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At least 577 records · Page 32Linked to original sources
PubMed1996

[Cancer pain: beneficial effect of ketamine addition to spinal administration of morphine-clonidine-lidocaine mixture].

OBJECTIVE: To assess the benefit of ketamine addition to a morphine-clonidine-lidocaine mixture administered continuously by the intrathecal route for the treatment of cancer pain. STUDY DESIGN: Case series analysis. PATIENTS AND METHOD: Four patients experiencing cancer pain with nociceptive and neuropathic components were treated with a continuous intrathecal administration of a mixture of ketamine (10 mg)-morphine (1-20 mg)-clonidine (30 micrograms)-lidocaine (20 mg) in 12 mL of normal saline, injected daily with an infusor (Baxter) pump. This treatment, associated with oral administration of sustained release morphine (SRM), was extended over 35 to 58 days, until the death of the patients. RESULTS: Either the secondary addition of ketamine to the morphine-clonidine-lidocaine mixture after the 40th and 15th days of treatment in patients no 1 and 2 respectively, because of a loss of efficiency of the mixture, or the immediate administration of the association of the four agents in patients no 3 and 4 provided efficient analgesia, unchanged over time, without significant adverse effects and allowed a decrease of the SRM doses. CONCLUSION: Ketamine by intrathecal route potentiates analgesia obtained with morphine-clonidine and lidocaine, while impeding the development of a tolerance vis-à-vis the former.

Aged↗
PubMed2005

A review of intrathecal morphine therapy related granulomas.

The development of catheter associated granulomatous masses in intrathecal morphine therapy is an uncommon, but potentially serious problem. While these systems have historically been used in patients with short life expectancies, more recently patients with pain from a benign source have benefited from this therapy, and new complications are being encountered secondary to the patients' longer life spans. Morphine is the most commonly used intrathecal opioid and evidence exists that the formation of granulomatous masses are related to the use of higher doses. When the patients' requirement of morphine increases significantly, the physician should be alert for signs of spinal cord compression, such as new neurological deficits, myelopathy, or radiculopathy. Patients that require these higher doses should be properly informed of the association with granulomas and their associated risks. Indolent infection may also be the etiology of granulomatous masses, and the presence of organisms, both aerobic and anaerobic, should be routinely investigated. Patients with catheter-associated granulomas appear to share several features. They exhibit the onset of symptoms several months following the initiation of intraspinal opioids and commonly present with an increase in pain that precedes signs and symptoms of neurological deterioration. While MRI might be the preferred method of detection of intrathecal granulomas, its cost and availability are prohibitive for routine screening. CT myelogram via pump side port injection of contrast can also be performed to detect catheter tip related granulomas/obstructions. Serial neurological examinations for new deficits may be performed and recorded during pump refill visits to recognize a granulomatous mass in its early stages. If an abnormality is identified, imaging studies are appropriate. Awareness of the condition and vigilance are the keys to successful management of this complication.

Analgesics, Opioid↗
PubMed1992

Influence of intrathecal morphine and naloxone intervention on postoperative ventilatory regulation in elderly patients.

Thirty elderly patients undergoing major hip surgery under spinal analgesia were randomly allocated in a double-blind manner into three groups. The aim was to evaluate the influence of intrathecal morphine and postoperative naloxone infusion on the regulation of ventilation. The Bupivacaine Group received spinal analgesia with 20 mg bupivacaine intrathecally. The Morphine Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally. The Naloxone Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally + postoperative naloxone infusion intravenously (1 microgram/kg/h over 12 h, 0.25 micrograms/kg/h over the next 12 h). Evaluation of resting ventilation and the ventilatory responses to hypercarbia and hypoxaemia was made on three occasions: before surgery, and 8, and 24 h after the intrathecal injection. Intrathecal morphine had no significant effect on ventilatory regulation in elderly patients undergoing major hip surgery performed under bupivacaine spinal analgesia. Postoperative administration of opioids or sedatives after intrathecal morphine as well as postoperative blood loss associated with a fall in blood pressure appeared to increase the risk of developing respiratory depression. Naloxone infusion seemed to reduce the risk of developing respiratory depression. Furthermore, one third of the elderly had a poor response to hypoxaemia before surgery.

Aged↗
PubMed2003

Spinal N-methyl-d-aspartate receptors may contribute to the immobilizing action of isoflurane.

UNLABELLED: We examined whether N-methyl-D-aspartate (NMDA) receptors influence the immobilizing effect of isoflurane by a spinal or supraspinal action. We antagonized NMDA receptors by intrathecal (IT), intracerebroventricular (ICV), and IV administration of MK 801 (a noncompetitive NMDA antagonist) and measured the decrease in isoflurane minimum alveolar anesthetic concentration (MAC). We also measured MK 801 tissue concentrations in homogenates of upper and lower spinal cord, a slice of cerebral cortex, and the whole brain. IT infusion of MK 801 decreased isoflurane MAC more potently than ICV or IV infusions. The change in MAC correlated with the MK 801 concentration in the lower part of the spinal cord (P < 0.01) but not with concentrations in supraspinal tissue. The maximal effect of IT MK 801 reached a plateau without achieving anesthesia. IV doses 270-fold larger than the largest IT dose also did not produce anesthesia in the absence of isoflurane. These results suggest that the capacity of MK 801 to decrease the MAC of isoflurane results from an effect on the spinal cord but that spinal NMDA receptors provide only partial mediation of the immobility produced by isoflurane. Because neither IT nor IV MK 801 provide complete anesthesia, these findings also call into question the notion that NMDA blockade alone suffices to produce anesthesia as defined by immobility in the face of noxious stimulation. IMPLICATIONS: Spinal cord NMDA receptors may mediate a portion of the immobilizing effect of isoflurane. Blockade of NMDA receptors in the cord by MK 801 has a MAC-sparing effect, but MK 801 does not, by itself, produce complete anesthesia.

Algorithms↗
PubMed1997

Clinical use of polysynaptic flexion reflexes in the management of spasticity with intrathecal baclofen.

The aim of this study was to evaluate the clinical usefulness of lower limb flexion reflexes (FR) in the assessment of spinal excitability responsible for spontaneous or induced spasms. FR were recorded on the short head of biceps femoris, after electrical stimulation of the ipsilateral sural nerve at the ankle, in 17 spastic patients selected for chronic intrathecal administration of baclofen. The results obtained before and after treatment were compared with clinical scores commonly used to assess spasticity (Ashworth and spasm scores). Before intrathecal baclofen 15/17 patients (88%) had pathologically enhanced flexor reflexes in the lower limbs, which were associated to clinical spasms. Reflex enhancement was accompanied in 47% of cases by abnormal decrease of reflex threshold. No significant correlation appeared between the magnitude or threshold of FR in control conditions and either the hypertonia (Ashworth scale) or the number of clinical spasms per unit of time. Intrathecal baclofen attenuated flexor reflex amplitude and increased reflex threshold in all patients. Our results suggest that FR investigate the intrinsic features of the spasms (threshold, intensity and duration) not assessed clinically, and that therefore the information gathered from FR recordings is not redundant with, and adds significantly to, that obtained by clinical scales. In our experience, FR recordings appeared to be a useful tool for quantifying the benefit of antispastic treatment and might be used as an ancillary indicator to determine the minimal effective dose of intrathecal baclofen.

Adult↗
PubMed2004

Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain: a pilot study.

Only about 60-70% of well selected patients with neuropathic pain syndromes of peripheral origin enjoy sufficient pain relief with spinal cord stimulation (SCS). Since recent animal experiments have demonstrated that the GABA-B receptor is pivotal in the effect of SCS on certain neuropathic symptoms, the use of baclofen as an adjunct to stimulation emerged as an option in patients not responding satisfactorily to SCS. Forty-eight patients with neuropathic pain of peripheral origin responding poorly to SCS were enrolled in a study with intrathecal baclofen; in a few cases adenosine was also tried. Twenty patients reported significant pain reduction at bolus trials and were offered implantation of a drug pump. Seven patients subsequently had pumps implanted together with SCS and four had pumps alone. Three patients had only peroral baclofen therapy as an adjunct to SCS. The 14 patients continuing with baclofen therapy as an adjunct to SCS, or alone, were followed for an average of 35 months after pump implant. The group with SCS+pump n=5; 2 explanted) reported an average decrease of pain ratings from VAS 82 to 33. The group with i.t. baclofen only had a pain decrease from VAS 63 to 33, while the three patients with peroral baclofen+SCS had less benefit from drug therapy. Adjunctive drug therapy for patients with unsatisfactory pain relief by SCS may offer a possibility to enhance pain alleviation.

Administration, Oral↗
PubMed1995

Intrathecal baclofen--a multicentre clinical comparison of the Medtronics Programmable, Cordis Secor and Constant Infusion Infusaid drug delivery systems.

A retrospective review was carried out of 34 consecutive traumatic spinal cord damaged patients who have had the Medtronics Programmable, Cordis Secor or Constant Infusion Infusaid intrathecal baclofen drug delivery systems inserted between July 1987 and 1992. The results indicate that whilst this treatment has many benefits there is a significant risk of complications, some potentially fatal. It should only be provided by a skilled and experienced team. The Medtronics Programmable pump is an excellent pump. It is of particular benefit where the therapeutic window is small or fine-tuning required. The Constant Infusion Infusaid is adequate if less precise control and continuous infusion is sufficient. It is of particular benefit in financially disadvantaged countries. The Cordis Secor device is helpful when unpredictable intermittent relief of spasticity is required but is otherwise limited by its complication rate.

Adolescent↗
PubMed1994

Technical problems and side effects associated with continuous intrathecal or epidural post-operative analgesia in patients undergoing hip arthroplasty.

Fifty-five patients undergoing hip arthroplasty under spinal anaesthesia (4 ml of 0.5% plain bupivacaine) were randomized to receive post-operative analgesia either using an intrathecal or an epidural catheter. Associated technical problems and side effects were studied. In both groups per-operative analgesia was achieved with intrathecal 0.5% plain bupivacaine, 4 ml. In the intrathecal infusion group a bolus dose of 100 micrograms morphine was injected through a spinal 28 gauge catheter followed by a 24 h infusion of 200 micrograms morphine (8.3 micrograms h-1). In the epidural infusion group a bolus dose of 2 mg of morphine was injected before the epidural 24 h infusion was started (morphine 200 micrograms h-1 + 0.25% bupivacaine 4 ml h-1). There were 10 catheter failures (two could not be inserted) in the intrathecal group and one in the epidural group. Three epidural catheter infusions failed due to other technical problems. The number of side effects was 21 in the remaining spinal group (n = 20) and 18 in the 20 epidural group patients with successful infusions. One patient in the spinal catheter group developed postdural puncture headache. For post-operative pain relief the patients in the epidural group needed less supplementary intramuscular oxycodone (five doses/four patients) than the spinal group (17 doses/nine patients) (P < 0.05).

Aged↗
PubMed1981

Spinal modulation of acoustic startle: opposite effects of clonidine and d-amphetamine.

Direct infusion of d-amphetamine (25--400 micrograms) or phenylephrine (12.5--50 micrograms) onto the spinal cord (intrathecal administration) increased acoustic startle amplitude. These effects were blocked by IP injection of the alpha 1-adrenergic antagonist WB-4101, but not the serotonin antagonist cyproheptadine. In contrast, intrathecal administration of clonidine (0.9--12.5 micrograms) markedly depressed startle. This effect was not blocked by IP administration of WB-4101 or cyproheptadine, but was blocked by IP or intrathecal administration of the alpha 2-adrenergic antagonist yohimbine (5 mg/kg), which by itself increased startle. Moreover, intrathecal yohimbine (100 micrograms) attenuated the depressant effect of IP clonidine, indicating that the spinal cord partially mediates the depressant effects on startle after systemic administration of clonidine. Thus clonidine does not behave like an alpha 1-agonist on acoustic startle, even when introduced directly onto the spinal cord. Conditions under which clonidine produces excitatory or depressant behavioral effects are discussed.

Acoustic Stimulation↗
PubMed1987

The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons.

In acute spinal rats (C2-C3) the transvesical infusion of saline activates a vesico-vesical excitatory reflex (Brain Res., 380 (1986) 83-93). In bladders containing a subthreshold amount of fluid the topical application of capsaicin on the outer surface of the bladder dome activated this spinal reflex and also produced a transient rise in blood pressure and heart rate. The effects of systemic capsaicin desensitization (50 mg/kg s.c. 5 min, 60 days before) on the sensory (activation of the spinal vesico-vesical reflex) and 'efferent' (tetrodotoxin-insensitive capsaicin-induced contraction) functions mediated by the capsaicin-sensitive sensory fibers were correlated to changes in substance P-like immunoreactivity (SP-LI) content of the urinary bladder in adult rats. Blockade of both sensory and efferent functions was observed at a time (60 min from capsaicin administration) when the SP-LI content of the urinary bladder was unaffected. Four days after capsaicin desensitization the SP-LI levels of the bladder are almost depleted indicating that the neuropeptide(s) are entirely stored in sensory structures. At this time the sensory-efferent functions mediated by these fibers are still blocked. At 15-60 days from systemic capsaicin desensitization there was a progressive, time-related recovery of SP-LI levels in the bladder as well as of the sensory-efferent functions. These findings indicate a role of the capsaicin-sensitive innervation of the urinary bladder in activating the spinal vesico-vesical reflex. The present findings suggest that measurement of SP-LI levels in the rat bladder may be a useful biochemical index for monitoring the function(s) of the capsaicin-sensitive, peptidergic sensory neurons.

Animals↗
PubMed1992

Alpha-adrenoceptors involved on the cardiovascular response induced by mianserin in the pithed rat.

1. The effects of the antidepressant drug mianserin on the cardiovascular responses induced by preganglionic electrical stimulation, and i.v. infusion of the adrenergic agonists noradrenaline (NA, alpha 1 and alpha 2), phenylephrine (alpha 1) and xylazine (alpha 2) in the pithed normotensive rat were studied. 2. Mianserin inhibited in a dose-dependent manner the pressor effect caused by electrical stimulation of spinal cord (Th7-Th9) and the infusion of NA, phenylephrine and xylazine. Cocaine increased the inhibitory effect of mianserin on the pressor effect caused by electrical stimulation and NA. 3. Mianserin blocked the xylazine-induced inhibition of cardiac nerve stimulation effect. 4. These results suggest that mianserin blocks the NA uptake, and it is more effective in blocking presynaptic alpha 2- than postsynaptic alpha-adrenoceptors.

Animals↗
PubMed1980

Intravenous albumin administration for prevention of spinal hypotension during cesarean section.

Five percent albumin in Ringer's lactate with 5% dextrose solution (D5RL) (15 ml/kg) was prophylactically infused preanesthetically over 15 to 20 minutes to prevent hypotension during spinal anesthesia in 46 patients undergoing elective cesarean section. Apgar scores and the incidence and severity of hypotension were compared to results obtained in 41 patients who were given D5RL solution without albumin (15 ml/kg). The incidence of hypotension was significantly less in patients given 5% albumin than in patients hydrated with D5RL alone. Mean arterial pressure decreased up to 18 torr from control values in patients hydrated with D5RL but mean arterial pressure did not change significantly in patients given 5% albumin. The Apgar scores, both at 1 minute and 5 minutes, were significantly higher (p < 0.01) in infants born of mothers given albumin than in infants whose mothers were given D5RL solution. Prophylactic administration of 5% albumin in D5RL solution is an effective method for prevention of spinal hypotension.

Adolescent↗
PubMed1998

Volume kinetics of Ringer's solution and dextran 3% during induction of spinal anaesthesia for caesarean section.

PURPOSE: To study how the body handles fluid given intravenously during the onset of spinal anaesthesia in women scheduled for Caesarean section. METHODS: The effect of spinal anaesthesia on the volume kinetics of a constant-rate infusion of 25 ml.kg-1 of Ringer's solution (n = 11) and 10 ml.kg-1 of dextran 3% 60 (n = 8) was studied before elective Caesarean section. Measurements of the blood haemoglobin concentration and urine excretion served as input variables in calculations of the size(s) of the body fluid spaces expanded by the infused fluid. The blood glucose level was also monitored. RESULTS: When a one-volume kinetic model were fitted to the data, spinal anaesthesia reduced the size of the expanded body fluid space by 30% (Ringer's) and 58% (dextran) (P < 0.02) When a two-volume model was statistically justified, anaesthesia reduced the rate of fluid equilibration between the two expanded body fluid spaces by 47% and 19%, respectively (P < 0.04) The baseline volume for the primary (central) fluid space was smaller than the expected plasma volume; 1.5 l for Ringer's solution and 0.9 l for dextran. Only small changes in the blood glucose concentration were found. CONCLUSION: The onset of spinal anaesthesia induces acute changes in the body's handling of infused fluid that can be described by volume kinetic analysis.

Adult↗
PubMed1988

Fetal blood flow during intrathecal anaesthesia for elective caesarean section.

Fetal aortic and umbilical blood flows were studied in 15 mothers before and during spinal (intrathecal) anaesthesia for elective Caesarean section, using a method combining real-time ultrasonography and a pulsed Doppler technique. Spinal anaesthesia with 0.5% bupivacaine hydrochloride 2.5 ml in 8% glucose monohydrate solution was administered after preloading with 2 litre of lactated Ringer's solution. Simultaneously with the subarachnoid injection, an infusion i.v. of ephedrine 50 mg in 500 ml normal saline was initiated. Maternal heart rate and systolic arterial pressure remained stable during the spinal anaesthesia, but diastolic arterial pressure decreased (P less than 0.05). Fetal heart rate increased (P less than 0.05) 30 min after the introduction of the spinal anaesthesia, but blood flows in the fetal descending aorta and umbilical vein were unaffected. The pulsatility index of the fetal blood velocity decreased (P less than 0.05) both in the fetal aorta and in the umbilical artery 30 min after induction of the spinal anaesthesia, indicating a possible decrease in the placental vascular resistance. We conclude that, when normotension is maintained in the mother with a preload infusion and an infusion of ephedrine, spinal anaesthesia for Caesarean section has no harmful effect on the fetal circulation.

Adult↗
PubMed1985

Absent aldosterone response to metoclopramide in patients with high spinal cord transection: evidence that metoclopramide stimulates aldosterone secretion through central pathways.

This study evaluates dopaminergic regulation of aldosterone secretion in 6 patients with high spinal cord transections. Administration of the dopamine antagonist metoclopramide resulted in a marked rise in plasma aldosterone and 18-hydroxycorticosterone levels in 12 normal individuals, but no change in plasma levels of these zona glomerulosa corticosteroid products in spinal cord patients. Spinal cord transected patients also did not have the rise in plasma renin activity that was observed in normals following metoclopramide administration. Basal levels of aldosterone, 18 hydroxycorticosterone, corticosterone and renin activity as well as the aldosterone responses to graded dose infusion of adrenocorticotropin were similar in the spinal cord patients and the normals. These data suggest that dopaminergic regulation of adrenal zona glomerulosa corticosteroid and renal renin secretion is absent in patients with high spinal cord transections, suggesting that intact neural pathways from the central nervous system are necessary for metoclopramide stimulation of aldosterone and renin secretion in men. Since basal plasma aldosterone levels were normal in spinal cord transected patients, it appears that the absence of dopaminergic control does not result in elevated secretion.

18-Hydroxycorticosterone↗
PubMed2003

Multiple phases of relief from experimental mechanical allodynia by systemic lidocaine: responses to early and late infusions.

Systemic lidocaine can relieve various forms of neuropathic pain that develop after nerve injury. Mechanical allodynia, defined by a significant drop in paw withdrawal threshold force following spinal nerve ligation (L5-L6) in rats, can be reversed by one 30min lidocaine infusion at a constant plasma concentration as low as 1-2 microg/ml, an effect that is still present when the rats are tested days and weeks afterwards. In this study, we resolved the detailed time course of reversal of ipsilateral and contralateral allodynia in rats with spinal nerve ligation by a single systemic infusion of lidocaine, to 4 microg/ml, given either 2 days after ligation (POD2) or 7 days after ligation (POD7). Male Sprague-Dawley rats were examined for 21 days after undergoing sham operation or spinal nerve ligation to produce allodynia, which was quantified by a lower force of von Frey hairs at the plantar hind paw just required to produce paw withdrawal (paw withdrawal threshold, PWT). Six experimental protocols were followed: rats were infused with lidocaine on POD2 (L2) or on POD7 (L7), or with saline on POD2 (S2) or on POD7 (S7), and sham operated rats were infused with lidocaine on POD2 or on POD7. PWTs were measured during the last 5min of a single 30min lidocaine infusion; at 30, 60, 90, 120, 240 and 360min, and 24, 48 and 72h after beginning infusion, and then every 1-3 days up to 21 days. Three distinct sequential phases of ipsilateral relief were apparent in both L2 and L7 groups: (1) an acute elevation of PWT during the infusion, returning to the pre-infusion allodynic level within 30-60min after infusion; (2) a second, transient elevation of PWT within the next 360min; (3) a sustained elevation of PWT developing slowly over 24h after infusion and maintained over the next 21 days. A significant, although weaker contralateral allodynia developed more slowly (>POD8) than the ipsilateral condition, and could be delayed for more than 2 weeks by lidocaine infusion on POD2 but for only 1 week by the same treatment on POD7. None of the sham operated animals had any allodynic signs and no saline infusions elevated PWT in ligated, allodynic rats. These results of separate phases imply that there are mechanistic differences between the acute relief and the sustained relief of allodynia after a single infusion of lidocaine, and may present an experimental paradigm for investigating the advantages of earlier rather than late therapeutic intervention.

Anesthetics, Local↗
PubMed1996

Randomized comparison of moderate-dose methotrexate infusions to oral methotrexate in children with intermediate risk acute lymphoblastic leukemia: a Childrens Cancer Group study.

Methotrexate (MTX) infusions of 500--1,000 mg/m2 over 24 hours may improve survival and prevent relapse in children with acute lymphoblastic leukemia (ALL). Childrens Cancer Group (CCG) Study 139 compared weekly oral methotrexate 20 mg/m2/week (oral MTX) to MTX 500 mg/m2 infused over 24 hours (IV MTX) three times during consolidation and every 6 weeks during maintenance in 164 children with intermediate-risk ALL, i.e., those patients over age 1 year with white blood cell count 10,000 to 49,999/ml and no bulky extramedullary disease. Median follow-up for CCG-139 exceeded 75 months. Thirty-four events occurred among 80 patients receiving IV and oral MTX and 36 events among 84 patients receiving oral MTX. Two children died during induction and one did not enter remission. Remission induction rate is 98%. There have been 26 marrow relapses, 11 combined marrow and extramedullary relapses, 24 CNS relapses, and five testicular or other relapses. The frequency and distribution of relapses does not differ between the two regimens. For the entire group, overall event-free survival (EFS) at 6 years is 57.9% (standard deviation=4.0%) and actuarial survival is 80.0% (standard deviation =3.3%). Of the 29 patients with isolated extramedullary relapse, 18 survive free of a second event, a median of 42 months from relapse. In contrast to other trials, this trial does not show that IV MTX in this dose and schedule offers an advantage over standard therapy for this group of children.

Administration, Oral↗