During a finite developmental phase – the brain growth spurt – the brain grows and matures at an accelerated rate. During this period the brain is more sensitive to harmful substances such as ethanol and environmental toxins than before or after. This period extends from the last trimester to the second year in humans and occurs postnatally in the mice used for these studies. The aims of this thesis were; to investigate common anaesthetics ability to promote acute apoptosis and late persistant behavioural aberrations measured with spontaneous behaviour in a novel home environment, learning in a radial arm maze and anxiety-like behaviour in an elevated plus maze, to measure alterations in BDNF, CaMKII, GAP-43, synaptophysin and tau after anaesthesia exposure, to evaluate clonidine as a potentially protecting agent and examine if theophylline, a chemically unrelated compound, causes similar effects as anaesthetics. Some of the results are: combinations of anaesthetics acting on the GABAA receptor (propofol or pentothal) and NMDA receptor (ketamine) exhibit more apoptosis and behavioural alterations than single anaesthetics. Ketamine, but not propofol, alters the content of CaMKII and GAP-43 proteins important in brain development. Propofol exposure alters the content of BDNF (brain derived neurotrophic factor) in hippocampus, frontal and parietal cortex. Neonatal propofol exposure leads to less sensitiveness to diazepam in adult age as measured with induced spontaneous behaviour and an elevated plus maze. Clonidine, an alpha2 adrenergic agonist does not cause any aberrations and appears to prevent apoptosis and behavioural alterations after ketamine. Theophylline, used as apnoea treatment in neonates, also increases apoptosis and alters normal behaviour. Thus, alterations both in neuronal survival, function and protein expression is apparent after neonatal exposure to anaesthetics. This is also shown in studies of Rhesus monkeys. However, it is still difficult to assess how these findings should extrapolate to humans. Epidemiological studies give conflicting results. Insufficient anaesthesia is not a solution as pain and stress cause even more pronounced problems. Minimizing anaesthetic exposure, delaying procedures until after the sensitive phase and finding protective agents, such as clonidine, are possible strategies. Evaluation of other substances that infants are exposed to is needed.

Ketamine is a non-competitive NMDA antagonist that has been shown to have antidepressant properties both clinically as well as in preclinical studies when administered at a subanesthetic dose. In vivo electrophysiological recordings were carried in male Sprague Dawley rats 30 minutes following ketamine administration (10 mg/kg) to first assess its effects on monoaminergic firing. Whilst no change in the firing activity of serotonin (5-HT) neurons was observed in the dorsal raphe nucleus (DRN), an increase in the firing activity was observed for dopamine (DA) and noradrenergic (NE) neurons in the ventral tegmental area (VTA) and locus coeruleus (LC), respectively. The effect of ketamine on these electrophysiological parameters was prevented by pre-administration of the AMPA receptor antagonist NBQX 10 minutes prior to ketamine administration. In a second series of experiments, an increase in AMPA-evoked response was observed within 30 minutes in the CA3 layer of the hippocampus (HPC) following acute ketamine administration. These findings suggest that acute ketamine administration produces a prompt enhancement of AMPA transmission in the forebrain and also results in increased catecholaminergic activity. These effects may play a crucial role in the rapid antidepressant effects of ketamine observed shortly following its infusion in the clinic.

Recent studies have demonstrated that an acute, low dose of ketamine, a non-competitive NMDA receptor antagonist, provides rapid and sustained antidepressant effects in patients with major depressive disorder. Studies in rodents have shown that the antidepressant properties of ketamine are due to an increase in dendritic spine density in the cortex. Our goal was to determine whether these effects are specific to ketamine and whether they are dependent on dose, drug regimen and brain region. We observed that the effects of ketamine on spine density were dependent on dose and drug regimen and were also brain region specific. In addition, MK-801, another NMDA receptor antagonist, did not demonstrate the same effects on spine density as ketamine. Furthermore, genetic NMDA receptor hypofunction significantly reduced spine density. Our studies demonstrate that while acute ketamine treatment leads to an increase in cortical spine density, chronic administration has opposite and potentially detrimental effects.

Recent studies have demonstrated that an acute, low dose of ketamine, a non-competitive NMDA receptor antagonist, provides rapid and sustained antidepressant effects in patients with major depressive disorder. Studies in rodents have shown that the antidepressant properties of ketamine are due to an increase in dendritic spine density in the cortex. Our goal was to determine whether these effects are specific to ketamine and whether they are dependent on dose, drug regimen and brain region. We observed that the effects of ketamine on spine density were dependent on dose and drug regimen and were also brain region specific. In addition, MK-801, another NMDA receptor antagonist, did not demonstrate the same effects on spine density as ketamine. Furthermore, genetic NMDA receptor hypofunction significantly reduced spine density. Our studies demonstrate that while acute ketamine treatment leads to an increase in cortical spine density, chronic administration has opposite and potentially detrimental effects.

Made available in DSpace on 2014-06-11T19:32:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T19:03:42Z : No. of bitstreams: 1 rojas_ac_dr_botfm.pdf: 407269 bytes, checksum: f0b704ea192a3bbac068bad59b8e628a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os pacientes vítimas de queimaduras frequentemente manifestam dor de grande intensidade e de difícil controle, requerendo o uso contínuo do opióide para a manutenção da analgesia adequada, sendo, muitas vezes, necessária a administração de medicações adjuvantes. Os antagonistas dos receptores N-metil D-aspartato (NMDA) produzem analgesia adequada e a cetamina, representante desta classe de fármacos, é muito utilizada em pacientes com queimaduras. O objetivo desta pesquisa foi avaliar o comportamento da cetamina S(+), administrada pela via intravenosa durante a anestesia, como fármaco coadjuvante no alívio da dor pós-operatória de pacientes queimados submetidos a procedimentos cirúrgicos e, também, o consumo de tramadol como indicador da qualidade desta analgesia.Após a aprovação do Comitê de Ética em Pesquisa da Faculdade de Medicina de Botucatu e assinatura do Termo de Consentimento Livre e Esclarecido, vinte e quatro pacientes foram divididos, por sorteio, em dois grupos (G): G1 (n=13), que receberam midazolam (2,5 mg), cetamina S(+) (1 mg.kg-1), fentanil (75 μg) e propofol em infusão alvo controlada (0,5 a 2,0μg.mL-1) e G2 (n=11), que receberam midazolam (2,5 mg), solução fisiológica 0,9%, fentanil (75 μg) e propofol em infusão alvo controlada (0,5 a 2,0 μg.mL-1). As seringas foram preparadas por enfermeira não participante do ato anestésico-cirúrgico, em seringas de 5 mL, contendo 3 mL de solução. Os pacientes foram monitorizados com cardioscópio, pressão arterial não invasiva e oximetria de pulso. A hidratação foi realizada com solução fisiológica 0,9%. Aos aumentos na freqüência cardíaca e na pressão arterial sistólica (acima de 20%), assim como ao esboço de sinais de desconforto por dor, administrava-se fentanil (50μg até o máximo de 3 μg.kg -1). A analgesia pós-operatória foi realizada com tramadol (100 mg) ao final da cirurgia... / Burn patients often present intense pain that is difficult to control, requiring continuous use of opioids to maintain adequate analgesia, such that it is often necessary to administer adjuvant medications. Receptor antagonists N-methyl D-aspartate (NMDA) produce analgesia and ketamine, a representative of this class of drugs, is widely used in burn patients. This study aimed to evaluate the behavior of ketamine S(+), administered intravenously during anesthesia, as an adjuvant drug in relieving postoperative pain for burn patients submitted to surgery and the consumption of tramadol as an indicator of the quality of this analgesia.Following approval by the Ethics Committee of the Botucatu School of Medicine and free, informed consent, 24 patients were divided randomly into two groups: G1 (n=13) received midazolam (2.5 mg), ketamine (S) (1 mg/kg of bw), fentanyl (75 mg) and propofol target controlled infusion (0.5 to 2.0 μg/mL); and G2 (n=11) received midazolam (2.5 mg), 0.9% saline, fentanyl (75 mg) and propofol target controlled infusion (0.5 to 2.0 μg/mL).The syringes were prepared by a nurse, who did not participate in the surgical anesthetic Introdução e Literatura 16 procedures, in a 5 ml syringe containing 3 ml of solution. The patients were monitored via a cardioscope, noninvasive blood pressure and pulse oximetry.Hydration was achieved with 0.9% saline. When heart rate and systolic blood pressure (above 20%) was increased and/or when signs of discomfort due to pain were observed, fentanyl was administered (from 50μg to a maximum of 3 mg/kg of bw). Postoperative analgesia was achieved with tramadol (100 mg) at the end of surgery. Patients were assessed for pain at discharge from the recovery room (M0) and 3 h (M1), 6 h (M2) and 12 h (M3) postsurgery, using verbal numeric and visual analogue scales. Postoperative analgesia was maintained with codeine (30 mg)... (Complete abstract click electronic access below)

Resumo: Os pacientes vítimas de queimaduras frequentemente manifestam dor de grande intensidade e de difícil controle, requerendo o uso contínuo do opióide para a manutenção da analgesia adequada, sendo, muitas vezes, necessária a administração de medicações adjuvantes. Os antagonistas dos receptores N-metil D-aspartato (NMDA) produzem analgesia adequada e a cetamina, representante desta classe de fármacos, é muito utilizada em pacientes com queimaduras. O objetivo desta pesquisa foi avaliar o comportamento da cetamina S(+), administrada pela via intravenosa durante a anestesia, como fármaco coadjuvante no alívio da dor pós-operatória de pacientes queimados submetidos a procedimentos cirúrgicos e, também, o consumo de tramadol como indicador da qualidade desta analgesia.Após a aprovação do Comitê de Ética em Pesquisa da Faculdade de Medicina de Botucatu e assinatura do Termo de Consentimento Livre e Esclarecido, vinte e quatro pacientes foram divididos, por sorteio, em dois grupos (G): G1 (n=13), que receberam midazolam (2,5 mg), cetamina S(+) (1 mg.kg-1), fentanil (75 μg) e propofol em infusão alvo controlada (0,5 a 2,0μg.mL-1) e G2 (n=11), que receberam midazolam (2,5 mg), solução fisiológica 0,9%, fentanil (75 μg) e propofol em infusão alvo controlada (0,5 a 2,0 μg.mL-1). As seringas foram preparadas por enfermeira não participante do ato anestésico-cirúrgico, em seringas de 5 mL, contendo 3 mL de solução. Os pacientes foram monitorizados com cardioscópio, pressão arterial não invasiva e oximetria de pulso. A hidratação foi realizada com solução fisiológica 0,9%. Aos aumentos na freqüência cardíaca e na pressão arterial sistólica (acima de 20%), assim como ao esboço de sinais de desconforto por dor, administrava-se fentanil (50μg até o máximo de 3 μg.kg -1). A analgesia pós-operatória foi realizada com tramadol (100 mg) ao final da cirurgia... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Burn patients often present intense pain that is difficult to control, requiring continuous use of opioids to maintain adequate analgesia, such that it is often necessary to administer adjuvant medications. Receptor antagonists N-methyl D-aspartate (NMDA) produce analgesia and ketamine, a representative of this class of drugs, is widely used in burn patients. This study aimed to evaluate the behavior of ketamine S(+), administered intravenously during anesthesia, as an adjuvant drug in relieving postoperative pain for burn patients submitted to surgery and the consumption of tramadol as an indicator of the quality of this analgesia.Following approval by the Ethics Committee of the Botucatu School of Medicine and free, informed consent, 24 patients were divided randomly into two groups: G1 (n=13) received midazolam (2.5 mg), ketamine (S) (1 mg/kg of bw), fentanyl (75 mg) and propofol target controlled infusion (0.5 to 2.0 μg/mL); and G2 (n=11) received midazolam (2.5 mg), 0.9% saline, fentanyl (75 mg) and propofol target controlled infusion (0.5 to 2.0 μg/mL).The syringes were prepared by a nurse, who did not participate in the surgical anesthetic Introdução e Literatura 16 procedures, in a 5 ml syringe containing 3 ml of solution. The patients were monitored via a cardioscope, noninvasive blood pressure and pulse oximetry.Hydration was achieved with 0.9% saline. When heart rate and systolic blood pressure (above 20%) was increased and/or when signs of discomfort due to pain were observed, fentanyl was administered (from 50μg to a maximum of 3 mg/kg of bw). Postoperative analgesia was achieved with tramadol (100 mg) at the end of surgery. Patients were assessed for pain at discharge from the recovery room (M0) and 3 h (M1), 6 h (M2) and 12 h (M3) postsurgery, using verbal numeric and visual analogue scales. Postoperative analgesia was maintained with codeine (30 mg)... (Complete abstract click electronic access below) / Orientador: Eliana Marisa Ganem / Coorientador: Guilherme Antonio Moreira de Barros / Banca: Norma Sueli Pinheiro Módolo / Banca: Leandro Gobbo Braz / Banca: José Fernanda Amaral Meletti / Banca: Eduardo Toshiyuki Moro / Doutor

A pré-medicação apesar de ser freqüentemente utilizada nos mamíferos, é raramente utilizada nas espécies aviárias. O objetivo deste estudo foi avaliar o efeito da pré-medicação na indução e anestesia com sevofluorano em papagaios. Foram utilizados trinta e seis animais adultos oriundos do Parque ecológico do Tietê. Os animais foram randomicamente distribuídos em três grupos: grupo I (n = 12), tratado com NaCl 0,9% como placebo, grupo II (n = 12), com cetamina 10 mg.Kg-1 e grupo III (n = 12), com cetamina 10 mg.Kg-1 e diazepam 0,5 mg.Kg-1, por via intramuscular. Quinze minutos após a pré-medicação, a indução foi realizada por meio de máscara facial conectada a um circuito sem reinalação, usando 4,5% de sevofluorano em 100% de oxigênio, com um fluxo de 1,5L. Tanto os efeitos cardiovasculares e respiratórios, bem como, a qualidade da pré-medicação, indução e recuperação da anestesia foram avaliadas. A Dose anestésica mínima obtida neste estudo foi de 2.4 ± 0.37%, 1.7 ± 0.39%, e 1.3 ± 0.32% para os grupos I, II e III respectivamente. Foi concluído que a cetamina isolada ou cetamina/diazepam diminuem consideravelmente a dose anestésica mínima em papagaios. A cetamina isolada ou em associação, promoveu uma boa qualidade de sedação, permitindo uma melhor indução da anestesia quando comparada a indução com o agente inalatório. Tanto a cetamina isolada quanto a associação, mostraram-se seguras, não alterando as funções cardiovasculares, a oxigenação ou ventilação, podendo ser utilizados com sucesso nesta espécie. Além disto, a anestesia com o sevofluorano foi considerada segura para esta espécie em todos os protocolos estudados. / Although pre-medication is commonly used in mammals, it is rarely used in avian species. The aim of this study was to evaluate the effect of pre-medication in the induction and anesthesia with sevoflurane in parrots. Thirty-six adults animals were utilized from Tietê ecologic park. The animals were randomically distributed in three groups: group I (n = 12), was pre-medicated with NaCl0.9% as a placebo, group II (n = 12), with ketamine 10 mg.kg-1 and group III (n = 12), with ketamine 10mg.kg-1 and diazepam 0.5mg.kg-1, intramuscularly. Fifteen minutes after pre-medication, the induction was accomplished with a facial mask connected to a non rebreathing circuit using 4.5% of sevoflurane in 100% oxygen with a flow rate of 1.5L. The cardiovascular and respiratory effects were evaluated as well as the quality of pre-medication, induction and recovery of anesthesia. The minimal anesthetic concentration obtained at this study was 2.4 ± 0.37%, 1.7 ± 0.39%, and 1.3 ± 0.32% for group I, II and III respectively. It was concluded that ketamine alone or ketamine/diazepam consider decreased the DAM of sevofluorano in parrots. ketamine alone or in association, promoted a good quality of sedation allowing better induction of anesthesia when compared with the induction with inhalant agent. Even ketamine alone or the association were considered a safe procedure, not changing cardiovascular, oxygenation and ventilation and could be successfully used in this specie. Furthermore, the anesthesia with sevoflurane was considered safe to this specie in all protocols.

Originalmente da Bahia, a espécie Leontopithecus chrysomelas foi introduzida no estado do Rio de Janeiro provavelmente por meio do tráfico e atualmente é encontrado em uma das áreas remanescentes de ocupação natural do mico-leão-dourado (Leontopithecus rosalia) podendo comprometer a sobrevivência do último. Visando mitigar esse problema foi criado um plano de ação, onde se recomenda a captura dos animais introduzidos. Procedimentos de captura e contenção química produzem estresse e afetam diretamente a homeostase, podendo alterar diretamente a saúde e o bem estar dos animais somando-se o fato de os protocolos de capturas atuais gerarem um período de recuperação prolongado. O objetivo deste trabalho consistiu em determinar e comparar os efeitos cardiorrespiratórios da dexmedetomidina, quando associada à cetamina S(+) ou à cetamina racêmica, e do midazolam associado à cetamina S(+), por via intramuscular, na contenção química de mico-leão-da-cara-dourada. Foram utilizados 45 animais da espécie Leontopithecus chrysomelas, adultos, machos, pesando em média 532 gramas, oriundos do Centro de Primatologia do Rio de Janeiro, em parceria com a ONG PRI-MATAS. Os animais foram distribuídos em três grupos onde receberam aleatoriamente as associações: CSM - cetamina S(+) (15 mg/kg) e midazolam (0,5 mg/kg); CSD - cetamina S(+) (15 mg/kg) e dexmedetomidina (10 µg/kg); e CD - cetamina racêmica (15 mg/kg) e dexmedetomidina (10 µg/kg). Foram avaliados os períodos de latência, hábil e de recuperação. A frequência e ritmo cardíacos, frequência respiratória, saturação da oxihemoglobina periférica, pressão arterial sistólica, temperatura retal, qualidade de indução e de recuperação, sedação, antinocicepção e grau de relaxamento muscular foram monitorados a cada cinco minutos durante 50 minutos. Os dados paramétricos foram avaliados pela análise de variância (ANOVA) seguida do teste de Tukey. Os dados não paramétricos foram avaliados pelo teste de Kruskal-Wallis seguido do teste de Dunn para identificar quais grupos apresentavam diferença estatística significativa. O grau de significância estabelecido para as análises foi de 5% (p<0,05). Os valores referentes aos parâmetros de frequência respiratória, saturação da oxihemoglobina periférica, temperatura, pressão arterial sistólica, início da perda de tônus muscular, latência e os períodos de recuperação parcial e total não apresentaram diferença entre os grupos. Já os valores de frequência cardíaca, relaxamento muscular, antinocicepção, grau de sedação e consumo de lidocaína apresentaram diferença significativa entre os mesmos momentos dos grupos CSM e CSD, e CSM e CD. Conclui-se que as associações de dexmedetomidina com cetamina racêmica e cetamina S(+) apresentaram os melhores índices de relaxamento muscular, sedação e antinocicepção e mostraram-se seguras para a realização de cirurgia de vasectomia em micos-leão-da-cara-dourada. Apesar dos grupos CSD e CD apresentarem bradicardia mais acentuada, os valores mantiveram-se dentro do limite esperado. / The Golden-headed lion tamarin, originally endemic to the southern Bahia region, was introduced in the state of Rio de Janeiro probably by illegal wildlife trade activity. The species is currently found in one of the remaining areas of natural occupation of the golden lion tamarin (Leontopithecus rosalia), which may compromise the survival of the latter. In order to mitigate this problem, an action plan was elaborated and the capture of golden-headed lion tamarins recommended. Both capture and chemical restraint procedures can cause stress and compromise homeostasis with a direct effect on the health and well-being of the animals. Besides that, current chemical immobilization protocols usually result in prolonged recovery times. This study aims to determine and compare the cardiovascular and respiratory effects of three different protocols for chemical immobilization of golden-headed lion tamarins. Thirty-five adult male specimens of Leontopithecus chrysomelas were studied. Animals were randomly separated into three groups: ketamine S(+) and midazolam (15 mg kg-1 and 0.5 mg kg--1-) (KSM group), ketamine S(+) and dexmedetomidine (15 mg kg--1- and 10 µg kg-1) (KSD group) and racemic ketamine and dexmedetomidine (15 mg kg-1 and 10 µg kg-1 ) (KD group). Periods of latency, immobilization and recovery were evaluated. Heart rate and rhythm, respiratory rate, peripheral oxyhemoglobin saturation, systolic blood pressure, rectal temperature, induction and recovery quality, sedation, antinociception, and degree of muscle relaxation were monitored every five minutes for 50 minutes. Parametric data were analyzed by using repeated measures analysis of variance (ANOVA) followed by a Tukey\'s test. Non-parametric data were analyzed by the Kruskal-Wallis test followed by Dunn\'s test. Values of P< 0.05 were considered statistically significant. No significant differences were found in respiratory rate, peripheral oxygen saturation, temperature, systolic blood pressure, onset of muscle tone loss, latency and partial and total recovery periods. Heart rate, sedation and muscle relaxation degrees, antinociception, and lidocaine consumption presented significant difference at the same moments between KSM and KSD and between KSM and KD. Marked bradycardia was presented on KSD and KD groups, with values remaining within the normal range. This study demonstrated that combinations of dexmedetomidine with racemic ketamine and S(+) ketamine presents the best outcomes for muscle relaxation, sedation and antinociception and were safe for vasectomy surgery in golden-headed lion tamarins.

Philosophiae Doctor - PhD / Conscious sedation or moderate sedation and analgesia is an effective and popular alternative option for procedures outside the operating theater. If conscious sedation is a viable alternative to general anaesthesia then we as sedation practitioners must use safe sedation techniques in facilities that meet all the requirements for safe practice. Three studies were done to determine the safety and efficacy of conscious sedation outside the operating theatre. In the first study post sedation satisfaction in one hundred children aged 3-9 years was evaluated. It was extremely important to determine whether the combination of midazolam, ketamine and propofol, called an advanced sedation technique (SASA, 2015), can be safely used for paediatric sedation outside the operating theatre. The incidence of side-effects after conscious sedation using multiple drugs were documented. It is clear that intravenous sedation with midazolam, ketamine and propofol is safe and effective to use. There may be side effects but they are not long lasting and usually not life-threatening. In the second study intravenous sedation was administered to 447 adults (aged 18 years and older) using fentanyl (sublimazeR), ketamine (ketalar), midazolam (dormicum) and propofol (Diprivan) (FKMP) called an advanced sedation technique. Post sedation satisfaction, post sedation recovery on arrival home, and the relationship between side effects and different dental procedures were evaluated. The results of the study show that side effects are possible, and can be expected, when we use sedative and analgesic drugs for sedation. However, we report a low incidence of side effects when we compare it with other studies in literature as mentioned. It is known that the use of combinations of drugs may cause unforeseen synergistic pharmacological effects which can be lifethreatening. Our results show that the drugs used can be safely used for advanced sedation techniques. In trying to demonstrate the safety of sedative and analgesic agents used during sedation we looked at the haemodynamic parameters, duration of sedation, pulse rate and systolic blood pressure, in the third study. The sedation records of 335 patients for dental surgery were assessed for the period 2010 – 2011. Our results show the mean Duration of sedation is substantially and statistically significantly greater with combination FKMP than with the other combinations. The mean duration of sedation is not significantly different between ketamine and propofol (KP) and fentanyl, ketamine and propofol (FKP) (Figure 10). The use of polypharmacy regarding the combination of drugs, specifically FKMP, will cause a longer duration of sedation. This has implications for safety, as well as the side effect profile during and after sedation. When we use combinations of drugs patients were more comfortable which shows that we do not yet have a single drug that has all the characteristics of an ideal drug for sedation. Different combinations of drugs are used by other practitioners with a higher incidence of side effects. It is difficult to explain the higher values of blood pressures when all four drugs were used. It may have been a ketamine effect, although one would not expect this when using propofol with ketamine. In clinical terms the higher blood pressures are no reason for concern as all our patients were classified as ASA I and II. Our research study support the view that ketamine can be used safely outside the operating theatre with exciting possibilities for Third World countries for procedures outside the operating theatre. Sedation can be considered a reasonable alternative to general anaesthesia for certain surgical procedures in the Third World. Sedation will be an attractive option not only as far as costs are involved but also the availability of sedation providers. The important lesson from all the results is that sedation providers must be trained in procedural sedation as defined by all international sedation guidelines. We proved in this research study that sedation can be done safely, however we need to make a contribution to train sedation providers. Sedation will become an attractive alternative to general anaesthesia because of the low side-effect profile and high patient satisfaction. It is interesting that few studies are available that looked at this aspect of sedation. It is clear that a high side-effect profile can contribute to an unsafe sedation technique. Severe nausea and vomiting can cause numerous haemodynamic disturbances and dehydration. Our research study support the findings of the study by Lapere et al., (2015) that there is a high rate of patient satisfaction, and a low side-effect profile during and after sedation. This is an extremely important research study and the results are crucial as far as an option for healthcare in developing countries. Sub-Saharan Africa is a densely populated and resource poor subcontinent that provides unique challenges in patient care. These challenges include a lack of facilities and staff for the performance of operative as well as non-operative procedures. In conclusion, we feel that we are part of Sub-Saharan Africa with all the problems mentioned as far as provision of healthcare is concerned. This research study can make a crucial contribution to safe and cost-effective management of healthcare in Africa for procedures outside the operating theatre.

Ketamine is a non-competitive NMDA antagonist that has been shown to have antidepressant properties both clinically as well as in preclinical studies when administered at a subanesthetic dose. In vivo electrophysiological recordings were carried in male Sprague Dawley rats 30 minutes following ketamine administration (10 mg/kg) to first assess its effects on monoaminergic firing. Whilst no change in the firing activity of serotonin (5-HT) neurons was observed in the dorsal raphe nucleus (DRN), an increase in the firing activity was observed for dopamine (DA) and noradrenergic (NE) neurons in the ventral tegmental area (VTA) and locus coeruleus (LC), respectively. The effect of ketamine on these electrophysiological parameters was prevented by pre-administration of the AMPA receptor antagonist NBQX 10 minutes prior to ketamine administration. In a second series of experiments, an increase in AMPA-evoked response was observed within 30 minutes in the CA3 layer of the hippocampus (HPC) following acute ketamine administration. These findings suggest that acute ketamine administration produces a prompt enhancement of AMPA transmission in the forebrain and also results in increased catecholaminergic activity. These effects may play a crucial role in the rapid antidepressant effects of ketamine observed shortly following its infusion in the clinic.