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PubMed2003

A computational model of direct interstitial infusion of macromolecules into the spinal cord.

Convection-enhanced interstitial infusion can deliver macromolecular drugs to large tissue volumes of the central nervous system. To characterize infusion into the spinal cord, an image-based three-dimensional finite element model of the rat spinal cord was developed. The model incorporated convection and diffusion through white and gray matter, including anisotropic transport due to alignment of white matter tracts. Spatial and temporal distribution of the marker substance albumin within the interstitial space was determined. Consistent with previous experiments, predicted distribution was highly anisotropic. Infusing into the dorsal column, albumin was primarily confined to, white matter with limited penetration into adjacent gray matter. Distribution was determined primarily by the ratio of fiber-parallel to fiber-perpendicular hydraulic conductivity tensor components (k(wm-z)/k(wm-x)), the ratio of transverse white and gray matter hydraulic conductivity (k(wm-x)/k(gm)), and tissue porosity. Fits to previous experimental measures of axial and transverse spread, distribution volume, and protein recovery yielded an optimum k(wm-z)/k(wm-x) of approximately 20 at 0.1 microl/min. k(wm-x)/k(gm) of 100 was sufficient to match experimental transverse distribution data. Best fits to data at 0.1 microl/min were achieved by porosities characteristic of moderate edema (e.g., 0.26). Distribution also varied with catheter placement with more medial placement resulting in greater distribution volumes.

Albumins↗
PubMed1993

The effect of long-term high-dose naloxone infusion in experimental blunt spinal cord injury.

The effect of long-term continuous subcutaneous infusion of naloxone on blunt spinal cord injury in the rat was assessed using four tests of neurological function, seven histological categories, and two electrophysiological measures. All four neurological function tests showed a trend toward improvement in naloxone-treated animals: the degree of improvement was statistically significant in two of the four categories. A significant reduction in myelin sheath edema was found in the naloxone-treated animals. Although there was a decrease in corticomotor-evoked potentials complexity following injury, there was no significant difference in naloxone-treated animals. Somatosensory-evoked potentials were significantly increased in amplitude and latency in naloxone-treated animals. This increase was most apparent at 60 min: no difference was found by 3 weeks postinjury. These results confirm earlier reports that naloxone can ameliorate the functional neurological deficits of spinal cord injury. Naloxone also produces alterations in the somatosensory-evoked responses in the early phase of treatment and significantly reduces myelin sheath edema.

Animals↗
PubMed2003

Effect of preoperative amino acid infusion on thermoregulatory response during spinal anaesthesia.

BACKGROUND: Intravenous amino acid infusion during general anaesthesia prevents decreases in core temperature resulting from increased energy expenditure and heat accumulation. METHODS: We investigated whether such stimulation also occurs during spinal anaesthesia, which blocks sympathetic nervous activity. We examined the effect of i.v. amino acid infusion on changes in core temperature during spinal anaesthesia. Thirty-five patients were divided into two groups: an i.v. amino acid infusion group (4 kJ kg(-1) h(-1) starting 2 h before surgery); and a saline infusion group. Tympanic membrane core temperature, forearm-fingertip temperature gradient (an index of peripheral vasoconstriction) and mean skin temperature were measured for 90 min after the onset of spinal anaesthesia. RESULTS: Changes in mean arterial pressure and heart rate did not differ significantly between the groups during the study period. Mean final core temperature 90 min after induction of spinal anaesthesia was 35.8 (SEM 0.1) degrees C in the saline group and 36.6 (0.1) degrees C in the amino acid group (P<0.05). The increased level of oxygen consumption in the amino acid group compared with the saline group was preserved even after the onset of spinal anaesthesia. The thermal vasoconstriction threshold, defined as the tympanic membrane temperature that triggered a rapid increase in forearm-fingertip temperature gradient, was increased in the amino acid group [36.8 (0.1) degrees C] compared with the saline group [36.5 (0.1) degrees C] (P<0.05). CONCLUSIONS: Preoperative infusion of amino acids effectively prevents spinal anaesthesia-induced hypothermia by maintaining a higher metabolic rate and increasing the threshold core temperature for thermal vasoconstriction.

Adult↗
PubMed1998

[Effect of epidural pressure gradient on buprenorphine flux through the dural hole after combined spinal-epidural anesthesia--comparison between bolus injection and continuous infusion].

Combined spinal-epidural anesthesia is a useful technique. However, there has been no attempt to investigate the risk of epidural opioid, especially buprenorphine, flux through the dural hole. The purpose of this study was to compare the effect of epidural buprenorphine administered across the dura into subarachnoid space, between two different methods of administration; bolus injection (Group I) and continuous infusion (Group II). Sixty patients for transvaginal hysterectomy were divided into two groups. Group I received buprenorphine 0.1-0.2 mg with 0.25% bupivacaine, and Group II 0.4 mg with 0.25% bupivacaine 40 ml continuously (infusion rate was 1.7 ml.h-1). Pain relief was similar in both groups, but the total buprenorphine requirement was lower in Group I than in Group II. The incidence of nausea and vomiting was significantly higher in Group I than that in Group II, 73% and 16%, respectively. It indicates that the increase of nausea and vomiting is predominantly determined by a high rate of flux into subarachnoid space and only partly determined by blood concentrations. In contrast to continuous infusion, the drug movement through the dural hole may increase by bolus injection due to its higher pressure. We recommend careful injection of epidural buprenorphine such as by continuous infusion with low pressure after combined spinal-epidural anesthesia.

Adult↗
PubMedDate not supplied

Diuresis during fluid infusion : buffer nerve and spinal influences on it.

The rate and cumulative volume of diuresis were measured sequentially for each incremental infusion dose of 5 ml/kg body weight till a 100 ml/kg or more dose was reached. Normal saline (NS), Ringer-Locke (RL) and tender coconut water (TCW) were infused in three groups each of paraldehyde (PLD), and chloralose and urethane (C & U) anaesthetised dogs. The slow infusion rate of about 0.5 ml/kg/min was used. The RL infusion was repeated in vagotomised and/or carotid sinus (CS) denervated dogs and spinal dogs with or without intact vagi. During the NS and RL infusion schedules in PLD anaesthetised dogs produced much less urine than C & U groups. The order of minimum to maximum diuretic effect caused by these fluids were RL, NA and TCW in PLD groups and NA, TCW and RL in C & U groups. The study indicates that the type of anaesthesia and the composition of infusion fluid determines the rate of infusion induced diuresis. PLD anaesthesia has antidiuretic effect, which is not overcome by vagotomy. In C & U anaesthetised dogs the vagotomy and CS denervation performed separately greatly increased the rate of infusion induced diuresis but the diuresis largely decreased when combined surgery was performed. The diuresis in spinal dogs was very low, though in the vagotomised-spinal dogs, the rate of diuresis was more than in the spinal dogs.

Animals↗
PubMed1982

Intraspinal narcotic tolerance: preliminary experience with continuous bupivicaine HCL infusion via implanted infusion device.

Spinal opiate receptor tolerance is the major limitation of continuous intraspinal narcotic analgesia delivered by implanted reservoir pump. Six intractable pain patients receiving continuous epidural morphine were given trials of low dose bupivicaine HCL in order to assess the effects on implanted reservoir function, analgesia, and safety. Daily infusion of 2.6-18.8 mg bupivicaine HCL had no consistent effect on flow rates. Subjectively, three patients had at least partial relief of pain while their intraspinal morphine doses were weaned. No sympathectomy was appreciated at these doses. The future of continuous intraspinal analgesia might require further advances in implantable infusion pump technology to allow manipulation of both daily infusion doses and multiple intraspinal analgesics. Further study is needed to assess the safety and effectiveness of higher continuous intraspinal bupivicaine doses for chronic pain relief.

Artificial Organs↗
PubMed1987

Determination of cross tolerance in rat spinal cord using intrathecal infusion via sequential mini-osmotic pumps.

Continuous intrathecal (IT) infusion via ALZET mini-osmotic pumps was used to induced spinal tolerance to morphine in the rat. Naloxone (1 mg/kg IP), injected on day 3 of continuous IT morphine (10 micrograms/hr), produced mild withdrawal symptoms in all morphine-treated animals. In rats pretreated with continuous IT morphine (10 micrograms/hr) or saline, systemic morphine (2, 4, 8, 10 and 15 mg/kg IP) produced equivalent, dose-dependent antinociception using the tail-flick and paw pressure tests. The rostral and caudal distribution of methylene blue dye in rat spinal cord was determined on days 1-7 of continuous IT infusion. The dye remained localized near the catheter tip throughout infusion; maximum distribution was 1.5 cm rostrally and 1.0 cm caudally. The data indicate that morphine, infused at the rate of 10 micrograms/hr, does not undergo extensive redistribution in the spinal cord. A sequential, double mini-osmotic pump technique for cross tolerance studies in rat spinal cord is described. In rats pretreated with continuous IT norepinephrine for 4 days, the antinociceptive actions of continuous IT morphine were reduced but not significantly different from saline-pretreated animals. These data suggest that morphine, injected into the spinal cord, does not produce behavioural analgesia by activation of local adrenergic systems.

Analgesics↗
PubMed2004

Postoperative magnesium sulphate infusion reduces analgesic requirements in spinal anaesthesia.

BACKGROUND AND OBJECTIVES: Magnesium sulphate infusion during general anaesthesia reduces anaesthetic consumption and analgesic requirements. The aim of this study was to assess the effects of postoperative magnesium infusion on duration of block, sedation and analgesic consumption after spinal anaesthesia. METHODS: Fifty ASA I-II patients were included in the randomized double blind study. Spinal anaesthesia was performed at L3-4 or L4-5 interspace with 12.5 mg 0.5% heavy bupivacaine, using a 25 G Quincke needle. Patients received a 5 mg kg(-1) bolus of magnesium sulphate followed by a 500 mg h(-1) infusion or saline in the same volumes for 24 h. Time to first pain, analgesic request, return of motor function, visual analogue pain and sedation scores were evaluated every 4 h during the 24 h postoperative period. The t- and U-tests were used for statistical analyses. Data were expressed as mean +/- SD, with P < 0.05 being considered significant. RESULTS: Vital signs were stable during spinal anaesthesia and postoperative period. When compared to the control group, time to analgesic need was increased and total analgesic consumption was reduced in the magnesium group (meperidine consumption 60.0 +/- 73.1 mg control group, 31.8 +/- 30.7 mg magnesium group, P = 0.02). CONCLUSIONS: Magnesium sulphate infusion may be used as an adjunct for reducing analgesic consumption after spinal anaesthesia.

Adult↗
PubMed1995

Long-term clinical, electrophysiological and urodynamic effects of chronic intrathecal baclofen infusion for treatment of spinal spasticity.

Seventeen patients with severe disabling spinal spasticity were selected and treated by chronic intrathecal baclofen infusion using an implanted programmable pump. Nine patients were tetraparetic, seven were paraplegic and one paraparetic. Patients were regularly followed for 5 to 69 months (mean 37.5 months). The clinical efficacy of baclofen was estimated by means of evaluation of: hypertonia, spasms, pain and functional disability. All patients experienced significant amelioration of quality of life secondary to reduction of hypertonia, spasms and pain related to contractures. Neurogenic pain improved in 3 cases and remained unchanged in 3 others. In patients whose motor functions were partially preserved, various degrees of motor improvement were detected. Electrophysiological recordings of Polysynaptic flexion reflexes (FR) were obtained to control conditions, and under intrathecal baclofen, in order to quantify the spinal excitability responsible for spontaneous or induced spasms. Flexion reflex threshold was increased and amplitude proved to be very significantly reduced by chronic baclofen infusion in all our patients. Twelve patients with neurogenic bladder dysfunction were also evaluated by a clinically oriented questionnaire and by quantitative urodynamic recordings, before and after pump implantation. In patients with normal micturition, this was not changed by intrathecal baclofen. In patients with spastic bladder, intrathecal baclofen produced a decrease of detrusor hypertonia and hyperactivity in 50% of cases, with reduction of leakage and increase in functional bladder capacity.

Adolescent↗
PubMed2004

Pharmacological complications of the chronic baclofen infusion in the severe spinal spasticity. Personal experience and review of the literature.

AIM: To evaluate the pharmacological complications and side effects of the chronic intrathecal baclofen infusion in patients suffering from intractable spinal spasticity in our Department as well as in the literature. METHODS: The pharmacological complications and side effects observed at long-term follow-up in 25 patients with chronic intrathecal baclofen infusion are evaluated; the search of the literature complications was carried out in Medline and in Ingenta web sites. RESULTS: We have been able to observe in our series 3 (12%) patients with hypotonia, 2 with impairment on erection (8%) and 1 (4%) with constipation; 5 (20%) patients showed also tolerance but only 1 (4%) needed a ''drug holiday''. In the literature the side effects range from 4% to 16%. Moreover the tolerance is reported from 3% to 15%. The overdose has been reported from 0% to 14%, while the syndrome of withdrawal is reported in 16 patients with 6 fatalities. In our series these two last complications were not observed. CONCLUSIONS: Lethal pharmacological complications are rare and, if promptly diagnosed and treated, are reversible. Side effects of minor importance can impair the patient quality of live and needed to be adjusted to patient's requirements. This kind of therapy should be restricted to specialized centres.

Adult↗
PubMed1976

[Pressor action of propranolol; with special reference to relationship between the pressor action and peripheral vascular tone].

We showed in previous studies that pro pranolol produced a pressor action in the rat, and that this action was also observed in the spinal rat infused with adrenaline, noradrenaline and a mixture of isoproterenol and vasopressin, but not with vasopression alone. The action was also observed in the guinea pig infused with adrenergic beta-stimulants. In the present work, conditions in the peripheral vessels in which propranolol observed in the spinal rat infused with a mixture of various doses of isoproterenol and vasopressin. The effect of propranolol on the blood pressure in guinea pigs and rabbits with a reduced vasoconstrictive tone in the peripheral vascular beds with alpha-blockade was studied. Propranolol produced a pressor action in the spinal rat infused with a mixture of isoproterenol and vasopressin, and the magnitude of the rise depended on the mixing rate of the doses of these two drugs. The drug also produced a sustained rise in blood pressure in guinea pigs and rabbits treated with alpha-blockers. Thus, it is concluded that propranolol produces a marked pressor action when peripheral vessels are maintained in conditions with an appropriate constrictive and beta-adrenoceptive vasodilator tone.

Adrenergic alpha-Antagonists↗
PubMed1994

Preservation of post-compression spinal cord function by infusion of hypertonic saline.

We tested the hypothesis that the administration of hypertonic saline, following traumatic injury to the spinal cord, could enhance blood flow to the cord and preserve function. Rats were used as the experimental model. Direct compression of the spinal cord for a period of 10 min was done to produce the injury. Somatosensory evoked potentials (SSEPs) and spinal cord blood flow were measured using a laser Doppler flow meter throughout the experiment. Comparisons of the blood flow values and SSEPs were made among four different groups of animals. The control group received no fluid resuscitation after injury. A second group received a bolus injection of isotonic saline (0.5 ml/100 g) as an i.v. infusion over a period of 1 min. A third group received a bolus infusion of 7.5% NaCl (0.5 ml/100 g) over a period of 1 min. The final group received 4 ml/100 g of 0.9% NaCl over a period of 10 min. The administration of hypertonic saline significantly reduced spinal cord vascular resistance during the first 10 min after infusion. During the first 30 min after the removal of compression, spinal cord blood flow was greater in the hypertonic saline group than in the other three groups. The hypertonic saline group had a reactive hyperemia whereas the flow in the other groups remained at or below control values. Beginning 10 min after injury and for the remainder of the 1-h observation period, the latency of the cortical peak of the SSEP in the group receiving hypertonic saline was significantly shorter than in any of the other three groups. These results indicate that the administration of hypertonic saline enhances blood flow and preserves spinal cord conduction following traumatic injury to the spinal cord.

Animals↗
PubMed2002

Epidural infusion pressure in degenerative spinal disease before and after epidural steroid therapy.

UNLABELLED: The analgesic mechanism of epidural steroids in reducing pain associated with degenerative spinal disease (DSD) is poorly understood. We report increased inline epidural infusion pressure in patients with DSD and assess whether this phenomenon is affected by administration of an epidural steroid injection. We collected data during epidural placement for routine surgery or epidural steroid therapy. Using a 17-gauge Tuohy needle, with patients in the right lateral decubitus position, loss of resistance to 2 mL of saline identified the epidural space. Two minutes later the needle was attached to saline-filled tubing connected to a pressure transducer (Baxter PX 260 pressure monitoring kit with Truwave TM disposable pressure transducer). In the first part of the study, 4 successive boluses of 3 mL of local anesthetic were administered at a rate of 6 mL/min to 15 patients (age 47 +/- 6 yrs) with radicular back pain and magnetic resonance imaging (MRI) or computed tomography (CT) evidence of DSD, and to 8 control patients with no history of back pain (age 44 +/- 5 yr) while inline epidural infusion pressure was measured. In the second part of the study 44 patients with low back pain and MRI or CT evidence of DSD presenting to the pain clinic were infused with 8 mL of 0.125% bupivacaine and 40 mg of methylprednisolone (20 mg/mL) at a rate of 6 mL/min while inline epidural infusion pressure was measure and recorded. This was repeated 3 wk later. Initially, DSD patients had significantly increased infusion pressures over normals, which most likely reflects outflow resistance or obstruction. A significant decrease in inline epidural infusion pressure was observed after epidural steroid treatment. This change in pressure may indicate efficacy from epidural steroid injection. IMPLICATIONS: During injection into the epidural space we observed increased resistance in patients with degenerative spinal disease. This resistance was significantly less when measured 3 wk after an epidural steroid injection. This change in pressure may indicate efficacy from epidural steroid injection.

Adult↗
PubMedDate not supplied

Functional improvement in patients with severe spinal spasticity treated with chronic intrathecal baclofen infusion.

In this retrospective study we evaluated the efficacy and functional benefits of chronic intrathecal baclofen infusion in severe spinal spasticity. Twenty patients with a diagnosis of severe intractable spinal spasticity were evaluated prior to implantation of a programmable pump for chronic intrathecal baclofen therapy and at follow up, which ranged from 12 to 36 months (mean 22.4 months). The mean age of the patients was 39.1 years. The prevailing pathology was multiple sclerosis. All were unable to walk. Patient assessment was based on the Ashworth Scale, the Spasms Frequency Scale, self-reported pain and Functional Independence Measure (FIM) scores. The Wilcoxon test was used for statistical analysis. A statistically significant decrease in muscle tone, spasms and pain was observed in all the patients. The Ashworth score decreased from 4.4 to 1.8, the spasms frequency score from 2.5 to 0.5 and the self-reported pain score from 5.5 to 2.3. The FIM score also showed a statistically significant change (increasing from a mean of 33.8 to 58.7). Two patients in employment were able to return to work. No severe side effects were observed. Chronic intrathecal baclofen infusion was seen to produce a functional improvement in patients with severe spinal spasticity, particularly as regards bathing, comfortable wheelchair sitting and mobility.

Adult↗
PubMed2001

A comparison of minidose lidocaine-fentanyl spinal anesthesia and local anesthesia/propofol infusion for outpatient knee arthroscopy.

UNLABELLED: Traditional methods of spinal anesthesia have proven problematic in the outpatient setting. Minidose lidocaine-fentanyl spinal anesthesia (SAB(MLF)) may be the adaptation necessary to reestablish spinal anesthesia in this venue. One hundred patients scheduled for outpatient knee arthroscopy were randomized to receive either local anesthesia plus a titrated IV propofol infusion (LA/PI) or SAB(MLF) using 20 mg lidocaine 0.5% + 20 microg fentanyl. Patients received midazolam 0.02-0.03 mg/kg IV and fentanyl 0.75-1.0 microg/kg IV upon arrival in the operating room before lumbar puncture or propofol infusion. The propofol infusion was begun at 50-75 microg. kg(-)(1). min(-)(1) and titrated to maintain patient comfort. Boluses (200-400 microg/kg) were given as needed. Local anesthesia included 30 mL lidocaine 1% with epinephrine 1:200,000 intraarticularly plus 10 mL at the portal sites. Three patients (6%) in the LA/PI group versus none in the SAB(MLF) group required general anesthesia. Airway support was required in 54% of the LA/PI patients and in none of the SAB(MLF) patients. Total operating room time (43 vs 45 min), time to home readiness (43 vs 45 min), actual discharge times (73.5 min in both groups), and the incidence of discharge >90 min (22% vs 24%) were the same for both LA/PI and SAB(MLF) groups. LA/PI and SAB(MLF) groups differed in terms of postoperative pruritus (8% vs 68%), pain (44% vs 20%), nausea (8% vs 22%), and ability to void before discharge (56% vs 32%). One patient in each group had mild difficulty initiating voiding at home, but neither required medical attention. In both groups, 90% of patients were either "satisfied" or "very satisfied" with their anesthetic. The two techniques provided comparable patient satisfaction and efficiencies both intraoperatively and in postoperative recovery and discharge. The efficiencies of these techniques were not dependent on special provisions of the physical plant or the practice model. IMPLICATIONS: Both local anesthesia supplemented by a titrated IV propofol infusion and minidose lidocaine-fentanyl spinal anesthesia for outpatient knee arthroscopy provide high patient satisfaction with equally rapid recovery and discharge.

Adolescent↗
PubMed1979

Effect of dopamine on hypotension induced by spinal anesthesia.

Chronically instrumented, near-term pregnant sheep were subjected to autonomic blockade with spinal anesthesia. Systemic arterial pressure, heart rate, and uterine blood flow decreased and uterine vascular resistance increased during the spinal blockade. Infusion of dopamine during the spinal hypotension corrected the disturbed circulatory parameters. These data provide evidence that: (1) the peripheral circulation of the near-term pregnant sheep is as sensitive as that of pregnant women to autonomic blockade, (2) the sensitivity is probably related to factors other than the changes in venous pressure in areas below the pelvis, and (3) dopamine represents a useful agent in the management of spinal hypotension.

Anesthesia, Spinal↗
PubMedDate not supplied

Effects of immediately initiating an epidural infusion in the combined spinal and epidural technique in nulliparous parturients.

BACKGROUND AND OBJECTIVES: Intrathecal fentanyl with bupivacaine provides rapid labor analgesia of limited duration. We investigated the effect of initiating an epidural infusion of 0.1% ropivacaine with fentanyl 2 microg/mL and epinephrine 1:400,000 (REF) on the duration of analgesia and incidence of side effects after intrathecal injection in the combined spinal and epidural technique. METHODS: Thirty-four nulliparous parturients with a cervical dilation of 3 to 5 cm were randomized to receive epidural saline or REF at 10 mL following the intrathecal injection of fentanyl 25 microg and bupivacaine 2.5 mg. Degree of analgesia, severity of pruritus, motor block, blood pressure, and sensory level to coolness were assessed until the patient requested additional analgesia. RESULTS: Analgesia was significantly longer in the REF group, 158.4 +/- 59.6 minutes versus 103.8 +/- 26.2 minutes. The decrease in blood pressure compared with the blood pressure at intrathecal injection was greater for the REF group at all times, but achieved statistical significance at 60 minutes. There was no difference in ephedrine use, pruritus, or motor block between groups. There was no difference in sensory level to coolness at 90 minutes after intrathecal injection between groups. CONCLUSIONS: Initiating an infusion of REF prolongs the duration of analgesia, but also results in a greater decrease in blood pressure. Despite this effect on blood pressure, there was no difference in ephedrine use.

Adjuvants, Anesthesia↗