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PubMed1982

Redistribution by 5-hydroxytryptamine of carotid arterial blood at the expense of arteriovenous anastomotic blood flow.

1. The effects of 5-hydroxytryptamine by intravenous (1, 5 and 10 mug kg(-1) min(-1) in cats) and intracarotid (0.5 and 2 mug kg(-1) min(-1) in pigs) routes were studied on the complete distribution of common carotid artery blood flow, measured with radioactive microspheres (15 mum). In addition, the amine was also infused (0.75-3 mug kg(-1) min(-1)) into the carotid artery of cats to observe its influence on the shunting of microspheres in the jugular venous blood.2. The basal total common carotid blood flow was distributed ipsilaterally mainly to extracerebral tissues and only little blood entered the brain. As shown by the presence of microspheres in the lungs after injection into the carotid artery (52% in cats; 82% in pigs), a major fraction of the carotid blood by-passed the capillary bed through arteriovenous anastomoses in the head (non-nutrient fraction).3. 5-Hydroxytryptamine redistributed the blood in favour of the nutrient compartment at the expense of arteriovenous anastomotic fraction. In cats, tissue blood flow did not significantly change but, in the pig, blood flow to all tissues, particularly to skin and ears, was substantially increased despite a reduction in total carotid blood flow. This reduction was entirely due to a change in the non-nutrient fraction.4. Intracarotid infusion of 5-hydroxytryptamine in vagosympathectomized intact or spinal cats decreased the number of microspheres appearing in the jugular venous blood, again indicating a reduction in arteriovenous anastomotic flow due to a constriction of these non-nutrient vessels.5. Cyproheptadine (1 mg kg(-1)) completely reversed the effect of 5-hydroxytryptamine on the total carotid blood flow. However, the vasoconstriction of arteriovenous anastomoses was only partially attenuated and the vasodilatatory response was either unchanged (muscle) or even enhanced (skin, ear and bones).6. It is suggested that 5-hydroxytryptamine causes vasoconstriction of the large arteries via D-receptors which are only partly involved in the constriction of arteriovenous anastomoses. A part of the vasoconstriction in these non-nutrient vessels and the vasodilatation in extracerebral tissues are mediated by atypical 5-hydroxytryptamine receptors that are yet to be fully characterized.

Animals↗
PubMed1994

Management of severe spasticity with intrathecal baclofen delivered by a manually operated pump.

Intrathecal baclofen abolishes spasticity in many patients with neurological diseases but there are few studies on its long-term effectiveness. Since 1986 a manually operated subcutaneous pump has been used to deliver baclofen intrathecally in 21 patients with a follow up of at least one year. Most patients had multiple sclerosis and all were wheelchair-bound. Sixteen patients had a complete and sustained benefit. In four other patients the treatment was effective in the short term but not in the long term. In the remaining patient the pump never worked. Complications included meningitis, pump failure, erosion through the skin, and baclofen overdose. Nevertheless, only three patients have asked to discontinue the treatment. We conclude that intrathecal baclofen, delivered by a manually operated implanted pump, is an effective treatment for severe spasticity in most patients.

Adult↗
PubMed1997

Effect of intrathecal baclofen delivered by an implanted programmable pump on health related quality of life in patients with severe spasticity.

OBJECTIVES: To compare clinical effectiveness and health related quality of life in patients with severe spasticity who received intrathecal baclofen or a placebo. METHODS: In a double blind, randomised, multicentre trial 22 patients were followed up during 13 weeks and subsequently included in a 52 week observational longitudinal study. Patients were those with chronic, disabling spasticity who did not respond to maximum doses of oral baclofen, dantrolene, and tizanidine. After implantation of a programmable pump patients were randomly assigned to placebo or baclofen infusion for 13 weeks. After 13 weeks all patients received baclofen. Clinical efficacy was assessed by the Ashworth scale, spasm score, and self reported pain, and health related quality of life by the sickness impact profile (SIP) and the Hopkins symptom checklist (HSCL). RESULTS: At three months the scores of the placebo and baclofen group differed slightly for the spasm score (effect size=0.20) and substantially for the Ashworth scale (effect size=1.40) and pain score (effect size=0.94); health related quality of life showed no significant differences. Three months after implantation the baclofen group showed a significant, substantial improvement on the SIP "physical health", "mental health", "mobility", and "sleep and rest" subscales and on the HSCL mental health scale; patients receiving placebo showed no change. After one year of baclofen treatment significant (P<0.05) improvement was found on the SIP dimensions "mobility" and "body care and movement" with moderate effect sizes. Improvement on the SIP subscale "physical health" (P<0.05; effect size 0.86), the SIP overall score (without "ambulation"), and the "physical health" and overall scale of the HSCL was also significant, with effect sizes >0.80. Changes in health related behaviour were noted for "sleep and rest" and "recreation and pastimes" (P<0.01, P<0.05; effect size 0.95 and 0.63, respectively). Psychosocial behaviour showed no improvement. CONCLUSIONS: Intrathecal baclofen delivered by an implanted, programmable pump resulted in improved self reported quality of life as assessed by the SIP, and HSCL physical health dimensions also suggest improvement.

Adult↗
PubMed1980

Mechanism of hemodynamic responses to occlusion of the descending thoracic aorta.

To examine left ventricular responses to aortic occlusion, changes in end-diastolic volume (EDV) and end-systolic volume (ESV) were estimated by ultrasonic recordings of myocardial distances in atropinized open-chest dogs. During aortic occlusion EDV and ESV increased equally, systolic left ventricular pressure (LVP) rose by 86 +/- 8 mmHg, and blood flow more than doubled in the superior vena cava and fell by 90% in the inferior vena cava. During combined occlusion of aorta and inferior vena cava, systolic LVP and superior vena cava flow did not rise above control and EDV declined. By infusing 25 +/- 2 ml/kg body wt of blood during combined occlusion, the effects of aortic occlusion could be reproduced; control values before blood infusion were reestablished by withdrawal of only one-third of the infused volume, indicating a shunt line along the spinal column. Thus during aortic occlusion, transfer of blood accounts for the rise in EDV and increased activation of the Frank-Starling mechanism; increased afterload raises ESV as much as EDV in anesthetized dogs not subjected to sympathetic stimulation. Consequently, stroke volume is maintained and systolic LVP increased.

Animals↗
PubMed2001

Cardiovascular effects of vasopressin following V(1) receptor blockade compared to effects of nitroglycerin.

Studies to more clearly determine the mechanisms associated with arginine vasopressin (AVP)-induced vasodilation were performed in normal subjects and in quadriplegic subjects with impaired efferent sympathetic responses. Studies to compare the effects of AVP with the hemodynamic effects of nitroglycerin, an agent that primarily affects venous capacitance vessels, were also performed in normal subjects. Incremental infusions of AVP following V(1)-receptor blockade resulted in equivalent reductions in systemic vascular resistance (SVRI) in normal and in quadriplegic subjects. However, there were major differences in the effect on mean arterial pressure (MAP), which was reduced in quadriplegic subjects but did not change in normal subjects. This difference in MAP can be attributed to a difference in the magnitude of increase in cardiac output (CI), which was twofold greater in normal than in quadriplegic subjects. These observations are consistent with AVP-induced vasodilation of arterial resistance vessels with reflex sympathetic enhancement of CI and are clearly different from the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and indexes of cardiac preload, with only minor changes in SVRI.

Antidiuretic Hormone Receptor Antagonists↗
PubMed2000

Continuous intrathecal clonidine administration for the treatment of neuropathic pain.

In many cases, the treatment of neuropathic pain by intrathecal opioids fails to meet expectations. In a trial involving 10 patients, the intrathecal administration of clonidine combined with opioids in the treatment of chronic pain was introduced in our department for the first time. Eight patients with neuropathic pain syndromes were subjected to a continuous intrathecal clonidine application in addition to intrathecal morphine. At an average dose of 44 microg clonidine/day, a 70-100% reduction in pain was achieved. Residual non-neuropathic pain in 4 of 8 patients was successfully treated with clonidine and low doses of opioids. On the basis of the results achieved so far, we recommend that clonidine should be routinely tested for intrathecal drug administration, especially in patients with a prominent neuropathic pain component.

Adrenergic alpha-Agonists↗
PubMed2003

The role of surgical placement and pump orientation in intrathecal pump system failure: a technical report.

Intrathecal pump catheter complications are the most common cause of failure in drug delivery. A previous report has documented that intra-abdominal positioning of the intrathecal pump may predispose the pump-catheter neck to premature catheter breakdown and leakage. Based on this report, we reviewed over 100 intrathecal pump cases to determine the frequency of malpositioning and its role in the pathogenesis of catheter failure. We found three specific cases where a 'fulcrum effect' occurred due to intra-abdominal positioning of the pump predisposing the catheter to breakdown. This study demonstrates that intra-abdominal placement of the pump can predispose the catheter to failure/breakdown and that surgeons should attempt to place the pump catheter neck in a superiomedial position, distant from any bony prominences, to prevent the 'fulcrum effect' on the pump-catheter neck junction and reducing the likelihood of either internal or external compressive forces.

Analgesia, Epidural↗
PubMed2003

Microfracture of a baclofen pump catheter with intermittent under- and overdose.

An 8-year-old boy with an implanted intrathecal baclofen pump presented with intermittent signs of baclofen under- and overdose. Pump interrogation, pump volumes, plain X-rays, catheter contrast fluoroscopy and CT of the intrathecal catheter tip were unremarkable. A microfracture of the extradural catheter was only seen at a magnification of x20 and confirmed by scanning electron microscopy. Symptoms resolved following replacement. Microfracture of the intrathecal catheter of baclofen pump systems may present puzzling symptomatology and be difficult to diagnose by conventional means.

Baclofen↗
PubMed2003

Pump implantation for intrathecal baclofen infusion after laparotomy for necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) and spastic cerebral palsy are both familiar complications of prematurity. Children who are otherwise candidates for intrathecal baclofen infusion occasionally have long, transverse, right midabdominal laparotomy incisions from past management of NEC, and these incisions may interfere with selection of a site for pump implantation. Successful pump implantation immediately beneath a laparotomy incision was accomplished using a modification of the popular subfascial technique.

Baclofen↗
PubMed2001

Intrathecal baclofen for spastic hypertonia from stroke.

BACKGROUND AND PURPOSE: We sought to determine whether continuous intrathecal delivery of baclofen can effectively decrease spastic hypertonia due to stroke. METHODS: Stroke patients with >6 months of intractable spasticity were screened via a randomized, double-blind, placebo-controlled crossover design of either intrathecal normal saline or 50 microgram baclofen. Those who dropped an average of 2 points in either their affected lower extremity side Ashworth or Penn spasm frequency scores were then offered computer-controlled pump implantation for continuous ITB and followed prospectively for up to 12 months. RESULTS: In 21 stroke patients 6 hours after the active drug bolus, the average (+/-SD) lower extremity Ashworth score on the affected extremities decreased from 3.3+/-1.2 to 1.4+/-0.7 (P<0.0001), spasm score from 1.2+/-1.2 to 0.1+/-0.3 (P=0.0224), and reflex score from 2.1+/-1.2 to 0.1+/-0.5 (P<0.0001). The average upper extremity Ashworth score on the affected extremities decreased from 2.8+/-1.1 to 1.8+/-0.8 (P<0.0001), spasm score from 0.7+/-1.0 to 0.2+/-0.4 (P=0.1544), and reflex score from 2.1+/-0.9 to 1.2+/-0.9 (P=0.0004). All active drug scores were statistically different from placebo scores at 6 hours (P<0.05). With up to 12 months of continuous infusion of ITB in 17 implanted patients, the average lower extremity Ashworth score on the affected extremities decreased from 3.7+/-1.0 to 1.8+/-1.1 (P<0.0001), the spasm score dropped from 1.2+/-1.3 to 0.6+/-1.0 (P=0.4282), and the reflex score decreased from 2.4+/-1.3 to 1.0+/-1.3 (P<0.0001). The average upper extremity Ashworth score in the affected extremities decreased from 3.2+/-1.1 to 1.8+/-0.9 (P<0.0001), the spasm score dropped from 0.7+/-1.0 to 0.3+/-0.8 (P=0.8685), and the reflex score decreased from 2.4+/-0.8 to 1.5+/-1.2 (P=0.3337). The average continuous ITB dose required to attain these effects was 268 microgram/d. CONCLUSIONS: Intrathecal infusion of baclofen is capable of maintaining a reduction in the spastic hypertonia resulting from stroke.

Adolescent↗
PubMed1991

Effects of positive end-expiratory pressure on the gradient for venous return.

The major mechanism whereby positive end-expiratory pressure (PEEP) decreases cardiac output is believed to be a decrease in the pressure gradient for venous return. However, although PEEP increases right atrial pressure (PRA), It may also elevate mean systemic pressure (PMS), the static circulatory filling pressure that is the upstream pressure for venous return. In an intact canine preparation, we studied the effects of 15 cm H2O PEEP on cardiac output, PRA, and PMS (the equilibrium PRA during ventricular fibrillation). To examine the role of neurovascular reflexes, PEEP was applied before and after either carotid sinus and vagal denervation (CSV) or total spinal anesthesia with arterial pressure restored by epinephrine infusion (SAE). To examine the effects of PEEP-induced elevations of abdominal pressure, the abdomen was bound or widely opened and the abdominal contents exteriorized. With reflexes intact, neither binding nor opening the abdomen altered the rise in PMS during PEEP. CSV attenuated the rise in Pms by 17% (Control, 4.89 +/- 0.3 SE; CSV, 4.04 +/- 0.22 mmHg; p less than 0.01), and SAE attenuated it by 49% (Control, 4.21 +/- 0.27; SAE, 2.14 +/- 0.31 mmHg; p less than 0.00005). After either CSV or SAE, the rise in Pms was not affected by binding. PEEP decreased (Pms-PRA) only when the abdomen was bound because of a greater rise in PRA, or during SAE because of a lesser rise in Pms. Under control conditions, PEEP increased Pms and PRA equally [(PRA-Pms) = 3.89 +/- 0.26 without PEEP versus 4.13 +/- 0.29 mm Hg with PEEP]. We conclude that PEEP increases Pms by both reflex and mechanical means independent of increased abdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed2000

Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial.

Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable.

Adolescent↗
PubMed2003

Functional assessment following intrathecal baclofen therapy in children with spastic cerebral palsy.

The purpose of this article is to describe outcomes of intrathecal baclofen therapy for 29 patients with cerebral palsy, focusing on impairments, functional limitations, and disability. Patients received individualized rehabilitation and were followed up to 24 months. The primary outcome measures were the Ashworth Scale and the functional skills and caregiver assistance scales of the Pediatric Evaluation of Disability Inventory (PEDI). Ashworth Scale scores were significantly reduced (P < or = .0005). All areas of functional skills and caregiver assistance improved. Comparing groups of adults and patients less than 18 years, there were no significant differences, but there was a relationship between age and dose. Comparing groups of patients in high and low levels of independent functional mobility, no significant differences were found. These results provide suggestive evidence that the combination of intrathecal baclofen therapy and rehabilitation has positive effects across the dimensions of disablement. This study serves as a basis for high-level scientific studies of these effects.

Activities of Daily Living↗
PubMed1996

Intrathecal baclofen in cerebral palsy movement disorders.

Intrathecal baclofen reduces spasticity in individuals with cerebral palsy. Intrathecal doses are far lower than oral doses and the effects are considerably greater, and the side effects are fewer. Response to intrathecal baclofen must be confirmed by a screening trial before implantation of a pump for chronic infusion. Intrathecal baclofen reduces spasticity in the upper and lower extremities and is often associated with improved gait and upper extremity function. Quality of life improves for patients and caregivers. The Medtronic pump has been exceedingly reliable and typically functions for 4 or 5 years. The currently available intrathecal catheter is associated with far fewer complications than the initial catheter. Baclofen overdoses are unusual and are usually caused by pump programming errors rather than pump malfunction. Preliminary studies suggest that continuous intrathecal baclofen infusion reduces generalized dystonia in cerebral palsy. Screening to determine response of dystonia to intrathecal baclofen is by continuous infusion. The doses required to reduce dystonia are higher than those for cerebral spasticity. Additional investigations are underway to quantify the effects of continuous intrathecal baclofen infusion on communication, disability, and dystonia.

Baclofen↗
PubMed2000

Prenatal and breast milk morphine exposure following maternal intrathecal morphine treatment.

A case of an infant who had morphine exposure during and following pregnancy while her mother was treated with intrathecal (i.t.) morphine is presented along with a review of the relevant literature. Successful maternal pain management was achieved during pregnancy and while breastfeeding. Minimal maternal serum and breast milk levels in the first 7 postpartum weeks were found. Also, infant sleep and arousal behavior and general development at 2 and 7 months were unremarkable, illustrating the possible safe and efficacious use of i.t. morphine during and following pregnancy. Further work is required to understand opioid pharmacology during breastfeeding, which will be used to develop an empirical approach to breastfeeding and morphine use.

Adult↗
PubMedDate not supplied

The conversion challenge: from intrathecal to oral morphine.

Numerous articles have described the methodologies used and outcomes achieved with the intrathecal (IT) administration of morphine for pain. However, only one case report has been published that describes converting a patient's IT morphine to an oral regimen. This case report describes the experience of converting a patient's IT morphine to oral morphine and discusses the scarcity of published data to validate suggested equianalgesic intraspinal morphine recommendations. The calculated equianalgesic oral to IT ratio in this case was 12:1. This is substantially lower than the 300:1 ratio published by Krames and the 90:1 ratio employed by a commercially available software program for calculating equianalgesic opioid doses. We recommend caution when applying existing guidelines for conversion of morphine from an IT to an oral regimen.

Administration, Oral↗