Como a dexmedetomidina e a clonidina devem ser prescritas no ambiente de terapia intensiva? / How should dexmedetomidine and clonidine be prescribed in the critical care setting?

RESUMO O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.

ABSTRACT Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

Avaliação cardiorrespiratória e de sedação da associação de dexmedetomidina-butorfanol-midazolam ou detomidina-butorfanol-midazolam em catetos (Pecari tajacu) / Cardiorespiratory and sedation evaluation of the combination of dexmedetomidine-butorphanol-midazolam or detomidine butorphanol-midazolam in collared peccaries (Pecari tajacu)

A presente pesquisa comparou os efeitos cardiorrespiratórios, hemogasométricos e sedativos da associação midazolam (0,41mg/kg) e butorfanol (0,31mg/kg) acrescida de detomidina (157µg/kg) (DTMB) ou dexmedetomidina (36µg/kg) (DXMB) em catetos. Catetos adultos (n=20) foram distribuídos em dois grupos, DTMB ou DXMB. As variáveis (FC, f, PAM, SpO2, EtCO2 e TR) foram avaliadas após aplicação dos fármacos. A sedação foi avaliada por meio de escala analógica visual, relaxamento muscular, postura e resposta auditiva. Foi realizada ANOVA, seguida de teste t pareado (paramétricos) e teste de Mann-Whitney rank-sum test (não paramétricos), com P<0,05. Não foi observada diferença estatística entre os grupos para o período de latência. Observou-se diferença significativa entre grupos para as variáveis f, PAM e SpO2, com maiores valores para DTMB, e EtCO2, com maiores valores para DXMB. Os dois grupos apresentaram redução da FC e da concentração de lactato, bem como aumento da concentração de bicarbonato. A SpO2 permaneceu abaixo de 90%, durante todo o período experimental, nos dois grupos estudados. Os animais dos dois grupos apresentaram sedação profunda e relaxamento muscular máximo. Conclui-se que os dois protocolos testados proporcionaram adequada sedação, podendo ser indicados para contenção química de catetos adultos.(AU)

The study compared the cardiorespiratory, hemogasometric and sedative effects of the combination of midazolam (0.41mg/kg) and butorphanol (0.31mg/kg) plus detomidine (157µg/kg) (DTMB) or dexmedetomidine (36µg/kg) (DXMB) in collared peccaries. Collared peccaries (n= 20) were divided into two groups, either DTMB or DXMB. The variables (FC, f, PAM, SpO2, EtCO2 and TR) were evaluated after application of the drugs. Sedation was assessed by visual analogue scale, muscle relaxation, posture and auditory response. ANOVA followed by paired t-test (parametric) and Mann Whitney Rank Sum Test (non-parametric) with P< 0.05 were performed. No statistical difference was observed for the latency period. A significant increase was observed between groups for the variables f, PAM and SpO2 with higher values for DTMB and EtCO2 with higher values for DXMB. The two groups presented a reduction in HR and lactate concentration, and an increase in bicarbonate concentration. SpO2 remained below 90% throughout the experiment in both groups. The animals of the two groups presented deep sedation and maximum muscle relaxation. It is concluded that the two protocols tested provided adequate sedation and could be indicated for chemical containment of collared peccaries.(AU)

​Comparison of Block Characteristics and Hemodynamic Effects of Low Doses of Clonidine and Dexmedetomidine as an Adjuvant to Hyperbaric Bupivacaine for Spinal Anesthesia in Patients Undergoing Lower-limb Surgeries

Background: Various adjuvants are being used with local anesthetics for prolongation of intraoperative and post-operativeanalgesia. Among them, clonidine and dexmedetomidine are two α2-agonists which can be used as neuraxial adjuvants.Dexmedetomidine, a highly selective α2- adrenergic agonist, is a newer neuraxial adjuvant gaining popularity.Objectives: The objective of the study was to compare sensory and motor block characteristics, hemodynamic effects and sideeffects of low doses of clonidine or dexmedetomidine as an adjuvant to 12.5 mg hyperbaric bupivacaine in spinal anesthesiain lower-limb surgeries.Materials and Methods: A total of 90 patients of American Society of Anesthesiology I and II posted for lower-limbsurgeries were randomly allocated into three groups of 30 each. Group B received plain 12.5 mg of hyperbaric bupivacainediluted to 3 ml with normal saline. Group C received 30 mcg clonidine added to 12.5 mg hyperbaric bupivacaine anddiluted to 3 ml. Group D received 3 mcg dexmedetomidine added to 12.5 mg hyperbaric bupivacaine and diluted to 3 mlwith normal saline.Results: Patients in Group D and Group C had a significantly shorter onset time of sensory and motor block and significantlylonger duration of sensory and motor block compared to bupivacaine group. The mean time for sensory regression to S1 segmentwas 301.90 ± 31.96 min in Group D, 283.23 ± 13.59 min in Group C, and 181.70 ± 18.55 min in Group B (B vs. D and B vs. C,P < 0.001). There was a statistically significant difference in the two segment regression of sensory block in Group D (140.32± 17.6 min) when compared to Group C (124.5 ± 16.10 min) and Group B (92.13 ± 11.45 min). The regression of motor blockto Bromage 0 was 262 ± 24.40 min in Group D, 261 ± 24.19 min in Group C, and 164.40 ± 15.26 min in Group B (B vs. D andB vs. C, P < 0.0001). The onset and regression times were comparable between Groups D and C. Time for the first request ofrescue analgesia was nearly equal in Groups D and C and prolonged compared to Group B. Patients were hemodynamicallystable in all the groups.Conclusion: Dexmedetomidine and clonidine have a similar onset of sensory and motor block, prolonged duration of analgesia.Dexmedetomidine provides better analgesia than clonidine

Avaliação da dexmedetomidina e do tramadol, associados ao midazolam, em gatas anestesiadas com isoflurano e submetidas à ovário-histerectomia / Evaluation of dexmedetomidine and tramadol, associated with midazolam, in cats anesthetized with isoflurane, undergoing ovariohysterectomy

Objetivou-se comparar as alterações cardiorrespiratórias e a analgesia pós-operatória promovidas pela dexmedetomidina e pelo tramadol, quando associados ao midazolam, em felinas. Para tal, foram selecionadas 18 gatas hígidas, divididas em dois grupos randomizados: GDM, tratadas com dexmedetomidina (10µg/kg) e GTM, tratadas com tramadol (2mg/kg), ambos associados a midazolam (0,2mg/kg,) IM. Após 15 minutos, procedeu-se à indução anestésica com propofol (1,46±0,79mL), mantendo-se a anestesia com isoflurano. As felinas foram submetidas à ovário-histerectomia, registrando-se as variáveis cardiorrespiratórias 15 minutos após a MPA (M0), 15 minutos após a indução (M15) e sequencialmente a cada cinco minutos, até o término do procedimento cirúrgico (M20, M25, M30, M35 e M40). A avaliação da dor iniciou-se 30 minutos após o término do procedimento cirúrgico (MP30) e sequencialmente em intervalos de 30 minutos (MP60, MP90, MP120). A partir do MP120, as avaliações foram registradas a cada hora (MP180, MP240 e MP360). A associação dexmedetomidina-midazolam infere diminuição inicial de frequência cardíaca (FC) sem significado clínico e está relacionada à sedação mais pronunciada, à analgesia menor e menos duradoura e a episódios de êmese, quando comparada à associação tramadol-midazolam. Ambos os protocolos denotaram estabilidade cardiorrespiratória e podem ser considerados seguros em felinas submetidas à ovário-histectomia.(AU)

The aim of this study was to compare cardiorespiratory changes and post-operative analgesia provided by dexmedetomidine or tramadol, associated with midazolam, in female cats. For that purpose, 18 healthy cats were assigned to two randomized groups: GDM, which received dexmedetomidine (10 µg/kg) and GTM, which received tramadol (2 mg/kg), both associated with midazolam (0.2 mg/kg) IM. After 15 minutes, anesthesia was induced with propofol (1.46±0.79 mL) and maintained with isofluorane. Ovariohysterectomy was performed and cardiorespiratory variables were registered 15 minutes after pre-anesthetic medication (M0), 15 minutes after anesthetic induction (M15), and every five minutes until the end of the surgical procedure (M20, M25, M30, M35 e M40). Pain evaluation started 30 minutes after the surgery (MP30) and sequentially at thirty-minute intervals (MP60, MP90, MP120). After MP120, each evaluation was registered at every hour (MP180, MP240 e MP360). Dexmedetomidine-midazolam association results in decreases on initial heart rate (HR) without clinical relevance and it is related to pronounced sedation, poor and less durable antinociception and vomiting events, when compared to tramadol-midazolam association. Both protocols indicate cardiorespiratoy stability and safety in cats undergoing ovariohysterectomy.(AU)