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PubMed1997

Memory disturbance and hippocampal degeneration induced by continuous intraventricular infusion of a protease inhibitor, leupeptin.

Effects of a protease inhibitor, leupeptin, on the memory function and the morphological changes in the hippocampus were examined in rats. The leupeptin was infused by an implanted-osmotic minipump into the lateral ventricle of the rats for 14 days. The acquisition and the maintenance of memory were evaluated by a step-down passive avoidance task. The control rats, infused with an artificial cerebral spinal fluid, showed good retention for the passive avoidance training for 21 days after training. The leupeptin-treated rats showed good retention for 7 days following training; however, pronounced impaired retention was observed on day 10 and thereafter. These rats were accompanied by a degeneration of the dentate gyrus in the histological examinations on Days 14 and 21. The granule cells in the dentate gyrus of the hippocampus appeared much more eosinophilic pyknotic. Numerous eosinophilic spherical structures of the cell processes were seen in the neuropil beneath the granule cell layer. Electron microscopic examination disclosed a marked accumulation of lipofuscin-like granules in the perikaryon of the cells and in the dendrites and the axons. These findings suggest that the memory impairment is closely related to the degeneration of the dentate gyrus in the hippocampus in the leupeptin-treated rats.

Animals↗
PubMed1987

The effect of intrathecal baclofen on electrical muscle activity in spasticity.

The efficacy of intrathecally administered baclofen was demonstrated in three patients with different types of muscular hypertonia (supraspinal rigidity, spasms shortly after spinal trauma, spasms for many years induced by multiple sclerosis) using integrated electromyography. Reduction of muscular electrical activity was accompanied by clinical improvement during long-term infusion via an implanted pump. The three patients have been observed for more than 1 year, during which time the antispastic activity of intrathecally infused baclofen has remained stable. Intrathecal application of baclofen may be considered as a possible alternative to surgery.

Adult↗
PubMed1991

Effect of delayed administration of U74006F (tirilazad mesylate) on recovery of locomotor function after experimental spinal cord injury.

Beginning at either 30 minutes, 2 hours, 4 hours, or 8 hours after 180 g compression of the cat L2 spinal cord for 5 minutes, infusion of U74006F was initiated. In this series, the cats received a total U74006F dose of 5 mg/kg/48 hours. An additional group of injured cats was treated at 8 hours postinjury with a three-fold higher dose of U74006F (i.e., a total 48-hour dose of 15 mg/kg). Controls received an equal volume of vehicle (citrate-buffered saline) delivered over 48 hours. The cats were evaluated weekly for 4 weeks for recovery of overground locomotion based on an 11-point scale by an investigator blinded to the time and type (i.e., vehicle or drug) of material administered. By 4 weeks postinjury, there was no significant difference in the locomotor recovery of cats that received U74006F at either 30 minutes, 2 hours, 4 hours, or 8 hours after injury. However, only recovery in the groups treated at 30 minutes, 2 hours, or 4 hours after injury was significantly greater than vehicle-treated controls. Locomotor function in cats receiving either 5 mg/kg/48 hours or 15 mg/kg/48 hours of U74006F at 8 hours postinjury was not significantly different from that of the vehicle-treated animals. Mean (+/- SEM) 4-week recovery scores were 6.8 +/- 0.9, 5.9 +/- 1.0, 7.2 +/- 1.1, and 4.7 +/- 2.9 out of 11 for cats treated at 30 minutes, 2 hours, 4 hours, or 8 hours postinjury, respectively, with the 5 mg/kg/48 hour dose. The mean recovery score for cats treated at 8 hours after injury with the 15 mg/kg/48 hour dose was 3.4 +/- 1.8. The average score for the vehicle-treated controls was 1.8 +/- 0.8. These findings demonstrate that U74006F can significantly protect locomotor function in our model of compression spinal cord injury if administered as late as 4 hours postinjury. Delaying administration of the compound to 8 hours after injury results in considerable loss of its protective capabilities even if the dose is increased threefold.

Animals↗
PubMed2004

Evidence that intravenous vasopressors can affect rostral spread of spinal anesthesia in pregnancy.

BACKGROUND: The authors have previously observed an apparent association between rostral spread of spinal anesthesia and choice of intravenous vasopressor given to maintain maternal systolic arterial pressure during cesarean delivery. This study tested the hypothesis that an intravenous infusion of phenylephrine can reduce rostral spread of spinal anesthesia in pregnancy, compared with ephedrine. METHODS: The study was randomized and double blind. It compared phenylephrine 100 microg/ml (phenylephrine group, n = 30), and ephedrine 3 mg/ml (ephedrine group, n = 30), given by infusion, to prevent maternal hypotension during combined spinal-epidural anesthesia for cesarean delivery. Two ml intrathecal plain levobupivacaine, 0.5%, combined with 0.4 ml intrathecal fentanyl, 50 microg/ml, and 10 ml epidural saline was given with the patient in the sitting position. The upper level of neural blockade to cold and light touch sensation was recorded at 10 and 20 min postspinal. Epidural space pressure was recorded at 5, 10, 15, and 20 min. RESULTS: At 20 min, the upper dermatome blocked to cold sensation was median T3 (interquartile range, T2-T4) for the phenylephrine group, compared with T1 (T1-T2) for the ephedrine group (P = 0.001). At 20 min, the upper dermatome blocked to light touch sensation was median T5 (T4-T8) for the phenylephrine group, compared with T3 (T2-T6) for the ephedrine group (P = 0.009). The mean epidural space pressure in the phenylephrine group was 16 (13-19) mmHg, compared with 16 (13-18) mmHg in the ephedrine group (P = 0.63). CONCLUSIONS: This study provides evidence that intravenous phenylephrine can decrease rostral spread of spinal anesthesia in pregnancy, compared with intravenous ephedrine. Further work is required to investigate possible mechanisms and to assess its clinical significance.

Adult↗
PubMed2005

Bolus injection of Ringer's solution and dextran 1 kDa during induction of spinal anesthesia.

BACKGROUND: Arterial hypotension following induction of spinal anesthesia is difficult to prevent with infusion fluids. In a randomized, unblinded and controlled study we evaluated whether a rapid fluid administration planned according to volume kinetic analysis is followed by a more stable blood pressure. METHODS: Spinal anesthesia was induced in 75 surgical patients, using one of three different fluid regimens: intravenous 'bolus injection' of 5 ml kg(-1) of Ringer's acetate over 3 min, 2 ml kg(-1) of low-molecular weight (1 kDa) dextran over 3 min, or a constant-rate infusion of 15 ml kg(-1) of Ringer's acetate over 40 min (controls). The kinetics of the fluid was studied in five patients in each group and also in eight volunteers. RESULTS: The decrease in mean arterial pressure averaged 28%, 27% and 26%, respectively, and was fully developed 16 min after the induction. The height of the block, but not the fluid programme, correlated with the hypotension. Nausea or near-fainting associated with marked hypotension or bradycardia was recorded in none, five (20%) and two (8%) of the patients, respectively. Both bolus injections were followed by translocation of fluid from the peripheral tissues to the bloodstream, which maintained the plasma dilution at about 10% for at least 30 min until surgery began. CONCLUSION: A brisk infusion of Ringer's solution or dextran 1 kDa over 3 min was followed by the same decrease in arterial pressure as a longer and 3-5-times larger infusion of Ringer's solution over 40 min during induction of spinal anesthesia.

Aged↗
PubMed1976

Spinal subarachnoid perfusion of rhesus monkeys.

A technique of spinal subarachnoid perfusion is descirbed which effectively isolates the spinal cord from the remainder of the central nervous system. A method of obtaining and analyzing spinal cord tissue after subarachnoid perfusion is presented. The spinal subarachnoid space of 12 rhesus monkeys was perfused with [14C]sucrose, [14C]ethylenediaminetetraacetic acid-calcium complex (EDTA), and dextran blue as test substances. The sucrose and EDTA spinal cord distribution spaces are 13.6 +/- 0.9% in white matter and 18.1 +/- 1.4% in gray matter. The diffusion coefficient in tissue of sucrose is 1.7 x 10(-6) cm2/s and of EDTA is 1.55 x 10(-6) cm2/s. The spinal cord tortuosity factor is 2.0-2.1. Six rhesus monkeys were infused intravenously with [3H]sucrose and [14C]EDTA; the spinal capillary exchange half-time from blood to extracellular fluid was greater than 6 h for both sucrose and EDTA.

Animals↗
PubMed1999

Comparison of midwife top-ups, continuous infusion and patient-controlled epidural analgesia for maintaining mobility after a low-dose combined spinal-epidural.

We studied 133 women given a combined spinal-epidural for analgesia in labour. The initial intrathecal dose contained bupivacaine 2.5 mg with fentanyl 25 micrograms. When the mothers were comfortable, they were allocated randomly to one of three groups: continuous infusion (group Cl, n = 46), midwife top-ups (group MW, n = 43) or patient-controlled epidural analgesia (group PCEA, n = 44), to maintain analgesia throughout labour. All epidural solutions contained 0.1% bupivacaine and fentanyl 2 micrograms ml-1. Motor block was assessed by the mother's ability to straight leg raise (SLR). Four hours after combined spinal-epidural analgesia, 88.1% of women could SLR in group MW, 83.7% in group PCEA and 57.8% in group Cl (P = 0.002). Total use of bupivacaine was highest in group Cl (mean 11.3 (SD 3.3) mg h-1) compared with group MW (7.5 (3.1) mg h-1) and group PCEA (9.1 (2.1) mg h-1) (P < 0.001). Analgesia was similar between groups and overall satisfaction was equally high.

Adolescent↗
PubMed1983

Development changes in pharmacological responsivity of the acoustic startle reflex: effects of picrotoxin.

Using the acoustic startle reflex as the behavioral measure, qualitatively different responses to the GABA antagonist picrotoxin were obtained in developing rats before and after 21 days postnatal (PN) age. Dose-dependent increases in acoustic startle were seen following picrotoxin in PN day 15-16 rat pups. In contrast, dose-dependent decreases in startle following picrotoxin were observed in adult rats. The switch from excitation to inhibition of startle was found to occur abruptly on PN day 21. Excitatory responses to picrotoxin were also found in adult rats following localized infusions of picrotoxin into lumbar spinal cord regions, but not into the forebrain. These results give evidence that picrotoxin-sensitive sites that modulate increases in startle reflex behavior mature first and are analogous to sites in the adult spinal cord, whereas picrotoxin-sensitive sites that modulate decreases in startle reflex behavior mature later (greater than or equal to PN day 21) and are localized in more rostral brain areas.

Acoustic Stimulation↗
PubMed1986

Simple catheter preparation for permitting bolus intrathecal administration during chronic intrathecal infusion.

This paper briefly describes a simple method for preparing a polyethylene "Y" catheter in which the stem of the "Y" is inserted into the intrathecal space, one arm of the "Y" is externalized for intrathecal injection and the other arm of the "Y" connected to an osmotic infusion pump. This simple preparation permits the chronic infusion of drug into the spinal space and without further surgical preparation, permits bolus injection of drugs through the same catheter.

Animals↗
PubMed2004

Intrathecal methods.

Although the use of opioids for intrathecal anesthesia was first reported in 1901, it was not until 25 years ago that the first report of selective blockade of pain by spinal opioids was described. Since its beginning, the promise of selective analgesics derived from intraspinal administration has generated much development in the field of pain management. In fact, many anesthesiologists who had previously relegated themselves to the confines of the operating room discovered that their needles and catheters could reach even beyond the inpatient wards, affording patients outside the hospital the opportunity to receive neuraxial drugs. The goal of this article is to report on the current state of spinal analgesic chemotherapy as it is now known.

Analgesia, Epidural↗
PubMed1995

Subcutaneous bupivacaine for treatment of spasticity: a case report.

In a previous report, we described heretofore undiscovered possibilities that neuropathic pain and spasticity may share some common pathophysiological mechanisms. Currently, systemically delivered local anesthetics are being used for the evaluation and treatment of neuropathic pain. We present a case describing the treatment of spasticity of spinal origin with continuous subcutaneous infusion of 0.75% bupivacaine in a patient who did not respond to traditional treatments and has become tolerant to intrathecal baclofen.

Adult↗
PubMed2001

Epidural fentanyl markedly improves thoracic epidural analgesia in a low-dose infusion of bupivacaine, adrenaline and fentanyl. A randomized, double-blind crossover study with and without fentanyl.

BACKGROUND: The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief, and side effects when removing fentanyl from an optimally titrated epidural infusion consisting of bupivacaine, fentanyl and adrenaline. METHODS: A prospective, randomized, double-blind, crossover study was carried out in 20 patients after major upper abdominal surgery requiring a large longitudinal incision. Patients with only mild pain when coughing during thoracic epidural infusion of about 10 ml per hour of bupivacaine 1 mg x ml(-1), fentanyl 2 microg x ml(-1), and adrenaline 2 microg x ml(-1) were included. On the 1st and 2nd postoperative days, each patient was given a double-blind epidural infusion, at the same rate, with or without fentanyl. The effects were observed for 6 h or until pain when coughing became unacceptable in spite of rescue analgesia. Rescue analgesia consisted of up to two patient-controlled epidural bolus injections (4 ml) per hour and intravenous morphine if necessary. RESULTS: Main outcome measures, i.e. pain intensity when coughing and at rest, increased (P<0.001) when fentanyl (19.2+/-5.2 microg x h(-1)) was omitted from the epidural infusion: after 6 h pain intensity when coughing had increased to unacceptable levels in spite of increased consumption of rescue bupivacaine and adrenaline (P<0.001). Within 15-20 min after restarting the triple epidural mixture with fentanyl, pain intensity was again reduced to mild pain when coughing. CONCLUSIONS: A low dose of epidural fentanyl (20 microg x h(-1)) markedly improved the pain-relieving effect of bupivacaine and adrenaline infused epidurally at a thoracic level after major upper abdominal surgery. This dose of fentanyl is much too small to relieve severe dynamic pain when given systemically. Therefore, this study indirectly supports the view that a low-dose thoracic epidural infusion of fentanyl has a spinal analgesic site of action.

Analgesics, Opioid↗
PubMed2005

[A case of spontaneous intracranial hypotension with multiple CSF leaks in the thoracic region].

A case of spontaneous intracranial hypotension (SIH) with multiple cerebrospinal fluid (CSF) leaks is reported. A 54-year-old man experienced a severe generalized headache associated with nausea and decreased hearing. The headache appeared when he was sitting or standing but was completely relieved by lying down. Cranial MRI with gadolinium infusion showed diffuse pachymeningeal enhancement. Spinal MRI demonstrated small amount of epidural fluid collection in the upper thoracic region. Radionuclide cisternography demonstrated CSF leaks at the Th2 and Th7 levels on the left side and at the Th3 through Th5 levels on the right side. Since bed-rest and intravenous transfusion for 10 days showed no beneficial effects, epidural blood patch (EBP) at the Th6/7 interspace was performed. After receiving EBP four times repeatedly, his symptoms entirely disappeared. SIH patients with multiple CSF leaks are rare in the literature. Although no consensus exists on the treatment strategy for such cases, our case suggests that at least 2 EBPs should be performed for each leak site before considering surgical treatment.

Blood Patch, Epidural↗
PubMed2006

The guidelines for the diagnosis and treatment of spasticity.

Spasticity is a predominant clinical sign appearing in different neurological diseases. It is always flanked by various degrees of muscle weakness. The clinical evaluation of a spastic patient is score according to varius internationally approved evaluation scales (Ashworth scale, muscle spasms scale, and FIM disability scale). The treatment of spasticity is mostly a symptomatic treatment aimed to relief muscle hypertonus thus increasing both motor performance and improving nursing. Many molecules are frequently being used orally with poor results or with the onset of undesired side effects. In fact oral baclofen, diazepam and tizanidine often have poor effect on spasticity and bring frequently to the appearance of undesired side effects caused by the concentration of these molecule at the brain level. Intrathecal baclofen is a good option to treat diffuse spasticity through the infusion of baclofen into the spinal CSF space. When baclofen is administered intrathecally at the spinal level it distributes with a concentration-gradient between caudal and rostral level of the spine that was calculated as 4:1 thus avoiding its concentration at the brain level when given at a therapeutical dosage. This fact avoids any undesired side effect due to the action of baclofen at the brain level. Botulinum toxin as well as peripheral neurotomies are very helpful in those cases in whom spasticity is mainly restricted to few muscular groups. A correct flow-chart to diagnose and treat the patient is mandatory to achieve the best results for each patient according to his spasticity and residual motor ability.

Baclofen↗
PubMed2004

Vasopressin during spinal anesthesia in a patient with primary pulmonary hypertension treated with intravenous epoprostenol.

Primary pulmonary hypertension (PPH) is a progressive disease with frequent morbidity and mortality, including the risk of cardiac decompensation and death, during general anesthesia. Administration of IV epoprostenol (Flolan) improves symptoms and survival of patients with PPH and thus is an increasingly used long-term treatment for this condition. This therapy is associated with impaired platelet aggregation, which may complicate the perioperative management of patients with PPH. We present a case report of a patient with severe PPH receiving a continuous epoprostenol infusion undergoing skin grafting for a leg ulcer under spinal anesthesia. An IV infusion of vasopressin was given to prevent systemic hypotension resulting from sympathetic blockade while avoiding increases in pulmonary vascular resistance that may have resulted from catecholamine usage.

Anesthesia, Spinal↗
PubMed1993

Opioid and substance P receptor adaptations in the rat spinal cord following sub-chronic intrathecal treatment with morphine and naloxone.

The effect of continuous intrathecal infusion with morphine (5 mu/h) or naloxone (2 micrograms/h) was investigated with regard to analgesia and the apparent density of mu- and delta-opioid and neurokinin-I/substance P receptors in the rat spinal cord. Morphine infusion increased tail-flick and paw-pressure responses until day 4 after the mini-osmotic pump implant. A decline in antinociception, reflecting tolerance to morphine, was then apparent in both tests. Quantitative in vitro receptor autoradiography of [125I]FK-33824, [125I][D.Ala2]deltorphin-I and [125I] Bolton-Hunter substance P binding sites, as ligands of mu, delta and neurokinin-I/substance P receptors, respectively, was performed on lumbosacral spinal cord sections of seven-days tolerant animals. Treatments with morphine and naloxone induced a similar increase (37%) in the number of delta binding sites in the superficial laminae of the dorsal horn. In contrast, the density of mu-opioid receptors was only affected by naloxone (50% increase). Neurokinin-I/substance P binding parameters were not altered by these treatments. Thus, it appears that delta-opioid binding sites may be of special relevance with regard to the development of tolerance to opiates in the spinal cord.

Analgesics↗
PubMed2000

Epidermal growth factor and fibroblast growth factor 2 cause proliferation of ependymal precursor cells in the adult rat spinal cord in vivo.

We investigated the mitogenic effect of continuous intrathecal infusion of epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF2) on ependymal precursor cells of the adult rat spinal cord in vivo. Either EGF, FGF2, EGF plus FGF2, or artificial cerebrospinal fluid (aCSF) was infused at a flow rate of 0.5 microl/h (15 ng/h of EGF or FGF2) for 3 or 14 days into the intrathecal space at T1 through a catheter attached to an osmotic minipump. To assess proliferation, the bromodeoxyuridine (BrdU) labeling index (LI) in the ependyma at T1 was calculated at 3 or 14 days. At 3 days there was no statistical difference in LI between these groups, but at 14 days the LI was significantly higher in the EGF plus FGF2 group (27.2% = 16.0%) than in the aCSF group (5.4% +/- 4.7%; p < 0.05). With EGF alone or FGF2 alone, the LI increases were not significantly different from the aCSF group. With EGF plus FGF2 for 14 days, some BrdU-positive cells in the ependyma also expressed nestin. These results suggest that the intrathecal infusion of EGF plus FGF2 has a mitogenic effect on precursor cells in the ependyma of the adult rat spinal cord.

Animals↗