Clinical and Histological Effects of the Intrathecal Administration of a Single Dose of Dexmedetomidine in Rabbits.

BACKGROUND: There is experimental evidence that dexmedetomidine has neuroprotective effects. So, it could be expected that its intrathecal or epidural administration presents no harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully elucidated. OBJECTIVE: To evaluate the effect of preservative-free dexmedetomidine administered as a subarachnoid single injection on the spinal cord and meninges of rabbits. STUDY DESIGN: Research article. SETTING: Experimental research laboratory. METHODS: Twenty young adult female rabbits, each weighing between 3200 and 4900 g, and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9% saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 µg). After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random 5 µl.cm-1 of spinal length (0.2 mL) of solution (saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group showed signs of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with signs of meningeal injury. The main histological changes observed were areas with meningeal thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further histological examination also revealed adherence areas among the pia and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. LIMITATIONS: Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine was not performed. CONCLUSION: On the basis of the present results, dexmedetomidine administered in the subarachnoid space in a single dose of 10 µg is capable of producing histological changes over the meninges of rabbits.

The blood-brain barrier and nasal drug delivery to the central nervous system.

BACKGROUND: The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain. METHODS: The objective of this study is to generally review these strategies of drug administration to the CNS. RESULTS: Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS. CONCLUSION: Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Intracisternal injection of palmitoylethanolamide inhibits the peripheral nociceptive evoked responses of dorsal horn wide dynamic range neurons.

Endogenous palmitoylethanolamide (PEA) has a key role in pain modulation. Central or peripheral PEA can reduce nociceptive behavior, but no study has yet reported a descending inhibitory effect on the neuronal nociceptive activity of Aδ- and C-fibers. This study shows that intracisternal PEA inhibits the peripheral nociceptive responses of dorsal horn wide dynamic range cells (i.e., inhibition of Aδ- and C-fibers), an effect blocked by spinal methiothepin. These results suggest that a descending analgesic mechanism mediated by the serotonergic system could be activated by central PEA.

Neurotoxicity of subarachnoid preservative-free S(+)-ketamine in dogs.

BACKGROUND: Subarachnoid S(+)-ketamine is a matter of much debate as the results regarding its toxicity are contradictory. OBJECTIVES: Our objective was to investigate possible histopathological alterations after subarachnoid administration of different doses of preservative-free S(+)-ketamine to dogs. STUDY DESIGN: A randomized, blind, prospective experimental study. SETTING: Center for Research on Pain at the Federal University of Maranhão, Brazil. METHODS: Sixteen adult mongrel dogs of both sexes, each weighing 11 to 20 kg were divided into 3 groups: Group I (n=6), 0.7 mg/kg-1 S(+)-ketamine; Group II (n=6), 0.5 mg/kg-1 S(+)-ketamine, and a control group, Group III, (n=4), 0.9% NaCl. All substances were administered in one mL volume doses. The animals were kept in captivity for 2 weeks; after this period, they were put down and lumbar and sacral portions of the spinal cords were removed for histological examination using conventional light microscopy. RESULTS: There were histological alterations in the spinal cords of the test subjects in the control group. Comparison showed significant histological abnormalities in Groups I and II when compared to the control group, including gliosis, axonal edema, central chromatolysis, lymphocyte infiltration and fibrous thickening of the dura mater. LIMITATIONS: Test subjects received only a single dose each. The observation period was not very long, less than a month. CONCLUSIONS: Subarachnoid administration of S(+)-ketamine without preservative caused histological lesions on the spinal cord and meninges in the dogs studied. S(+)-ketamine should not be given to clinical patients in this way until further evaluation of the significance of this toxicity has been conducted.

Bupivacaina isobárica ou hiperbárica, para anestesia subaracnóidea / Plain or hyperbaric bupivacaine for spinal anesthesia

Três ml com bupivacaína a 0,5% isobárica ou com glicose a 8% foram injetados no espaço subaracnóideo em dois grupos de 15 pacientes. O grupo 1 recebeu bupivacaína com glicose a 8% e o grupo 2, o mesmo agente em soluçäo isobárica. As injeçöes foram realizadas em decúbito lateral e os pacientes imediatamente colocados em posiçäo dorsal horizontal. A diferença entre o nível máximo de bloqueio sensitivo nos grupos 1 e 2 (T5 e T9, respectivamente) foi estatisticamente significante. Näo houve diferença entre o início da analgesia, na duraçäo do bloqueio sensitivo e motor, na incidência dos efeitos colaterais. Näo foi observado nenhum caso de cefaléia pós-punçäo espinhal. A hipotensäo arterial foi diretamente relacionada ao nível do bloqueio. A bupivacaína hipebárica foi associada com uma maior incidência de hipotensäo arterial

Efeito da posiçäo de Trendelenburg (0- versus 10-) na difusäo da bupivacaína hiperbárica / Effects of Tendelenburg position (0- versus 10-) on the spread of hyperbaric bupivacaine

La evaluación del efecto de 10- en la posición de Trendelenburg por 120 segundos versus la posición horizontal, en la difusión de 3 ml de bupivacaína al 0.5% en glucosa al 8%, fue realizada en 40 pacientes. Todos los pacientes fueron operados bajo el nivel de T10. Aunque el nivel promedio de la difusión fue mayor en la posición horizontal, ísto no fue significativo. No fueron observadas diferencias en el bloqueio motor, duración de la analgesia o alteraciones cardiovasculares en ambos grupos. Este estudio sugiere que 3 ml de bupivacaína al 0.5%b hiperbárica y colocación de la mesa en Tendelenburg de 10- proporciona una rápida y controlable difusión de la analgesia para cirurgías del abdomen inferior, perineales y extremidades inferiores