A comparison of two doses of epidural fentanyl during Caesarean section

A prospective, randomized, double-blind study was performed to compare the analgesic efficacy and side effects of epidural fentanyl, 25 pg vs 50 pg, when used to supplement epidural anaesthesia for elective Caesarean section. Fifty ASA I and II patients were randomized into two groups: Group I (n =24) received 25 pg and Group II (n = 26) received 50 pg of epidural fentanyl after the epidural test dose. No differences between the two groups were found on any measures of intraoperative pain, nausea, drowsiness, respiratory depression, hypotension, pruritus and neonatal outcome. The low levels of pain experienced by patients indicates that doses higher than 50 μg of epidural fentanyl are usually unnecessary for optimal analgesia.     

Effects of Different Doses of Epidural Midazolam on Spinal Somatosensory Evoked Potentials

Summary  The aim of this study is to find out the effects of different doses of midazolam, when used epidurally, on somatosensory evoked potentials (SEP) by delaying neuronal conduction. Thirty two New Zeland albino male rabbits were divided into four groups. All rabbits were anesthetised with ketamine and xylasine combination and atracurium was used as muscle relaxant. 10 mg/kg/hr ketamine infusion was used for maintenance of anesthesia. After insertion of the epidural catheter surgically; Group 1 received 1.5 ml isotonic saline (Control), Group 2 received 150 μg/kg, Group 3 received 250 μg/kg, and Group 4 received 500 μg/kg midazolam epidurally. With the stimulation of sciatic nerve, SEP records were recorded from the epidural space. Records were received before the injection of the drug, and 20, 40, 60 minutes after injection of the drug.  “Latancy” results were increased according to control in all groups (including isotonic saline-control-group). Increase in latancy in the control group was interpreted as due to the effect of temperature mismatch of the saline and the rabbits. While in the first and second group amplitudes showed no differences, group 3 and 4 showed decreases of up to 50%. Epidurally administered midazolam up to 150 μg/kg caused no change in SEP records, but 250 and 500 μg/kg doses caused decreases in SEP records which can lead to misinterpretation as neurological damage.     

A two-dose epidural morphine regimen for cesarean section patients: therapeutic efficacy

A single dose of epidural morphine (EM) usually produces 24 h of post-cesarean section (CS) analgesia and patients require supplemental analgesics beyond this period. This study assesses if a second dose of EM administered 24 h after the first one offers superior therapeutic efficacy compared to conventional analgesics. Patients (n = 100) were randomized to receive one or two doses of epidural morphine. In all patients, EM 5 mg was administered after delivery. After 24 h patients received epidurally either normal saline (n = 50, Group 1) or morphine 5 mg (n = 50, Group 2). An independent observer used a visual analogue scale to assess nausea, itching, and analgesia 24 h after each injection. Results were expressed as mean +/- 1 s.e. mean and analyzed using nonparametric methods. The second dose of EM produced a significantly lower incidence and severity of nausea and itching than did the first dose (P < 0.01) in Group 2 with no difference in analgesia. The second day postoperative pain score in Group 1 was significantly greater than the first day score in the same group, and significantly greater than the severity score in Group 2. Only 36% of patients receiving two doses of EM required supplemental analgesics beyond 48 h compared to 76% of those receiving one dose (P < 0.01). No serious complications were noted. In summary, the use of a second dose of EM for post-CS analgesia produces better analgesia and reduces the need for oral analgesics. The second dose produced fewer side-effects, probably due to acute tolerance to morphine.     

Reinforcement of spinal anesthesia by epidural injection of saline: a comparison of hyperbaric and isobaric tetracaine

Purpose. An epidural injection of saline was reported to extend spinal anesthesia because of a volume effect. The aim of this study was to evaluate the influence of the baricity of spinal local anesthetics upon the extension of spinal anesthesia by epidural injection of saline. Methods. Forty patients undergoing elective lower-limb surgery were randomly allocated to four groups of 10 patients each. Group A received no epidural injection after the spinal administration of hyperbaric tetracaine (dissolved in 10% glucose). Group B received an epidural injection of 8 ml of physiological saline 20 min after spinal hyperbaric tetracaine. Group C received no epidural injection after spinal isobaric tetracaine (dissolved in physiological saline). Group D received an epidural injection of 8 ml of saline 20 min after spinal isobaric tetracaine. The level of analgesia was examined by the pinprick method at 5-min intervals. Results. The levels of analgesia 20 min after spinal anesthesia were significantly higher in hyperbaric groups than in isobaric groups [T5 (T2–L2) vs. T7 (T3–12)]. After epidural injection of saline, the levels of analgesia in groups B and D were significantly higher than in groups A and C. The segmental increases after epidural saline injection were 2 (0–3) in group B and 2 (1–7) in group D. Sensation in the sacral area remained 20 min after spinal block in one patient in group D; however, it disappeared after epidural saline injection. Conclusion. In this study, 8 ml of epidural saline extended spinal analgesia. However, there was no difference between the augmenting effect in isobaric and hyperbaric spinal anesthesia. We conclude that the reinforcement of spinal anesthesia by epidural injection of saline is not affected by the baricity of the spinal anesthetic solution used. Received for publication on March 11, 1999; accepted on December 13, 1999     

Prevention of spinal cord injury after cross-clamping of the thoracic aorta

Paraplegia has been a devastating and unpredictable complication following cross-clamping of the thoracic aorta. In this study, the effect of the pressure gradient between the aortic pressure distal to occlusion and cerebrospinal fluid pressure (CSFP), defined as relative spinal cord perfusion pressure (RSPP), on the development of spinal cord injury was investigated. In 32 mongrel dogs, the thoracic aorta just distal to the left subclavian artery was cross-clamped. After a complete loss of somatosensory evoked potentials (SEP) had been confirmed, the dogs were divided into six groups by an additional cross-clamp interval and RSPP as follows: Group I (n = 6): 0 mmHg for 10 minutes; Group II (n = 8): 0 mmHg for 20 minutes; Group III (n = 3): 7.5 mmHg for 20 minutes; Group IV (n = 3): 7.5 mmHg for 40 minutes; Group V (n = 6): 15 mmHg for 40 minutes and Group VI (n = 6): 15 mmHg for 60 minutes. RSPP was adjusted by either withdrawal of cerebrospinal fluid or injection of normal saline solution into the subarachnoid space. SEP were generated by the stimulation of bilateral peroneal nerves. The incidence of postoperative paraplegia was 0% in Groups I and V, 33% in Group III, 50% in Group VI and 100% in Groups II and IV. This study showed that RSPP plays an important role in the development of spinal cord injury during cross-clamping of the thoracic aorta. Therefore, RSPP should be maintained at as high a level as possible in order to prevent spinal cord injury even if SEP disappear during aortic occlusion.     

Spinal cord blood flow change by intravenous midazolam during isoflurane anesthesia

We investigated the effects of IV midazolam on spinal cord blood flow in 32 cats anesthetized with isoflurane. Cats underwent laminectomy, and the lumbar spinal cord was exposed. A platinum electrode was inserted stereotaxically into the spinal cord to a depth of 1 mm-2 mm lateral to midline at L2. Arterial blood pressure, heart rate, and spinal cord blood flow (using the hydrogen clearance method) were measured before and at 5, 15, 30, 60, 90, and 120 min after an IV bolus of midazolam (0, 1, 2, or 4 mg/kg in saline 5 mL; n = 8 cats per dose). Arterial blood pressure was not affected by 0 or 1 mg/kg of midazolam but was decreased for 30 min by 2 or 4 mg/kg of midazolam. Heart rate did not change. Spinal cord blood flow was increased for 90 min by midazolam 1 mg/kg and for 15 min by midazolam 2 mg/kg but was not changed by midazolam 4 mg/kg. In conclusion, 1 mg/kg of midazolam increased feline spinal cord blood flow without changing arterial blood pressure. In contrast, a larger dose of midazolam (4 mg/kg) did not change spinal cord blood flow but substantially decreased arterial blood pressure during isoflurane anesthesia.     

Hyperbaric bupivacaine affects the doses of midazolam required for sedation after spinal anaesthesia

BACKGROUND AND OBJECTIVE: Patients having spinal anaesthesia with hyperbaric bupivacaine may become sensitive to sedative drugs but no data exists about any dose-related effect of the local anaesthetic on the sedative requirement. We aimed to investigate whether hyperbaric bupivacaine dose in spinal anaesthesia has any effect on midazolam requirements. METHODS: Sixty unpremedicated patients were allocated to three equal groups. Patients in Groups I and II received hyperbaric bupivacaine 0.5% 10 and 17.5 mg respectively for spinal anaesthesia and Group III was a control group without spinal anaesthesia. In Groups I and II, after the evaluation of sensory block, patients received intravenous midazolam 1 mg per 30 s until the Ramsay sedation score reached 3 (drowsy but responsive to command). In Group III, general anaesthesia was induced after sedation score had reached 3 using midazolam. The total dose of midazolam (mg kg(-1)) given to each patient, the level of sensory block and complications were recorded. RESULTS: The level of sensory block was higher in Group II (T7) than Group I (T9) (P < 0.01). The doses of midazolam were 0.063 mg kg(-1) in Group I, 0.065 mg kg(-1) in Group II and 0.101 mg kg(-1) in Group III (P < 0.001). There was no correlation between level of sensory block and dose of midazolam in Group I (r = -0.293, P = 0.21) and Group II (r = 0.204, P = 0.39). CONCLUSIONS: Different doses of hyperbaric bupivacaine for spinal anaesthesia do not affect the midazolam requirements for sedation. However, spinal anaesthesia with hyperbaric bupivacaine with a maximum spread in the middle thoracic dermatomes may be associated with sedative effects and thus a reduced need for further sedation with midazolam.     

五种药物对兔脊髓的神经毒性实验研究

目的 对硬膜外术后镇痛用药是否对脊髓有神经毒性进行研究，以指导临床用药。方法 健康家兔４８只，硬膜外穿刺成功后，随机分为６组，每组８只，生理盐水对照组，布比卡因组，芬太尼组，曲巴多，氟哌利多，咪在唑仓组。６组均给药２次／ｄ，间隔１２小时，连续给药３天，继续观察至第７天处死兔作光交易和电镜检查。     

Comparison of midazolam and hydroxyzine as premedicants for combination of spinal and epidural anesthesia with midazolam sedation

Midazolam 4 mg i.m. (Group M, n = 15) was compared with hydroxyzine 50 mg i.m. (Group H, n = 13) in a randomized double-blind study, as premedicants for patients undergoing simple total hysterectomy under combination of spinal and epidural anesthesia with midazolam sedation. Reduction of anxiety and amnesic effects about procedure under regional anesthesia with sufficient patient co-operation were greater following midazolam. The doses for intraoperative sedation of midazolam and pentazocine were the same in both groups. Mean doses of midazolam 2 mg and pentazocine 6 mg were required to induce sleep. Maintenance doses of midazolam and pentazocine were 3.7 and 11.4 mg.hr-1, respectively. No patient had recall of surgical procedure. Midazolam did not delay the postoperative resedation which lasted about 2 hours. The decrease in O2 saturation by pulse oxymetry is significant in Group M (4.5%) than Group H (2.7%). Nevertheless two patients in each group required oxygen 2 liter.min-1 via a nasal catheter. These results indicate that premedication by midazolam is more effective for procedures under regional anesthesia.     

Acute phase histopathological study of spinally administered midazolam in cats.

Midazolam may be a useful analgesic when administered intrathecally. However, neurotoxicity must be excluded. The purpose of this study was to investigate whether spinally administered midazolam induces acute-phase histopathological or inflammatory reactions of the spinal cord. A lumbar laminectomy was performed on 40 cats, and their spinal cords were exposed. Midazolam 10 mg (2 mL, n = 20 cats) or saline 2 mL (20 cats) was administered directly to the spinal cord. At 1, 2, 4, or 6 h after the administration, cats were killed, and the lumbar spinal cord was removed and fixed in 10% formalin. Histology was examined using light microscopy with hematoxylin and eosin staining. Both groups showed slight to moderate changes in the spinal cord, but no severe damage was observed. Inflammatory reactions were seen in only one cat in the saline group with slight neutrophil infiltration. These changes were not different between the midazolam group and the saline group. In conclusion, up to 6 h after direct exposure to midazolam, no acute histological damage or inflammatory reaction of the spinal cord was seen in cats. IMPLICATIONS: Spinally administered midazolam, even in large doses, does not cause acute neurotoxicity or inflammation of the spinal cord.     

The effect of segmental epidural analgesia on the neurobehavioural responses of newborn infants

The effects of maternal segmental epidural analgesia on neonatal neurobehavioural responses were studied at the ages of 3 h, 1 day, 2 days and 4-5 days. Subjects were healthy, term neonates born vaginally to 14 mothers with an epidural block and to 15 mothers without analgesia. The only statistically significant differences were found at the age of 1 day, when the epidural group infants habituated and oriented better to inanimate auditory stimuli. It is concluded that segmental epidural analgesia with a low dose of bupivacaine can be regarded as being a safe obstetric analgesic method as regards neonatal behavioural responses.     

Continuous infusion epidural analgesia in parturients receiving bupivacaine, chloroprocaine, or lidocaine--maternal, fetal, and neonatal effects

The effects of epidural analgesia for labor and delivery using a continuous infusion technique on fetal heart rate, uterine activity, maternal blood pressure, Apgar scores, neonatal acid-base status, and the Neurologic and Adaptive Capacity Scoring System were studied in 61 parturients. Group I (n = 23) received initial test and therapeutic doses of 2 and 6 ml of 0.5% bupivacaine followed by an infusion of 0.125% at a rate of 14 ml/hr. Group II (n = 19) received 2 and 6 ml of 2% chloroprocaine followed by an infusion of 0.75% at a rate of 27 ml/hr. Group III (n = 19) received 2 and 6 ml of 1.5% lidocaine followed by an infusion of 0.75% at a rate of 14 ml/hr. None of the three local anesthetics used had any significant effect on baseline fetal heart rate or uterine activity. In cases in which monitoring of fetal heart rate was both technically satisfactory and continuous, late and variable decelerations in fetal heart rate were seen in 10 of 17, 3 of 18, and 2 of 19 of the fetuses in groups I, II, and III, respectively. The incidence was significantly higher in group I than in groups II or III (P less than 0.05). Apgar scores and neonatal acid-base status were equally good in all three groups. Neurologic and adaptive capacity scores did not differ among the three groups of neonates, nor did any of the neonates in the three groups score lower than a control group of 19 neonates whose mothers did not receive any analgesia or medications for labor and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of effects of propofol and midazolam at sedative concentrations on sympathetic tone generation in the isolated spinal cord of neonatal rats

BACKGROUND: Propofol and midazolam are common sedatives for critically ill patients. Little is known about the effects of propofol and midazolam on central sympathetic activity when drug concentrations in extracellular milieu are under precise control. Previous work using an in vitro neonatal rat splanchnic nerve-spinal cord preparation has demonstrated that tonic sympathetic activity is generated spontaneously in the thoracic spinal cord. The aim of this study was to investigate the concentration effects of propofol and midazolam on spinally generated sympathetic activity. METHODS: Using an in vitro neonatal rat splanchnic nerve-spinal cord preparation that allows the precise control of drug concentrations, the central sympathetic effects elicited by the application of propofol (10-640 microM) and midazolam (10-640 microM) were compared. RESULTS: There was a prompt decrease in sympathetic activity on application of propofol or midazolam in a concentration-dependent manner. A significant decrease in sympathetic activity was observed on application of propofol at 80-640 microM; however, the application of propofol at 10-40 microM caused only a slight alteration in activity. The sympathetic activity was not altered significantly by 10 microM of midazolam, but the application of midazolam at 20-640 microM caused a significant decrease in activity. Thus, in these experimental conditions, the minimum concentration of propofol causing a significant decrease in sympathetic activity was 80 microM and that of midazolam was 20 microM. CONCLUSIONS: The current findings suggest that the administration of 9-19 microM of propofol or 0.7-0.9 microM of midazolam, the clinically relevant concentrations for sedation, does not alter central sympathetic outflow at the spinal cord level. However, propofol at a concentration of 86 microM, which could be achieved by a single-bolus loading dose to induce sedation, depresses central sympathetic activity.     

Epidural cooling for the prevention of ischemic injury to the spinal cord during aortic occlusion in a rabbit model: determination of the optimal temperature

PURPOSE: This experiment was designed for the determination of the optimal epidural cooling temperature for the allowance of spinal cord protection with minimal side effects during an aortic occlusion-induced spinal cord ischemia model in rabbits. METHODS: Spinal cord ischemia was induced in rabbits with infrarenal aortic occlusion for 40 minutes. Spinal cord cooling was effected with epidural infusion of normal saline solution at the following different temperatures: group 1, 17 degrees C (n = 6); group 2, 24 degrees C (n = 6); group 3, 32 degrees C (n = 6); and group 4, 39 degrees C (n = 3). Sham-operated rabbits without aortic occlusion were used as controls with epidural infusion at healthy body temperature (39 degrees C; n = 3). Motor function was assessed at 48 hours with Tarlov's criteria, and the animals were killed. The spinal cord was sectioned into multiple segments, and semiquantitative histologic scoring (0 to 5) was used to grade ischemic injury. RESULTS: Cooling solution and spinal cord temperatures showed linear correlation (r = 0.95). All the rabbits in groups 1 (except one with mild weakness), 2, and 3 were neurologically intact, and all in group 4 had paraplegia develop (P < .001). One rabbit in group 1 died from increased intracranial pressure (ICP). Mean blood pressure, ICP, and body temperature were similar among the groups. Histology correlated with the clinical findings. In groups 1 and 2, minimal histologic changes were noted. Low-grade ischemic changes were present in group 3 in the low-lumbar and mid-lumbar segments. Severe ischemic injury occurred at the same segments in group 4 (P < .05). CONCLUSION: These study results suggest that in rabbits satisfactory spinal cord protection during aortic occlusion can be achieved at moderate regional hypothermia (24 degrees C). Large volume infusion for the achievement of profound hypothermia may cause deleterious effects of increased ICP and is not warranted.     

The neurotoxic effects of intrathecal midazolam and neostigmine in rabbits

In parallel with improvements in understanding pain neurophysiology, many chemicals have recently been investigated for spinal anaesthesia and analgesia. However, studies discussing the effects of these drugs on neural tissue indicate that knowledge about some aspects of neurotoxicity is limited. Forty-nine New Zealand albino rabbits, weighing 2.2 +/- 0.2 kg, were randomly assigned to seven groups of seven animals each. Single dose groups received intrathecally through the atlantooccipital membrane 0.9% saline 1.5 ml; midazolam 100 microg/kg (low dose midazolam group) or 500 microg/kg (high dose midazolam group); neostigmine 10 microg/kg (low dose neostigmine group) or 50 microg/kg (high dose neostigmine group). Two groups had seven days of repeated dosing with either midazolam 100 microg/kg/day (repeat midazolam group) or 10 microg/kg/day neostigmine (repeat neostigmine group). The animals were sacrificed on day 8, and two spinal cord sections from the fourth cervical level and fourth lumbar level were removed and prepared for histopathological study. Transmission electron microscopic evaluations were performed on transverse spinal cord sections by a neuropathologist blinded to the group allocation. Twenty myelinated axons and neurones in the cervical and lumbar sections were investigated for the histopathological study. This study indicates that midazolam and neostigmine have different neurotoxic effects that depend on the dose and the repetition of dosing when these drugs are administered intrathecally.     

Epidural catheter placement in neonates: sonoanatomy and feasibility of ultrasonographic guidance in term and preterm neonates

BACKGROUND: We report the first prospective sonoanatomic study in neonates with the aim to perform ultrasonographic-guided epidural catheter placement in this age group. METHOD: One hundred forty-five neonates with a body weight < or =4 kg (0.53-4 kg) were included in this prospective study. The study was divided into 3 consecutive parts. In the first part, the neuraxial sonoanatomy of 60 neonates was evaluated. In the second part, 50 neonates scheduled for major abdominal surgery were enrolled. In this part, the depth of the ligamentum flavum measured with ultrasound was matched up to the depth evaluated clinically with the loss-of-resistance technique. In the third part, ultrasonographic epidural catheter placement was performed in 35 neonates weighing between 620 g and 4 kg. RESULTS: The ligamentum flavum, the dura mater, and the termination of the spinal cord could be identified in all patients. The first part showed a good correlation between body weight and depth of the ligamentum flavum. The median termination of the spinal cord corresponded to vertebral level L2. The second part confirmed a good correlation between depth of the ligamentum flavum evaluated clinically and the depth predicted with ultrasound. Finally, real-time ultrasound-guided epidural placement was possible in all 35 neonates. CONCLUSION: Ultrasound examination of the spinal cord anatomy provides valuable information for epidural catheter placement in neonates. Ultrasonography enables a real-time identification of the tip of the needle within the epidural space and a visualization of the spread of local anesthetic in these patients.     

Concentrations of lactate and pyruvate in maternal and neonatal blood with different intravenous fluids used for prehydration before epidural anesthesia

This study assesses the effects of infusion of 1200 ml of four different intravenous solutions before epidural anesthesia for cesarean section on maternal and neonatal whole blood lactate (L), pyruvate (P), excess lactate (XL), L/P ratio, and base excess (BE) in four equal groups of patients. Patients in group I (n = 15) received normal saline; those in group II, Ringer's lactate (RL); those in group III, RL with 20 g of glucose; and those in group IV, Plasma-Lyte A. Maternal venous concentrations of L increased significantly in all groups after infusion, but P increased only in group III. Both XL concentrations and L/P ratios remained unchanged after infusion in group III mothers, but increased in the other three groups. Umbilical venous (UV) and arterial (UA) blood L concentrations (1.85 +/- 0.13, 1 SEM mmol/L in both) were greater in group III than in groups I and II, and P concentrations (0.12 +/- 0.01 mmol/L in both) were significantly greater in group III than in groups I, II, and IV. Both UV XL (0.9 +/- 0.1 mmol/L) and L/P ratio (32 +/- 8) were significantly greater in group IV neonates than in the other groups. However, neither neonatal Apgar scores nor maternal and neonatal BE significantly differed among the four groups. No neonate developed hypoglycemia. It is concluded that all the four intravenous fluids, despite differences in their effects on blood L and P concentrations, produce clinically satisfactory maternal and neonatal outcome.     

The effects of regional anaesthesia for caesarean section on maternal and fetal blood flow velocities measured by doppler ultrasound

We studied the effects of spinal anaesthesia (Group S), epidural anaesthesia (Group E), and combined spinal and epidural anaesthesia (Group SE), on maternal and fetal blood flow in 24 healthy parturients (n = 8/group) with uncomplicated singleton pregnancies using Doppler technique. Prior to the induction of anaesthesia, the patients were prehydrated with balanced electrolyte solution 15 ml kg^-1 over a period of 15 min. After the induction of regional anaesthesia, the systolic blood pressure was maintained within 15% limits of the preoperative values using prophylactic etilefrine infusion in Groups S and SE. The flow velocity waveforms of the maternal femoral artery, the main branch of the uterine artery (placental side), the foetal umbilical and middle cerebral arteries were recorded by Doppler technique before and after prehydration as well as after onset of T7 analgesia and the pulsatility indices (PI) were derived. Rapid intravenous prehydration had no effects on uteroplacental or fetal circulation as indicated by unaltered uterine, umbilical, and fetal middle cerebral artery Pis. After the onset of T7 analgesia, the uterine artery PI was increased in Group S indicating increased uterine vascular resistance while no changes occurred in Groups E and SE. No adverse effects were observed on the neonates as indicated by the Apgar score and the umbilical artery and vein acid–base status in any of the groups.     

Haemodynamic effects of clonidine injected epidurally in halothane-anaesthetized dogs

The haemodynamic effects of clonidine administered in the epidural space were studied in 16 halothane-anaesthetized dogs. The animals were randomly assigned to two groups: Group I received three doses of 3 ml of normal saline, Group II received three doses of 3 micrograms X kg-1 of clonidine, through an epidural catheter, whose tip was located between L2-T11. Control haemodynamic measurements were taken one hour after completion of the surgical preparation (period P1); they were repeated every 45 minutes after each incremental dose (periods P2, P3, P4) and 105 minutes after a total cumulative dose of 9 micrograms X kg-1 of clonidine or 9 ml of saline were given (period P5). No significant changes over time were observed in Group I. In Group II clonidine produced statistically significant reductions of systemic blood pressure (BP), mean left ventricular pressure (LV), heart rate (HR), cardiac output (CO) and peak LV dP/dt only after a total clonidine dose of 9 micrograms X kg-1 and these changes were sustained. BP fell 15 per cent, CO 21 per cent, HR 25 per cent, LV 20 per cent and peak LV dP/dt 30 per cent when P5 measurements were compared to control values within Group II (p less than 0.05). These haemodynamic effects of clonidine are likely due to minimal systemic absorption and/or cephalad spread of the drug towards its site of action in the brain stem. The reductions of HR, CO, BP, and isovolemic indices of contractility are likely explained by a reduction of sympathetic outflow at the spinal cord and medulla oblongata levels as well as increased parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection

Background. Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia.

Methods. In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg).Group IV (n = 8) received retrograde infusion of room temperature saline (22°C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL · kg⁻¹ · min⁻¹ during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale.

Results. Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean ± SEM): group I, 0.50 ± 0.50; group II, 0.25 ± 0.46; group IV, 1.63 ± 0.56; group V, 4.13 ± 0.23; and group VI, 4.22 ± 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time.

Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia.