Titulacao do sevoflurano utilizando o indice bispectral em anestesia pediatrica. Influencia da medicacao pre-anestesica no tempo de despertar e no consumo de anestesico inalatorio

Background and Objectives - Sevoflurane is an inhalational anesthetic drug with low blood/gas solubility providing fast anesthesia induction and emergence. Its ability to maintain cardiovascular stability makes it ideal for pediatric anesthesia. The aim of this study was to evaluate hemodynamic stability, consumption of inhalational anesthetics and emergence time in children with and without premedication (midazolam or clonidine) anesthetized with sevoflurane titrated according to BIS monitoring. Methods - Participated in this study 30 patients aged 2 to 12 years, physical status ASA I, undergoing elective surgeries who were divided into 3 groups: G1 - without premedication, G2 - 0.5 mg.kg-1 oral midazolam, G3 - 4 μg.kg-1 oral clonidine 60 minutes before surgery. All patients received 30 μg.kg-1 alfentanil, 3 mg.kg-1 propofol, 0.5 mg.kg-1 atracurium, sevoflurane in different concentrations monitored by BIS (values close to 60) and N2O in a non rebreathing system. Systolic and diastolic blood pressure, heart rate, expired sevoflurane concentration (EC), sevoflurane consumption (ml.min-1) and emergence time were evaluated. Emergence time was defined as time elapsed between the end of anesthesia and patients' spontaneous movements trying to extubate themselves, crying and opening eyes and mouth. Results - There were no differences among groups as to systolic and diastolic blood pressure, EC, sevoflurane consumption and emergence time. Heart rate was lower in G3 group. Conclusions - Sevoflurane has provided hemodynamic stability. Premedication with clonidine and midazolam did not influence emergence time, inhaled anesthetic consumption or maintenance of anesthesia with sevoflurane. Anesthesia duration has also not influenced emergence time. Hypnosis monitoring was important for balancing anesthetic levels and this might have been responsible for the similarity of emergence times for all studied groups.

Clonidina como medicação pré-anestésica em facectomias: Comparação entre as doses de 100 μg e 200 μg

BACKGROUND AND OBJECTIVES: The objective of the present study was to evaluate the degree of sedation, intraocular pressure, and hemodynamic changes with premedication with low doses of oral clonidine, 100 μg and 200 μg, in outpatient cataract surgeries. METHODS: This is a randomized, double-blind, clinical study undertaken at the Universidade Federal de São Paulo with 60 patients of both genders, physical status ASA 1 and 2, ages 18 to 80 years. Patients were separated into three groups: placebo, clonidine 100 μg, and clonidine 200 μg. Intraocular pressure, heart rate, and blood pressure besides assessment of sedation were measured before and 90 minutes after the administration of clonidine. Sedation levels were classified according to the Ramsay sedation scale. RESULTS: Patients who received placebo and 100 μg of clonidine did not show reduction in heart rate, while a reduction in heart rate was observed in patients who received 200 μg of clonidine, and this difference was statistically significant. Patients who received 200 μg of clonidine also had a reduction in systolic and diastolic blood pressure (p < 0.05). One patient who received 200 μg of clonidine developed severe hypotension, with systolic pressure < 80 mmHg. Patients treated with clonidine had a reduction in intraocular pressure (p < 0.05). Ninety minutes after the oral administration of placebo and 100 μg and 200 μg of clonidine, 25%, 60%, and 80% of the patients respectively were classified as Ramsay 3 or 4. CONCLUSIONS: Clonidine 100 μg can be indicated as premedication for fasciectomies, being effective in sedation and reduction of intraocular pressure, without adverse effects on blood pressure and heart rate.

Oral Medication With Diazepam or Midazolam Associated or Not With Clonidine for Oculoplastic Office Surgery Under Local Anesthesia

Purpose: To compare the level of sedation of oral administration of diazepam or midazolam associated or not with clonidine and their effects on upper eyelid margin position, heart rate, arterial pressure, and oxygen saturation. Methods: Seventy consecutive healthy patients American Society of Anesthesiologists (ASA) grade I-II scheduled for lower eyelid blepharoplasty were randomized into 4 groups according to the oral sedative agent used (group 1, diazepam 10 mg; group 2, diazepam 10 mg plus clonidine 0.15 mg; group 3, midazolam 15 mg; group 4, midazolam plus clonidine 0.15 mg). For all patients, the midpupil-to-upper eyelid margin distance, the heart rate, systolic and diastolic blood pressure, and oxygen saturation were recorded before and 1 hour after the administration of oral medication. The level of sedation at the time of surgery was measured with the Michigan University scale. Results: The depth of sedation was significantly more pronounced with midazolam (median score = 2) than with diazepam (median score = 1). Clonidine slightly increased the level of sedation of both diazepam and midazolam. The diastolic arterial blood pressure drop with midazolam associated or not with clonidine was significantly greater than with diazepam. The mean upper eyelid margin position shift (-1.42 mm) verified when clonidine was associated with midazolam was also significantly greater than with diazepam. Discussion: Oral sedation with diazepam or midazolam associated or not with clonidine is safe for ASA grade I-II patients. The systemic effects of diazepam and midazolam were small and very similar. The sedation induced by midazolam was clearly greater than that induced by diazepam. However, this higher level of sedation was accompanied by a more important shift in upper eyelid margin position.

Effect of chronic clonidine treatment on transmitter release from sympathetic varicosities of the guinea-pig vas deferens

1 Previous studies have demonstrated that chronic pre-synaptic inhibition of transmitter release by morphine evokes a counter-adaptive response in the sympathetic nerve terminals that manifests itself as an increase in transmitter release during acute withdrawal. In the present study we examined the possibility that other pre-synaptically acting drugs such as clonidine also evoke a counter-adaptive response in the sympathetic nerve terminals. 2 In chronically saline treated (CST) preparations, clonidine (0.5 muM) completely abolished evoked transmitter release from sympathetic varicosities bathed in an extracellular calcium concentration ([Ca2+](o)) of 2 mM. The inhibitory effect of clonidine was reduced by increasing [Ca2+](o) from 2 to 4 mM and the stimulation frequency from 0.1 to 1 Hz. 3 The nerve terminal impulse (NTI) was not affected by concentrations of clonidine that completely abolished evoked transmitter release. 4 Sympathetic varicosities developed a tolerance to clonidine (0.5 muM) following 7-9 days of chronic exposure to clonidine. 5 Acute withdrawal of preparations following chronic clonidine treatment (CCT) resulted in a significant (P

Effects of the α₂-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine in healthy volunteers.

The mechanism of action of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) involves the carrier-mediated and potentially vesicular release of monoamines. We assessed the effects of the sympatholytic α₂-adrenergic receptor agonist clonidine (150 μg p.o.), which inhibits the neuronal vesicular release of norepinephrine, on the cardiovascular and psychotropic response to MDMA (125 mg p.o.) in 16 healthy subjects. The study used a randomized, double-blind, placebo-controlled crossover design with four experimental sessions. The administration of clonidine 1 h before MDMA reduced the MDMA-induced increases in plasma norepinephrine concentrations and blood pressure but only to the extent that clonidine lowered norepinephrine levels and blood pressure compared with placebo. Thus, no interaction was found between the cardiovascular effects of the two drugs. Clonidine did not affect the psychotropic effects or pharmacokinetics of MDMA. The lack of an interaction of the effects of clonidine and MDMA indicates that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the effects of MDMA in humans. Although clonidine may be used in the treatment of stimulant-induced hypertensive reactions, the present findings do not support a role for α₂-adrenergic receptor agonists in the prevention of psychostimulant dependence.

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. Setting: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. Participants: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). Main outcome measures: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

Severe hypertension following accidental clonidine overdose during the refilling of an implanted intrathecal drug delivery system.

BACKGROUND:   Complications associated with intrathecal pumps may be linked to the surgical procedure, the implanted device, or the medication itself.¦CASE REPORTS:   Three patients treated chronically with intrathecal clonidine presented with clonidine overdose due to inadvertent extravasation during the refilling procedure. All patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment.¦DISCUSSION:   Clonidine is an alpha-2 agonist with a nearly 100% bioavailability after oral or rectal administration. With high plasma concentration secondary to massive systemic overdose, the specificity for the alpha-2 receptor is lost and an alpha-1 agonist activity predominates and causes marked hypertension. Management of clonidine overdose consists of supportive therapy guided by signs and symptoms.¦CONCLUSION:   Inadvertent injection into the subcutaneous pocket rather than the reservoir is rare but very dangerous as the drug cannot be retrieved and massive doses are involved. Signs and symptoms of systemic overdose with drugs commonly used in implanted drugs delivery system should be well known to ensure early diagnosis and treatment.

Topiramate in opiate withdrawal- comparison with clonidine and with carbamazepine/mianserin

There are some rationales for developing anticonvulsants for the treatment of substance abuse. The blockade of the AMPA/kainate subtype of glutamate receptor by topiramate may be of particular interest, as preclinical studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both physical and emotional consequences of withdrawal. Methods. Ten consecutively admitted patients treated with topiramate were compared in a retrospective naturalistic drug utilization observation study with 10 consecutively admitted patients treated with clonidine and with 10 consecutively admitted patients treated with a carbamazepine/ mianserin combination. Results. In 9 cases of the clonidine group and in 7 carbamazepine/mianserin treated patients the dose had been reduced, whereas this occurred in only 2 topiramate treated patients (p < 0.01). Patients in the topiramate group received less p.r.n. myorelaxant medication than the two other groups, and there was a significant difference between the three groups with regard to p.r.n. analgesics (p < 0.05), topiramate and clonidine treated patients receiving fewer analgesics than the carbamazepine/mianserin group. Conclusions. Compared to clonidine and carbamazepine/mianserin, a detoxification scheme using high initial and then decreasing doses of topiramate appeared to be appropriate for most patients and as associated with less analgesic and myorelaxant comedication, indicating a more promising efficacy at the used doses

Impacto en la calidad de la Inducción anestésica con premedicación en pacientes pediatricos

La inducción anestésica en niños es uno de los mayores retos para los anestesiólogos ya que es la fase más estresante del período perioperatorio para el paciente pediátrico. Existen diferentes intervenciones para minimizar la ansiedad perioperatoria y aumentar la cooperación del paciente pediátrico con la inducción anestésica. Entre las intervenciones exitosas la premedicación farmacológica con midazolam ha mostrado grandes beneficios en pacientes pediátricos. Metodología: Se realizó un estudio de casos y controles en pacientes pediátricos llevados a cirugía en la Fundación Cardioinfantil entre 2011-2014. Por medio de muestreo aleatorio por conveniencia se tomaron como casos pacientes con premedicación y controles pacientes sin premedicación. El éxito en la inducción se midió por medio de la escala ICC, usada a nivel mundial. Resultados: El promedio de edad fue 4.9 σ 3.01 años para los casos y 5.02σ3.2 años para controles, presentaron la misma distribución por género, 40.6% femenino, 59.3% masculino. El éxito de la inducción anestésica con midazolam mostró resultados significativos (OR 7.3 IC95% 4.3 – 12.5 p0,000), en hombres (OR 9.44 IC95%4.5 – 19.8 p0,000), en menores de 5 años (OR 10.33 IC95% 5.07 – 21.04 p0,000), en pacientes con antecedentes quirúrgicos (OR 12.2 IC95% 5.28 – 27.8 p0.000) o anestesias previas (OR 7.9 IC95% 4.4 – 14.4 p0,000). Discusión: El midazolam como agente farmacológico usado para premedicación en pacientes pediátricos presenta resultados exitosos contundentes, por lo cual debe usarse en todos los casos.

Comparison between S-ketamine and clonidine in caudal analgesia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)