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PubMed2002

Group I metabotropic glutamate receptor antagonists block secondary thermal hyperalgesia in rats with knee joint inflammation.

Activation of ionotropic glutamate receptors has been shown previously to be essential for the development of secondary thermal hyperalgesia. The present study assessed involvement of group I metabotropic glutamate receptors (mGlu) in both the induction and maintenance phases of secondary thermal hyperalgesia initiated by knee joint inflammation in rats. The dose dependence of each drug in antagonism of thermal hypersensitivity was demonstrated in pre- and post-treatment paradigms. Knee joint inflammation was induced by injection of kaolin and carrageenan. Four hours later the paw withdrawal latencies were significantly shorter than baseline values. Rats were pretreated by spinal microdialysis infusion of group I mGlu receptor antagonists, LY393053 [(+/-)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid], LY367385 [(S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid], or AIDA [(R,S)-1-aminoindan-1,5-dicarboxylic acid/UPF 523] before knee joint injection. The paw withdrawal latencies measured 4 h after the injection were significantly longer in the presence of group I mGlu receptor antagonists than those of the artificial cerebrospinal fluid-treated arthritic control group. Post-treatment with the group I mGlu receptor antagonists LY367385 and AIDA allowed significant recovery of the paw withdrawal latencies after the onset of the knee joint inflammation. The knee joint inflammation itself was not affected by either treatment. The results of the present study indicate that secondary thermal hyperalgesia can be effectively attenuated during both the development and maintenance phases of acute knee joint inflammation by spinal application of specific group I mGlu receptor antagonists.

Animals↗
PubMed1997

Intrathecal baclofen in tetanus: four cases and a review of reported cases.

OBJECTIVE: Spasms in patients with generalized tetanus can be suppressed by a spinal intrathecal infusion of baclofen. We report on four patients and review reported cases treated by this method elsewhere. DESIGN: Intrathecal baclofen infusion was started with a bolus dose (300-500 micrograms) and continued at a steady rate of 500-1000 micrograms/day. The dose was increased in daily steps as needed. RESULTS: Doses of baclofen of 500, 1000, or 2000 micrograms/day were effective in three patients, while 1500 micrograms/day was insufficient in the fourth. Bradycardia and hypotonia occurred in one patient at a dose of 2000 micrograms/day but resolved after the dose was reduced to 1500 micrograms/day. Another patient developed hypotonia when a bolus of 500 micrograms was given after a steady infusion of 1500 micrograms/day. Voluntary movements were preserved in one and returned in two patients when sedation, induced by initial diazepam infusions, receded. The fourth patient needed diazepam during most of the treatment with intrathecal baclofen and required mechanical ventilation while being treated with baclofen. CONCLUSIONS: A catheter position higher than T11 would possibly have yielded better results. It may be necessary to adapt the dose during the course of the illness. The preservation of respiratory drive and voluntary movements is the main advantage of treating tetanus with intrathecal baclofen. Additionally it helps to reduce sympathetic hyperactivity. Mortality may thereby be reduced.

Adult↗
PubMed1994

Comparison of prophylactic angiotensin II versus ephedrine infusion for prevention of maternal hypotension during spinal anesthesia.

OBJECTIVE: Our purpose was to study the efficacy of ephedrine versus angiotensin II prophylactic infusions to counter maternal hypotension that occurs during spinal anesthesia at cesarean delivery. STUDY DESIGN: Healthy pregnant women undergoing elective repeat cesarean delivery at term with spinal anesthesia were randomized either to a control group (n = 10) or to one of two prophylactic infusion groups: angiotensin II (n = 10) or ephedrine (n = 10). Prophylactic infusions were titrated to a maternal diastolic blood pressure 0 to 10 mm Hg above baseline. Maternal and fetal blood samples for angiotensin II levels and acid-base status were obtained. Student's t test, chi 2, and analysis of variance were used. RESULTS: Mean arterial pressures were maintained after spinal anesthesia in the ephedrine and angiotensin II groups but decreased (p < 0.05) in the control group. Maternal angiotensin II levels rose with angiotensin II infusions but were unaltered in the other groups. Umbilical artery and vein angiotensin II levels were unaltered by angiotensin II infusions. Mean umbilical artery blood pH was lower (p < 0.05) in the ephedrine group than in the angiotensin II and control groups. CONCLUSIONS: In the healthy term fetus there is an advantage in using angiotensin II to maintain maternal blood pressure during regional anesthesia.

Adult↗
PubMed1980

Role of the autonomic nervous system in the mediation of LHA electrical stimulation-induced effects on insulinemia and glycemia.

The short-term effects of bilateral electrical stimulation of the lateral component of the lateral hypothalamic/medial forebrain bundle area (LHA) on peripheral plasma levels of glucose (G), immunoreactive insulin (IRI) and glucagon (IRG) were measured in food-derived, anesthetized rats in the presence of continuous low i.v. glucose infusion. In normal rats LHA stimulation induced a rapid but moderate rise in IRI in the presence of a simultaneous rapid rise in G. At the end of the 5 min stimulation period the glucose-induced IRI response was clearly attenuated. In rats receiving a continuous phentolamine (i.v.) infusion, the rapid IRI response was much larger in spite of only marginal rises of G. These findings suggest that electrical LHA stimulation activates two opposing mechanisms on IRI secretion, an excitatory component which is masked in normal animal by a sympathetic alpha-adrenergic inhibitory component. In an attempt to define the mediating pathway of this LHA stimulation-induced IRI excitatory component, both the parasympathetic and sympathetic divisions of the autonomic nervous system were pharmacologically and surgically manipulated, all in the presence of phentolamine infusion. Neither bilateral subdiaphragmatic vagotomy, atropine, propranolol infusion, nor spinal cord transection at T1 were able to block the IRI response. The findings are consistent with a humoral mediation of this IRI stimulatory response and support the existence of a lateral hypothalamic or hypophyseal factor which is released by LHA stimulation. The implications and physiological role of the LHA in the neural control of insulin secretion and ingestive behavior are discussed.

Animals↗
PubMed2001

Factors determining length of stay of surgical day-case patients.

BACKGROUND AND OBJECTIVE: Factors which lead to prolonged stay in the day-care unit and unplanned admission after day-case surgery are poorly understood. METHODS: Data sets of 3152 day-case patients were collected with a computerized online record keeping system (NarkoData). Predictors of prolonged postoperative stay including unanticipated admission were identified using univariate analysis. Charts of patients, who needed admission, were reviewed. RESULTS: 13.2% of day-case patients had a postoperative stay < or = 3 h, 55.3% 3-6 h and 26.2% > or = 6 h. The rate of unanticipated admission was 5.4%. Intraoperative haemoglobin concentration and blood loss were the best predictors of a prolonged postoperative stay. Other significant predictors were female gender, advanced age, longer duration of surgery, larger volume of infusions, intubation, spinal anaesthesia, intraoperative use of opioids and non-depolarizing muscle relaxants, high pain score, nausea and vomiting and prolonged preoperative waiting time. Chart review of patients admitted to hospital confirmed the validity of the statistically significant predictors. CONCLUSIONS: In day-case surgery, the predictors of prolonged stay in the day-care unit and unplanned Hospital admission are mainly related to the surgical procedure.

Ambulatory Surgical Procedures↗
PubMed1986

Spectral analysis of the CSF pulse wave at different locations in the craniospinal axis.

The frequency spectrum and the amplitude transfer function from arterial pulse pressure to the CSF pulse wave were estimated in the lateral ventricle, cisterna magna and lumbar subarachnoid space of anaesthetised ventilated cats under various conditions: (a) normal status, (b) inhalation of 5% CO2 and (c) saline infusion into the CSF space (0.045 ml/min). The CSF pulse waveforms in the lateral ventricle and cisterna magna were almost identical in all conditions. Inhalation of CO2 and saline infusion increased the values of the amplitude transfer function from blood pressure to the CSF pulse wave in the lateral ventricle and cisterna magna to a similar extent. The CSF pulse in the lumbar sac was remarkably damped under both normal conditions and during CO2 inhalation, but the damping was diminished by saline infusion. During the saline infusion, the spinal canal appeared to function as a low-pass filter to the conduction of the CSF pulse.

Animals↗
PubMed1982

Renin-angiotensin and development of collateral circulation after renal ischemia.

Aortic ligation between the origins of the renal arteries in the rat produces a left renal ischemia, renin-dependent hypertension, and a transitory hindlimb paralysis of less than 2 h. Removal of the left ischemic kidney at the time of aortic ligation curtails the rise of blood pressure, plasma renin activity is normal, and paralysis is still present 24 h after surgery. Administration of an angiotensin-converting enzyme inhibitor or saralasin also prevents recuperation from paralysis after aortic ligation. Independent manipulation of the mean arterial pressure or plasma renin activity by pretreatment with reserpine or deoxycorticosterone before surgery shows that the presence or absence of paralysis is dependent on the plasma renin activity and not on the high blood pressure. Blood flow measurements show that paralysis is due to a persistent impairment of blood supply to the hindlimb muscle and not to ischemia of the spinal cord. Infusion of angiotensin II to aortic-ligated, left-renoprival animals tends to restore blood flow to muscle. It is concluded that after renal ischemia the renin-angiotensin system, independent of its hypertensive effect, restores blood flow by stimulating the development of collateral circulation.

Animals↗
PubMed1998

Prevention of spinal cord ischemia by selective intercostal arterial infusion of prostaglandin E1.

PURPOSE: A new protective method against the spinal cord ischemia that occurs during aortic clamping was investigated in dogs. Oxygenated blood containing prostaglandin E1 (PGE1) was administered at the clamped aortic segment, and the effect was evaluated by measurement of the sensory evoked spinal potential (SESP). METHODS: In 30 dogs, a thoracotomy was made with dissection of the thoracic aorta. After intravenous heparin (100 units/kg) was administered, the proximal and distal descending thoracic aortas were cross-clamped for 60 minutes. Group A (n=10) received oxygenated blood at the rate of 1.0 ml/kg/min. Groups B (n=10) and C (n=10) received oxygenated blood at the same rate, with PGE1 at the dosage of 25 and 50 ng/kg/min, respectively. The infusion was continuously administered throughout the entire period of ischemia. SESP was measured with epidural electrodes before clamping, 10 and 60 minutes after clamping, and 10 and 60 minutes after declamping. Neurologic outcome was assessed at 24 hours after the operation and graded according to the method of Tarlov. RESULTS: There was no significant hemodynamic change in any group. At 60 minutes after damping and at 10 and 60 minutes after declamping, the amplitude of SESP was lower than that at preclamping in groups A and B (p < 0.05). At 60 minutes after damping and at 10 and 60 minutes after declamping, the SESP was more markedly decreased in group A compared with groups B and C. Regarding postoperative neurologic outcome, the dogs with SESP amplitude of more than 50% of the preclamping control value at 60 minutes after clamping showed neither paralysis nor paraplegia. Seven of nine dogs with less than 50% SESP amplitude showed neurogenic deficit. In a comparison of groups A, B, and C, the Tarlov score for group A dogs was significantly lower than that for group C dogs (p < 0.05). CONCLUSION: In this model, PGE1 administration at the rate of 50 ng/kg/min showed sufficient spinal cord protection against ischemia without a decrease in the blood pressure. Further studies are needed to determine the dose that will provide the maximal protective effect and to determine the maximum duration of ischemia against which PGE1 shows protective effects.

Alprostadil↗
PubMed1993

Comparison of an ephedrine infusion with crystalloid administration for prevention of hypotension during spinal anesthesia.

This study was designed to compare the efficacy of an ephedrine infusion with crystalloid administration for reducing the incidence of hypotension during spinal anesthesia. Fifty-four ASA I patients scheduled for postpartum tubal ligations under spinal anesthesia were randomly allocated to receive either 15 mL/kg of crystalloid (crystalloid group) or an ephedrine infusion (infusion group). Spinal anesthesia was performed using 70-90 mg of hyperbaric 5% lidocaine. Patients in the infusion group immediately thereafter received an ephedrine infusion at a rate of 5 mg/min for the first 2 min and then 1 mg/min for the next 18 min. The incidence of hypotension was 15/27 (55%) in the crystalloid group and 6/27 (22%) in the infusion group (P < 0.05). There was no significant difference between the groups in relation to the level of anesthesia or maximal heart rate, and hypertension did not occur in either group. We conclude that a prophylactic ephedrine infusion is effective for minimizing and managing hypotension associated with spinal anesthesia and compares favorably with crystalloid administration in this patient population in terms of efficacy and incidence of side effects.

Adult↗
PubMed1986

Transfer kinetics of pefloxacin into cerebro-spinal fluid after one hour i.v. infusion of 400 mg in man.

Nine subjects (5 women) aged between 17-66 years, with hydrocephalus were studied. An external ventricular drain was introduced for diagnostic purposes. Cerebro-spinal fluid (CSF) and plasma samples were obtained at suitable intervals after 1 h infusion of 400 mg pefloxacin. In plasma, pefloxacin Cmax was 8.54 +/- 1.53 (mean +/- S.E.M.) mg/l, at the end of infusion, whereas N-desmethyl pefloxacin concentration was 0.17 +/- 0.03 mg/l. The metabolite accounted for only 2% of plasma levels of pefloxacin. In CSF, pefloxacin Cmax was 2.97 +/- 0.32 mg/l, 5-6 h after the start of infusion, whereas N-desmethyl pefloxacin Cmax varied between 0.1-0.2 mg/l. Apart from the 1 h sample, the CSF/plasma ratio of pefloxacin was 60% which is similar to the unbound fraction of pefloxacin in plasma. The apparent half-life (T1/2) of transfer of pefloxacin from plasma to CSF was 1.26 +/- 0.18 h, assuming a first order process, while the apparent elimination T1/2 in CSF was 13.40 +/- 1.76 h, which is similar to the elimination T1/2 found previously in plasma, thus accumulation of pefloxacin in CSF is unlikely. With the present dosage regimen, CSF quickly attains therapeutic levels of pefloxacin.

Adolescent↗
PubMed2006

Effects of recurrent withdrawal on spinal GABA release during chronic morphine infusion in the rat.

Chronic opioid administration is associated with altered nociception. The mechanisms underlying these changes are not fully understood. Nociceptive transmission within the spinal cord is modulated by both excitatory and inhibitory neurotransmitters. Using spinal microdialysis, the effects of recurrent withdrawal on the release of gamma-aminobutyric acid (GABA), at rest or after naloxone stimulation, was investigated in rats chronically exposed to morphine. For comparison purpose, the release of glutamate was investigated in parallel. We observed that chronic morphine treatment alone significantly inhibited resting GABA release; and recurrent withdrawal appeared to reverse this effect. Recurrent withdrawal also significantly elevated resting glutamate levels. In addition, we observed that only acute withdrawal moderately increased stimulated GABA release. In contrast, both acute and recurrent withdrawal markedly increased stimulated glutamate release. These observed changes in GABA release offer direct evidence that GABA may contribute to the altered nociceptive response mediated by opioids.

Analgesics, Opioid↗
PubMed1991

Continuous infusion of intrathecal baclofen: long-term effects on spasticity in spinal cord injury.

The effects of intrathecal baclofen infusion were studied in 9 spinal cord injury patients whose spasticity had been refractory to oral medications. In a two stage, placebo controlled trial, baclofen was administered into the lumbar intrathecal space and subsequent clinical and neurophysiologic changes were assessed. In stage 1, 9 patients underwent a 5 day percutaneous infusion of baclofen and placebo via an external pump. Ashworth and reflex scores were assessed at time of enrollment, after infusion of that amount of baclofen which provided optimal spasticity control and after intrathecal infusion of placebo. The mean Ashworth grade decreased from 3.78 +/- 1.34 to 1.16 +/- 0.48 (p less than 0.001) while mean reflex score decreased from 3.57 +/- 1.05 to 0.64 +/- 0.87 (p less than 0.001). These values differed significantly from those associated with placebo therapy (Ashworth grade--2.54 +/- 1.04, p less than 0.001; reflex score--2.56 +/- 1.04, p less than 0.01). Objective improvements in functional abilities and independence were noted in 8 patients, while somatosensory and brainstem auditory evoked potentials were unchanged in all patients. Urodynamic evaluation revealed increased bladder capacity in 3 patients, while in 4 no change was observed. In Stage 2, permanent programmable infusion pumps were implanted in 7 patients who demonstrated a good response during Stage 1. In this group, mean Ashworth score decreased from 3.79 +/- 0.69 to 2 +/- 0.96 (p less than 0.001) and mean reflex score decreased from 3.85 +/- 0.62 to 2.18 +/- 0.43 (p less than 0.001). Baclofen dosage increased from 182 +/- 135 to 528 +/- 266 mcg/day over the 3-22 month follow-up period. Most of the dosage increase occurred within the initial 12 months following infusion pump implantation and tended to plateau thereafter. Minor complications such as catheter dislodgement/kinking and nausea occurred infrequently while no device related infections were observed. There was no clinical evidence of any significant baclofen neurotoxicity either in Stage 1 or 2. The only ambulatory patient developed marked lower extremity weakness during Stage 1 intrathecal baclofen infusion and was temporarily unable to walk. We conclude that continuous administration of intrathecal baclofen is an effective and safe modality for spasticity control in patients who are refractory to oral medications.

Administration, Cutaneous↗
PubMed2004

Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord injury.

Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral level of the spinal cord in adult rats. The rats received MP intravenously immediately after the injury and BDNF was infused intrathecally using an osmotic mini-pump for six weeks. Immunohistochemical methods were used to detect ED-1, Growth associated protein-43 (GAP-43), neurofilament (NF), and choline acethyl transferase (ChAT) levels. BDNF did not alter the effect of MP on hematogenous inflammatory cellular infiltration. MP treatment with BDNF infusion resulted in greater axonal survival and regeneration compared to MP treatment alone, as indicated by increases in NF and GAP-43 gene expression. Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test. This study demonstrated that continuous infusion of BDNF after initial MP treatment improved functional recovery after severe spinal cord injury without dampening the acute effect of MP.

Animals↗
PubMed2006

A prospective randomized comparison of spinal versus local anesthesia with propofol infusion for knee arthroscopy.

PURPOSE: Knee arthroscopy is the most common orthopaedic procedure performed in the United States, and there are few randomized studies comparing local anesthesia, in conjunction with propofol, with regional anesthesia for knee arthroscopy. The purpose of the study was to test the hypothesis that patients receiving local anesthesia combined with propofol infusion (LAP) will recover from anesthesia faster and experience less postoperative headache and back pain compared with spinal anesthesia (SA). TYPE OF STUDY: Randomized trial. METHODS: A randomized trial was used to compare SA and LAP in adults undergoing knee arthroscopy. A simple randomization scheme in sealed envelopes was used. An independent observer collected data the day of surgery and contacted patients by telephone on the first postoperative day to inquire about back pain or headaches, and to have them rate their anesthesia (excellent, good, fair, or poor). RESULTS: Eighteen patients (average age, 53 years) received LAP and 14 received SA. Baseline assessment of the 2 groups was similar. The mean time spent in the postoperative anesthesia care unit (PACU) was 2.8 hours for the LAP group and 4.0 hours for the SA group (P < .0001). Spinal anesthesia was associated with back pain in 5 of 14 patients in the SA group compared with none in the LAP group (P = .004). There were no statistically significant differences between the 2 groups with respect to headache (P = .5) or overall patient satisfaction (P = .3). The amount of time required to administer anesthesia was similar between the 2 groups (P = .2). The number of patients requiring additional sedation intraoperatively was higher in the LAP group compared with the SA group, 9 of 18 and 1 of 14, respectively (P = .02). CONCLUSIONS: Although subjects receiving LAP were more likely to require additional sedation intraoperatively compared with the SA group, LAP was associated with significantly less time to home readiness as measured by time in the PACU. LEVEL OF EVIDENCE: Level I.

Anesthesia Recovery Period↗
PubMed1988

Cardiovascular effects of sedative infusions of propofol and midazolam after spinal anaesthesia.

The cardiovascular effects of intravenous sedation were studied in fifty patients after spinal anaesthesia for lower limb or pelvic surgery. Twenty patients received propofol (mean dosage 74 (SD 4) micrograms/kg/min for 0-20 minutes and 51 (SD 7) micrograms/kg/min for 20-40 minutes), twenty received midazolam (35 micrograms/kg + 2.54 (SD 0.2) micrograms/kg/min for 0-20 minutes and 1.35 (SD 0.2) micrograms/kg/min for 20-40 minutes) and ten patients received saline infusion only. The forearm vasoconstriction in response to the spinal anaesthesia was measured by strain gauge plethysmography. Spinal anaesthesia lowered systolic and diastolic blood pressure by 18 (SED 4) mmHg and 9 (SED 2) mmHg respectively. (SED = standard error of the difference.) This was associated with a 32% decrease in mean forearm blood flow. Propofol and midazolam caused similar additional reductions in systolic and diastolic blood pressure (10 (SED 4) mmHg and 4 (SED 2) mmHg) and a decrease in heart rate (P less than 0.005), but forearm vasoconstriction was not altered. In the control group, however, forearm vasoconstriction increased during 40 minutes in theatre (P less than 0.05). Recovery from propofol was far more rapid than after midazolam and was virtually complete in ten minutes. This was reflected by an increase in blood pressure and in forearm vasoconstriction in the recovery period.

Aged↗