Has botulinum toxin type A a place in the treatment of spasticity in spinal cord injury patients?

OBJECTIVE: To present and discuss treatment of severe spasms related to spinal cord injury with botulinum toxin type A. DESIGN: A 2-year follow-up study of an incomplete T12 paraplegic patient, who was reluctant to undergo intrathecal baclofen therapy, presenting severe painful spasms in his lower limbs treated with intramuscular injections of botulinum toxin type A. SETTING: Department of Physical Medicine and Rehabilitation, H?pital de Gravelone, Sion, Switzerland. SUBJECT: Single patient case report. MAIN OUTCOME MEASURE: Spasticity, spasms and pain measured with the modified Ashworth scale, spasm frequency score and visual analogue scale. RESULTS: Treatment of spasticity with selective intramuscular injections of botulinum toxin type A resulted in subjective and objective improvement. CONCLUSION: Botulinum toxin type A has its place in the treatment of spasticity in spinal cord injury patients. This treatment is expensive and its effect is reversible. It can complement intrathecal baclofen in treating upper limb spasticity in tetraplegic patients. Tolerance does occur to the toxin. Although high doses of the product are well tolerated, the quantity should be tailored to the patient's need. The minimal amount necessary to reach clinical effects should be adhered to and booster doses at short period intervals should be avoided.     

Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury: a case study

Spasticity and pain are common disabling sequelae following spinal cord injury (SCI) and are often difficult to manage. The two problems are also not infrequently related. A variety of pharmacological and other approaches have been described for management of these problems in SCI. This case study reports a 32-year-old woman with an established incomplete C5 tetraplegia (anterior cord syndrome) who developed severe, intractable anal spasm following a hemorrhoidectomy, which persisted despite very good healing. This prevented evacuation of her bowels and resulted in severe rectal pain and episodes of autonomic dysreflexia. Attempts to modify the rate and mode of delivery of intrathecal baclofen through an existing programmable infusion pump failed to reduce anal sphincter spasm or improve symptoms. A right-sided pudendal block with lignocaine provided some relief. Clonidine was added to baclofen in the pump reservoir and both drugs were administered intrathecally in combination. This resulted in an immediate improvement in anal sphincter spasm and pain relief, allowing rapid reestablishment of her normal bowel pattern without need for any supplemental analgesia. It appears that intrathecal clonidine may have an important role in the treatment of spasticity, either as a single or an adjuvant agent, when intrathecal baclofen alone is ineffective or there is increasing tolerance to baclofen. Intrathecal clonidine may also prove useful in the management of intractable neuropathic pain.     

Intrathecal baclofen for severe spasticity secondary to spinal cord injury

OBJECTIVE: To evaluate the use of intrathecal baclofen for the treatment of muscle spasticity in patients with spinal cord injury. DATA SOURCES: A MEDLINE search was used to identify relevant and pertinent literature. Information was obtained from open-label clinical trials, abstracts, conference proceedings, and review articles. Index terms in the search included baclofen, spasticity, intrathecal drug infusion, spinal cord disease, and neurosurgery. DATA EXTRACTION: Studies were selected for review if they evaluated intrathecal baclofen in patients with spinal cord injury. Emphasis was placed on human studies published in the English language. Trials were reviewed by dosage regimen, therapeutic response, adverse effects, and complications. DATA SYNTHESIS: Thus far, intrathecal baclofen administration shows promise in the treatment of spasticity resulting from spinal cord trauma. Few complications and adverse effects have been reported. CONCLUSIONS: Muscle spasms and spasticity constitute a significant problem in spinal cord injuries, interfering with rehabilitation and leading to inconveniences and complications in these patients. Oral baclofen is the drug of choice for spasticity due to spinal cord trauma. It often is ineffective, however, because of the large dosages required to cross the blood-brain barrier and the subsequent appearance of central nervous system adverse effects. These adverse effects are not tolerated by many patients. Intrathecally administered baclofen has been approved by the Food and Drug Administration (FDA) for the treatment of spasticity in patients with spinal cord injury who are refractory to or cannot tolerate oral baclofen. It is intended for use only in implantable pumps approved by the FDA for the administration of baclofen into the intrathecal space. Intrathecal administration achieves high concentrations in the spinal cord with small dosages, thus reducing the incidence of central nervous system adverse effects. To date, approximately 350 patients with spinal cord injury have been treated with intrathecal baclofen. Reductions in spasticity have been demonstrated in both open-label and placebo-controlled trials. Patients also often make substantial gains in activities of daily living. Few adverse effects and complications have been reported. However, tolerance to the clinical effects of intrathecal baclofen has been reported. Further studies are needed to determine specific patient populations that may benefit most from intrathecal baclofen administration. Individual dosage ranges and follow-up care also need to be defined more completely. In addition, the question of whether tolerance detracts from long-term clinical benefits with intrathecal baclofen needs to be addressed.     

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.     

Selective intrathecal phenol block to improve activities of daily living in patients with spastic quadriplegia. A preliminary report

To eliminate severe leg spasms of 15 quadriplegics, 0.3 ml 10% phenol-glycerin was injected into the subarachnoid space at the T12/L1 interspace. The effectiveness for leg spasm was evaluated by the Penn spasticity and Ashworth rigidity scales. Three patients remained completely flaccid; however three had slight, six had moderate and three had complete recurrence of spasms in a follow up period of observation for 1 to 22 (average 13) months. The result of selective intrathecal phenol block was significantly valuable, improving the activities of daily living (ADL) of quadriplegic patients. There were no systemic side effects nor disturbance of bladder, bowel or sexual functions.     

Clinical assessment of spasticity in spinal cord injury: a multidimensional problem

OBJECTIVE: To determine the relation between various components of spasticity evaluated clinically in persons with spinal cord injury (SCI). DESIGN: Case series evaluating spasticity using clinical scales commonly referenced in contemporary literature, including the Penn Spasm Frequency Scale, the Ashworth Scale, and standard scales of tendon taps, clonus, and plantar stimulation. SETTING. A Veterans Affairs Medical Center Spinal Cord Injury Center. PATIENTS. Eighty-five spinal cord injured individuals with varying degrees of spasticity. RESULTS: Correlations demonstrated weak relationships between Spasm Frequency Scale and self-report scales of interference with function (.407) and painful spasms (.312). No clinical examination score correlated with self-report scores greater than 0.4. Three clinical examination scores correlated modestly (> 0.5)-Ashworth score with patellar tendon taps (.553), ankle clonus with Achilles tendon tap (.663), and patellar tendon tap with adductor tendon tap (.512). Two other clinical scales correlated weakly (> 0.4)-Achilles tendon tap with patellar tendon tap (.417) and plantar reflex with adductor tendon taps (.423). CONCLUSIONS: Clinical scales currently used to evaluate spasticity in SCI correlate poorly with each other, suggesting that they each assess different aspects of spasticity. The use of any single scale is likely to underrepresent the magnitude and severity of spasticity in the SCI population. In the absence of agreement among these various scales and with the absence of an appropriate criterion standard for evaluation of spasticity, assessments of spasticity, whether clinical or neurophysiological in nature, should be comprehensive in scope.     

Comparison of treatment of tardive dystonia and idiopathic cervical dystonia with botulinum toxin type A

To compare clinical parameters of patients treated with botulinum toxin type A (BTX) for treatment of idiopathic cervical dystonia (ICD) and for tardive cervical dystonia (TCD), we studied 156 patients (149 with ICD and 7 with TCD) who were treated with serial injections of BTX over 5 years. We hypothesized that patients with TCD and ICD would demonstrate similar improvement in severity scores after treatment with BTX. The diagnosis, dates, dosages, and frequency of BTX injected and severity assessments were recorded into a computerized database. Nonparametric Wilcoxon rank sum and signed-rank tests were used to assess statistical significance. The change in severity scores between the first treatment and last treatment in both groups was not statistically significant (p = 0.4859), indicating similar improvement. The difference in BTX doses was significant (p = 0.0045). ICD patients (n = 149) received an average of 219.8 +/- 63.5 units and those with TCD (n = 7) were treated with an average dose of 287.4 +/- 60.3 units. The average number of days between treatments for individuals with ICD was 142.9 +/- 85.8, similar to that for persons with TCD (144.7 +/- 64.5) (p = 0.6075). Our analysis provides preliminary evidence that the improvement from the administration of BTX for patients with ICD and TCD is similar.     

Anatomy of cerebrospinal fluid system and blood-brain barrier

Baclofen is used for the treatment of post-traumatic spasticity. It carries a risk of overdose as well as of an acute withdrawal syndrome. We report two cases of severe hypertonia and hyperthermia (> 42 degrees C), occurring after accidental discontinuation of intrathecal infusion of baclofen. Both hypertonia and hyperthermia ceased when administration of baclofen was resumed. In parallel, the patients developed transient life-threatening alterations of hepatic (cytolysis), haematologic (coagulopathy) and cardiorespiratory functions for some days. It is concluded that the occurrence of such a withdrawal syndrome should be prevented, especially in patients with chronic intrathecal administration and first symptoms should be recognized without delay. Relationships with other malignant hyperthermias are discussed.     

Effect of subarachnoid bupivacaine block on anesthetic requirements for thiopental in rats

BACKGROUND: Subarachnoid bupivacaine blockade has been reported to reduce thiopental and midazolam hypnotic requirements in patients. The purpose of this study was to examine if local anesthetically induced lumbar intrathecal blockade would reduce thiopental requirements for blockade of motor responses to noxious and nonnoxious stimuli in rats. METHODS: After intrathecal and external jugular catheter placement, rats were assigned randomly to two groups in a crossover design study, with each rat to receive either 10 microl of 0.75% bupivacaine or 10 microl of normal saline intrathecally. The doses of intravenously administered thiopental required to ablate the eyelid reflex, to block the withdrawal reflex of a front limb digit, and to block the corneal reflex were compared. In two separate groups of animals, hemodynamic parameters and concentrations of thiopental in the brain were compared between intrathecally administered bupivacaine and saline. RESULTS: The thiopental dose required to block the described responses was decreased with intrathecally administered bupivacaine versus intrathecally administered saline from (mean +/- SD) 40 +/- 5 to 24 +/- 4 mg/kg (P < 0.001) for the eyelid reflex, from 51 +/- 6 to 29 +/- 6 mg/kg (P < 0.005) for front limb withdrawal, and from 67 +/- 8 to 46 +/- 8 mg/kg (P < 0.01) for the corneal reflex. The concentration of thiopental in the brain at the time of corneal reflex blockade for the group given bupivacaine was significantly lower than in the group given saline (24.1 vs. 35.8 microg/g, P = 0.02). CONCLUSION: This study demonstrates that lumbar intrathecally administered local anesthetic blockade decreases anesthetic requirements for thiopental for a spectrum of end points tested. This effect is due neither to altered pharmacokinetics nor to a direct action of the local anesthetic on the brain; rather, it is most likely due to decreased afferent input.     

Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure

An autonomic reflex screen, which consisted of a quantitative sudomotor axon reflex test, orthostatic blood pressure and heart rate response to tilt, heart rate response to deep breathing, the Valsalva ratio, and beat-to-beat blood pressure measurements during phases II and IV of the Valsalva maneuver, tilt, and deep breathing, was used to develop a 10-point composite autonomic scoring scale of autonomic function. The scheme allots 4 points for adrenergic and 3 points each for sudomotor and cardiovagal failure. Each score is normalized for the compounding effects of age and sex. Patients with a score of 3 or less on the composite autonomic scoring scale have only mild autonomic failure, those with scores of 7 to 10 have severe failure, and those with scores between these two ranges have moderate autonomic failure. The sensitivity and specificity of the method were assessed by evaluating the composite autonomic scoring scale in four groups of patients with known degrees of autonomic failure: 18 with multisystem atrophy, 20 with autonomic neuropathy, 20 with Parkinson's disease, and 20 with peripheral neuropathy but no autonomic symptoms. The composite scores (means +/- SD) for these four groups, respectively, were as follows: 8.5 +/- 1.3, 8.6 +/- 1.2, 1.5 +/- 1.1, and 1.7 +/- 1.3. Patients with symptomatic autonomic failure had scores of 5 or more, those without symptomatic autonomic failure had scores of 4 or less, and no overlap existed in these groups. Thus, autonomic laboratory tests should be useful in grading the degree of autonomic failure.     

Solitary fibrous tumour: clinicopathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate

Heart-rate variability (HRV), a measure of fluctuation around the mean heart rate, reflects the sympathetic and parasympathetic balance of the autonomic nervous system, and is an excellent technique to study cardiovascular tone in patients with neurological injuries. The purpose of this study was to determine whether abnormal HRV is present in patients with traumatic brain injury (TBI) during the post-acute recovery phase. Using a prospective, case/control design, we performed 24-h ambulatory ECG monitoring in seven TBI patients and in seven controls (C). There was a significant difference in root mean squared successive difference of RR intervals (C 40.4 +/- 10.3, TBI 23.3 +/- 16.5, p = 0.04) between TBI and C. Four patients with TBI (compared to one control) had abnormal standard deviation of the RR interval. When these four patients were compared to their matched controls, significant differences were found in frequency domain measure (In total power: TBI 4.4 +/- 0.9 ms2, C 7.1 +/- 1.4 ms2, In low frequency: TBI 3.3 +/- 1.1 ms2, C 6.4 +/- 1.4 ms2; In high frequency TBI 2.0 +/- 1.0 ms2, C 4.8 +/- 1.3 ms2, all p < 0.05). Thus, abnormalities in both time and frequency domains of HRV are present in TBI during the post-acute recovery phase.     

Osteoporosis after spinal cord injury

Immobilisation secondary to spinal cord injury (SCI) is associated with marked and rapid atrophy of trabecular bone. The purpose of this study was to evaluate bone mineral density (BMD) in both the upper and lower extremities following SCI sustained for various lengths of time and to correlate the BMD to the level of the lesion, time from injury, spasticity and serum calcium, phosphorus and alkaline phosphatase (ALP) levels. A study was undertaken in 41 SCI patients with a mean age of 35.8 +/- 12.7 years. A significant difference in BMD between upper and lower extremities of the paraplegics were found. BMD of upper and lower extremities were similar in tetraplegies. The BMD values were significantly different when the upper extremity scores of paraplegics and tetraplegics were compared but BMD scores of the lower extremities were similar in the two groups. The decrease in BMD was less in the spastic patients when compared to the flaccid group. There was a positive correlation between time from injury and the degree of BMD deficit in the paralysed areas. In the whole group of patients a significant positive correlation was found between the duration of SCI and serum ALP levels.     

Differences in responses to norepinephrine and adenosine triphosphate in isolated, perfused mesenteric vascular beds between normotensive and spontaneously hypertensive rats

OBJECT: Although nitric oxide (NO) has been shown to play an important role in the pathophysiological process of cerebral ischemia, its contribution to the pathogenesis of traumatic brain injury (TBI) remains to be clarified. The authors investigated alterations in constitutive nitric oxide synthase (NOS) activity after TBI and the histopathological response to pharmacological manipulations of NO. METHODS: Male Sprague-Dawley rats underwent moderate (1.7-2.2 atm) parasagittal fluid-percussion brain injury. Constitutive NOS activity significantly increased within the ipsilateral parietal cerebral cortex, which is the site of histopathological vulnerability, 5 minutes after TBI occurred (234.5+/-60.2% of contralateral value [mean+/-standard error of the mean ?SEM?], p < 0.05), returned to control values by 30 minutes (114.1+/-17.4%), and was reduced at 1 day after TBI (50.5+/-13.1%, p < 0.01). The reduction in constitutive NOS activity remained for up to 7 days after TBI (31.8+/-6.0% at 3 days, p < 0.05; 20.1+/-12.7% at 7 days, p < 0.01). Pretreatment with 3-bromo-7-nitroindazole (7-NI) (25 mg/kg), a relatively specific inhibitor of neuronal NOS, significantly decreased contusion volume (1.27+/-0.17 mm3 [mean+/-SEM], p < 0.05) compared with that of control (2.52+/-0.35 mm3). However, posttreatment with 7-NI or pre- or posttreatment with nitro-L-arginine-methyl ester (L-NAME) (15 mg/kg), a nonspecific inhibitor of NOS, did not affect the contusion volume compared with that of control animals (1.87+/-0.46 mm3, 2.13+/-0.43 mm3, and 2.18+/-0.53 mm3, respectively). Posttreatment with L-arginine (1.1+/-0.3 mm3, p < 0.05), but not 3-morpholino-sydnonimine (SIN-1) (2.48+/-0.37 mm3), significantly reduced the contusion volume compared with that of control animals. CONCLUSIONS: These data indicate that constitutive NOS activity is affected after moderate parasagittal fluid percussion brain injury in a time-dependent manner. Inhibition of activated neuronal NOS and/or enhanced endothelial NOS activation may represent a potential therapeutic strategy for the treatment of TBI.     

Peridural anesthesia versus subarachnoid anesthesia in cesarean section. Prospective clinical study

OBJECTIVE: To compare technical and clinical differences between epidural and spinal anesthesia for cesarean section. STUDY DESIGN: Randomized prospective trial. PATIENTS AND METHODS: 64 pregnant women at term scheduled for elective cesarean section. Two groups were randomized: A) PD Group (n = 32): continuous epidural anesthesia by administration of bupivacaine 0.5% plus epinephrine 1/400,000 via an epidural catheter. Epidural morphine 3 mg was administered at the end of surgery. B) SP Group (n = 32): "single shot" spinal anesthesia by intrathecal administration of hyperbaric 1% bupivacaine 1-1.4 ml plus morphine 0.2 mg. The pin prick block level reached T2-T6 at incision time. DATA COLLECTION: 1) Time from the beginning of anesthesia to surgical incision. 2) Hypotension episodes. 3) Ephedrine consumption. 4) Intraoperative discomfort at delivery, traction and uterine manipulation, peritoneal toilette. 5) Nausea and vomiting. 6) Apgar score. 7) Postoperative headache. RESULTS: Women in the SP group had more hypotensive episodes (81% vs 53%: p < 0.05) and more ephedrine consumption with a large individual variability (29.12 mg +/- 20.4 vs 12.83 +/- 13.8: p < 0.01) when compared to PD group, without any difference in the Apgar score. The SP group required less time consumption (10.5 min. +/- 6.7 vs 35.9 min. +/- 17.3: p < 0.01) and had less intraoperative discomfort with less analgesic and/or sedative drugs consumption (9.7% vs 29%: p < 0.05) and less vomiting (3% vs 22.5%: p < 0.05). No postoperative headache was noticed in both groups. CONCLUSIONS: With the described pharmacological and technical approach, spinal anesthesia is more suitable than continuous epidural technique for cesarean section, unless contraindicated.     

Effect of radiation and tirapazamine (SR-4233) on three melanoma cell lines

Locally acting treatments for spasticity such as nerve and motor point blocks have the advantage of reducing harmful spasticity in one area, while preserving useful spasticity in another area. This randomized, double-blind study is the first trial that was designed to find out whether botulinus toxin Type A and phenol relieves the signs and symptoms of ankle plantar flexor and foot invertor spasticity after stroke and if either of these methods offers any advantages and disadvantages over the other. Twenty patients who were included in this preliminary study were randomly assigned to receive a single treatment of 400 mouse units of botulinus toxin Type A injected into the calf muscles or to receive a tibial nerve blockade with 3 ml of 5% phenol. A combination of subjective and objective measures were used to assess functional change at baseline and at Weeks 2, 4, 8, and 12. At follow-up, significant improvement (P < 0.05) in the Ashworth score for dorsiflexion was observed in both groups. The change in the Ashworth score for eversion was significant in the group that received botulinus toxin Type A (P < 0.05) but not in the group that received phenol (P > 0.05). When those variables were compared between the two groups, the change in the Ashworth score at Weeks 2 and 4 was significantly better in the group that received botulinus toxin Type A (P < 0.05) but there was not a significant difference between the two groups at Weeks 8 and 12 (P > 0.05). The decrease in clonus duration that was detected by electromyography was significant in both groups at all visits, but the decrease in the group that received botulinus toxin Type A was significantly better at Weeks 2 and 4 (P < 0.05). It is concluded that both motor point injections with botulinus toxin Type A and tibial nerve blockade with phenol are effective in plantar flexor spasticity, but the changes were more significant in the group that received botulinus toxin Type A at Weeks 2 and 4, whereas there was not a significant difference between the two groups at Weeks 8 and 12. Future research should explore the long-term effect of these two treatment modalities.     

Spondyloarthropathies

OBJECTIVE: Prediction of outcome of ambulatory capacity and hand function in tetraplegic patients with spinal cord injury (SCI) using neurologic examination, according to the protocol of the American Spinal Injury Association (ASIA) and motor-evoked potentials (MEP). DESIGN: Correlation study on a prospective cohort. SETTING: SCI center, university hospital. PATIENTS: Thirty-six patients with acute and 34 with chronic SCI. OUTCOME MEASURES: (1) ASIA motor and sensory scores, (2) MEP recordings of upper and lower limb muscles, and (3) outcome of ambulatory capacity and hand function. RESULTS: In acute and chronic SCI, both the initial ASIA scores and the MEP recordings were significantly related (p < .0001) to the outcome of ambulatory capacity and hand function. In tetraplegic patients, the MEP of the abductor digiti minimi muscle (Spearman correlation coefficient, .75; p < .0001) and the ASIA motor score for the upper limbs (Spearman correlation coefficient, .83; p < .0001) were most related to the outcome of hand function. Ambulatory capacity could be predicted by the ASIA motor score of the lower limbs (Spearman correlation coefficient, .78; p < .0001) and by MEP recordings of the leg muscles (Spearman correlation coefficient, .77; p < .0001). In patients with acute SCI, for the period 6 months posttrauma, the ASIA motor score increased significantly (ANOVA, p < .05), whereas the ASIA sensory scores and MEP recordings were unchanged (ANOVA, p > 0.1). CONCLUSION: Both ASIA scores and MEP recordings are similarly related to the outcome of ambulatory capacity and hand function in patients with SCI. MEP recordings are of additional value to the clinical examination in uncooperative or incomprehensive patients. The combination of clinical examination and MEP recordings allows differentiation between the recovery of motor function (hand function, ambulatory capacity) and that of impulse transmission of descending motor tracts.     

A mammographic evaluation of the morphostructural variations of the breast during hormone-replacement therapy in the postmenopause

OBJECTIVE: To compare i.v. ketorolac with i.v. prochlorperazine as the initial treatment of migraine headaches in the ED. METHODS: A prospective, double-blind comparison study was performed, using a convenience sample of 64 patients suffering from migraine headaches presenting to the ED at a tertiary care university teaching hospital. Patients were randomly assigned to receive either 10 mg of prochlorperazine i.v. or 30 mg of ketorolac i.v.. Patients scored the severity of their headaches using a 10-cm visual analog pain scale. An initial mark was made on the scale at the time of entry into the study and later another mark was made on a new unmarked pain scale 1 hour after medication administration. Changes in pain scores within each treatment group and between groups were analyzed using the Wilcoxon rank sum test. RESULTS: Prior to treatment, the patients assigned to receive prochlorperazine had a median score of 9.2 cm (mean +/- SD pain score of 8.3 cm +/- 2.1 cm), while the patients receiving ketorolac had a median score of 9.0 (mean pain score of 8.4 cm +/- 1.7 cm). There was no significant difference between the pain scores of the participants in the 2 groups prior to treatment (p = 0.80). One hour after medication administration, the patients in the prochlorperazine group had a median score of 0.5 cm (mean 2.1 +/- 3.2 cm), while those patients receiving ketorolac had a median pain score of 3.9 (mean 4.0 +/- 3.3 cm). The decrease in pain score was significant for both groups of patients (p = 0.0001). The change in pain score for the patients in the prochlorperazine group (median 7.1) was significantly greater than the change in pain score for the patients in the ketorolac group (median 4.0; p = 0.04). CONCLUSION: Although both drugs were associated with a significant reduction in pain scores, benefit over a placebo agent was not tested. Furthermore, the patients who received prochlorperazine i.v. for migraine headaches had a statistically significant greater decrease in their pain scores than did those receiving ketorolac i.v.     

Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study

OBJECT: To determine the extent and duration of change in extracellular glutamate levels after human traumatic brain injury (TBI), 17 severely brain injured adults underwent implantation of a cerebral microdialysis probe and systematic sampling was conducted for 1 to 9 days postinjury. METHODS: A total of 772 hourly microdialysis samples were obtained in 17 patients (median Glasgow Coma Scale score 5+/-2.5, mean age 39.4+/-20.4 years). The mean (+/-standard deviation) glutamate levels in the dialysate were evaluated for 9 days, during which the mean peak concentration reached 25.4+/-13.7 microM on postinjury Day 3. In each patient transient elevations in glutamate were seen each day. However, these elevations were most commonly seen on Day 3. In all patients there was a mean of 4.5+/-2.5 transient elevations in glutamate lasting a mean duration of 4.4+/-4.9 hours. These increases were seen in conjunction with seizure activity. However, in many seizure-free patients the increase in extracellular glutamate occurred when cerebral perfusion pressure was less than 70 mm Hg (p < 0.001). Given the potential injury-induced uncoupling of cerebral blood flow and metabolism after TBI, these increases in extracellular glutamate may reflect a degree of enhanced cellular crisis, which in severe head injury in humans appears to last up to 9 days. CONCLUSIONS: Extracellular neurochemical measurements of excitatory amino acids may provide a marker for secondary insults that can compound human TBI.     

Noninvasive capnometry monitoring for respiratory status during pediatric seizures

OBJECTIVE: To determine the reliability and clinical value of end-tidal CO2 by oral/nasal capnometry for monitoring pediatric patients presenting post ictal or with active seizures. DESIGN: Clinical, prospective, observational study. SETTING: University affiliated children's hospital. INTERVENTIONS: One hundred sixty-six patients (105 patients with active seizures, 61 post ictal patients) had end-tidal CO2 obtained by oral/nasal sidestream capnometry, and respiratory rates, oxygen saturation, and pulse rates recorded every 5 mins until 60 mins had elapsed. End-tidal CO2 values were compared with a capillary PCO2 and clinical observation. MEASUREMENTS AND MAIN RESULTS: The mean end-tidal CO2 reading was 43.0 +/- 11.8 torr [5.7 +/- 1.6 kPa] and the mean capillary PCO2 reading was 43.4 +/- 11.7 torr [5.7 +/- 1.6 kPa]. The correlation between end-tidal CO2 and capillary PCO2 was significant (r2 = .97; p < .0001). A relative average bias of 0.33 torr (0.04 kPa) with end-tidal CO2 lower than capillary PCO2 was established with 95% limits of agreement +/-4.2 torr (+/-0.6 kPa). Variability of difference scores was not related to range of mean scores (r2 = .00003), age (r2 = .0004), or respiratory rates (r2 = .0009). End-tidal CO2 (r2 = .22; p < .001) correlated better with respiratory rate changes when compared with oxygen saturation (r2 = .02; p = .01). CONCLUSIONS: Dependable end-tidal CO2 values can be obtained in pediatric seizure patients using an oral/nasal cannula capnometry circuit. Continuous end-tidal CO2 monitoring provides the clinician with a reliable assessment of pulmonary status that can assist with decisions to provide ventilatory support.     

Population pharmacokinetics of nitroglycerin and of its two metabolites after a single 24-hour application of a nitroglycerin transdermal matrix delivery system

OBJECTIVES: To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs. STUDY DESIGN: Prospective controlled study. ANIMAL POPULATION: A total of 15 purpose-bred beagles and 17 client-owned dogs. METHODS: CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay. RESULTS: Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 +/- 2.0 pg/mL and 3.61 +/- 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 +/- 0.86 pg/mL and 6.80 +/- 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls (P < .005 and P < .0001 respectively). CONCLUSIONS: Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs. CLINICAL RELEVANCE: In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.