectively. CONCLUSION: We demonstrated that the excitability of spinal motor neurones was suppressed during sedation by propofol TCI, but this suppressive effect vanished at return of consciousness by mild physical stimulation even at a constant Cpt. Our data suggested that the effect of propofol on the excitability of spinal motor neurones might be affected by consciousness level rather than propofol Cpt in humans.

Adult↗

PubMed2006

Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS.

Excitotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has been proposed to play a major role in the selective death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), and motor neurons are more vulnerable to AMPA receptor-mediated excitotoxicity than are other neuronal subclasses. On the basis of the above evidence, we aimed to develop a rat model of ALS by the long-term activation of AMPA receptors through continuous infusion of kainic acid (KA), an AMPA receptor agonist, into the spinal subarachnoid space. These rats displayed a progressive motor-selective behavioral deficit with delayed loss of spinal motor neurons, mimicking the clinicopathological characteristics of ALS. These changes were significantly ameliorated by co-infusion with 6-nitro-7-sulfamobenso(f)quinoxaline-2,3-dione (NBQX), but not with d(-)-2-amino-5-phosphonovaleric acid (APV), and were exacerbated by co-infusion with cyclothiazide, indicative of an AMPA receptor-mediated mechanism. Among the four AMPA receptor subunits, expression of GluR3 mRNA was selectively up-regulated in motor neurons but not in dorsal horn neurons of the KA-infused rats. The up-regulation of GluR3 mRNA in this model may cause a molecular change that induces the selective vulnerability of motor neurons to KA by increasing the proportion of GluR2-lacking (i.e. calcium-permeable) AMPA receptors. This rat model may be useful in investigating ALS etiology.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Pain management after lumbar spinal fusion surgery using continuous subcutaneous infusion of buprenorphine.

PURPOSE: The continuous subcutaneous infusion (CSI) technique is a simple, inexpensive method for managing postoperative pain. We examined the analgesic effects of CSI of buprenorphine in patients undergoing lumbar spinal fusion surgery. METHODS: The patients were randomly assigned to one of three groups for postoperative pain management: control group (n = 17), high-dose buprenorphine group (BH group, n = 17), and low-dose buprenorphine group (BL group, n = 16). Infusion solutions containing buprenorphine at concentrations of 25.0 and 16.7 microg x ml(-1) combined with droperidol at a concentration of 52.0 microg x ml(-1) were used in the BH and BL groups, respectively; and an infusion solution containing droperidol at a concentration 52.0 microg x ml(-1) was used in the control group. CSI of each solution was started at a rate of 1 ml x h(-1) and was continued for 48 h. RESULTS: The BH and BL groups showed significantly lower scores than the control group on the Visual Analogue Scale. There were significantly fewer administrations of flurbiprofen as a supplemental analgesic in the BL and BH groups than in the control group. The incidences of sedation and nausea were comparable in the three groups. The median number of administrations of flurbiprofen was significantly less in the BH group than in the control group on the day of the operation and on the first postoperative day, whereas the number in the BL group was less than that in the C group only on the day of the operation. CONCLUSION: CSI of buprenorphine effectively reduces pain after lumbar spinal fusion surgery without apparent side effects. This technique is simple and useful for postoperative pain management.

Adult↗

PubMed1999

[Ketamine infusion therapy for refractory neuralgia in spinal disease: report of two cases].

We report two cases of refractory pain in a spinal disease. One case was a 60-year-old male who presented intractable pain in bilateral upper extremities after anterior fusion (C5/6, 6/7) for cervical spondylosis. The other was a 63-year-old female who also had intractable pain in the left anterio-lateral chest wall with no remarkable past history. Both cases were refractory to nonsteroidal anti-inflammatory drugs (NSAIDs) or minor tranquilizer or local anesthesia with bupivacaine. However, their pain was significantly relieved by the intravenous administration of a test dose (5mg) of ketamine which is a noncompetitive blocker of N-methyl-D-aspartate (NMDA) receptors. As for case 1, the effect of the injection of the test dose lasted, so continuing infusion therapy of ketamine was cancelled. In case 2, recurrence of the pain was recognized gradually. She underwent continuing infusion therapy of 2mg/kg of ketamine, and it brought about continued pain relief. We conclude that ketamine infusion therapy should also be considered for therapy of refractory neuralgia in spinal disease.

Analgesics↗

PubMed2002

High-dose methylprednisolone for acute closed spinal cord injury--only a treatment option.

BACKGROUND: A systematic review of the evidence pertaining to methylprednisolone infusion following acute spinal cord injury was conducted in order to address the persistent confusion about the utility of this treatment. METHODS: A committee of neurosurgical and orthopedic spine specialists, emergency physicians and physiatrists engaged in active clinical practice conducted an electronic database search for articles about acute spinal cord injuries and steroids, from January 1, 1966 to April 2001, that was supplemented by a manual search of reference lists, requests for unpublished additional information, translations of foreign language references and study protocols from the author of a Cochrane systematic review and Pharmacia Inc. The evidence was graded and recommendations were developed by consensus. RESULTS: One hundred and fifty-seven citations that specifically addressed spinal cord injuries and methylprednisolone were retrieved and 64 reviewed. Recommendations were based on one Cochrane systematic review, six Level I clinical studies and seven Level II clinical studies that addressed changes in neurological function and complications following methylprednisolone therapy. CONCLUSIONS: There is insufficient evidence to support the use of high-dose methylprednisolone within eight hours following an acute closed spinal cord injury as a treatment standard or as a guideline for treatment. Methylprednisolone, prescribed as a bolus intravenous infusion of 30 mg per kilogram of body weight over fifteen minutes within eight hours of closed spinal cord injury, followed 45 minutes later by an infusion of 5.4 mg per kilogram of body weight per hour for 23 hours, is only a treatment option for which there is weak clinical evidence (Level I- to II-1). There is insufficient evidence to support extending methylprednisolone infusion beyond 23 hours if chosen as a treatment option.

Acute Disease↗

PubMed2006

BIS guided sedation with propofol during spinal anaesthesia: influence of anaesthetic level on sedation requirement.

BACKGROUND: In this prospective, clinical study we tested the hypothesis whether two different doses of spinal administered bupivacaine and accordingly, two different levels of spinal anaesthesia can affect the dose requirement of propofol during BIS guided sedation. METHODS: Fifty women undergoing vaginal hysterectomy (high spinal group, HS) or transvaginal tape (TVT) procedure for urinary incontinence (low spinal group, LS) under spinal anaesthesia were enrolled to the study. In group HS, 17.5 mg and in group LS, 7.5 mg of hyperbaric bupivacaine were given intrathecally. After 15 min to obtain the appropriate level of spinal anaesthesia, propofol infusion was started at a rate of 100 microg kg(-1) min(-1) to reach a BIS level of less than 75 (onset time), and titrated to maintain the BIS value between 65 and 75. Propofol infusion was stopped 45 min after placing the spinal to measure the time to reach a BIS level of 90 (recovery time). RESULTS: Median anaesthetic level was T3 (T1-4) in the HS group and T10 (T9-11) in the LS group. In both the HS and the LS groups, onset time was 226 (47) vs 273 (48) s (P=0.001), recovery time was 234 (47) vs 202 (56) s (P=0.03), total dose of propofol was 2.17 (0.43) vs 3.14 (0.56) mg kg(-1) (P<0.001), respectively. CONCLUSION: A high spinal block obtained with hyperbaric bupivacaine 17.5 mg was associated with a faster onset, delayed recovery and lower doses of propofol sedation compared with a low spinal block with 7.5 mg of the same drug.

Adult↗

PubMed1995

Chronic intrathecal baclofen in severely disabling spasticity: selection, clinical assessment and long-term benefit.

Flexor and extensor spasms associated with severe spasticity frequently cause pain and suffering in neurologically impaired patients, and greatly interfere with comfort and activities. When high doses of oral medications are necessary to keep the symptoms under control and are poorly tolerated, the long-term spinal-selective intrathecal infusion of baclofen by means of implanted drug pump and catheter is a safe, efficient and reversible alternative to destructive surgical procedures. Between September 1991 and March 1995, intrathecal baclofen was infused in 18 selected patients out of a series of 42 severely disabled spastic cases. We report here our preliminary experience with the criteria of selection, the initial intrathecal bolus test and the long-term benefit of the selected patients. Our results confirm the dramatic immediate and long-term benefit reported in other series. After a period of treatment of 1 to 42 months, 13 patients had a complete disappearance of their spastic symptoms without any oral treatment, one patient kept unchanged clonus despite the use of low-dose oral treatment and another one a severe, not improved dysuria although in both of them hypertonia and spasms were abolished. Finally, 2 patients had important joint stiffness slightly impairing the benefit from the treatment. None of the 18 patients had central side-effects related to baclofen. With time, a slight increase in daily dose (inferior to 10%) was necessary in most patients.

Adult↗

PubMed1995

Failure of methylprednisolone to improve the outcome of spinal cord injuries.

The infusion of methylprednisolone (MP) within 8 hours of injury for spinal cord injuries (SCI) has been advocated to improve the motor function of patients after this catastrophic injury. However, clinical improvement in the outcome of SCI has not been consistently identified, despite the use of MP. We reviewed the outcome of SCI patients with MP to those without MP (No-MP) at two Level I Trauma Centers from 1989-1992. Acute SCI patients were identified from the trauma registries with trauma demographics and hospital data obtained from registry and medical records. Rehabilitation data for Functional Independence Measure (FIM) was obtained from the rehabilitation institute database. Primary outcome parameters were mortality, and for survivors, patient mobility (6 point scale) and FIM scores. There were 145 acute SCI patients: 80 treated with MP and 65 with No-MP. FIM data was available on 45 MP and 25 No-MP patients. There was no difference in the admission trauma score, ICU length of stay (LOS), or hospital LOS between the two groups. The MP patients were significantly younger (30 years vs 38 years, P = < 0.05) and had lower ISS scores (24 vs 31, P = < 0.05). There was no statistically significant difference in mortality (MP, 3.8% vs No-MP, 10.7%) between the two groups. Although admission mobility was not statistically different (MP, 5.99 vs No-MP, 5.90), there was a significantly poorer discharge mobility in the MP group when compared to the No-MP group (MP, 5.16 vs No-MP, 4.67, P = < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

PubMedDate not supplied

Intrathecal baclofen infusion: an innovative approach for controlling spinal spasticity.

Severe and disabling spasticity frequently occurs in people with multiple sclerosis and spinal cord injury. Approximately 30% of these people are treated with oral antispasmodic medications that do not provide adequate relief from spasticity (Hattab, 1980). Clinical trials with spinal stimulation and ablative neurosurgical procedures have not been as uniformly successful for controlling spasticity as has intrathecal baclofen injection (Kasdon, 1986). Delivered by an implantable programmable drug pump, intrathecal baclofen injection has proven to be successful in treating individuals with intractable spasticity. Significant reduction in muscle tone and frequency of spasms have contributed to improved function with activities of daily living, bladder management, overall comfort, and quality of sleep (Penn et al., 1989; Parke, Penn, Savoy, & Corcos, 1989). This article introduces an innovative therapy for controlling spasticity and discusses the nurse's role in patient selection and management.

Activities of Daily Living↗

PubMed1966

Evidence for centers in the central nervous system that regulate fat mobilization in dogs.

Infusions of 2-deoxyglucose (2-DG) into intact, adrenalectomized, and adrenalectomized-hypophysectomized dogs caused increases in plasma free fatty acid (FFA) levels which could be reversed by infusing hexamethonium, or prevented by epidural anesthesia or destruction of the thoracic spinal cord. Similar infusions of 2-DG were given to adrenalectomized dogs after transection of the spinal cord. Lesions between C 4 and T 7 prevented the increase in FFA while lesions at T 8 or C 2-3 did not. These results indicate that inhibition of glucose metabolism by 2-DG causes an increase in plasma FFA by a pathway involving the sympathetic nervous system and that there are centers regulating this activity in the cervical portion of the spinal cord.

Adrenalectomy↗

PubMed2000

Intravenous infusion of 4-AP in chronic spinal cord injured subjects.

STUDY DESIGN: A prospective double blind cross over trial of intravenous 4-Aminopyridine (4-AP). OBJECTIVE: To determine the efficacy of this drug in the treatment of spinal cord injured (SCI) patients for neurologic impairment, pain and spasticity. SETTING: The post anesthesia care unit (PACU) of a tertiary care acute hospital. METHODS: Twelve paraplegic patients were enrolled in a double blind cross over intravenous trial of 4-Aminopyridine (4-AP). Thirty milligrams of 4-AP or placebo were administered over a 2 h period. Patients were serially examined during and after the infusion clinically for pain, sensorimotor function, hypertonicity and motor control using electromyography (EMG). Samples of blood and cerebrospinal fluid (CSF) were also analyzed at similar intervals. RESULTS: Despite penetration of 4-AP into the CSF, no significant differences were noted in the clinical and EMG parameters at the times measured. Individual changes in sensory function were reported by some patients in both the placebo and 4-AP trials, however mean values were not robust. Frequently, patients complained of unpleasant symptoms during the 4-AP infusion. CONCLUSION: The intravenous route may not be the best way to administer this drug as no short term benefits were observed.

4-Aminopyridine↗

PubMed2005

Involvement of spinal GABA receptors in the regulation of intraspinal acetylcholine release.

It has been shown that analgesics such as morphine, lidocaine and clonidine increase the release of spinal acetylcholine. Acetylcholine may therefore play an important role in the regulation of spinal pain threshold. Since behavioral as well as in vitro studies have shown a clear involvement of GABA (gamma-amino butyric acid) receptors in the regulation of spinal nociceptive mechanisms, the present study focused on the role of GABA receptors for spinal acetylcholine release control. GABA receptor agonists and antagonists were infused via a spinal microdialysis probe and acetylcholine release was measured. The GABA(A) receptor agonist muscimol decreased acetylcholine release and the antagonist bicuculline increased acetylcholine release. The GABA(B) receptor agonist baclofen decreased acetylcholine release whereas the antagonist saclofen did not change acetylcholine release. The results suggest that both GABA receptor subtypes have an inhibitory role on spinal dorsal horn acetylcholine release and that the GABA(A) receptors are tonically regulating acetylcholine release.

Acetylcholine↗

PubMed2005

Effects of music on target-controlled infusion of propofol requirements during combined spinal-epidural anaesthesia.

The sedative effects of music were evaluated using the bispectral index (BIS) during target-controlled infusion (TCI) propofol. A total of 110 women undergoing hysterectomy were randomly allocated to receive either music or no music. Propofol was administered using target-controlled infusion and the concentration adjusted gradually to achieve an observer's assessment of alertness/sedation (OAA/S) score of 3 intra-operatively. The haemodynamic and bispectral index values during the sedation phase were recorded. Interleukin-6 was evaluated before, immediately after and 1 h following intervention. The music group had a significant reduction in mean (SD) induction time of sedation: 12 (12) min vs. 18 (12) min, p < 0.01; propofol target concentration: 1.6 (0.3) microg.ml(-1) vs. 2.4 (0.4) microg.ml(-1), p < 0.0001; intra-operative amount of propofol: 171 (98) mg vs. 251 (92) mg, p < 0.0001; and significantly higher levels of satisfaction with their peri-operative care: 9.6 (0.6) compared to the control group: 8.1 (1.0), p < 0.0001. No other differences were found. The results show the influence of music on the induction time of sedation, concentration and level of propofol during surgery, and suggest sedative benefits of music.

Adult↗

PubMed2002

Recovery of psychomotor function after propofol sedation is prolonged in the elderly.

PURPOSE: To assess the effects of age on recovery of psychomotor function for propofol sedation during spinal anesthesia. METHODS: Propofol was continuously infused during surgery and spinal anesthesia in 15 elderly patients (65-85 yr-old) and 15 younger patients (20-50 yr-old). Infusion rates were adjusted to maintain an appropriate level of sedation using the bispectral index (range 60-70). The sedative infusion was discontinued at the end of surgery. The early recovery times from the end of propofol infusion to opening of eyes on command, sustaining a hand grip, and recall of name were noted. Psychomotor function, as measured by the Trieger's dot test, was evaluated before anesthesia and 30, 60, 90, 120 min after the end of propofol infusion. RESULTS: The duration of anesthesia was 142 +/- 55 min and 134 +/- 61 min in the elderly and younger patients, respectively. No differences were observed in early recovery times between elderly and younger patients (opened their eyes on command, 6.3 +/- 4.0 min and 5.2 +/- 2.6 min; sustained a hand grip, 7.2 +/- 3.9 min and 6.1 +/- 3.5 min and recalled their name, 8.0 +/- 4.5 min and 6.5 +/- 3.8 min, P > 0.05 ). The recovery of psychomotor function in the elderly took longer compared with the younger patients, and psychomotor function in the elderly recovered at 120 min after the end of propofol infusion. CONCLUSION: Early recovery times following propofol sedation is similar between elderly and younger patients, but recovery of psychomotor function in the elderly is delayed compared with younger patients.

Adult↗

PubMed1998

Infusion of GDNF into the cerebral spinal fluid through two different routes: effects on body weight and corticospinal neuron survival.

Survival of axotomized adult rat corticospinal neurons (CSN) is supported by glial cell line-derived neurotrophic factor (GDNF). We have evaluated the trophic effects of intrathecally applied GDNF on CSN survival and rat body weight. Body weight reduction is the major side effect of intracerebral neurotrophic factor treatment. GDNF was tested at total doses of 30, 100 and 300 microg over 7 days after axotomy via different application routes: intracerebroventricularly (i.c.v.) and cisternally (cis). Animals injected i.c.v. displayed severe body weight reduction at all doses tested but CSN rescue only at the highest dose. In contrast, cis-infusion of GDNF promoted CSN survival at all doses and only the highest dose reduced the body weight. These results show that intracisternal, but not i.c.v., GDNF infusion at low doses can promote CSN survival without negatively affecting rat body weight. This finding may have implications for the clinic use of GDNF.

Animals↗

PubMed1994

Spinal anaesthesia for caesarean section: comparison of infusions of phenylephrine and ephedrine.

Maternal cardiovascular changes and neonatal acid-base status were assessed in 29 healthy women undergoing elective lower segment Caesarean section under spinal anaesthesia. The patients were allocated randomly to one of three groups to receive an i.v. infusion of one of the following: ephedrine 1 mg min-1 (group E1: n = 10), ephedrine 2 mg min-1 (group E2: n = 9), or phenylephrine 10 micrograms min-1 (group P: n = 10). Invasive arterial pressure was monitored continuously and if hypotension occurred (defined as a 20% decrease from baseline, taken after i.v. preload administration), bolus doses of either ephedrine (6 mg in groups E1 and E2) or phenylephrine (20 micrograms in group P) were given. Only four patients became hypotensive in group E2, compared with eight patients in group E1 and nine patients in group P. The total time that the patients remained hypotensive was greatest in group P (P < 0.005), less in group E1 and least in group E2. Neonatal Apgar scores and acid-base profiles were similar in all three groups. In this study, an infusion of phenylephrine 10 micrograms min-1 with bolus doses of 20 micrograms was shown to be significantly less effective in maintaining systolic arterial pressure within 20% limits of baseline compared with an infusion of ephedrine 1 or 2 mg min-1 with bolus doses of 6 mg.

Adult↗

PubMed1990

Spinal neuronal pathology associated with continuous intrathecal infusion of N-methyl-D-aspartate in the rat.

Continuous intrathecal infusion of N-methyl-D-aspartate (NMDA) at the level of the lumbar enlargement of the spinal cord in middle-aged rats produced dose-dependent toxicity of spinal cord neuronal systems. Toxicity was enhanced by coadministration of glycine, but was significantly reduced when NMDA was co-administered with the competitive inhibitor DL-2-amino-5-phosphovaleric acid or the noncompetitive inhibitor MgSO4. The toxic effects of NMDA were manifest most dramatically and at the lowest concentrations in the neuropil, while neuronal loss was obvious at higher concentrations. The distribution and intensity of reactive astrocytosis was consistent with the known regional and subcellular distribution of NMDA receptors in the spinal cord of rats. The increase in ribosomes and rough endoplasmic reticulum observed in anterior horn cells suggested an increase of cell metabolism reflecting either a nonspecific response to injury or a specific increase in cell metabolism secondary to sustained activation of NMDA receptors. The present studies implicate excitatory amino acid receptors of the NMDA type in producing toxicity to selected neuronal populations of the spinal cord. This model provides a system for studies of the protective effects and rescue of neuronal populations susceptible to the toxic effects of excitatory amino acids.

2-Amino-5-phosphonovalerate↗

PubMed1975

Spinal autonomic afferents in elicitation of tachycardia in volume infusion in the dog.

Intravenous infusion of blood (36 ml/kg body wt) elicited tachycardia in artificially ventilated anesthetized dogs with intact autonomic innervation and in dogs with cardiac beta-receptor blockade. In contrast, infusion elicited bradycardia in dogs with section of the spinal cord at C6-C7, and in dogs with combined spinal section and cardiac beta-receptor blockade. The control heart rate was less than or equal to 110 beats/min in all the animals. The presence of infusion-induced tachycardia in dogs with beta-receptor blockade, i.e., dogs in which cardiac sympathetic efferents were blocked, and its absence in dogs with combined spinal section and beta-receptor blockade, i.e., dogs in which spinal autonomic afferents plus cardiac sympathetic efferents were blocked, may be the result of an additional interruption of spinal autonomic afferents by spinal section. It is concluded that tachycardia elicited by infusion may be partly due to a reflex with its afferent pathway in the spinal cord and its efferent pathway in the vagus nerves.

Afferent Pathways↗