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PubMed1983

Pressure-absorption responses to the infusion of fluid into the spinal cord central canal of kaolin-hydrocephalic cats.

The resistance to cerebrospinal fluid (CSF) absorption through the alternative CSF absorption pathway in kaolin-induced hydrocephalic cats was measured by the constant infusion-manometric test. The cerebral ventricles were bypassed, and artificial CSF was infused directly into the central canal of the spinal cord. The infusion rates were increased stepwise from 0.022 to 0.168 ml/min when the capacity to absorb CSF was exceeded. There was an initial increase in resistance which was associated with the emergence of infusion fluid through a slit-like opening in the dorsal columns of the lower lumbar spinal cord. The resistance to flow decreased when the infusion rate was greater than 0.086 ml/min. Fluid accumulated in the spinal subarachnoid space when the ability to absorb was exceeded. The diversion of this fluid caused the pressure in the spinal cord central canal to fall rapidly. The results suggest that the CSF absorption deficit in chronic kaolin-induced hydrocephalic cats is probably caused by the restriction of CSF flow from the central canal through the spinal cord and into the spinal subarachnoid space. As a result of kaolin, the central canal is sufficiently dilated to permit, during infusion, the flow of at least five times as much CSF as the hydrocephalic cats produce. It is not clear whether the overloading of the CSF absorption mechanism is due to the restrictions imposed by the size of the subarachnoid space, or to the structures in this space involved with the return of CSF to the blood.

Absorption↗
PubMed2001

The effects of lactated Ringer's solution infusion on cardiac output changes after spinal anesthesia.

UNLABELLED: We evaluated the effects of an infusion of lactated Ringer's (LR) solution on changes in cardiac output (CO) after spinal anesthesia. Seventy-five patients scheduled for lower extremity surgery under spinal anesthesia were studied. We measured CO (impedance cardiography method) and blood pressure for 25 min before and 30 min after spinal anesthesia. Patients were randomly assigned to three groups. In the No Infusion group, no LR solution was given during the period of measurements. The LR Before group received 12 mL/kg of LR solution within 20 min before spinal anesthesia. The LR After group received 12 mL/kg of LR solution within 20 min starting immediately after spinal anesthesia. After spinal anesthesia, CO decreased by 13.9% in the No Infusion group. In the LR Before group, CO increased after the infusion by 20% and returned to baseline value 30 min after spinal anesthesia. In the LR After group, CO increased after spinal anesthesia, and 30 min after spinal anesthesia, CO was 11.3% above baseline. We conclude that the decrease in CO after spinal anesthesia can be prevented by the infusion of an LR solution, with CO reaching the highest value while the infusion is running. IMPLICATIONS: We studied the effects of lactated Ringer's solution infusion on cardiac output changes after spinal anesthesia. If the patients received no infusion, cardiac output decreased after spinal anesthesia. However, if the patients received lactated Ringer's solution infusion, cardiac output was maintained.

Adult↗
PubMed2001

Metaraminol infusion for maintenance of arterial blood pressure during spinal anesthesia for cesarean delivery: the effect of a crystalloid bolus.

We randomly allocated women having elective cesarean delivery to receive either no bolus (Control Group, n = 31) or 20 mL/kg lactated Ringer's solution (Bolus Group, n = 35) IV before spinal anesthesia. An infusion of metaraminol started at 0.25 mg/min was titrated to maintain systolic arterial blood pressure in the target range 90%-100% of baseline. The total dose of metaraminol required up to the time of uterine incision was similar between the Control Group and the Bolus Group (3.62 +/- 1.20 vs 3.27 +/- 1.39 mg, P = 0.3). However, the Control Group required more metaraminol in the first 5 min (1.29 +/- 0.60 vs 0.96 +/- 0.58 mg, P = 0.025) and a faster maximum infusion rate (0.45 +/- 0.20 vs 0.32 +/- 0.13 mg/min, P = 0.002) compared with the Bolus Group. There was no difference between groups in regards to changes in systolic arterial blood pressure or heart rate over time, or maternal or neonatal outcome. We conclude that when metaraminol is used to maintain arterial pressure during spinal anesthesia for cesarean delivery, crystalloid bolus is not essential provided that sufficient vasopressor is given in the immediate postspinal period.

Adult↗
PubMed2003

Periodic abstinence enhances nociception without significantly altering the antinociceptive efficacy of spinal morphine in the rat.

Naloxone administration in the opioid dependent rat is associated with spinal glutamate release and NMDA receptor activation which reportedly is also responsible for opioid tolerance. We hypothesized that episodic withdrawal during chronic infusion of spinal morphine might paradoxically enhance tolerance. Rats (24/group) infused with intrathecal morphine (M) for 4 days (20 nmol/microl per h) were given a daily subcutaneous (s.c.) injection of naloxone 0.6 mg/kg per 0.2 ml (MN) or saline 0.2 ml (MS). A third saline infused group was given daily s.c. saline 0.2 ml (SS). Latencies (rear paw hot box) were tested immediately prior to each daily injection. After termination of each infusion, the dose effect of spinal morphine (0.1, 1, 10, and 100 nmol) was examined. The MN group showed a significantly greater decline in daily latencies compared with the MS group, but also had greater withdrawal hyperalgesia upon termination of the infusion. Dose response to spinal morphine was not significantly different in either MS or MN groups. Periodic abstinence thus enhanced nociception without significantly altering the antinociceptive effect of spinal morphine in this group.

Analgesics, Opioid↗
PubMed1987

Long-term intrathecal baclofen infusion for treatment of spasticity.

Seven patients with spasticity of spinal cord origin have been maintained for up to 2 years with continuous spinal intrathecal infusion of baclofen. Prior to treatment, all of the patients had severe rigidity in their lower limbs and most had frequent and extensive spontaneous spasms, all of which greatly interfered with their activities of daily living. Oral antispasmodic medications were ineffective or caused central side effects. The patients underwent implantation of a programmable drug pump connected to a lumbar subarachnoid catheter. Within days of beginning continuous intrathecal baclofen infusion, the muscle tone was reduced to normal levels and spasms were eliminated. Over the ensuing months, muscle tone remained normal, but short-duration spasms could be induced by some activities. The greatest benefits to the patients were improvement in activities of daily living and better sleep due to reduced spasms. The baclofen doses were increased over the first few months but then were stabilized or only increased slightly, with the maximum dose being 650 micrograms/day. The most serious complications were two drug overdoses which took several days to clear up and were due to malfunctions of an earlier pump model. Baclofen clearance from the cerebrospinal fluid occurs with a half-life of 5 hours. The most serious concern in maintaining patients indefinitely on intrathecal baclofen is whether drug tolerance will eventually occur.

Adult↗
PubMed1995

Selective degeneration of inhibitory interneurons in the rat spinal cord induced by intrathecal infusion of acromelic acid.

We investigated the characteristics of the neurotoxicity mediated by non-N-methyl-D-aspartic acid (NMDA)-type glutamate receptors in the spinal cord by infusing rats intrathecally with three specific agonists (acromelic acid A (ACRO), kainic acid and 1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)). When ACRO was infused intrathecally continuously for 2 h, the rats developed dose-dependent flaccid paraplegia during the infusion, followed by pure motor, rigid-spastic, long-lasting paraparesis (ED50: 220 pmol/h). The paraparetic rats showed selective degeneration of interneurons in the spinal cord with about 50% loss of their contents of glycine and aspartic and glutamic acids. The alpha-motoneurons in the ventral horns were largely free from permanent damage. These changes were selectively ameliorated by concomitant administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist at non-NMDA receptors. Kainate induced long-lasting paraplegia with neuronal damage at doses about 40-times higher than those of ACRO that caused paraplegia. When examined 30 days after kainate infusion, the neurotransmitter markers had decreased markedly in the lumbar cords of the rats with long-lasting paraplegia. Intrathecal infusion of large doses of AMPA caused long-lasting flaccid paraplegia, which were accompanied by extensive necrosis in the caudal spinal cord. It seems that ACRO exerts its unique pharmacological actions by activating a subclass of non-NMDA receptors distinct from those activated by kainate and AMPA, and may become a useful tool for investigating the biological roles of glutamate receptors.

Animals↗
PubMed2004

Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery.

UNLABELLED: In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery. IMPLICATIONS: In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine.

Acid-Base Equilibrium↗
PubMed1989

Time course characteristics of tolerance development to continuously infused antinociceptive agents in rat spinal cord.

By using a constant-rate, fixed concentration intrathecal infusion model, the time course of change in hot plate (HP) response latencies over a 7-day period was examined in rats receiving constant infusion of saline (vehicle), morphine (MOR (2, 6 or 20 nmol/hr), sufentanil (SUF) (0.06, 0.2 or 0.6 nmol/hr), D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO) (0.1, 0.3 or 1.0 nmol/hr) (mu opioids), D-Ala2-D-Leu5-enkephalin (DADLE) (2,6 or 20 nmol/hr) (delta opioid), ST-91 (3, 10 or 30 nmol/hr) (alpha-2 agonist) or the combination of ST-91 + MOR. Three important observations were made: 1) A concentration-dependent elevation in HP latency was observed on day 1 (order of potency: DAMGO = SUF greater than MOR greater than or equal to DADLE greater than or equal to ST-91 + MOR greater than or equal to ST-91) with a gradual return to saline-infused values observed for all concentrations of all drugs by 3 to 5 days. 2) The rate of tolerance development, estimated by calculation of the exponential decay half-life from peak day 1 HP, was not different as a function of drug dose. The area under the 7-day tolerance curve (response latency x day) was directly proportional to infusion concentration and to peak HP effect on day 1. These two calculations both suggest that the rate at which the tolerance adaptation of drug occurs to agonist effects is similar for agents acting upon mu, delta and alpha-2 receptors in rat spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1990

Use of infusion devices for epidural or intrathecal administration of spinal opioids.

The use of infusion devices for epidural or intrathecal administration of spinal opioids is described. The risks of infection and mechanical catheter complications, the need for escalating doses, reservoir volume, drug stability, and cost are practical considerations associated with use of both external and internal infusion systems. Use of patient criteria to identify suitable candidates for intraspinal administration of pain medication helps ensure successful management. The criteria for intraspinal delivery pumps are safety, accuracy, reliability, ease of management by the patient and the health-care professional, and compatibility of the drug with the pump components. The primary factors to consider when comparing pumps to be used for intraspinal delivery of pain medication are the volume and flow rate requirements of the devices. External portable infusion devices are classified according to the mechanism of operation into three primary groups: syringe pumps, peristaltic mechanisms, and elastomeric reservoir pumps. Portable patient-controlled analgesia pumps that have syringes, flexible reservoir bags, and elastomeric reservoirs have been developed. Implanted systems with flow rates that are preset at the factory make pain management more difficult when the patient requires changes or escalations in doses over time. A programmable implanted pump is available. Two advantages of continuous epidural or intrathecal infusion are (1) the peaks and valleys of pain relief with bolus injections are eliminated and (2) the need for multiple injections is reduced. Patient-controlled analgesia (PCA) pumps enhance the efficacy of continuous infusions by allowing the patient to administer bolus doses to control acute pain.

Humans↗
PubMed2000

The use of intravenous atropine after a saline infusion in the prevention of spinal anesthesia-induced hypotension in elderly patients.

UNLABELLED: We investigated the efficacy of IV atropine for preventing spinal anesthesia-induced hypotension in elderly patients. Seventy-five patients undergoing transurethral prostate or bladder surgery were randomized to receive either placebo (n = 25), atropine 5 microg/kg (small-dose atropine, n = 25) or atropine 10 microg/kg (large-dose atropine, n = 25) after the induction of spinal anesthesia. All the patients received an IV infusion of 10 mL/kg 0.9% normal saline over 10 min before the induction of anesthesia. The systolic blood pressure decreased in all three groups after spinal anesthesia. There was a significant increase in the mean heart rate in both atropine groups as compared to the placebo group (placebo group: 78 bpm, 95% confidence interval [CI]: 76.6-78.5; small-dose atropine group: 86 bpm, 95% CI 83.9-88.8; large-dose atropine group: 97 bpm, 95% CI 94.5-100.3; P: = 0.001). There was a significant decrease in the incidence of hypotension in patients who received atropine (placebo group: 76%, small-dose atropine group: 52%, large-dose atropine group: 40%, P: = 0.03). The mean dose of ephedrine required was significantly decreased in the atropine groups (placebo group: 12.2 mg [SD= 10.5], small-dose atropine group: 7.4 mg [SD= 10.0], large-dose atropine group: 5.4 mg [SD= 8.7 mg], P: = 0.048). The total amount of IV fluid and number of patients requiring metaraminol in addition to 30 mg of ephedrine were not significantly different among the three groups. Significant side effects, such as confusion, ST segment changes or angina were not detected in any of the patients. We conclude that IV atropine may be a useful supplement to the existing methods in preventing hypotension induced by spinal anesthesia. IMPLICATIONS: IV atropine increases heart rate in a dose-dependent manner in elderly patients undergoing spinal anesthesia. It reduces the incidence of hypotension and the dose of ephedrine required. Small-dose atropine may be a useful supplement in preventing spinal anesthesia-induced hypotension in elderly patients.

Aged↗
PubMed1982

Dopaminergic effects on tail-flick response in spinal rats.

R-Apomorphine (0.02-1.75 mumol/kg), administered by intrathecal infusion to spinalized rats, caused a dose-dependent increase in tail-flick latency. The effect of R-apomorphine was counteracted significantly by the dopaminergic receptors antagonists cis-flupenthixol (0.20-3.94 mumol/kg) and (+)-butaclamol (0.78 mumol/kg), but not by their enantiomers nor by phenoxybenzamine (29.40 mumol/kg) or methysergide (29.40 mumol/kg). The findings suggest that dopaminergic mechanisms play a role in the modulation of nociception in the spinal cord.

Animals↗
PubMed2001

Comparison of metaraminol and ephedrine infusions for maintaining arterial pressure during spinal anesthesia for elective cesarean section.

BACKGROUND: Although ephedrine is usually recommended as the first-line vasopressor in obstetrics, its superiority over other vasopressors has not been proven in humans. METHODS: In a double-blind study, the authors randomized women having elective cesarean section with spinal anesthesia to receive an intravenous infusion of ephedrine, starting at 5 mg/min (n = 25), or metaraminol, starting at 0.25 mg/min (n = 25), titrated to maintain systolic arterial pressure in the target range 90-100% of baseline. Umbilical cord gases, maternal hemodynamics, uterine artery puLsatility index, and Apgar scores were compared. RESULTS: Systolic arterial pressure was maintained more closely in the target range in the metaraminol group compared with the ephedrine group. In the metaraminol group, umbilical arterial pH was greater (median and interquartile range, 7.31 and 7.31-7.33 vs. 7.24 and 7.14-7.29; P < 0.0001), and umbilical venous pH was greater (7.36 and 7.35-7.38 vs. 7.33 and 7.26-7.34; P < 0.0001) compared with the ephedrine group. No patient in the metaraminol group had umbilical arterial pH less than 7.2, compared with nine patients (39%) in the ephedrine group (P = 0.0005). Apgar scores were similar between groups. Changes in uterine artery pulsatility index were similar between groups. CONCLUSIONS: When used by infusion to maintain arterial pressure during spinal anesthesia for cesarean section, metaraminol was associated with less neonatal acidosis and more closely controlled titration of arterial pressure compared with ephedrine.

Adult↗
PubMed2005

Resting and evoked spinal substance P release during chronic intrathecal morphine infusion: parallels with tolerance and dependence.

Spinal opiate analgesia is associated with presynaptic inhibition of release of excitatory neurotransmitters/neuromodulators, e.g., substance P (SP), from primary afferent terminals. Chronic intrathecal (i.t.) administration of opiates such as morphine results in an initial analgesia followed by tolerance and a state of dependence. In this study, we examined the resting and evoked neurokinin 1 receptor (NK1r) internalization, indicative of endogenous SP release, in dorsal horn neurons of the lumbar spinal cord by immunocytochemistry during chronic i.t. infusion of morphine in rats. Noxious mechanical stimulation (compression) applied to unilateral hind paw evoked a significant increase in NK1r internalization in lamina I neurons in the ipsilateral dorsal horn. Intrathecal morphine infusion (40 nmol/microl/h) for 1 day possessed similar analgesic efficacy as acute morphine and blocked compression-induced spinal NK1r internalization. After 5 days of morphine infusion, thermal escape latencies were the same as in preinfusion animals or saline-infused controls, and compression-evoked NK1r internalization was no longer suppressed. Systemic administration of naloxone to rats on day 6 of morphine infusion resulted in prominent withdrawal behaviors and a concomitant increase in NK1r internalization in dorsal horn. The naloxone-induced internalization was blocked by NK1r antagonist L-703,606 [cis-2-(diphenylmethyl)-N-[(2-iodophenyl)methyl]-1 azabicyclo[2.2.2]octan-3-amine] or pretreatment with capsaicin, confirming that the internalization is due to the endogenous SP release from the primary afferents. We conclude that inability to suppress release of excitatory neurotransmitters/neuromodulators from primary afferents by morphine after chronic exposure is an important component in spinal morphine tolerance, and excessive release from these afferents contributes to the spinal morphine withdrawal syndrome.

Animals↗
PubMed2005

[Metabolic and immune response to spinal vs intravenous morphine for analgesia after radical prostatectomy].

OBJECTIVE: To study differences between the endocrine-metabolic and immune cell responses to spinal or intravenous administration of morphine for analgesia after radical prostatectomy. MATERIAL AND METHODS: Prospective study of 60 patients randomized to 2 groups: in group A (n=30) morphine for postoperative analgesia was infused intravenously and in group B (n=30) morphine was infused into the spinal canal. Changes in leukocyte populations and lymphocyte subpopulations in peripheral blood and blood from surgical drains (local) were analyzed to study immune cell response to morphine administration. Cortisol, corticotropin, growth hormone, glucose, and immunoglobulin levels in peripheral blood were measured as indicators of metabolic and humoral immune responses. RESULTS: Both groups developed lymphopenia in peripheral blood. The group treated with spinal morphine had significantly lower CD4+ cell counts in peripheral blood P<0.05. No differences were found in the local leukocyte response in either group. Significant differences were found in natural killer and CD4+ cell counts both locally and in peripheral blood P<0.05. There was humoral immune response suppression in both groups; however, it was more marked in the group treated with spinal morphine and the difference was significant P<0.05. The metabolic response was greater in the group treated with intravenous morphine. CONCLUSION: Patients who received morphine by spinal infusion had a less marked endocrine-metabolic response. Although local cell responses were similar in the 2 groups, the response in peripheral blood was different, possibly reflecting different mechanisms of central modulation of the inflammatory response to stress.

Adrenocorticotropic Hormone↗
PubMed1991

Long-term, open catheterization of the spinal subarachnoid space for continuous infusion of narcotic and bupivacaine in patients with "refractory" cancer pain. A technique of catheterization and its problems and complications.

The technique of long-term, open catheterization of the spinal subarachnoid space for infusion of analgesics in patients with refractory cancer pain is sparsely reported in the literature. We report on a technique using 18G Portex nylon catheters and 16G-17G Tuohy needles, and its problems and complications. One hundred fifty-seven catheters were inserted in 142 patients, in most of them (79%) under deep sedation and local anesthesia. Attempts were made to place the catheter tip as close to the painful segments as possible. The catheters were tunneled subcutaneously (87% of them paravertebrally, over the shoulder, and further parasternally to the third chondrocostal cartilage). The Luer connections of the catheters were fixed to the patients' skin with monofilament steel sutures of dimension 0 and connected to a bacterial filter. At the end of the procedure, 10 ml isotonic saline was injected intrathecally to prevent postspinal puncture headache. Absorbent and impermeable dressings were applied over the tunnel exit, catheter Luer connection and bacterial filter. Antibiotics were given on the day of insertion and 2 days thereafter. During the insertion procedure, the following problems and complications were encountered; two or more attempts before successful spinal-dural puncture (32%), accidental puncture of an extradural vessel (10%), difficult dural puncture (18%), absence of free dripping of cerebrospinal fluid (CSF) in spite of successful dural puncture (4%), blood-stained CSF (9%), radicular pain and paresthesiae (4%), difficult advancement of the catheter (6%), difficult tunneling (11%), and bleeding in the tunnel (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Complete prevention of postischemic spinal cord injury by means of regional infusion with hypothermic saline and adenosine.

Spinal cord injury after operations on the descending thoracic and thoracoabdominal aorta remains a persistent clinical problem. Previous attempts to decrease the risk of this devastating complication by lowering the rate of metabolism of the spinal cord have met with varying success. We hypothesized that the tolerance of the spinal cord to an ischemic insult could be improved by means of adenosine. Twenty New Zealand white rabbits underwent 40 minutes of isolated infrarenal aortic occlusion after heparin anticoagulation. Clamps were placed both below the left renal vein and above the aortic bifurcation. In 10 rabbits (group A), a bolus of adenosine (100 mg) was infused into the isolated aortic segment immediately after crossclamping and this bolus was followed by a flush of hypothermic saline (8 degrees C, 30 ml/kg) over the first 10 minutes of ischemia. In one control group of five animals (group B), the descending infrarenal aorta was crossclamped without infusion of adenosine or saline. In another control group of five animals (group C), the aortic segment was flushed with normothermic saline (37 degrees C) in a fashion identical to that of the study group. The aortic clamps were removed after 40 minutes, the abdomen was closed, and the animals were allowed to recover from anesthesia. Spinal cord function was assessed 12, 24, 48, 72, and 96 hours after operation by the Tarlov scale. All animals were put to death at 96 hours after operation and spinal cords were harvested for histologic analysis. The spinal cord function of all group A animals was fully intact with Tarlov scores of 5; group B and group C animals were all paraplegic with Tarlov scores of 0 (p < 0.001, general linear models analysis of variance). Histologic examination of spinal cords from group A rabbits revealed no evidence of cord injury, whereas spinal cords from groups B and C had evidence of extensive cord injury with central gray necrosis, axonal swelling, dissolution of Nissl substance, and astrocyte and macrophage infiltration. Regional infusion of the crossclamped infrarenal rabbit aorta with hypothermic saline and adenosine completely prevented paraplegia in our model despite a 40-minute ischemic insult.

Adenosine↗