Effects of Dexmedetomidine Infusion During Sevoflurane Anesthesia on Otoacoustic Emissions

BACKGROUND AND OBJECTIVES: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). SUBJECTS AND METHODS: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. RESULTS: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). CONCLUSIONS: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

The effect of dexmedetomidine on the acute pain after cardiothoracic surgeries: a systematic review

Abstract Introduction: Acute post-operative pain remains a troublesome complication of cardiothoracic surgeries. Several randomized controlled trials have examined the efficacy of dexmedetomidine as a single or as an adjuvant agent before, during and after surgery. However, no evidence-based conclusion has been reached regarding the advantages of dexmedetomidine over the other analgesics. Objective: To review the effect of dexmedetomidine on acute post-thoracotomy/sternotomy pain. Methods: Medline, SCOPUS, Web of Science, and Cochrane databases were used to search for randomized controlled trials that investigated the analgesia effect of dexmedetomidine on post-thoracotomy/sternotomy pain in adults' patients. The outcomes were postoperative pain intensity or incidence, postoperative analgesia duration, and the number of postoperative analgesic requirements. Results: From 1789 citations, 12 trials including 804 subjects met the inclusion criteria. Most studies showed that pain score was significantly lower in the dexmedetomidine group up to 24 hours after surgery. Two studies reported the significant lower postoperative analgesia requirements and one study reported the significant lower incidence of acute pain after surgery in dexmedetomidine group. Ten studies found that the total consumption of narcotics was significantly lower in the dexmedetomidine group. The most reported complications of dexmedetomidine were nausea/vomiting, bradycardia and hypotension. Conclusion: Dexmedetomidine can be used as a safe and efficient analgesic agent for reducing the postoperative pain and analgesic requirements up to 24 hours after cardiothoracic surgeries. However, further well-designed trials are needed to find the optimal dosage, route, time, and duration of dexmedetomidine administration.

The effects of loading dose administration rate of dexmedetomidine on sedation and dexmedetomidine requirement in elderly patients undergoing spinal anesthesia

BACKGROUND: This study evaluated the effect of decrease in loading dose administration rate of dexmedetomidine (DMT) on sedation and DMT requirement in elderly patients. METHODS: Fifty-eight patients over 65 years old with ASA I–II who were planned to receive DMT sedation during spinal anesthesia were randomly assigned to two groups. Group S (n = 29) received a 0.5 µg/kg DMT loading dose over 20 minutes, while group C (n = 29) received the DMT loading dose over 10 minutes. Then, both groups received a continuous infusion of 0.4 µg/kg/h. The sedative status was recorded before and at 5, 10, 15, 20, 25, and 30 minutes after administration of DMT and at the end of the anesthesia according to the Ramsay sedation scale (RSS). Also, the time to reach RSS-3 (patients asleep, responsive to commands) and the dose of DMT until reaching RSS-3 were recorded. RESULTS: The time to reach RSS-3 was similar between the two groups (group S = 16.0 ± 4.3 minutes vs. group C = 15.5 ± 4.2 minutes, P = 0.673). However, the DMT required to reach RSS-3 in group S was significantly lower than that in group C (23.3 ± 7.1 vs. 32.5 ± 6.0 µg, P < 0.001). There was no difference in RSS between the two groups from the administration of DMT to the end of the anesthesia (P = 0.927). CONCLUSIONS: Decreasing the administration rate of the DMT loading dose did not delay the onset of RSS-3 sedation and reduced the DMT requirement in elderly patients.

The effect of pre-anesthetic administration of dexmedetomidine on the consumption of opioids in postoperative gynecologic patients

BACKGROUND: This study was designed to assess whether pre-anesthetic administration of dexmedetomidine reduces the postoperative consumption of opioids, in patients receiving patient-controlled fentanyl after gynecological laparotomy. METHODS: This was a prospective, randomized, double-blind, controlled study. Ten minutes before induction of anesthesia, 36 patients scheduled for elective gynecological laparotomy were assigned to receive either normal saline (group N) or dexmedetomidine 1 µg/kg (group D). A patient-controlled analgesia (PCA) device was used to administer fentanyl for the postoperative 24 h period. Cumulative fentanyl consumption and pain score were assessed at postoperative 30 min, 6 h and 24 h. Patient's satisfaction for pain control and other side effects (nausea, sedation score) were recorded for all corresponding time points. RESULTS: There was no significant difference between the groups in cumulative fentanyl consumption (Group N: 11.1 ± 3.2 µg/kg, Group D: 10.3 ± 2.9 µg/kg, P value: 0.706). The incidence of side-effects did not differ between the groups. Both groups showed similar blood pressure after anesthesia induction. However, 10 min after anesthesia induction, the heart rates in group D were significantly lower than group N (P = 0.0002). CONCLUSIONS: In patients undergoing gynecological laparotomy, the pre-anesthetic administration of single loading dose dexmedetomidine (1 µg/kg) given 10 min before anesthesia induction did not reduce the PCA consumption of postoperative fentanyl or the pain score.

Brimonidine tartrate effect on retinal spreading depression depends on Müller cells / O efeito do tartarato de brimonidina sobre a depressão alastrante retiniana depende das células de Müller

Objective: Demonstrate the Brimonidine effect over Retinal Spreading Depression (SD). Brimonidine is an alpha-2–adrenergic receptor agonist, used in the management of glaucoma. Alpha2-agonists have been shown to be neuroprotective in various experimental models, however the molecular and cellular targets leading to these actions are still poorly defined. The SD of neuronal electric activity is a wave of cellular massive sustained depolarization that damages the nervous tissue. Local trauma, pressure, ischemic injuries and other chemical agents as high extracellular potassium concentration or glutamate, can trigger SD, leading to exaggerated focal electrical followed by an electrical silence. Methods: Using chicken retina as model, we performed alpha2-receptor detection by Western Blotting and Immunohistochemistry. After that we obtained electrical signals of SD by microelectrodes on retina in the absence or presence of Brimonidine. For in vivo visualization we observed retina with optical coherence tomography on normal state, with SD passing, and with SD + Brimonidine. Results: Our data demonstrated that: (1) alpha2-adrenergic receptors are present in Müller cells, (2) the treatment with Brimonidine decreases the SD‘s velocity as well as the voltage of SD waves and (3) OCT revealed that SD creates a hyper reflectance at inner plexiform layer, but on retinal treatment with brimonidine, SD was not visualized. Conclusions: Our study about brimonidine possible pathways of neuroprotection we observed it reduces SD (a neuronal damage wave), identified a new cellular target – the Müller cells, as well as, firstly demonstrated SD on OCT, showing that the inner plexiform layer is the main optically affected layer on SD. .

Objetivo: Demonstrar o efeito do Tartarato de Brimonidina, um alfa2-agonista usado no manejo do glaucoma, sobre a depressão alastrante (DA) retiniana. Esses agonistas têm demonstrado ser neuroprotetores em vários modelos experimentais, contudo seus alvos celulares e moleculares continuam indefinidos. A DA da atividade elétrica neuronal é uma onda de despolarização celular massiva e sustentada que leva ao dano no tecido nervoso. Trauma local, pressão, isquemia e outros agentes químicos como o aumento do potássio extracelular e o glutamato podem disparar a DA, levando a uma atividade elétrica exagerada seguida de silêncio elétrico. Métodos: Usando a retina de pinto como modelo, realizamos a detecção do alfa2-receptor por Western Blotting e ensaio Imunohistoquímico. Após isso, obtivemos os sinais elétricos da DA através de microeletrodos inseridos na retina durante sua passagem na presença ou ausência de Brimonidina. Para visualização do tecido utilizamos o tomógrafo de coerência optica (OCT), analisando como é a retina no seu estado de repouso, durante a passagem da DA, e a DA + brimonidina. Resultados: Nossos dados demonstraram que: (1) os receptores alfa adrenérgicos presentes na retina são do subtipo-2A e estão localizados nas células de Müller; (2) o tratamento com Brimonidina diminui a velocidade e a voltagem da onda de DA; (3) A OCT demonstrou que a DA retiniana possui um sinal óptico de maior reflectância na camada plexiforme interna, fato não observado quando foi associada à Brimonidina. Conclusão: A Brimonidina foi capaz de reduzir a DA (uma onda de lesão neuronal) e identificamos um novo possível alvo celular – a célula de Müller e demonstramos pela primeira vez uma OCT da DA, visualizando a camada plexiforme interna como a mais afetada opticamente pelo fenômeno. .

Estresse Isolado ou Associado ao Etanol Libera Prostanóides em Aorta de Ratos via ?2-Adrenoceptores / Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via ?2-Adrenoceptor

Fundamento: Estresse e etanol são ambos, independentemente, importantes fatores de risco cardiovascular. Objetivo: avaliar o risco cardiovascular do consumo de etanol e exposição ao estresse, isolados e em associação, em ratos machos adultos. Métodos: Os ratos foram separados em quatro grupos: controle, etanol (20% na água de beber durante seis semanas), estresse (imobilização 1h dia/5 dias por semana/ 6 semanas) e estresse/etanol. As curvas de concentração-resposta à noradrenalina - na ausência e na presença de ioimbina, L-NAME ou indometacina - ou fenilefrina foram determinadas em aortas torácicas com e sem endotélio. EC50 e resposta máxima (n = 8-12) foram comparadas através de ANOVA de dois fatores (two-way) / método de Bonferroni. Resultados: Estresse ou estresse em associação com o consumo de etanol aumentaram as respostas máximas de noradrenalina em aortas intactas. Essa hiper-reatividade foi eliminada pela remoção do endotélio, ou pela presença da indometacina ou ioimbina, mas não foi alterada pela presença de L-NAME. Enquanto isso, o consumo de etanol não alterou a reatividade à noradrenalina. As respostas da fenilefrina em aortas com e sem endotélio também permaneceram inalteradas independentemente do protocolo. Conclusão: O estresse crônico aumentou as respostas aórticas dos ratos à noradrenalina. Esse efeito é dependente do endotélio vascular e envolve a liberação de prostanóides vasoconstritores através da estimulação de α-2 adrenoceptores endoteliais. Além disso, o consumo crônico de etanol pareceu não influenciar as respostas de noradrenalina em aorta de rato, nem modificar o aumento de tais respostas observadas em consequência da exposição ao estresse. .

Background: Stress and ethanol are both, independently, important cardiovascular risk factors. Objective: To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Methods: Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results: Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Conclusion: Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure. .

Safe Sedation and Hypnosis using Dexmedetomidine for Minimally Invasive Spine Surgery in a Prone Position / 대한통증학회지

Dexmedetomidine, an imidazoline compound, is a highly selective alpha2-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an alpha2-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

Safe Sedation and Hypnosis using Dexmedetomidine for Minimally Invasive Spine Surgery in a Prone Position

Dexmedetomidine, an imidazoline compound, is a highly selective alpha2-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an alpha2-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

Spinal anesthesia for elective ceasarean section: use of different doses of hyperbaric bupivacaine associated with morphine and clonidine

PURPOSE: To comparatively study the efficacy and maternal and fetal side-effects of two doses of bupivacaine associated with morphine and clonidine, administered by the subarachnoid route for cesarean section. METHODS: The study included 66 pregnant women at term, distributed into two groups. GI: bupivacaine 8.0 mg (1.6mL) + clonidine 75µg (0.5mL) + morphine 100µg (1.0mL) and GII: bupivacaine 10mg (2.0mL) + clonidine 75µg (0.5mL) + morphine 100µg (1.0mL). The following parameters were assessed: onset and maximum level of sensory block; quality of intraoperative and postoperative analgesia; degree and duration of motor block; maternal repercussions and Apgar score. RESULTS: The onset of sensory block, quality of intraoperative analgesia and total duration of analgesia were similar in both groups; maximum extent of sensory block predominated in T4; maximum degree of motor block (Bromage 3); time motor block regression was significantly longer in GII; Hemodynamic, respiratory repercussions, adverse maternal effects and Apgar scores were similar between groups. In both groups, there was a predominance of drowsy or sleeping patients. CONCLUSION: The addition of morphine and clonidine to low doses of hyperbaric bupivacaine produced adequate anesthesia for cesarean section and good postoperative analgesia, without any maternal and fetal repercussions.