Dextran 40 (Rheomacrodex) or Polygeline (Haemaccel) as an epidural patch for post dural puncture headache: a neurotoxicity study in a rat model of Dextran 40 and Polygeline injected intrathecally.

BACKGROUND AND OBJECTIVE: Although an epidural autologous blood patch is considered the most effective treatment for post dural puncture headache, which sometimes occurs following spinal or inadvertent spinal anaesthesia, there remains a need for alternative materials for epidural patches. We investigated the potential neurotoxicity of Dextran 40 (Rheomacrodex) and Polygeline (Haemaccel) used for this purpose in a rat model. METHODS: Repeated boluses of 10% Dextran 40, 3.5% Polygeline or 0.9% saline were injected intrathecally over a period of 1 month in three groups of rats. RESULTS: No behavioural or clinical derangements were observed in any of the three groups during this period. After sacrifice of the animals at the end of the experiment, no significant differences in the histopathological appearances of the spinal cords in the three groups were observed. No toxic effects diminishing viability of spinal cord cells were evident. Similarly, viability of renal, hepatic and peripheral blood mononuclear cells remained unaffected (98% +/- 2%). CONCLUSIONS: No deleterious effects, clinical or cellular, were evident in this rat model when Dextran 40 or Polygeline were injected intrathecally. Thus, both substances can be considered as possible alternative materials for epidural patches.

Fluid preload before spinal anaesthesia in Caesarean section: the effect on neonatal acid-base status.

BACKGROUND AND OBJECTIVE: We evaluated the effect of two different preload solutions: (i) Ringer's lactate (compound sodium lactate intravenous infusion BP) and (ii) 0.9% sodium chloride solution on the neonatal acid-base status of the newborn infants. The two standard regimens were compared to detect a possible difference. METHODS: A 2 L crystalloid fluid bolus was administered immediately before spinal anaesthesia for elective Caesarean section in two groups of 20 healthy parturients, while rigorously maintaining maternal normotension. RESULTS: No significant differences in the Apgar scores at 1 and 5 min, or infant well-being were demonstrated in either of the two groups. The data show that umbilical artery PCO2 is lower in the Ringer's lactate group and that pH is insignificantly higher by 0.03. CONCLUSIONS: The choice of Ringer's lactate or saline for fluid preload does not have any effect on neonatal well-being.

Intracellular Ca++/Mg++ homeostasis during postnatal growth of experimental rats. Multiple time-point study.

In most tissues, various cell membrane ion transporting systems are not fully developed and/or maximally active at the prenatal and early postnatal stage. Their progressive development and expression are a function of growth and maturity. We performed a multiple time-point study, in order to investigate the ability of a variety of tissues to maintain appropriate Ca++ and Mg++ homeostasis at different stages of postnatal development. Total intracellular Ca++ in one-week-old rat liver, brain and spinal cord tissues was significantly elevated, compared to mature animals. It increased further through the first three weeks of gestation. Intracellular Ca++ gradually and significantly declined in adult and mature animal groups. Alterations in total intracellular Mg++ of the same tissue samples, although not so profound, paralleled changes in total intracellular Ca++. We conclude that a developmental switch in intracellular Ca++ and Mg++ homeostasis occurs one to three weeks following birth. It might be related to the incomplete development of Ca++ and Mg++ transmembrane transporting systems, previously reported as being only partially expressed at the early postnatal stage. These developmental alterations in total intracellular Ca++ and Mg++ content might serve as a regulatory mechanism, adjusting cell activities to the physiological requirements of the growing and maturing animal.

Intrathecal anaesthesia alters intracellular Ca2+/Mg2+ homeostasis in the spinal cord neurones of experimental rats.

BACKGROUND AND OBJECTIVE: The effect of anaesthesia induced by intrathecal injection of 6.3% MgSO4 or 4% lidocaine on intracellular electrolyte homeostasis in spinal cord neurones of a rat model was investigated. METHODS: Intracellular Ca2+, Mg2+, Na+ and K+ concentrations were determined at different times after intrathecal administration of NaCl (saline, a control group), MgSO4 or lidocaine. RESULTS: In both thoracic and lumbar spinal cord segments, Ca2+ concentrations rose significantly 30 min and 2 h after 6.3% MgSO4 injection, and after 24 h were still significantly increased compared with the values obtained from the control group which were subjected to sham 'anaesthesia' by saline injection (172, 121 and 108 ng mg-1 protein vs. control 23 ng mg-1 protein, respectively, in the thoracic segment and 222, 229 and 176 ng mg-1 protein vs. control 43 ng mg-1 protein, respectively, in the lumbar segment). Lidocaine injection also produced a significant increase in intracellular Ca2+ in the thoracic and lumbar spinal cord segments (69, 64 and 53 ng mg-1 protein vs. control 33.4 ng mg-1 protein and 26, 94 and 46 ng mg-1 protein vs. 23 ng mg-1 protein respectively). Only a modest rise in intracellular Mg2+ was observed after intrathecal MgSO4 or lidocaine injection (27 ng mg-1 protein vs. 23 ng mg-1 protein). Na+ and K+ concentrations decreased 24 h after MgSO4 and 1 h after lidocaine injection. CONCLUSION: Intrathecal anaesthesia by MgSO4 or lidocaine alters intracellular electrolyte homeostasis in spinal cord neurones of experimental rats. A possible common mechanism of action via Ca2+ ion channels is discussed.

Lateral recumbent head-down posture for epidural catheter insertion reduces intravascular injection.

PURPOSE: The unintentional and unrecognized cannulation of an extradural vein is a potentially serious complication of an epidural anesthetic. The present study was undertaken to assess the incidence of blood vessel puncture related to epidural catheterization performed in three different body positions. METHODS: The study was conducted in 900 (three groups of 300) obstetric patients undergoing continuous epidural analgesia during their labour and who were randomly allocated to three groups. Epidural catheterization was performed with patients in the sitting, lateral recumbent horizontal, or lateral recumbent head-down position. RESULTS: There was a lower incidence of vessel cannulation when this procedure was performed in the lateral recumbent head-down position (2%) than in the lateral recumbent horizontal (6%) and in the sitting position (10.7%). CONCLUSION: Adoption of the lateral recumbent head-down position for the performance of lumbar epidural blockade, in labour at term, reduces the incidence of lumbar epidural venous puncture.

Substances used for local and general anaesthesia in major surgery suppress proliferative responsiveness of normal rat peripheral blood mononuclear cells in culture.

We studied the direct effect of intravenous anaesthetics, local anaesthetics and premedication drugs in common use for major surgery, on the spontaneous versus lectin induced proliferation of cultured normal rat peripheral blood mononuclear cells, not exposed to surgical or any other trauma prior to culture. Peripheral blood mononuclear cells were incubated in cell-culture medium in the presence or in the absence of propofol, ketamine, fentanyl, midazolam, thiopental sodium, lidocaine or etomidate. The cells proliferated either spontaneously or under stimulation with a lectin phytohaemagglutinine P for 72 h. The proliferation rate was evaluated by 2H-Thymidine incorporation. Fentanyl, thiopental sodium, lidocaine and etomidate significantly inhibited phytohaemagglutinine P induced 3H-Thymidine incorporation in cultured rat peripheral blood mononuclear cells. Counts per minute of the cultures treated with these drugs were 1667.80 +/- 745.72, 1614.1 +/- 615.00, 1688.0 +/- 615.0 and 1549 +/- 560.41, respectively, compared with the phytohaemagglutinine P stimulated positive control counts per minute, 13488 +/- 4305.6 (P < 0.001 in each comparison). Propofol, ketamine and midazolam inhibited the lectin-induced cell proliferation to levels not statistically different from the baseline. Counts per minute of these cultures were 1361.90 +/- 745.73; 1108.90 +/- 751.33 and 1518.10 +/- 848.88, respectively. Compared either with the baseline 972.57 +/- 356.73 counts per minute or to the positive control culture counts per minute, 13488 +/- 4305.6 the difference was statistically significant (P < 0.001) in each comparison. All the substances tested in this study proved capable of exerting direct inhibitory effect on circulating immunocompetent cells, because the latter were not subjected to any other immunosuppressive factor, be it operative trauma, blood transfusion, malnutrition, drug abuse, prior to culture. The possible theoretical and practical implications are discussed in this study.

Spinal anaesthesia with gamma hydroxybutyrate. A study in a rat model.

Gamma hydroxybutyric acid, a central inhibitory neurotransmitter and a cerebral metabolite of gamma-aminobutyric acid, is present in high concentrations in the mammalian hypothalamus and basal ganglia. Its sodium salt gamma hydroxybutyrate has been effectively used as an intravenous anaesthetic agent, and as an oral sedative, and in the management of the alcohol withdrawal syndrome. In an animal model, using 72 Wistar strain rats allocated to one of six groups of 12 animals each, with implanted lumbar intrathecal catheters, we examined whether gamma hydroxybutyrate, 20% 40 microL (32 mg kg-1) administered alone or combined with fentanyl, gamma hydroxybutyrate 20% 20 microL (16 mg kg-1), fentanyl 0.005% 20 microL (4 mg kg-1) as an intrathecal bolus, provides intraoperative anaesthesia, comparable with that produced by intrathecal lignocaine. We demonstrated that gamma hydroxybutyrate, given by an intrathecal bolus in the rat model, produced reversible segmental antinociception, together with muscular relaxation of the abdominal wall and rear limbs. This is accompanied by moderate sedation without haemodynamic or respiratory depression. This agent may thus be promising for use as a spinal anaesthetic drug.

An investigation of the possible neurotoxic effects of intrathecal midazolam combined with fentanyl in the rat.

In previous work, midazolam was injected intrathecally and produced reversible, segmental, spinally mediated anti-nociception sufficient for abdominal surgery in a rat model. The neurotoxic effect of midazolam, alone or combined with fentanyl, injected intrathecally repeatedly on 15 occasions over a period of 1 month, was studied in the same model. We sought to establish whether this would produce neurological damage or neurotoxic injury. Histopathological examination of the excised spinal cord and paraspinal tissues was carried out. Thirty Wistar strain rats with nylon catheters chronically implanted in the lumbar subarachnoid space were divided into five groups: group 1 (n = 6) received 40 microL of midazolam 0.1%; group 2 (n = 6) received 40 microL of fentanyl 0.005%; group 3 (n = 6) received 20 microL of midazolam 0.1% plus 20 microL of fentanyl 0.005%; group 4 (n = 6) received 40 microL of lignocaine 2%; group 5 (n = 6) received 40 microL of phenol in water. All substances were injected through the implanted catheters. The neurological recovery of all the animals in the four groups that received intrathecal midazolam alone, fentanyl alone, midazolam plus fentanyl and lignocaine alone was similar and complete. There were no significant differences in the histological changes in the neural tissues of these groups, despite repeated application of the test substances. Group 5 demonstrated the typical neurolytic lesions of phenol when injected intentionally into the subarachnoid space.

Serum electrolyte and blood gas changes after intrathecal and intravenous bolus injections of magnesium sulphate. An experimental study in a rat model.

The effect of intrathecally administered magnesium sulphate on serum levels of magnesium, sodium, potassium, calcium and blood gas variables was studied in a rat model. Magnesium sulphate given intrathecally has previously been shown to produce segmental spinal blockade with no permanent neurological damage. The previous studies, however, had not investigated the possible systemic effects of the magnesium sulphate. The serum magnesium level increased significantly at 1 and 2 h after the intrathecal injection of both 6.3% and 12.6% magnesium sulphate (6.3%: 28% at 1 h, 24% at 2 h; 12.6%: 22% at 1 h, 16% at 2 h). These changes were not as great as occurred when the same dose of magnesium sulphate was administered intravenously. In all cases, the serum magnesium had returned to normal by 24 h. There were no significant changes in calcium, sodium or potassium levels, nor in arterial blood gas variables. These results show that intrathecally administered magnesium sulphate has little effect on electrolyte homeostasis.

Neurotoxicity after spinal anaesthesia induced by serial intrathecal injections of magnesium sulphate. An experimental study in a rat model.

We have previously demonstrated in a rat model that the lumbar intrathecal injection of 0.02 ml 6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, produces a state of spinal anaesthesia and general sedation which reversed completely after 6 h, without evidence of neurotoxicity, immediately or during the week thereafter. Using the same model and five groups of six animals in each, we administered the same volume and concentration of magnesium sulphate and compared its clinical effects with those of 0.02 ml 12.6% magnesium sulphate, 0.02 ml 2% lignocaine and 0.02 ml 0.9% sodium chloride solution, given as a series of 15 injections on alternate days for a period of 1 month. The animals were then killed and their spinal cords and meninges examined histologically. No significant differences were noted in the times of onset, durations of sensory and motor blockade and the times to full recovery throughout the entire period of 1 month's observation in the animals receiving intrathecal 6.3% magnesium sulphate. In the group receiving 12.6% magnesium sulphate, the time of onset of sensory and motor blockade was shorter and the duration of both parameters was significantly longer than in the former group. Full clinical recovery and resumption of normal eating and drinking took place in both groups throughout the entire series of 15 successive intrathecal injections. Identical, mild, uniform histopathological changes in the spinal cord were seen in all the five groups, including the group in which only the intrathecal catheter was implanted. The complete recovery and benign consequences of repeated intrathecal injections of iso-osmolar magnesium sulphate in a rat model indicate a lack of neurotoxicity and provide an impetus for further trials in larger animal species, before initial clinical trials of this substance, given intrathecally, in humans.

Spinal anaesthesia with midazolam in the rat.

PURPOSE: This study examined in an animal model whether intrathecal midazolam, alone or with fentanyl, can achieve anaesthesia sufficient for laparotomy, comparable to lidocaine. Effects on consciousness and whether anaesthesia was segmental were also examined. The haemodynamic and respiratory changes were compared with those of intrathecal lidocaine or intrathecal fentanyl alone. METHODS: Sixty Wistar strain rats, with nylon catheters chronically implanted in the lumbar subarachnoid theca, were divided into six groups. Group 1 (n = 12) received 75 microL intrathecal lidocaine 2%. Group 2 (n = 12) received 75 microL intrathecal midazolam 0.1%, Group 3 (n = 12) received intrathecal 37.5 microL midazolam 0.1%, plus 37.5 microL fentanyl 0.005%. Group 4 (n = 12) received intrathecal 50 microL fentanyl 0.005%. Group 5 (n = 6) received 75 microL midazolam 0.1% iv. Group 6 (n = 6) received halothane 0.6% in oxygen by inhalation. RESULTS: Both groups that received intrathecal midazolam, alone or combined with fentanyl, developed effective segmental sensory and motor blockade of the hind limbs and abdominal wall, sufficient for a pain-free laparotomy procedure. Neither of these groups, unlike the group that received intrathecal lidocaine, developed a reduction in blood pressure or change in heart rate at the time of maximal sensory or motor blockade, nor were there changes in the arterial blood gases or respiratory rate. CONCLUSION: Midazolam, when injected intrathecally, produces reversible, segmental, spinally mediated antinociception, sufficient to provide balanced anaesthesia for abdominal surgery.

Spinal anaesthesia induced by intrathecal magnesium sulphate.

We have demonstrated in a rat model that the intrathecal injection of 0.02 ml of 6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, will produce a state of spinal anaesthesia and general sedation, lasting approximately 1 h. These effects reversed completely after 6 h, without evidence of neurotoxicity, immediately or during the period 1 week following the injection. The accompanying changes in haemodynamic and respiratory functions were minimal throughout the period of anaesthesia and compare favourably with those induced by an intrathecal bolus of 0.04 ml of 2% lignocaine.