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PubMedDate not supplied

Treatment of low back pain with intraspinal opioids delivered via implanted pumps.

Low back pain, more recently defined as "failed back surgery syndrome" is a common, yet devastating, pain complaint. Although physical therapy and systemic analgesics provide relief in most patients, intraspinal opioids delivered via implanted pumps may be indicated in those individuals who cannot tolerate oral medications. Orthopaedic nurses are essential in the identification and care of patients who might benefit from this therapy.

Aged↗
PubMed1997

Induction of tolerance to intrathecal butorphanol in rats.

BACKGROUND: Butorphanol, an opioid agonist/antagonist, has been administered spinally and epidurally in humans for moderate to severe pain. However, unlike intrathecal (i.t.) morphine, virtually no information is available regarding butorphanol's ability to induce analgesic tolerance at the spinal cord level upon chronic i.t. administration. METHODS: Continuous infusion of i.t. butorphanol was given via an osmotic minipump. Rats were randomly assigned to four groups (n = 7 each) to receive i.t. infusion (1 microliter/h) consisting of saline, or butorphanol (13, 26, or 52 nmol/h) for 96 h. Tail-flick (TF) latencies were measured during the period of i.t. infusion. RESULTS: A dose-dependent antinociceptive effect, as measured by TF latency, was demonstrated in the groups receiving i.t. butorphanol as compared to the saline group. The overall antinociceptive effects calculated from the areas under the curve (AUC's) were 372 +/- 3.0, 394 +/- 7.5, and 433 +/- 20 for the 13, 26, and 52 nmol/h butorphanol-infused groups, respectively; the AUC's of the 26 and 52 nmol/h groups were significantly different from the AUC of 356 +/- 3.4 for the saline-infused group (p < 0.01, one way ANOVA; p < 0.05, post hoc Dunnett's test). The TF latencies of the 26 and 52 nmol/h groups were 3.77 +/- 0.05 and 3.73 +/- 0.03 s at the baseline (before the i.t. infusion), respectively; and gradually increased significantly (p < 0.01, two way repeated measure ANOVA; p < 0.05, post hoc Student-Newman-Keuls or SNK test) to the peak values of 4.31 +/- 0.14 and 4.90 +/- 0.28 s, respectively; then decreased significantly from the peaks (p < 0.05, post hoc SNK test) to the final values of 3.87 +/- 0.06 and 4.10 +/- 0.13 s at the end of the 96-h infusion, respectively. The TF values of the saline and the 13 nmol/h groups did not show statistically significant differences throughout the 96-h infusion period. CONCLUSIONS: Therefore, continuous infusion of i.t. butorphanol at the rate of 26 and 52 nmol/h induced tolerance to tail-flick analgesia within 96 h.

Analgesics, Opioid↗
PubMed1998

Incidence and time course of cardiovascular side effects during spinal anesthesia after prophylactic administration of intravenous fluids or vasoconstrictors.

UNLABELLED: We studied the time course of arterial hypotension and/or bradycardia requiring treatment during spinal anesthesia and compared the efficacy of i.v. fluid or vasoconstrictor administration for the prevention of these side effects. Patients (n = 1066) were randomly allocated to either a volume group (lactated Ringer's solution 15 mL/kg within 15 min before spinal anesthesia), a dihydroergotamine group (10 microg/kg i.m. 15 min before anesthesia), or a placebo group. All patients breathed O2-enriched air during spinal anesthesia (4 mL of plain 0.5% bupivacaine). With the placebo, there were side effects (mean incidence 22.9%) for up to 45 min after the start of anesthesia. Dihydroergotamine reduced the incidence of side effects, preferentially the late ones, more (mean incidence 11.8%) than fluid administration (mean incidence 16.9%), which was effective only during the first 15 min of anesthesia. Both heart rate and arterial pressure decreased within 15 min before the manifestation of symptoms. In a subgroup of patients, the incidence of side effects (8%) was greatly reduced by the intraoperative application of both sedatives and opioids. We conclude that cardiovascular side effects may occur at any time during spinal anesthesia. Fluid administration reduced the incidence of early events, but dihydroergotamine the late events. IMPLICATIONS: Cardiovascular side effects requiring treatment occurred at any time during spinal anesthesia in our placebo-controlled study, regardless of the prophylactic regimen (fluid infusions versus dihydroergotamine).

Adult↗
PubMed1998

[Continuous intrathecal infusion of baclofen. A new therapeutic method for spasticity].

Intrathecal administration of baclofen is now generally accepted as a powerful treatment of spasticity caused by spinal lesions. 35 patients with severe spasticity, 29 of spinal origin and six of supraspinal origin resistant to conservative treatment, had a programmable pump (Synchromed, Medtronic) for continuous intrathecal baclofen infusion implanted. The patients were followed-up for an average of 29 months (0-68). The initial effect of the treatment was positive for all patients; spasms were less frequent, there was remission of pain caused by cramps, and in some cases improved ambulation. In five patients, however, the pump was later removed: in two patients the pump ceased to be effective, two patients became infected, and one experienced multiple catheter problems. Problems with the catheter was the most common complication experienced, and this was seen in nine patients. Three patients died of the underlying disease. The majority of patients became accommodated to intrathecal baclofen and it was necessary to administer increasingly larger doses to maintain the clinical effect. Long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients, but close follow-up is necessary for assessing efficacy and refilling the pump.

Adolescent↗
PubMed1991

Role of calcitonin gene-related peptide in gastric hyperemic response to intragastric capsaicin.

Stimulation of sensory neurons in the rat stomach by intragastric capsaicin leads to a marked rise in gastric mucosal blood flow (GMBF). The gastric mucosa, in particular submucosal blood vessels, is densely innervated by afferent neurons containing peptides, of which calcitonin gene-related peptide (CGRP) is the most potent vasodilator. Using selective ablation of either the vagal or spinal sensory innervation to the stomach by perineural application of capsaicin, and by intra-arterial infusion of the CGRP receptor antagonist hCGRP-(8-37) close to the stomach, we investigated 1) the origin (vagal or spinal) of the sensory neurons and 2) whether CGRP mediates this hyperemic response. Perivagal application of capsaicin to the rat 10-20 days before experiments had no effect on the hyperemic response to intragastric capsaicin. In contrast, periceliac application of capsaicin significantly reduced this response by 60%. Intra-arterial infusion of CGRP (20 pmol/min) close to the stomach produced a marked rise in GMBF and this was completely blocked by hCGRP-(8-37) (500 pmol/min). intra-arterial infusion of hCGRP-(8-37) or its vehicle, bovine serum albumin, had no significant effect on basal GMBF. However, the increment in GMBF in response to intragastric capsaicin was significantly attenuated by 79%. We conclude that 1) spinal sensory neurons innervating the gastric mucosa partially mediate the increase in GMBF induced by intragastric capsaicin and 2) CGRP is the major vasodilator released by these fibers.

Animals↗
PubMed1983

Regional blood flow during cross-clamping of the thoracic aorta and infusion of sodium nitroprusside.

Labeled microspheres, 15 microns in diameter, were used to determine cardiac output and regional blood flow response to cross-clamping of the midthoracic aorta and subsequent sodium nitroprusside (SNP) infusion in 11 dogs. During aortic cross-clamping, mean arterial pressure above the occlusion (MAPa) increased 30% to 35%, mean arterial pressure below the occlusion (MAPb) decreased 87%, cardiac index decreased 12% to 14%, left atrial pressure (LAP) doubled, and renal and spinal cord (lower part) blood flows decreased substantially (85% to 94%). SNP infusion returned MAPa to baseline values, decreased MAPb by half, and substantially and further decreased renal blood flow (to 3% to 5% of baseline values). Myocardial and cerebral blood flows increased substantially (up to 250% to 400%). An increase in preload (fluid load) was accompanied by an increase in LAP, cardiac index, and myocardial blood flow only but not in renal or spinal cord flow. There was a strong association between cortical renal blood flow and MAPb (r2 = 0.92; p less than 0.0001), which suggests that blood flow through organs and tissues below the occlusion is pressure dependent. The data show that SNP infusion during thoracic aortic cross-clamping improves systemic and regional circulation above the occlusion but decreases MAPb and therefore blood flow below the occlusion. SNP infusion should be used with caution during aortic cross-clamping, since arterial hypotension of any degree may be deleterious to organs below the cross-clamp.

Animals↗
PubMed1984

A sheep preparation for studying interactions between blood flow and drug disposition. III: Effects of general and spinal anaesthesia on regional blood flow and oxygen tensions.

In awake unrestrained sheep the infusions i.v. of five drugs (cefoxitin, pethidine, chlormethiazole, tocainide and lignocaine) with potentially flow-limited clearance were shown to have no significant haemodynamic effects of their own, nor to have any effects on arterial or venous oxygen tensions. Under general anaesthesia (1.5% end-tidal halothane), haemodynamic changes similar to those previously documented in man occurred. Cardiac output and hepatic blood flow were decreased to 70%, and renal blood flow to 50% of control values; heart rate was unchanged and mean arterial pressure decreased by an average of 10%. Hepatic and renal vein oxygen tensions were decreased significantly. Under spinal anaesthesia, apart from a 10% decrease in hepatic blood flow, there were no significant changes in any haemodynamic variables or in the arterial or in any of the venous oxygen tensions. The i.v. infusion of adequate volumes of saline at the time of blockade probably contributed to the maintenance of these indices at their baseline values.

Anesthesia, General↗
PubMed2003

Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol.

OBJECTIVE: To evaluate the clinical benefit of increasing the osmotic load of the hypertonic solution administered for the treatment of refractory intracranial hypertension episodes in patients with severe head injury. DESIGN: Prospective, randomized study. SETTINGS: A trauma center in a university hospital. PATIENTS: Twenty consecutive patients with head trauma and persistent coma who required infusions of an osmotic agent to treat episodes of intracranial hypertension resistant to well-conducted standard modes of therapy were studied. Intracranial hypertension was considered refractory when it persisted despite deep sedation, optimal hemodynamic status, and, in some patients, drainage of cerebral spinal fluid. INTERVENTIONS: Patients were randomly assigned to receive isovolume infusions of either 7.5% hypertonic saline solution (2400 mOsm/kg/H(2)O) or 20% mannitol (1160 mOsm/kg/H(2)O). The patients were given 2 mL/kg (body weight) of either solution, i.e., 361 +/- 13 mOsm of saline or 175 +/- 12 mOsm of mannitol per injection. MEASUREMENTS AND MAIN RESULTS: The main variables studied were the number and the duration of episodes of intracranial hypertension per day during the study period, which was stopped after the last episode of intracranial hypertension was recorded from intracranial pressure monitoring or after the allocated treatment failure. Patients in the HHS group were monitored for 7 +/- 5 days and those in the mannitol group for 7 +/- 6 days (not significant). The rate of failure for each treatment was also evaluated. Failure was defined as the persistence of intracranial hypertension despite two successive infusions of the same osmotic agent. The mean number of osmotic solute infusions was 3.7 +/- 5.3 in the mannitol group and 3.3 +/- 4.1 in the hypertonic saline solution group (not significant). The mean number (6.9 +/- 5.6 vs. 13.3 +/- 14.6 episodes) of intracranial hypertension episodes per day and the daily duration (67 +/- 85 vs. 131 +/- 123 min) of intracranial hypertension episodes were significantly lower in the hypertonic saline solution group (p <.01). The rate of clinical failure was also significantly lower in the hypertonic saline solution group: 1 of 10 patients vs. 7 of 10 patients (p <.01). CONCLUSION: In this study, when a hypertonic solute was required for the treatment of refractory intracranial hypertension episodes in patients with severe head trauma, increasing the osmotic load by giving 2 mL/kg (body weight) of 7.5% saline (361 +/- 13 mOsm) was more effective than giving 2 mL/kg (body weight) of 20% mannitol (175 +/- 12 mOsm). Within the limitations of the present study, these data suggest that giving 2 mL/kg hypertonic saline solution (approximately 480 mOsm/70 kg body weight) is an effective and safe initial treatment for intracranial hypertension episodes in head-trauma patients when osmotherapy is indicated.

Adult↗
PubMed1997

Identification of the midbrain locomotor nuclei and their descending pathways in the teleost carp, Cyprinus carpio.

In order to identify the mesencephalic spinal pathways for initiation of swimming in the carp, we employed electrical and chemical microstimulation of the mesencephalic tegmentum. Electrical stimulation of the midbrain in decerebrate carp produced bilateral or unilateral rhythmic movements of the tail. Bilateral alternating movements were induced by stimulation with the lowest threshold currents to the brain region just beneath the third ventricle at the level of the mid mesencephalon. The region included the nucleus of medial longitudinal fasciculus (Nflm), the medial longitudinal fasciculus (flm), the red nucleus (Nrb). To specify the nuclei of the origin of the descending pathway, we microinjected 0.1 M L-glutamic acid to the region. Both bilateral and unilateral tail movements were induced, the majority being the latter. The unilateral movements were accompanied with tail flips toward the ipsilateral side of stimulation sites. The smallest injection volume required for initiation of the movement was recorded at the Nflm. Bilateral tail movements were produced only by injections into the medial region between the nucleus of the both sides. The present results imply a crucial role of Nflm neurons in the initiation of swimming Nflm neurons on one side project through flm to the ipsilateral spinal cord along its entire length and regulate activities of the individual central pattern generators.

Animals↗
PubMed2002

Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery.

BACKGROUND: In our routine practice, we observed a reduced incidence of fetal acidosis (umbilical artery pH < 7.20) at cesarean delivery during spinal anesthesia when a combination of phenylephrine and ephedrine was used as first line vasopressor therapy, compared with using ephedrine alone. METHODS: The study was randomized and double blind. It compared phenylephrine 100 microg/ml (phenylephrine group), ephedrine 3 mg/ml (ephedrine group), and phenylephrine 50 microg/ml combined with ephedrine 1.5 mg/ml (combination group), given by infusion, to maintain maternal systolic arterial pressure at baseline during spinal anesthesia for elective cesarean delivery. RESULTS: Fetal acidosis was less frequent in the phenylephrine group (1 of 48) (P = 0.004) and less frequent in the combination group (1 of 47) (P = 0.005) than in the ephedrine group (10 of 48). The mean systolic arterial pressure was similar for the three groups: Phenylephrine group median 98% (IQR 94-103) of baseline, ephedrine group 100% (96-106) and combination group 101% (97-108) (P = 0.11). The mean heart rate was higher in the ephedrine group (median 107% [IQR 99-118] of baseline) than in the phenylephrine group (88% [82-98]) (P < 0.0001), or the combination group (96% [86-102]) (P < 0.0001). Nausea and vomiting were less frequent in the phenylephrine group (nausea 17%, vomiting 0%) than in the ephedrine group (nausea 66%, vomiting 36%) (P < 0.0001), or the combination group (nausea 55%, vomiting 18%) (P < 0.0001). CONCLUSIONS: Giving phenylephrine alone by infusion at cesarean delivery was associated with a lower incidence of fetal acidosis and maternal nausea and vomiting than giving ephedrine alone. There was no advantage to combining phenylephrine and ephedrine because it increased nausea and vomiting, and it did not further improve fetal blood gas values, compared with giving phenylephrine alone.

Acidosis↗
PubMed2003

Spinal blood flow in 24-hour megadose glucocorticoid treatment in awake pigs.

OBJECT: Because of the controversy regarding the benefits of 24-hour administration of methylprednisolone in patients with spinal cord injury (SCI), it is important to investigate its mechanism of action and side effects. This study was conducted to determine if high-dose methylprednisolone modulates neural and vertebral blood flow in an awake large-sized animal model without SCI. METHODS: From a group of 18 immature female domestic pigs born to nine different litters, nine animals were randomly allocated to receive methylprednisolone treatment, whereas their nine female siblings served as controls. Drug or placebo was applied in a blinded fashion by a third person not involved in the study. The following treatment for SCI, as suggested by the North American Spinal Cord Injury Study, was administered to the awake pig: methylprednisolone (30 mg/kg of body weight) was infused into the jugular vein during a 15-minute period, followed by a 45-minute pause, and the infusion was maintained over a 23-hour period at a dose of 5.4 mg/kg body weight/hour. By means of the radioactive tracer microsphere technique, spinal cord blood flow (SCBF) was measured in the awake standing pig in the cerebrum, and in spinal gray and white matter, nerve roots, endplates, cancellous bone, cortical shell, and T12-L2 discs. Blood flow was measured before, 1 hour after initiation of infusion, and 24 hours postinfusion. Examination of blood flow in the neural and vertebral tissue samples, as well as of central hemodynamics, revealed no significant difference between the experimental and control groups, and this parity was maintained throughout the experimental phases. CONCLUSIONS: In the awake pig model, 24-hour methylprednisolone treatment does not modulate cerebral or SCBF, nor does it increase the risk for vertebral osteonecrosis by producing vertebral ischemia.

Animals↗
PubMed1989

Intraventricular or epidural injection of morphine for severe pain.

Intraventricular or epidural injection of morphine through implantable infusion devices was used for severe pain in 50 patients with advanced cancer, arachnoiditis, or spinal injury. Intraventricular catheter was inserted for injection of morphine in 21 patients, 29 were treated through epidural infusion. For the evaluation of results the multimodal evoked potential (MEP) has been obtained before and after each treatment. 80% of the patients experienced good results. No significant side effects have been noted in patients with either epidural or intraventricular injection of morphine. These may be excellent methods for pain control in well selected patients.

Adult↗
PubMed2000

Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord.

N-Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance was induced by intrathecal (i.t.) morphine infusion (10 micrograms h-1) for 5 days. Co-administered (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (10 micrograms h-1 i.t.) with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-tolerant rats (mean (SEM) KD = 0.41 (0.09) nM) than in control rats (1.50 (0.13) nM). There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS (nNOS) protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord.

Analgesics, Opioid↗
PubMed1991

Subdural compartment in pig: a morphologic study with blood and horseradish peroxidase infused subdurally.

The dura-arachnoid junction is examined in normal animals and in animals subjected to subdural infusion of blood immediately prior to death, simulating acute subdural hemorrhages. The Norwegian landrace pig is used as the experimental animal. Horseradish peroxidase (HRP) has been added to the injected blood to serve as a macromolecular tracer. The material is studied by light and electron microscopy. Special attention is given to the level of the induced subdural cleavage plane, the total distribution of the infused blood, and the natural sites of drainage. The dura-arachnoid junction, identified here as the subdural compartment (the dural border layer of others), consists of an avascular tissue with flake-like, relatively electron-lucent cells stacked upon each other in several layers with narrow intercellular clefts. Under normal conditions there is no evidence of a so-called "subdural space." When under the present experimental conditions bleeding takes place into this cellular tissue, it splits without any particular, predestined cleavage plane, although most often close to the fibrous matter of the dura. The bleeding extends throughout the cerebral and spinal parts of the compartment and also along the spinal nerve roots. Contamination of the subarachnoid space occurs only in some cases subjected to large infusions and apparently only at spinal levels. The HRP diffuses into the dura, but does not traverse the arachnoid barrier layer.

Animals↗
PubMed1992

Effects of intrathecal baclofen on lumbosacral and cortical somatosensory evoked potentials.

We analyzed lumbosacral and cortical somatosensory evoked potentials in three spinal cord injury patients undergoing evaluation of intrathecal baclofen infusion for management of spasticity. The cauda equina propagating root wave (R wave) and conus medullaris postsynaptic responses (S and P waves) were analyzed before and during baclofen infusion. Baclofen abolished the concomitantly recorded H-reflex and markedly suppressed the P wave amplitude and area. The S wave amplitude and area were suppressed to a lesser degree. In contrast, there were no significant changes in cortical somatosensory evoked potentials.

Adult↗
PubMed1994

Spinal anaesthesia for caesarean section following epidural analgesia in labour: a relative contraindication.

Three cases are described in which epidural analgesia was performed during labour using an infusion of bupivacaine 0.125-0.25%. When, in all 3 cases, caesarean section was required for failure to progress, hyperbaric bupivacaine was given in doses of 10 mg, 12.5 mg and 15 mg respectively. Within 2-4 min all 3 patients had a high block, complained of difficulty in breathing and subsequently developed apnoea. The trachea was intubated after administration of thiopentone and succinylcholine and the operation continued. Cardiovascular support was provided by the administration of ephedrine injected intermittently intravenously. The spinal block receded and the patients were able to return to the ward without any further complications. All three mothers remain in good health and do not regret having had spinal anaesthesia for caesarean section. In contrast to previously reported cases of high spinal anaesthesia following unsuccessful epidural anaesthesia for caesarean section, this report describes 3 cases of high spinal following the administration of spinal anaesthesia upon an ongoing epidural infusion of local anaesthetic during labour. As no guidelines are available as to the recommended dose of spinal anaesthetic under such circumstances and, in view of the several case reports describing a similar complication under different circumstances, we suggest that spinal anaesthesia is contraindicated upon ongoing epidural analgesia or following a failed epidural.

Journal Article↗
PubMed1988

Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip.

The purpose of this study was to determine the distribution of cells in the medial reticular formation (MRF) and the pontomedullary locomotor strip (PLS), which can induce locomotion when activated. Controlled microinjections of neuroactive substances (Goodchild et al., 1982) into the MRF or PLS were made in order to activate cell bodies in those areas. The ability of trigeminal receptive field stimulation to induce locomotion before and after drug infusion into the PLS was also assessed since the PLS and the spinal nucleus of the trigeminal nerve are similar in their anatomical distribution. Experiments were performed on precollicular-postmamillary decerebrate cats walking on a treadmill. Injections of glutamic acid (GA; 500 nmol) into the MRF produced locomotion that was antagonized by infusion of glutamic acid diethyl ester into the same spot. Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol). Injections of GA (100 nmol), DL-HCA (700 nmol), PIC (10-50 nmol), and substance P (2 nmol) into the PLS also produced locomotion. Locomotion produced by injections of PIC into the PLS was blocked by infusion of equal amounts of muscimol or GABA. Effective PLS injection sites were all confined to the trigeminal spinal nucleus or immediately ventral and medial to this in the adjacent lateral reticular formation. Trigeminal nerve peripheral field stimulation evoked locomotion after microinjection of PIC into the PLS, although this same facial stimulus was not effective prior to drug injection. We conclude that the MRF and PLS regions of the cat brain stem contain cells that produce locomotion when chemically stimulated, and we suggest that the PLS is closely related to or synonymous with the spinal nucleus of the trigeminal nerve. Furthermore, we suggest that stimulation of trigeminal afferents is analogous to stimulation of segmental afferent pathways in the production of locomotion (Sherrington, 1910; Jankowska et al., 1967; Afelt, 1970; Budakova, 1972; Grillner and Zangger, 1979).

Animals↗