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PubMed2005

Patient-controlled epidural analgesia following combined spinal-epidural analgesia in labour: the effects of adding a continuous epidural infusion.

Patient-controlled epidural analgesia (PCEA) is used to maintain epidural analgesia following initial intrathecal analgesia. This trial investigated whether a continuous background infusion with PCEA provides superior analgesia to PCEA alone among patients who received combined spinal-epidural (CSE) analgesia during labour Eighty parturients were randomized to either PCEA alone (PCEA) or PCEA with a background infusion of ropivacaine 0.15% with sufentanil 0.75 microg/ml at 2 ml/h (PCEA + CEI). PCEA settings were a bolus of 4 ml of the same analgesic solution with a lockout interval of 15 minutes. Significantly more patients in the PCEA group required at least one anaesthetist intervention for breakthrough pain (27 [71%] vs 10 [25%] in the PCEA + CEI group, P<0.05). Consumption of local anaesthetic (excluding manually administered boluses) was similar between the groups. If anaesthetist-administered boluses were included, more local anaesthetic was consumed by the PCEA group (47.1 +/- 19.4 mg vs 35.6 +/- 12.0 mg in the PCEA + CEI group, P<0.05). We conclude that PCEA with a background infusion provides effective analgesia with less anaesthetist workload and reduced local anaesthetic consumption as compared with PCEA without a background infusion.

Adult↗
PubMedDate not supplied

Modulation of brain angiotensin-converting enzyme by dietary sodium and chronic intravenous and intracerebroventricular fusion of angiotensin II.

Angiotensin-converting enzyme (ACE) in rat brain closely resembled that in lung in its kinetics with the substrate Hip-His Leu, the inhibitors SQ 20,881 and SQ 14,225, and iun its Cl- activation profile. Modification of dietary NaCl intake was associated with marked changes in brain ACE activity. Sodium-loaded rats had lower activity of ACE in hypothalamus, striatum, and midbrain, and higher activity in spinal cord compared to controls. In sodium-restricted rats, ACE was elevated in pituitary and depressed in spinal cord. Chronic intravenous infusion of angiotensin (AII) was associated with a pattern of changes partly resembling sodium loading: ACE was depressed in hypothalamus and striatum but elevated in midbrain. After chronic intracerebroventricular infusion of AII, ACE was elevated in striatum and hippocampus, and depressed in spinal cord; a pattern of changes quite different from those associated with intravenous AII. These results show that ACE in several brain regions is sensitive to dietary sodium intake and support the hypothesis that angiotensin-containing neurons in these areas might be responsive to NaCl status of the animal. The observed changes in brain ACE do not seem to be explained in any simple manner by changes in circulating or central angiotensin II.

Angiotensin II↗
PubMed1994

Epidural cooling for regional spinal cord hypothermia during thoracoabdominal aneurysm repair.

PURPOSE: We investigated the feasibility of achieving regional hypothermia of the spinal cord with an infusion of iced (4 degrees C) saline solution administered into an epidural catheter while monitoring cerebral spinal fluid (CSF) temperature in eight patients undergoing thoracic or thoracoabdominal aneurysm resection. METHODS: As part of the anesthetic management, an epidural catheter was placed at T11-12, and a subarachnoid thermistor catheter was placed at L3-4. Approximately 30 minutes before aortic cross-clamping, iced (4 degrees C) saline solution was infused into the epidural catheter until CSF temperature decreased to approximately 25 degrees C. The infusion was then adjusted to maintain this temperature until the aorta was unclamped. The subarachnoid catheter was also used to measure CSF pressure and provide for CSF drainage. Surgery was performed in all patients with a clamp-and-sew technique with selective intercostal vessel reattachment. RESULTS: Infusion of a mean volume of 489 ml (range 80 to 1700 ml) of iced saline solution into the epidural space before aortic cross-clamping led to a decrease in mean CSF temperature to 26.9 degrees C (range 25 degrees to 28.8 degrees C) in 15 to 90 minutes. During cross-clamping and aortic replacement the mean CSF temperature was maintained between 25.2 degrees to 27.6 degrees C and, with discontinuation of the infusion, returned to within 1 degrees C of body core temperature by the end of the procedure. Body core temperature was not significantly affected by the epidural infusion. Mean CSF pressure increased during the epidural infusion but could be reduced by removing saline solution from the epidural space. No postoperative neurologic deficits were observed. CONCLUSION: Epidural cooling appears to be a satisfactory method of achieving regional spinal cord hypothermia in patients requiring resection of thoracic or thoracoabdominal aortic aneurysms.

Adult↗
PubMed1998

Volume preload: lack of effect in the prevention of spinal-induced hypotension at caesarean section.

A randomized double-blind study of 40 women was performed to compare blood pressure changes between two groups of women following induction of spinal anaesthesia for elective caesarean section. One group received a 1 L Ringer's solution preload, administered over 10 min, before spinal anaesthesia while the other group received no preload. In both groups a prophylactic infusion of ephedrine (60 mg in Ringer's solution 1000 ml) was started immediately following intrathecal injection of local anaesthetic. There was no significant difference either in the ephedrine requirements or the incidence of hypotension between the two groups. There were no differences between the groups in terms of neonatal outcome as assessed by Apgar score, umbilical arterial and venous blood pH, and Neonatal Adaptive Capacity Scores. When ephedrine is infused prophylactically immediately following spinal anaesthesia for elective caesarean section, a 1000 ml crystalloid preload confers no advantages in terms of maternal blood pressure control or neonatal outcome.

Clinical Trial↗
PubMed1963

Mechanism of the initial adrenergic effects of bretylium and guanethidine.

Treatment with phenoxybenzamine and dichloroisoprenaline prevented the rise of blood pressure, contraction of the nictitating membrane and increase in cardiac contractile force produced by intravenous injections of bretylium and guanethidine in anaesthetized or spinal cats. Treatment with cocaine, imipramine or reserpine reduced the sensitivity to bretylium and guanethidine of the spinal cat. In the spinal cat treated with reserpine, sensitivity to the drugs could be restored by an infusion of noradrenaline. Chlorpromazine also blocked the pressor and nictitating membrane responses to bretylium and guanethidine. The drug effects were unaltered 1 hr after bilateral adrenalectomy. During the intravenous infusion of noradrenaline into spinal cats the pressor responses to bretylium and guanethidine were increased, whilst those to adrenaline and to noradrenaline were decreased. Guanethidine (3 to 5 mg/kg) injected intravenously into the cat caused a sudden relaxation of the rat isolated stomach-strip bathed in blood. In seven similar experiments bretylium (3 to 5 mg/kg) relaxed the strip only once; in the other six experiments there was either no effect (four experiments) or an increase in the tone of the strip (two experiments). It is concluded that the initial adrenergic effects of bretylium and guanethidine are mediated, at least in part, through a release of catechol amines from stores in the effector organ.

Adrenergic Agents↗
PubMed1999

Attenuated additional hypocapnic constriction, but not hypercapnic dilation, of spinal pial arterioles during spinal ropivacaine.

UNLABELLED: Ropivacaine constricts spinal vessels. Because the CO2 response of spinal vessels is similar to that of cerebral vessels, we tested to see if hypocapnia would cause further spinal vasoconstriction during ropivacaine administration. In 12 pentobarbital-anesthetized dogs, spinal pial arteriolar diameter was measured using a closed spinal window preparation. Either ropivacaine solution (0.1%; n = 6) or artificial cerebrospinal fluid (n = 6) was infused continuously into the spinal window. After a period of hypocapnia (Paco2, 20-25 mm Hg) had been induced, inspired CO2 levels were adjusted to produce normocapnia (35-40 mm Hg) followed by hypercapnia (55-60 mm Hg). When the desired Paco2 was reached, measurements were made of the arteriolar diameter and physiological variables. During normocapnia, ropivacaine infusion produced a significant constriction of pial arterioles, whereas artificial cerebrospinal fluid caused no change. Hypocapnia induced a much smaller (almost nonexistent) additional vasoconstriction in the ropivacaine group than in the control group (P < 0.01). The final hypercapnic vasodilation was somewhat greater during ropivacaine (P < 0.05 versus control group). Topical ropivacaine induced no change in hemodynamic variables. We conclude that hypocapnia of the magnitude tested did not cause further constriction in spinal vessels during spinal ropivacaine. IMPLICATIONS: During topical application of the local anesthetic ropivacaine in dogs, hypocapnia (Paco2, 20-25 mm Hg) induced almost no additional constriction of spinal arterioles, and the hypercapnic vasodilation was maintained. These data suggest that an additional constriction in spinal vessels is unlikely when hypocapnia occurs during spinal ropivacaine.

Administration, Topical↗
PubMed1975

Synchronous cystosphincterometry in patients with spinal cord injury. Studies with continuous bladder and urethral infusions and physical factors influencing interpretation.

A technique of synchronous study for monitoring the bladder activity and simultaneous urethral sphincteric responses is described. This study was made possible by using a 12 F trilumen catheter with which intravesical infusion and independent bladder pressure recording were conducted. Constant urethral infusion with intrasphincteric pressure recording was arranged through the third lumen of the trilumen catheter. This radiologic aided study was used for functional evaluation of the bladder and its outlet. The bulit-in artefacts of the technique were assessed. The physical factors, such as urethral infusion flow rate and the compliance of infusion catheter hydraulic system governing interpretation of the study during nonvoiding states, are described. With an experience of 100 studies on 75 patients with spinal cord injury and 5 normal subjects, this method has been found to be a useful clinical urodynamic technique well suited even to a nonambulatory patients with spinal cord injury.

Adult↗
PubMed1992

Long-term hypotensive technique with nicardipine and nitroprusside during isoflurane anesthesia for spinal surgery.

Short-term infusion of nicardipine can be used to induce deliberate hypotension but may result in plasma drug accumulation. To assess long-term nicardipine administration for deliberate hypotension in 10 patients in a moderately hemodiluted state who were undergoing spinal surgery, hemodynamics and plasma nicardipine concentrations were concomitantly measured before and 20, 80, and 140 min after starting nicardipine, at drug discontinuation, and 20 and 80 min later. A dose of 6.2 +/- 0.9 mg (mean +/- SEM) of nicardipine was initially required to obtain mean arterial blood pressures at 55-60 mm Hg. Maintenance doses of nicardipine were 3-5 mg/h. The duration of nicardipine administration was 270 +/- 20 min (mean +/- SEM). Hypotension was associated with decreased systemic and pulmonary vascular resistances, increased cardiac index, and decreased arteriovenous difference in O2 contents. Only two patients required homologous blood transfusion. Plasma nicardipine concentrations peaked at 110 +/- 21 ng/mL (mean +/- SEM) and then decreased to 38 +/- 11 ng/mL (mean +/- SEM) without changes in arterial blood pressure. After vasodilator discontinuation, hypotension was observed during a mean time of 43 min (range 27-88 min) despite plasma concentrations less than 20 ng/mL. No relationship was found between plasma nicardipine concentrations and hemodynamics. These findings suggest that an increasing effect of nicardipine over time may occur during prolonged administration. Because the reasons for this hysteresis remain unclear, use of nicardipine infusion during major surgery and anesthesia requires particular caution.

Adult↗
PubMed1999

Convective delivery of macromolecules into the naive and traumatized spinal cords of rats.

OBJECT: Many macromolecules have the potential to enhance recovery after injury and other lesions of the spinal cord, but because of the limited penetration of these compounds across the blood-spinal cord barrier, they cannot be used effectively. To determine if convective delivery could be used in a common animal model to investigate potential therapeutic macromolecules and to examine the effects of trauma on convective delivery in that model, the authors examined the distribution of a macromolecule in naive and traumatized rat spinal cords. METHODS: Using convection, various infusion volumes ([Vi]; 1, 2, and 4 microl) of 14C-albumin were infused into the dorsal columns of 13 naive and five traumatized rat spinal cords. Volume of distribution (Vd), homogeneity, percentage of recovery, and anatomical location were determined using quantitative autoradiography, scintillation analysis, calculation of kurtosis (K) value, and histological analysis. In the nontraumatized group, Vd was linearly proportional (R2 = 0.98) to Vi (Vd/Vi, 4.3+/-0.6; mean +/- standard deviation), with increases in Vd resulting from linear expansion (R2 = 0.94) primarily in the craniocaudal dimension. In the traumatized spinal cords, the Vd/Vi ratio (3.7+/-0.5) was smaller (p<0.02) and distributions were less confined to the craniocaudal dimension, with significantly larger cross-sectional distributions in the region of injury (p<0.02) compared to the noninjured spinal cords. Histological analysis revealed that after infusion into the dorsal columns, albumin distribution in naive cords was limited to the dorsal white matter, but in the traumatized cords there was penetration into the central gray matter. The distribution of the infusate was homogeneous in the nontraumatized (K = -1.1) and traumatized (K = -1.1) spinal cords. Recovery of radioactivity was not significantly different (p>0.05) between the nontraumatized (84.8+/-6.8%) and traumatized (79.7+/-12.1%) groups. CONCLUSIONS: Direct convective delivery of infusate can be used to distribute macromolecules in a predictable, homogeneous manner over significant volumes of naive and traumatized rat spinal cord. These characteristics make it a valuable tool to investigate the therapeutic potential of various compounds for the treatment of injury and spinal cord disease.

Albumins↗
PubMed1992

Continuous intrathecal baclofen in spinal cord spasticity. A prospective study.

Continuous intrathecal infusion of the well known antispastic medication baclofen was evaluated in ten consecutive patients. One year after pump implantation the average Ashworth scale for muscle tone decreased, compared with before treatment, 2.32 points (P < 0.0001), reflexes decreased 2.22 points (P < 0.0001) and the spasm score decreased 1.65 points (P < 0.0001). The average dose increased from 92.22 to 290.95 micrograms (P < 0.0001) between the 1st month of treatment and 1 yr of treatment. The dosage for all patients more than doubled (P < 0.0022) between 3 months and 1 yr postimplantation. There was no significant difference for muscle tone, reflexes or spasms at 3 months v 1 yr. Complications were not unusual and included temporary atelectasis, orthostatic hypotension with escalation of baclofen dose, loss of penile erections, postsurgical pseudo-meningoceles, catheter disruptions and exhausted pump reservoirs. One patient suffered a seizure apparently related to a rapid withdrawal from intrathecal baclofen as a result of catheter sequestration. All patients required a period of intensive inpatient rehabilitation to benefit functionally from the decreased motor tone and/or increased voluntary motor control. The procedure is expensive and close follow-up is necessary for assessing efficacy and refilling the pump. Intrathecal baclofen infusion by subcutaneous pump is useful in treating the effects of spinal spasticity resistant to oral medications. However, there appears to be accommodation to intrathecal baclofen necessitating escalating doses to maintain clinical effects.

Adult↗
PubMed1997

Intravenous infusion of low dose propofol for conscious sedation in cesarean section before spinal anesthesia.

BACKGROUND: Conscious sedation, not affecting the safety of both mother and fetus, is especially favorable in anxious patients undergoing Cesarean delivery. However, when sedation is started before performing intrathecal anesthesia, the infusion time before delivery will be prolonged. In this study, the incidence of maternal and fetal complications under propofol infusion were evaluated as well as the blood concentrations of propofol during delivery at different time of sedation. METHODS: Maternal and fetal effects of pre-spinal sedation with low dose propofol infusion technique (3 mg/mg/h following 0.3 mg/kg bolus) in 37 Cesarean parturients were evaluated, compared with another 33 parturients under spinal anesthesia without any sedatives. RESULTS: The induction to delivery time was 32.6 +/- 7.7 min. Satisfactory, airway-maintaining conscious sedation was shown without increasing the incidence of post-spinal hypotension and hypoxemia compared with non-sedative group. The plasma propofol concentrations in the mean time of delivery in maternal vein and umbilical vein were 0.86 +/- 0.29 and 0.33 +/- 0.11 microgram/ml, respectively. Umbilical venous concentration neither correlated with infusion time nor exceeded the maternal venous concentration. The 1-min and 5-min Apgar scores as well as umbilical venous blood gas analyses did not differ significantly between two groups. CONCLUSIONS: Conscious sedation by low dose propofol infusion is safe for both mother and fetus in spite of longer infusion time.

Adult↗
PubMed1997

AMPA receptor-mediated slow neuronal death in the rat spinal cord induced by long-term blockade of glutamate transporters with THA.

Excitotoxicity secondary to the loss of glutamate transporters (GluT) has been proposed as a possible pathogenetic mechanism for neuronal degeneration in amyotrophic lateral sclerosis. We therefore investigated whether prolonged in vivo pharmacologic inhibition of GluT would result in neuronal damage in the rat. DL-Threo-beta-hydroxyaspartate (THA), a potent GluT inhibitor, and glutamate were continuously infused into the rat spinal subarachnoid space by using a mini-osmotic pump. Animals that received both THA and glutamate, but not those received either singly, displayed tail paralysis with or without hind-limb paralysis and urinary incontinence after the third postoperative day. Pathologically, symptomatic animals exhibited neuronal loss with a variable extent of gliosis preferentially involving the dorsal horn of the lumbosacral cord. In the rostral spinal segments adjacent to those regions of intense pathologic changes, small neurons in the dorsal horn were selectively destroyed, a pattern similar to the late-onset neuronal damage induced by continuous intrathecal administration of 1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) [R. Nakamura et al., Brain Res. 654 (1994) 279-285]. These behavioral and pathologic changes were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that pharmacologic blockade of GluT causes selective neuronal damage in vivo by AMPA receptor activation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2006

Fluid challenge in patients submitted to spinal block.

AIM: The practice of routinely prehydrating patients by infusing a colloid solution for prevention of spinal anesthesia-induced hypotension has been challenged recently. The aim of the study was to evaluate the influence of a 15 mL/kg pre-emptive bolus of colloids (6% hydroxyhethyl starch) on heart rate (HR), mean arterial blood pressure (MAP), cardiac index (CI) in patients submitted to subarachnoid block with hyperbaric bupivacaine 0.5%, 0.2 mg/kg for orthopedic surgery of the lower limb. METHODS: Patients were monitored by a Model Flow method. Forty patients (ASA I-II) scheduled to undergo to spinal anesthesia for elective orthopedic surgery of the lower limb were enrolled in the study. The 20 patients in Group A were treated with a preanesthetic infusion of 15 mL/kg of hydroxyhaethyl starch 6%, Group B (20 untreated patients) was the control group. HR, MAP, CI were collected at T0 (first relevation); T1 (after 5 min from the spinal block); T2 (after 10 min); T3 (after 15 min); T4 (after 20 min); T5 (after 25 min); T6 (after 30 min); T7 (after 35 min). RESULTS: Our data show that MAP value is higher in treated patients than in control group (ANOVA: P<0.001) and at T1 in Group B MAP was lower than at T0 (P<0.05). HR and CI trend appear similar in the 2 groups. Our results show that heart rate is not affected by colloid infusion. This may be due to the substantial cardiovascular stability of the selective spinal anesthesia, which does not activate a clinical relevant compensatory vagal effect. Fluid prehydration would expand the vascular space and hence compensate for the reduction in systemic vascular resistance, although MAP reduction following the induction of spinal anesthesia is present in both treated and control groups. CONCLUSION: Our data show that despite to fluid challenge, we could not prevent MAP decrease in Group A, even if it is more marked in Group B.

Aged↗
PubMed2004

Effect of low-dose ketamine on redistribution hypothermia during spinal anesthesia sedated by propofol.

Mild hypothermia is a common complication during spinal anesthesia and may induce a serious adverse outcome. We investigated the effect of low-dose ketamine infusion on the core temperature during spinal anesthesia sedated by propofol infusion. Twenty patients who were scheduled to undergo spinal anesthesia were assigned to one of two groups: after intrathecal injection of bupivacaine, patients who received infusion of ketamine (0.3 mg/kg/hr) and propofol (initial rate of 10 mg/kg/hr) (KP group), and patients who received infusion of placebo (saline) and propofol (initial rate of 10 mg/kg/hr) (P group). The rate of propofol administration was reduced as much as possible while maintaining sedation with an OAA/S score of 3 or below. The core temperature, forearm temperature, and fingertip temperature were recorded before spinal anesthesia, and just before (baseline) and 15, 30, 45, and 60 minutes after the start of propofol administration. The core temperature, reduction in core temperature from baseline (delta CT), and forearm-fingertip temperature gradient were compared between the two groups. In the P group, the core temperature linearly decreased over time. The core temperature at 30, 45, and 60 minutes was significantly higher in the KP group than in the P group (36.3 +/- 0.2 and 35.9 +/- 0.3, at 60 minutes, mean +/- SD, p < 0.05). The delta CT at 15, 30, 45, and 60 minutes was significantly smaller in the KP group than in the P group. There were no significant differences in the forearm-fingertip temperature gradient between the two groups over the study period. In conclusion, low-dose ketamine administration may confer thermoprotection during spinal anesthesia sedated by propofol.

Adult↗
PubMed2006

Spinal ERK activation contributes to the regulation of bladder function in spinal cord injured rats.

The extracellular signal-regulated kinase 1 and 2 (ERK) pathway, regulated by phosphorylation on specific amino acids, is emerging as an important signaling cascade in neurones, transducing sensory input into cellular responses. In the mammalian nervous system, the ERK pathway has been found to mediate plasticity events. Particularly, in the spinal cord, ERK play an important role in allodynia and hyperalgesia. Recently, it was demonstrated that ERK activation is upregulated in the spinal cord of rats with chronic bladder inflammation and contributes to bladder overactivity. Thus, in this study we sought to assess the involvement of ERK in micturition reflexes associated to spinal cord injury (SCI) in the rat. Bladder function in chronic SCI rats was altered compared to spinal intact rats. PhosphoERK levels were upregulated in the L6 spinal cord segment, particularly after saline infusion for 2 h. The increase in spinal ERK phosphorylation was specifically restricted to L6 spinal segment. No variation in the levels of total ERK protein was observed. Intrathecal administration of PD98059, a specific inhibitor of ERK phosphorylation, reduced the frequency and amplitude of bladder contractions in SCI animals but not in spinal intact ones. Overall, our results demonstrate increased activation of the ERK pathway in the spinal cord from SCI rats, restricted to spinal segments that receive sensory input arising from the bladder. Since the use of PD98059 reduced the frequency and amplitude of bladder contractions, ERK inhibitors may provide a new therapeutic approach to the treatment of bladder overactivity after spinal injuries.

Animals↗