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PubMed1996

Intrathecal infusion of the nitric oxide synthase inhibitor N-methyl L-arginine after experimental spinal cord injury in guinea pigs.

The potential role of nitric oxide (NO) production in secondary pathologic processes that follow spinal cord injury was examined in a guinea pig model that shows secondary loss of function for at least 3 days after trauma. Lateral compression injury of the lower thoracic cord was performed under ketamine/xylazine/acepromazine anesthesia. A fine polyethylene cannula was inserted through an incision in the dura rostral to the injury and run along the dorsal subdural space to the lesion level. The tube was connected to an osmotic pump delivering 1 microL/h of a 10 mM solution of either N-methyl-L-arginine or N-methyl-D-arginine in normal saline (pH 7.2). N-Methyl-L-arginine blocks both constitutive and inducible forms of NO synthase (NOS), present in neurons and inflammatory cells, respectively: N-methyl-D-arginine is the inactive stereoisomer. Two groups of 10 animals were used. Behavioral analysis and somatosensory evoked potential measurements were performed daily for 3 days, then the animals were fixed and survival of white matter at the center of the injury was evaluated, using toluidine-blue stained, 1 microns plastic sections. No significant difference was found between treated and control groups in degree or rate of secondary loss of spinal cord function or in the cross-sectional area of surviving white matter. These data do not support the hypothesis that local NO production by phagocytes, neurons, or other cells plays a significant role in secondary pathology of injury in this model.

Animals↗
PubMed2004

The protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury.

Pre- and post-injury Cyclosporin A (CsA) administration has shown neuroprotective properties by ameliorating mitochondrial damage. The aim of this study was to assess the effect of CsA upon N-acetylaspartate (NAA) reduction and ATP loss, two sensitive markers of mitochondrial dysfunction and bioenergetic impairment. Adult male Sprague-Dawley rats were exposed to impact acceleration traumatic brain injury (2 m/450 g) and randomized into the following experimental groups: intrathecal CsA/vehicle treated (n = 12), intravenous CsA/vehicle treated (n = 18) and sham (n = 12). Intrathecal treatment consisted of post-injury (30 min) cisternal bolus of CsA or Vehicle (0.15 mL, 10 mg/kg). Intravenous administration consisted of 30 min post-injury continuous 1 hour infusion of either 20 or 35 mg/kg CsA or Vehicle. Quantitative HPLC analysis of whole brain samples was performed 6 h post-injury for levels of NAA and ATP. Following intrathecal delivery CsA demonstrated significant neuroprotection blunting a 30% NAA reduction (p < 0.001) and restoring 26% of the ATP loss (p < 0.005). The 20 mg/kg intravenous dose failed to ameliorate the biochemical damages while the 35 mg/kg dosage showed 36% NAA recovery and 39% ATP restoration (p < 0.001). In conclusion, CsA is capable of restoring ATP and blunting NAA reduction. Intravenous infusion of 35 mg/kg appears to be the optimal therapeutic strategy in this model. These findings contribute to the notion that CsA achieves neuroprotection, preserving mitochondrial function, and provides a rationale for the assessment of CsA in the clinical setting where MR spectroscopy can monitor NAA and ATP in brain-injured patients.

Animals↗
PubMed1992

Continuous subarachnoid infusion of 0.125% bupivacaine for analgesia during labour.

We have studied 20 primiparous women requesting pain relief for labour, to determine the feasibility of subarachnoid infusions of bupivacaine for analgesia. A 28-gauge catheter was inserted into the subarachnoid space through a modified 22-gauge Sprotte needle. After a bolus dose of up to 1.5 ml of 0.25% bupivacaine, a continuous infusion of 0.125% bupivacaine was commenced. If analgesia became inadequate, additional 0.5-ml boluses of 0.25% bupivacaine were given (mean number of top-ups 2.8; range 0-6). Persistent perineal pain occurred in four women and this was relieved by 0.5% hyperbaric bupivacaine. Analgesia was good or excellent in 15 of 20 mothers within 10 min and in 19 of 20 within 30 min, and it remained good or excellent throughout labour and delivery. Motor block was complete in three of the women who needed hyperbaric 0.5% bupivacaine. There were no difficulties with insertion of the catheter, no episodes of significant hypotension (systolic arterial pressure less than 100 mm Hg) or postdural puncture headache. Seven mothers delivered their babies vaginally, eight required assistance with forceps and five needed a Caesarean section.

Adolescent↗
PubMed1995

Determination of the in vivo post-antibiotic effects of ciprofloxacin and rifampicin.

A modified rabbit meningitis model is described for determining the PAE in vivo, which utilised a self-standing device for repeatedly sampling pure CSF. The model allowed the PAEs of ciprofloxacin and rifampicin on Escherichia coli ATCC 25922 to be determined following PAE induction in vitro, or in vivo in CSF after intrathecal injection or during the last 1.5 h of a 7 h iv continuous infusion. The estimated volumes of distribution of ciprofloxacin and rifampicin in CSF were 0.68 +/- 0.24 mL and 0.74 +/- 0.04 mL, respectively, and the terminal elimination half lives were 1.8 +/- 0.5 h and 2.2 +/- 0.3 h, respectively. PAEs of approximately 2 h were obtained in vivo and in vitro after exposing E. coli to 3 x MIC of ciprofloxacin in vitro and to 1 x MIC of drug in vivo. When the organism was exposed to rapidly declining concentrations in vivo, only a minimal PAE was observed for both antibiotics. Moreover, a PAE of 3.1 +/- 1.3 h of rifampicin was obtained in vivo, being smaller than the 4.8 h PAE observed in vitro, which might be explained by the binding of 45 +/- 6.5% rifampicin to proteins in the CSF.

Animals↗
PubMed1999

Determination of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma after intravenous and intrathecal morphine administration using HPLC with electrospray ionization and tandem mass spectrometry.

High-performance liquid chromatography (HPLC) coupled to atmospheric pressure ionization (API) mass spectrometry (MS) has become a useful technique in the direct analysis of low concentrations of conjugated opiate metabolites. Previous methods using HPLC with traditional detection methods do not have the sensitivity to detect low concentrations of most conjugated drug metabolites. Methods using gas chromatography-mass spectrometry (GC-MS) require hydrolysis and derivatization of the sample followed by an indirect quantitation of conjugated metabolites. Recently, several reports have described direct analysis of opiates and their glucuronide conjugates by HPLC and API-MS. These methods report lower limits of detection than GC-MS methods and quantitation in the low nanogram-per-milliliter range for the glucuronide metabolites of morphine. This report describes an HPLC-electrospray-MS-MS method capable of detecting subnanogram concentrations of morphine (MOR) and its 3- and 6-glucuronide metabolites (M3G and M6G, respectively). The assay has a dynamic range of 250-10,000 pg/mL for M3G and M6G and 500-10,000 pg/mL for MOR. Inter- and intra-assay precision and accuracy varied by less than 8% for all analytes at 750-, 2500-, and 7500-pg/mL concentrations. This assay was used for the determination of MOR, M3G, and M6G in human plasma after intravenous (i.v.) and intrathecal (i.t.) administration of MOR and its effects on the ventilatory response to hypoxia. Peak plasma concentrations of MOR and M6G were measured 1 h after i.v. administration of MOR. Peak concentrations of M3G were measured 2 h after i.v. administration of MOR. After i.t. administration of MOR, peak concentrations of M3G were measured 8 h postdose. MOR was not detected in plasma of patients administered MOR i.t.. Subnanogram concentrations of M6G were measured in the plasma of five of nine patients administered MOR i.t..

Chromatography, High Pressure Liquid↗
PubMed1997

Intrathecal morphine for coronary artery bypass grafting and early extubation.

Aggressive control of pain during the immediate postoperative period after cardiac surgery with early tracheal extubation may decrease morbidity and mortality. This prospective, randomized, double-blinded, placebo-controlled clinical study examined the use of intrathecal morphine in patients undergoing cardiac surgery and its influence on early tracheal extubation and postoperative analgesic requirements. Patients were randomized to receive either 10 micrograms/kg of intrathecal morphine (n = 19) or intrathecal placebo (n = 21). Perioperative anesthetic management was standardized (intravenous (IV) fentanyl, 20 micrograms/kg, and IV midazolam, 10 mg) and included postoperative patient-controlled morphine analgesia. Of the patients who were tracheally extubated during the immediate postoperative period, the mean time from intensive care unit arrival to extubation was significantly prolonged in patients who received intrathecal morphine (10.9 h) when compared to patients who received intrathecal placebo (7.6 h). Three patients who received intrathecal morphine had extubation substantially delayed because of prolonged ventilatory depression. Although mean postoperative IV morphine use for 48 h was less in patients who received intrathecal morphine (42.8 mg) when compared to patients who received intrathecal placebo (55.0 mg), the difference between groups was not statistically significant. In conclusion, intrathecal morphine offers promise as a useful adjunct in controlling postoperative pain in patients after cardiac surgery. However, the optimal dose of intrathecal morphine in this setting, along with the optimal intraoperative baseline anesthetic that will provide significant analgesia, yet not delay extubation in the immediate postoperative period, remains to be elucidated.

Adult↗
PubMed2005

Role for cyclooxygenase 2 in the development and maintenance of neuropathic pain and spinal glial activation.

BACKGROUND: Lines of evidence have indicated that cyclooxygenase 2 plays a role in the pathophysiology of neuropathic pain. However, the site and mechanism of its action are still unclear. Spinal glia has also been reported to mediate pathologic pain states. The authors evaluated the effect of continuous intrathecal or systemic cyclooxygenase-2 inhibitor on the development and maintenance of neuropathic pain and glial activation in a spinal nerve ligation model of rats. METHODS: Continuous intrathecal infusion of meloxicam (32 or 320 mug . kg . day) or saline was started immediately after L5-L6 spinal nerve ligation. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively. Spinal astrocytic activation was evaluated with glial fibrially acidic protein immunoreactivity on day 7. In other groups of rats, continuous intrathecal meloxicam was started 7 days after spinal nerve ligation, and effects on established neuropathic pain and glial activation were evaluated. Last, effects of continuous systemic meloxicam (16 mg . kg . day) on existing neuropathic pain and glial activation were examined. RESULTS: Intrathecal meloxicam prevented the development of mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation. It also inhibited spinal glial activation responses. In contrast, when started 7 days after the nerve ligation, intrathecal meloxicam did not reverse established neuropathic pain and glial activation. Systemic meloxicam started 7 days after ligation partially reversed neuropathic behaviors but not glial activation. CONCLUSIONS: Spinal cyclooxygenase 2 mediates the development but not the maintenance of neuropathic pain and glial activation in rats. Peripheral cyclooxygenase 2 plays a part in the maintenance of neuropathic pain.

Animals↗
PubMedDate not supplied

Continuously infused intrathecal baclofen for spastic/dystonic hemiplegia: a preliminary report.

The objective of this study was to determine whether the continuous intrathecal delivery of baclofen will control spastic hypertonia associated with long-standing hemiplegia from acquired brain injury. Six hemiparetic patients (average age, 50 (range, 42-66) yr) with more than 6 mo of disabling lower limb spastic hypertonia on one side caused by either a unilateral traumatic brain injury or a stroke were recruited in a consecutive manner. The setting was a tertiary care outpatient and inpatient rehabilitation center directly attached to a university hospital. Patients were screened via a randomized, double-blind, placebo-controlled, crossover design to receive either an intrathecally administered bolus injection of normal saline or 50 microg of baclofen. Data for Ashworth rigidity scores, spasm scores, and deep tendon reflex scores were collected on the affected upper limb and lower limb side. Those who dropped an average of two points on their affected lower limb side Ashworth scores were then offered computer-controlled pump implantation for continuous intrathecal administration of baclofen. Differences over time were assessed via descriptive statistics and Wilcoxon's signed-rank test. After 3 mo of treatment, the average lower limb Ashworth score on the affected side decreased from 3.7 +/- 1.0 to 1.9 +/- 0.6 standard deviation (SD) (P < 0.0001), the reflex score from 1.8 +/- 1.3 to 0.5 +/- 0.8 SD (P = 0.0208), and the spasm score from 1.3 +/- 1.2 to 0.8 +/- 1.3 SD (P > 0.05). The average upper limb Ashworth score on the affected side decreased from 3.4 +/- 0.9 to 2.1 +/- 0.9 SD (P = 0.0002), the reflex score from 2.3 +/- 0.5 to 1.7 +/- 0.5 SD (P > 0.050, and the spasm score from 0.8 +/- 1.3 to 0 +/- 0 SD (P > 0.05). The average intrathecally administered dose of baclofen that was required to attain these effects was 205.3 microg, which was continuously infused for 24 h. Continuous intrathecal infusion of baclofen is capable of maintaining a reduction in the dystonia on the hemiparetic side without significantly affecting motor strength on the normal side.

Adult↗
PubMed1995

Raynaud's phenomenon and the vascular disease in scleroderma.

Raynaud's phenomenon (RP) is the most common feature of vascular disease in scleroderma. The diagnostic methods and mechanisms involved in the development of RP continue to be defined, and deficiency in the endothelial-dependent vasodilatory mechanism is suggested. Neuronal involvement in the pathogenesis of vasospasm is illustrated by a defective neuromediated vasodilatory mechanism in both spontaneous RP and vibration white-finger syndrome. The exact neuronal-related mechanism(s) is not known, but the development of scleroderma-like dermal changes following spinal cord injury suggests an important role for neuronal participation in the development of scleroderma. Mechanisms involved in endothelial injury are still not known, but the complement system may be involved, as suggested by the finding of decreased endothelial expression of the complement protective molecular system in scleroderma. Occurrence of vasculitis in the digital arteries in patients with digital ischemic lesions suggests that immune-mediated vascular injury occurs in the disease. The role of antiendothelial antibodies is questioned in view of the lack of endothelial specificity for the antibodies, but the association of anticentromere antibodies with vascular occlusion was confirmed. Therapeutic interventions stressing an individualized approach are recommended. Spinal cord stimulation and continued iloprost infusion are some of the newer proposed therapies for patients with difficult vascular complications.

Humans↗
PubMed1992

Bacteriology, drug stability and exchange of percutaneous delivery systems and antibacterial filters in long-term intrathecal infusion of opioid drugs and bupivacaine in "refractory" pain.

OBJECTIVE: To provide a basis for recommendations on the exchange of containers (syringes and cassettes) and antibacterial filters, and for choice of administration device in patients with "refractory" pain treated with long-term percutaneous intrathecal (IT) infusions of opioid (morphine or buprenorphine) and bupivacaine mixtures. DESIGN: Prospective, cohort, nonrandomized control trial-case series, with consecutive sample, no standard criterion, and cost-benefit analysis. SETTING: Tertiary care center, institutional practice as well as hospitalized and ambulatory care. PATIENTS: Eighty-nine (51 women and 38 men); 81 with malignant pain and 8 with benign "refractory" pain. INTERVENTIONS: (a) The chemical stability of the drugs in the containers during 30 days. (b) The results of bacteriologic culture of the residual volumes of the analgesic mixtures from used and reused (1-16 times) syringes (n = 135) and cassettes (n = 258), and of 5 ml of sterile isotonic saline filtered through the used Millipore filters (n = 149). The bacteriologic samples from the 89 patients were taken after 1-40 (median = 7), 1-86 (median = 20), and 5-78 (median = 31) days of IT treatment, respectively. MAIN OUTCOME MEASURES: Chemical stability: buprenorphine and bupivacaine concentrations-liquid chromatography; morphine concentrations--gas chromatography. Bacteriologic cultures: standard laboratory procedures. The hypothesis (repeated use of the infusion systems and their exchange once a month does not significantly affect drug concentrations or increase the infection risk) was elaborated before data collection began. RESULTS: The bupivacaine-opioid mixtures were found to be chemically stable within 3-10% of the original doses up to 30 days. Seventeen cultures (from five syringes, six cassettes, and six filters) in 13 patients (having no signs of meningeal infection) were found to be colonized with Staphylococcus aureus (n = 4), coagulase negative staphylococci (n = 7), viridans streptococci (n = 3), Neisseria sp (n = 4), Corynebacterium sp (n = 4), Enterobacter sp (n = 2), Klebsiella sp (n = 3), gram-negative bacilli (n = 1), and yeasts (n = 2). The place of IT treatment, its duration, and patient-related infection risk factors (age; malignancy; diabetes; presence of a colostomy, pyelostomy, or indwelling urinary catheter; and the presence and location of infection foci) were not related to the results of the cultures. However, 9 of the 17 positive cultures came from patients with skin ulcers, a notable incidence. The positive cultures had no connection with the cultured item, its in-use duration, the number of times of reuse, the analgesic drugs used, their concentrations or the presence of preservatives (sodium metabisulfite and sodium edetate), or the antiseptic agent (70% ethanol or 0.5% chlorhexidine gluconate) used during bacteriologic sampling. The bacterial growth was sparse in 14 and massive in 3 of the 17 positive cultures. One item (filter) from one patient with meningitis was sterile. CONCLUSIONS: In our population, exchange of the infusion systems when they are empty (within 1 month) and of the antibacterial filters once a month does not appear to affect the concentrations of, or increase the infection risk from, the opioid-bupivacaine mixtures. The risk of bacterial contamination/colonization of the syringes from syringe drivers does not seem to be higher than that of cassettes from external portable pumps.

Adolescent↗
PubMed2000

Intrathecal baclofen for intractable cerebral spasticity: a prospective placebo-controlled, double-blind study.

OBJECTIVE: To conduct a placebo-controlled prospective study of the effectiveness of intrathecal bolus injections and continuous administration of baclofen on functional parameters in patients with severe spasticity of cerebral origin. To compare this functional evaluation with spasticity scores in different muscle groups. METHODS: In 11 patients with spasticity of cerebral origin (mainly cerebral palsy), double-blind scoring of spasticity (Ashworth scale score and visual analog score), spasms, pain, and functional abilities was performed during tests with bolus injections including a placebo control. Eight patients were considered good responders and received a subcutaneous device for intrathecal drug delivery. Six of these patients were followed up for 2 years, during which they underwent the same scoring procedures as after their bolus injections. These patients were subjected to a blinded dose reduction test. RESULTS: There was a noticeable placebo effect on spasticity scores during tests with bolus injections. Eight patients demonstrated a significant beneficial effect of intrathecal bolus injections compared with this placebo effect. Functional improvements were noted in most patients. During continuous infusion, Ashworth scale scores were less favorable but still significantly lower than at baseline. Subjective evaluation (visual analog scores) remained positive, functional improvements were maintained, and patient comfort was invariably and significantly improved. CONCLUSION: Intrathecal administration of baclofen is a safe and effective treatment for spasticity of cerebral origin. Functional improvement was demonstrated. The presence of a placebo effect on the spasticity scores suggests the need for double-blind screening in each patient.

Adolescent↗
PubMed1979

Candida meningitis in the newborn.

The incidence of Candida meningitis in the neonatal period is increasing, and 63% of reported patients have either died or are mentally retarded. We report a newborn with Candida meningitis and arthritis who did well after treatment with intravenous and intrathecal amphotericin B, along with oral flucytosine.

Administration, Oral↗
PubMed1997

The use of intrathecal morphine for analgesia after posterolateral lumbar fusion: a prospective, double-blind, randomized study.

STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of intrathecal morphine for postoperative analgesia after posterolateral lumbar fusion. OBJECTIVES: To compare the early postoperative analgesia in patients who receive a single dose of intrathecal morphine intraoperatively with that of patients using a patient-controlled analgesia pump only. SUMMARY OF BACKGROUND INFORMATION: Although intrathecal morphine is used as an analgesic in a variety of medical and surgical conditions, very little has been published on its use after posterior lumbar spine surgery. Because the thecal sac is readily available during these procedures, the addition of a single injection of morphine before wound closure can be done with technical ease. If its efficacy and safety can be verified, then it could serve as a useful adjuvant to the postoperative analgesia regimen. METHODS: Sixty-eight consecutive patients undergoing posterolateral lumbar fusion were randomly assigned to two groups. The experimental group was injected intrathecally with morphine 30 minutes before wound closure, and the control group was similarly injected with a placebo of normal saline solution. All patients were connected to an on-demand patient-controlled analgesia pump to provide any additional necessary analgesia. Their use of the patient-controlled analgesia pump was tabulated by counting the number of demands and the actual amount of morphine delivered. Additionally, a visual analog scale was used to assess pain levels at pre-established regular intervals. RESULTS: The visual analog scale measurements were significantly lower for the intrathecal morphine group initially, but they surpassed those of the control group after 24 hours. Likewise, the number of patient-controlled analgesia pump demands and the amount of narcotic delivered initially were significantly lower in the experimental patients, but again reversed after the first postoperative day. The late rebound in pain and patient-controlled analgesia pump use did not reach statistical significance. There were no significant complications related to the analgesia. CONCLUSIONS: Intrathecal morphine can be safe and efficacious as an early postoperative analgesic after lumbar fusion when respiratory monitoring is used.

Adult↗
PubMed2006

Amnioinfusion to facilitate external cephalic version after initial failure.

OBJECTIVE: To evaluate the effectiveness of antepartum transabdominal amnioinfusion to facilitate external cephalic version after initial failure. METHODS: Women with a structurally normal fetus in breech lie at term, with a failed external cephalic version and an amniotic fluid index (AFI) less than 15 cm, were asked to participate in our study. After tocolysis with indomethacin, a transabdominal amnioinfusion was performed with an 18G spinal needle. Lactated Ringers solution was infused until the AFI reached 15 cm, with a maximum of 1 L. External cephalic version was performed directly afterward. RESULTS: Seven women participated in the study. The gestational age of the women was between 36(+4) and 38(+3) weeks, and three women were primiparous. The AFI ranged from 4 cm to 13 cm. A median amount of 1,000 mL Ringers solution (range 700-1,000 mL) was infused per procedure. The repeat external cephalic versions after amnioinfusion were not successful in any of the patients. CONCLUSION: In our experience, amnioinfusion does not facilitate external cephalic version.

Adult↗
PubMed2005

Prevention of severe contractures might replace multilevel surgery in cerebral palsy: results of a population-based health care programme and new techniques to reduce spasticity.

During the 1990s three new techniques to reduce spasticity and dystonia in children with cerebral palsy (CP) were introduced in southern Sweden: selective dorsal rhizotomy, continuous intrathecal baclofen infusion and botulinum toxin treatment. In 1994 a CP register and a health care programme, aimed to prevent hip dislocation and severe contractures, were initiated in the area. The total population of children with CP born 1990-1991, 1992-1993 and 1994-1995 was evaluated and compared at 8 years of age. In non-ambulant children the passive range of motion in hip, knee and ankle improved significantly from the first to the later age groups. Ambulant children had similar range of motion in the three age groups, with almost no severe contractures. The proportion of children treated with orthopaedic surgery for contracture or skeletal torsion deformity decreased from 40 to 15% (P = 0.0019). One-fifth of the children with spastic diplegia had been treated with selective dorsal rhizotomy. One-third of the children born 1994-1995 had been treated with botulinum toxin before 8 years of age. With early treatment of spasticity, early non-operative treatment of contracture and prevention of hip dislocation, the need for orthopaedic surgery for contracture or torsion deformity is reduced, and the need for multilevel procedures seems to be eliminated.

Anti-Dyskinesia Agents↗