Outcomes of dexmedetomidine as adjuvant drug in patients undergoing videolaparoscopic cholecystectomy: A randomized and prospective clinical trial.

OBJECTIVE: The repercussions of ischemia-reperfusion and inflammatory response to surgical injury may compromise the return of physiologic processes in video-laparoscopic surgeries. Dexmedetomidine, as an adjuvant drug in general anesthesia, alters the neuroinflammatory reaction, provides better clinical outcomes in the perioperative period, and may reduce the excessive use of chronic medication in patients with a history of addiction. This study evaluated the immunomodulatory potential of dexmedetomidine on perioperative organ function in video-laparoscopic cholecystectomy patients. METHODS: There were two groups: Sevoflurane and Dexmedetomidine A (26 patients) vs. Sevoflurane and Saline 0.9% B (26 patients). Three blood samples were collected three times: 1) before surgery, 2) 4-6h after surgery, and 3) 24h postoperatively. Inflammatory and endocrine mediators were protocolized for analysis. Finally, hemodynamic outcomes, quality upon awakening, pain, postoperative nausea and vomiting, and opioid use were compared between groups. RESULTS: We have demonstrated a reduction of Interleukin 6 six hours after surgery in group A: 34.10 (IQR 13.88-56.15) vs. 65.79 (IQR 23.13-104.97; p = 0.0425) in group B. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure was attenuated in group A in their measurement intervals (p < 0.0001). There was a lower incidence of pain and opioid consumption in the first postoperative hour favoring this group (p < 0.0001). We noticed better quality upon awakening after the intervention when comparing the values of peripheral oxygen saturation and respiratory rate. CONCLUSIONS: Dexmedetomidine provided anti-inflammatory benefits and contributed to postoperative analgesia without the depressive side effects on the respiratory and cardiovascular systems commonly observed with opioids. TRIAL REGISTRATION: Immunomodulatory Effect of Dexmedetomidine as an Adjuvant Drug in Laparoscopic Cholecystectomies, NCT05489900, Registered 5 August 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05489900?term=NCT05489900&draw=2&rank=1.

Efficacy and safety of dexmedetomidine in maintaining hemodynamic stability in pediatric cardiac surgery: a systematic review and meta-analysis

Abstract Objectives: Dexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery. Sources: Databases such as PubMed, Cochrane, Web of Science, WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb. 2021. Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation (SMD), odds ratio (OR) and 95% confidence interval (CI). Summary of the findings: Fifteen articles were included for this meta-analysis, and 9 articles for qualitative analysis. The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and reducing heart rate (HR) (SBP: SMD = -0.35,95% CI: -0.72, 0.01; MAP: SMD = -0.83, 95% CI: -1.87,0.21; DBP: SMD = -0.79,95% CI: -1.66,0.08; HR: SMD = -1.71,95% CI: -2.29, -1.13). In addition, the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group. Conclusions: The application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability, and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences.

Efficacy and safety of dexmedetomidine in maintaining hemodynamic stability in pediatric cardiac surgery: a systematic review and meta-analysis.

OBJECTIVES: Dexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery. SOURCES: Databases such as PubMed, Cochrane, Web of Science, WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb. 2021. Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation (SMD), odds ratio (OR) and 95% confidence interval (CI). SUMMARY OF THE FINDINGS: Fifteen articles were included for this meta-analysis, and 9 articles for qualitative analysis. The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and reducing heart rate (HR) (SBP: SMD = -0.35,95% CI: -0.72, 0.01; MAP: SMD = -0.83, 95% CI: -1.87,0.21; DBP: SMD = -0.79,95% CI: -1.66,0.08; HR: SMD = -1.71,95% CI: -2.29, -1.13). In addition, the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group. CONCLUSIONS: The application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability, and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences.

Comparative effects of dexmedetomidine and propofol on brain and lung damage in experimental acute ischemic stroke.

Acute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8-15.3) vs. 19.5(18-24), p = 0.007)], bronchoconstriction index [2.28(2.08-2.36) vs. 2.64(2.53-2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1ß compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1ß compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.

A comparative study of the cardiopulmonary and sedative effects of a single intramuscular dose of ketamine anesthetic combinations in rabbits.

The aim of this prospective, randomized, blinded crossover study was compare the cardiopulmonary and sedative effects of ketamine in combination with acepromazine, diazepam, dexmedetomidine, midazolam or xylazine, injected intramuscularly in rabbits, using eight one-year-old male New Zealand rabbits (4.1 ± 0.40 kg). All treatments included ketamine (K; 30 mg/kg) in combination with one of the following: acepromazine 0.5 mg/kg (treatment KA); diazepam 1 mg/kg (KD); dexmedetomidine 0.025 mg/kg (KDex); midazolam 1 mg/kg (KM); or xylazine 3 mg/kg (KX) mixed in the same syringe and injected intramuscularly. Cardiopulmonary variables, blood gases and sedative scores were measured before injection (T0 or baseline) and every 10 min thereafter, over a 60-min period. There were reductions in heart rate, compared with the baseline, at all evaluation times in treatment KX. Treatments KDex, KM and KX presented reductions in respiratory rate at all evaluation times, in comparison with the baseline. There were reductions in mean arterial pressure in KA and KX at times T10-T60 and in PaO2 in KDex, KM and KX at T10-T50. The sedation scores were similar in KA, KDex, KM and KX at T10-T20. Ketamine in combination with acepromazine, dexmedetomidine, midazolam or xylazine promoted similar sedative effects for twenty minutes, but the α2-agonists can promote hypoxemia.

HYPERKALEMIA IN TWO JAGUARS ( PANTHERA ONCA) ANESTHETIZED WITH DEXMEDETOMIDINE, KETAMINE, AND ISOFLURANE.

Two jaguars were anesthetized with dexmedetomidine, ketamine, and isoflurane. Arterial blood samples analyzed shortly after darting revealed no abnormalities. Samples analyzed 2 and 1.5 hr after darting revealed moderate hyperkalemia in both animals (6.8 and 6.2 mEq/L, respectively). Shortly after hyperkalemia was recognized, one jaguar developed electrocardiographic abnormalities (sinoventricular rhythm and widened QRS complexes), and a few minutes later, suffered cardiopulmonary arrest. Resuscitation with chest compressions, intermittent positive-pressure ventilation, and epinephrine was successful, and autonomous breathing and circulation resumed within a few minutes. Anesthesia-related hyperkalemia has been reported in a variety of large felids but has not been reported previously in jaguars. In all reports, α-2 adrenergic agonists were used as part of the immobilization protocol. Due to the presumptively high incidence and mortality caused by this complication, frequent monitoring of electrolyte concentrations and prompt treatment of hyperkalemia is recommended when anesthetizing large felids, including jaguars.

Cardiorespiratory effects of epidural anesthesia using lidocaine with morphine or dexmedetomidine in capuchin monkeys (Sapajus sp.) undergoing bilateral tubal ligation surgery, anesthetized with isoflurane.

BACKGROUND: Epidural anesthesia is indicated to decrease other anesthetic requirements, prolong analgesia, and reduce side effects. In primates, its use has been scarcely described. The aim was to evaluate the cardiorespiratory effects of epidural anesthesia with lidocaine and dexmedetomidine (DEX) or morphine (MOR). METHODS: Ten female capuchin monkeys (Sapajus sp.) received epidural anesthesia with lidocaine and DEX or MOR under general anesthesia. RESULTS: There was a significant decrease in heart rate with DEX and in blood pressure in all groups, with no changes in SpO2 . There was a significant reduction in rectal temperature over time. A stable cardiac rhythm was observed; however, there was a prolonged QT interval with DEX. CONCLUSIONS: Epidural anesthesia with access to the lumbosacral space was safe and easy to perform. DEX decreased heart rate. All groups promoted a decrease in rectal temperature with respiratory and cardiac rhythm stability; however, hypotension should be considered.

What is the level of evidence for the amnestic effects of sedatives in pediatric patients? A systematic review and meta-analyses.

BACKGROUND: Studies have suggested that benzodiazepines are amnestic drug par excellence, but when taken together, what level of evidence do they generate? Are other sedatives as amnestic as benzodiazepines? The aim of this study was to assess the level of scientific evidence for the amnestic effect of sedatives in pediatric patients who undergo health procedures. METHODS: The literature was searched to identify randomized controlled trials that evaluated anterograde and retrograde amnesia in 1-19-year-olds who received sedative drugs during health procedures. Electronic databases, including PubMed, Scopus and Cochrane Library besides clinical trial registries and grey literature were searched. Two independent reviewers performed data extraction and risk of bias assessment using the Cochrane Collaboration's Tool. The meta-analyses were performed by calculating relative risk (RR) to 95% confidence intervals (CI). The quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Fifty-four studies were included (4,168 participants). A higher occurrence of anterograde amnesia was observed when benzodiazepines, the most well-studied sedatives (n = 47), were used than when placebo was used (n = 12) (RR = 3.10; 95% CI: 2.30-4.19, P<0.001; I2 = 14%), with a moderate level of evidence. Higher doses of alpha2-adrenergic agonists (clonidine/dexmedetomidine) produced more anterograde amnesia than lower doses (n = 2) (RR = 1.83; 95% CI: 1.03-3.25; P = 0.038; I2 = 0%), with a low level of evidence; benzodiazepines' amnestic effects were not dose-dependent (n = 3) (RR = 1.54; 95% CI: 0.96-2.49; P = 0.07; I2 = 12%) but the evidence was low. A qualitative analysis showed that retrograde amnesia did not occur in 8 out of 10 studies. CONCLUSIONS: In children, moderate evidence support that benzodiazepines induce anterograde amnesia, whereas the evidence for other sedatives is weak and based on isolated and small studies. Further clinical trials focused on the amnesia associated with non-benzodiazepine sedatives are therefore needed. TRIAL REGISTRATION: PROSPERO CRD42015017559.

Prolonged Infusion of Dexmedetomidine in Critically-ill Children.

OBJECTIVE: To describe main indications, doses, length of infusion and side effects related to dexmedetomidine infusion. METHODS: Observational and retrospective study evaluating dexmedetomidine use in pediatric intensive care unit. RESULTS: 77 children received dexmedetomidine infusion longer than 6 hours for mechanical ventilation weaning (32.5%), post- neurosurgery and post-upper airway surgery (24.7%), non-invasive ventilation (13%), refractory tachycardia (6.5%) and other causes (23.3%). After 6 hours of infusion, significant decrease in mean arterial pressure and heart rate was observed in all groups. Six children (8%) required withdrawal of drug because of possible side effects: hypotension, bradycardia and somnolence. CONCLUSION: Dexmedetomidine may be used as sedative in critically ill children without much side effects.

Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock.

BACKGROUND: Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. METHODS: Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 µg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiments. RESULTS: Dexmedetomidine and esmolol were hemodynamically well tolerated. The dexmedetomidine group exhibited lower epinephrine levels, but no difference in muscle lactate. Despite progressive hypotension in all groups, both dexmedetomidine and esmolol were associated with lower arterial and portal vein lactate levels. Exogenous lactate clearance was significantly higher in the dexmedetomidine and esmolol groups. CONCLUSIONS: Dexmedetomidine and esmolol were associated with lower arterial and portal lactate levels, and less impairment of exogenous lactate clearance in a model of septic shock. The use of dexmedetomidine and esmolol appears to be associated with beneficial effects on gut lactate generation and lactate clearance and exhibits no negative impact on systemic hemodynamics.

Sedation with dexmedetomidine for conducting electroencephalogram in a patient with Angelman syndrome: a case report / Sedação com dexmedetomidina para realização de eletroencefalograma em paciente portadora de síndrome de Angelmann: relato de caso

ABSTRACT INTRODUCTION: Angelman syndrome is characterized by severe mental retardation and speech and seizure disorders. This rare genetic condition is associated with changes in GABAA receptor. Patients with Angelman syndrome need to be sedated during an electroencephalogram ordered for diagnostic purposes or evolutionary control. Dexmedetomidine, whose action is independent of GABA receptor, promotes a sleep similar to physiological sleep and can facilitate the performing of this examination in patients with Angelman syndrome. CASE REPORT: Female patient, 14 years old, with Angelman syndrome; electroencephalogram done under sedation with dexmedetomidine. The procedure was uneventful and bradycardia or respiratory depression was not recorded. The examination was successfully interpreted and epileptiform activity was not observed. CONCLUSION: Dexmedetomidine promoted satisfactory sedation, was well tolerated and enabled the interpretation of the electroencephalogram in a patient with Angelman syndrome and seizure disorder.

RESUMO INTRODUÇÃO: a síndrome de Angelman (SA) é caracterizada por retardo mental grave, distúrbio da fala e desordem convulsiva. Essa condição genética rara está associada a alterações do receptor GABA-A. Pacientes portadores de SA necessitam ser sedados durante a feitura de eletroencefalograma (EEG), indicado para fins diagnósticos ou controle evolutivo. A dexmedetomidina, cuja ação independe do receptor GABA, promove sono semelhante ao fisiológico e pode viabilizar a feitura desse exame em pacientes com SA. RELATO DE CASO: paciente feminina, 14 anos, portadora de SA, fez EEG sob sedação com dexmedetomidina. O procedimento transcorreu sem intercorrências e não foi registrada bradicardia ou depressão respiratória. O exame foi interpretado com sucesso e atividade epileptiforme não foi observada. CONCLUSÃO: a dexmedetomidina promoveu sedação satisfatória, foi bem tolerada e possibilitou a interpretação do EEG em paciente com SA e desordem convulsiva.

Sedation with dexmedetomidine for conducting electroencephalogram in a patient with Angelman syndrome: a case report.

INTRODUCTION: Angelman syndrome is characterized by severe mental retardation and speech and seizure disorders. This rare genetic condition is associated with changes in GABAA receptor. Patients with Angelman syndrome need to be sedated during an electroencephalogram ordered for diagnostic purposes or evolutionary control. Dexmedetomidine, whose action is independent of GABA receptor, promotes a sleep similar to physiological sleep and can facilitate the performing of this examination in patients with Angelman syndrome. CASE REPORT: Female patient, 14 years old, with Angelman syndrome; electroencephalogram done under sedation with dexmedetomidine. The procedure was uneventful and bradycardia or respiratory depression was not recorded. The examination was successfully interpreted and epileptiform activity was not observed. CONCLUSION: Dexmedetomidine promoted satisfactory sedation, was well tolerated and enabled the interpretation of the electroencephalogram in a patient with Angelman syndrome and seizure disorder.

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.

Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study.

BACKGROUND AND OBJECTIVES: Intraoperative use of opioids may be associated with postoperative hyperalgesia and increased analgesic consumption. Side effects due to perioperative use of opioids, such as postoperative nausea and vomiting may delay discharge. We hypothesized that total intravenous anesthesia consisting of lidocaine and dexmedetomidine as an opioid substitute may be an alternative technique for laparoscopic cholecystectomy and would be associated with lower fentanyl requirements in the postoperative period and less incidence of postoperative nausea and vomiting. METHODS: 80 Anesthesiologists I-II adults were scheduled for elective laparoscopic cholecystectomy. Patients were randomly allocated into two groups to have either opioid-free anesthesia with dexmedetomidine, lidocaine, and propofol infusions (Group DL) or opioid-based anesthesia with remifentanil, and propofol infusions (Group RF). All patients received a standard multimodal analgesia regimen. A patient controlled analgesia device was set to deliver IV fentanyl for 6h after surgery. The primary outcome variable was postoperative fentanyl consumption. RESULTS: Fentanyl consumption at postoperative 2nd hour was statistically significantly less in Group DL, compared with Group RF, which were 75 ± 59 µg and 120 ± 94 µg respectively, while it was comparable at postoperative 6th hour. During anesthesia, there were more hypotensive events in Group RF, while there were more hypertensive events in Group DL, which were both statistically significant. Despite higher recovery times, Group DL had significantly lower pain scores, rescue analgesic and ondansetron need. CONCLUSION: Opioid-free anesthesia with dexmedetomidine, lidocaine and propofol infusions may be an alternative technique for laparoscopic cholecystectomy especially in patients with high risk for postoperative nausea and vomiting.

Does dexmedetomidine as a neuraxial adjuvant facilitate better anesthesia and analgesia? A systematic review and meta-analysis.

BACKGROUND: Neuraxial application of dexmedetomidine (DEX) as adjuvant analgesic has been invetigated in some randomized controlled trials (RCTs) but not been approved because of the inconsistency of efficacy and safety in these RCTs. We performed this meta-analysis to access the efficacy and safety of neuraxial DEX as local anaesthetic (LA) adjuvant. METHODS: We searched PubMed, PsycINFO, Scopus, EMBASE, and CENTRAL databases from inception to June 2013 for RCTs that investigated the analgesia efficacy and safety for neuraxial application DEX as LA adjuvant. Effects were summarized using standardized mean differences (SMDs), weighed mean differences (WMDs) or odds ratio (OR) with suitable effect model. The primary outcomes were postoperative pain intensity and analgesic duration, bradycardia and hypotension. RESULTS: Sixteen RCTs involving 1092 participants were included. Neuraxial DEX significantly decreased postoperative pain intensity (SMD, -1.29; 95% confidence interval (CI), -1.70 to -0.89; P<0.00001), prolonged analgesic duration (WMD, 6.93 hours; 95% CI, 5.23 to 8.62; P<0.00001) and increased the risk of bradycardia (OR, 2.68; 95% CI, 1.18 to 6.10; P = 0.02). No evidence showed that neuraxial DEX increased the risk of other adverse events, such as hypotension (OR, 1.54; 95% CI, 0.83 to 2.85; P = 0.17). Additionally, neuraxial DEX was associated with beneficial alterations in postoperative sedation scores and number of analgesic requirements, sensory and motor block characteristics, and intro-operative hemodynamics. CONCLUSION: Neuraxial DEX is a favorable LA adjuvant with better and longer analgesia. The greatest concern is bradycardia. Further large sample trials with strict design and focusing on long-term outcomes are needed.

A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal.

OBJECTIVES: To evaluate dexmedetomidine as adjunctive therapy to lorazepam for severe alcohol withdrawal. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Single center; medical ICU. PATIENTS: Twenty-four adult patients with a Clinical Institute Withdrawal Assessment score greater than or equal to 15 despite greater than or equal to 16 mg of lorazepam over a 4-hour period. INTERVENTIONS: Patients received a symptom-triggered Clinical Institute Withdrawal Assessment protocol with lorazepam and were randomized to dexmedetomidine 1.2 µg/kg/hr (high dose), 0.4 µg/kg/hr (low dose), or placebo as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms. MEASUREMENT AND MAIN RESULTS: High-dose and low-dose groups were combined as a single dexmedetomidine group for primary analysis with secondary analysis exploring a dose-response relationship. The difference in 24-hour lorazepam requirements after versus before study drug was greater in the dexmedetomidine group compared with the placebo group (-56 mg vs -8 mg, p = 0.037). Median differences were similar for high dose and low dose. The 7-day cumulative lorazepam requirements were not statistically different between dexmedetomidine and placebo (159 mg vs 181 mg). Clinical Institute Withdrawal Assessment or Riker sedation-agitation scale scores representing severe agitation (13% vs 25%) or moderate agitation (27% vs 22%) within 24 hours of initiating study drug were similar for dexmedetomidine and placebo groups, respectively. Bradycardia occurred more frequently in the dexmedetomidine group versus placebo group (25% vs 0%, p = not significant), with the majority of bradycardia occurring in the high-dose group (37.5%). Study drug rate adjustments occurred more often in the dexmedetomidine group compared with the placebo group (50% vs 0%, p = 0.02). Neither endotracheal intubation nor seizure occurred in any group while on study drug. CONCLUSIONS: Adjunctive dexmedetomidine for severe alcohol withdrawal maintains symptom control and reduces lorazepam exposure in the short term, but not long term, when using a symptom-triggered protocol. Monitoring for bradycardia is needed with dexmedetomidine but the occurrence may be lessened with low dose. Further study is needed to evaluate the clinical impact of dexmedetomidine.

[Postsurgical delirium complicated with sepsis. Dexmedetomidine versus midazolam]. / Delirio posquirúrgico complicado con sepsis. Dexmedetomidina contra midazolam.

OBJECTIVE: to determine which drug dexmedetomidine or midazolam produces greater delirium in septic patients. METHODS: observational, analytical, comparative, prospective and longitudinal in 59 postsurgical patients both sexes, with mechanical ventilation (MV), sepsis, and sedation with dexmedetomidine or midazolam complicated with sepsis was done. We evaluated age, severity of sepsis with SOFA and APACHE. Complications associated with delirium were registered. The "t" Student test and χ(2) were used. RESULTS: Midazolam group, 33 patients, mean age 49.75 ± 19.48 years, SOFA 15.81 ± 7.48 points and APACHE 7.51 ± 5.41, delirium was present in 29 patients, days of MV 15.86 ± 14.12, reintubation rate 24 %, ICU stay 16.41 ± 14.41, hospital stay 28.58 ± 19.91 days and death rate 34.5 %. Dexmedetomidine group: 26 patients, mean age 49.57 ± 13.76 years, in SOFA 13.34 ± 7.66 points and 6.23 ± 4.51 in APACHE scale, delirium in 11 patients, days of MV 17.9 ± 12.53 and reintubation in 45.5 %, ICU days 14.36 ± 9.25, hospital stay 22.63 ± 14.87 and death in 36.4 %. CONCLUSIONS: delirium was increased in complicated post-surgical patients with sepsis, mechanical ventilation and midazolam.

Dexmedetomidina: papel atual em anestesia e cuidados intensivos / Dexmedetomidine: current role in anesthesia and intensive care

JUSTIFICATIVA E OBJETIVOS: Atualizar e rever a aplicação da dexmedetomidina em anestesia e cuidados intensivos. Este trabalho é uma revisão abrangente dos usos clínicos, farmacologia, farmacocinética, mecanismo de ação e efeitos adversos da dexmedetomidina. CONTEÚDO: O uso efetivo de agentes sedativo-hipnóticos e analgésicos é parte integral do conforto e segurança dos pacientes. A dexmedetomidina é um potente e altamente seletivo agonista dos adrenoceptores α-2 com propriedades simpaticolíticas, sedativas, amnésicas e analgésicas, que tem sido descrito como um adjuvante útil e seguro em várias aplicações clínicas. Proporciona uma "sedação consciente" única, analgésica, sem depressão respiratória. Os usos correntes revistos incluem sedação na unidade de tratamento intensivo - UTI (adulta e pediátrica), departamento de emergência, anestesia regional e geral, neurocirurgia, sedação para procedimentos pediátricos, intubação por fibra ótica em doentes acordados, cirurgia cardíaca e cirurgia bariátrica. CONCLUSÕES: A dexmedetomidina oferece a capacidade única de fornecer sedação e analgesia sem depressão respiratória. É um agente novo com uma grande margem de segurança, excelente capacidade sedativa e moderadas propriedades analgésicas. Embora o seu amplo uso seja, atualmente, em pacientes de unidades de cuidados intensivos cirúrgicos e não cirúrgicos, a dexmedetomidina parece ter futuras aplicações promissoras nas áreas de neuroproteção, cardioproteção e renoproteção. São necessários mais estudos detalhados para definir o seu papel como sedativo em doentes críticos, neurocirúrgicos e pediátricos, como adjuvante da anestesia e como sedativo durante procedimentos.

BACKGROUND AND OBJECTIVES: To update and review the application of dexmedetomidine in anesthesia and intensive care. This study is a comprehensive review of clinical uses, pharmacology, pharmacokinetics, mechanism of action and adverse effects of dexmedetomidine. CONTENT: The effective use of sedative-hypnotic agents and analgesics is an integral part of comfort and safety of patients. Dexmedetomidine is a potent and highly selective α-2 adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties, which has been described as a useful and safe adjunct in many clinical applications. It provides a unique "conscious sedation", analgesia, without respiratory depression. The current reviewed uses include sedation at Intensive Care Unit - ICU (both adult and pediatric), emergency department, regional and general anesthesia, neurosurgery, sedation for pediatric procedures, awake fiber-optic intubation, cardiac surgery and bariatric surgery. CONCLUSIONS: Dexmedetomidine offers a unique ability of providing both sedation and analgesia without respiratory depression. It is a new agent with a wide safety margin, excellent sedative capacity and moderate analgesic properties. Although its wide use is currently in patients of surgical and non-surgical intensive care units, dexmedetomidine seems to have promising future applications in neuroprotection, cardioprotection and renoprotection. More detailed studies are required to define its role as sedative in critical, neurosurgical and pediatric patients, as anesthesia adjunct and sedative during procedures.

JUSTIFICATIVA Y OBJETIVOS: Actualizar y analizar nuevamente la aplicación de la dexmedetomidina en la anestesia y en los cuidados intensivos. Este trabajo es una revisión bastante exhaustiva de los usos clínicos, farmacología, farmacocinética, mecanismo de acción, y de los efectos adversos de la dexmedetomidina. CONTENIDO: El uso efectivo de los agentes sedativo-hipnóticos y analgésicos, forma parte integral de la comodidad y de la seguridad de los pacientes. La dexmedetomidina es un potente y altamente selectivo agonista de los adrenoceptores α-2 con propiedades simpaticolíticas, sedativas, amnésicas y analgésicas, que se ha venido describiendo como un adyuvante útil y seguro en varias aplicaciones clínicas. Proporciona una "sedación conciente" única, analgésica, y sin depresión respiratoria. Sus usos más comunes ya analizados, incluyen la sedación en la Unidad de Cuidados Intensivos (UCI) (adulta y pediátrica), en Urgencias, anestesia regional y general, neurocirugía, sedación para procedimientos pediátricos, intubación por fibra óptica en enfermos despiertos, cirugía cardíaca y cirugía bariátrica. CONCLUSIONES: La dexmedetomidina ofrece la capacidad única de suministrar sedación y analgesia sin depresión respiratoria. Es un agente nuevo con un gran margen de seguridad, excelente capacidad sedativa y moderadas propiedades analgésicas. Aunque su amplio uso sea hoy por hoy, para pacientes de unidades de cuidados intensivos quirúrgicos y no quirúrgicos, la dexmedetomidina parece tener aplicaciones futuras promisorias en las áreas de neuroprotección, cardioprotección y renoprotección. Aunque de todas formas, son necesarios más estudios detallados para definir su rol como sedativo en los enfermos criticos, neuroquirúrgicos y pediátricos, como adyuvante en la anestesia y como sedativo durante los procedimientos.

[Synergistic effect between dexmedetomidine and 0.75% ropivacaine in epidural anesthesia]. / Efeito sinérgico entre a dexmedetomidina e a ropivacaína 0,75% na anestesia peridural.

BACKGROUND: This study aimed to evaluate clinical characteristics of epidural anesthesia performed with 0.75% ropivacaine associated with dexmedetomidine. METHODS: Forty patients scheduled for hernia repair or varicose vein surgeries under epidural anesthesia participated in this study. They were assigned to: Control Group (n = 20), 0.75% ropivacaine, 20 ml (150 mg); and Dexmedetomidine Group (n = 20), 0.75% ropivacaine, 20 ml (150 mg), plus dexmedetomidine, 1 mg x kg-1. The following variables were studied: total analgesic block onset time, upper level of analgesia, analgesic and motor block duration time, intensity of motor block, state of consciousness, hemodynamics, postoperative analgesia and incidence of side-effects. RESULTS: Epidural dexmedetomidine did not affect onset time or upper level of anesthesia (p > 0.05) however it prolonged sensory and motor block duration time (p < 0.05) and postoperative analgesia (p < 0.05), and also resulted in a more intense motor block, l (p < 0.05). Values of bispectral index were lower in Dexmedetomidine Group (p < 0.05). There was no difference in incidence of hypotension and bradycardia (p > 0.05). Occurrence of side-effects (shivering, vomiting and SpO2 < 90%) was low and similar between groups (p > 0.05). CONCLUSION: There is clear synergism between epidural dexmedetomidine and ropivacaine, further this drug association does not bring about additional morbidity.

Efeito sinérgico entre a dexmedetomidina e a ropivacaína 0,75 por cento na anestesia peridural / Synergistic effect between dexmedetomidine and 0.75 percent ropivacaine in epidural anesthesia

OBJETIVO: O objetivo deste estudo foi avaliar as características clínicas da anestesia peridural realizada com ropivacaína associada à dexmedetomidina. MÉTODOS: Quarenta pacientes submetidos à correção cirúrgica de hérnia inguinal ou varizes de membros inferiores sob anestesia peridural participaram deste estudo. Os pacientes foram divididos em: Grupo Controle (n = 20), ropivacaína 0,75 por cento, 20 ml (150 mg); e Grupo Dexmedetomidina (n = 20), ropivacaína 0,75 por cento, 20 ml (150 mg), mais dexmedetomidina, 1 µg.kg-1. As variáveis estudadas foram: tempo de latência do bloqueio sensitivo, dermátomo máximo de anestesia, tempo de duração dos bloqueios analgésico e motor, intensidade do bloqueio motor, nível de sedação, variáveis hemodinâmicas, analgesia pós-operatória e ocorrência de efeitos colaterais. RESULTADOS: A dexmedetomidina não influenciou o tempo de latência da anestesia nem o nível máximo do bloqueio sensitivo (p > 0,05), mas prolongou o tempo de duração dos bloqueios analgésico e motor (p < 0,05) e da analgesia pós-operatória (p < 0,05), além de determinar bloqueio motor de maior intensidade (p < 0,05). Os valores do índice bispectral foram menores no Grupo Dexmedetomidina (p < 0,05). Não houve diferença na incidência de hipotensão arterial e de bradicardia (p > 0,05). A ocorrência de efeitos colaterais (tremor, náuseas e SpO2 < 90 por cento) foi baixa e semelhante entre os grupos (p > 0,05). CONCLUSÃO: Há sinergismo evidente entre a dexmedetomidina e a ropivacaína na anestesia peridural sem que haja elevação da morbidade relacionada a associação dos fármacos.

BACKGROUND: This study aimed to evaluate clinical characteristics of epidural anesthesia performed with 0.75 percent ropivacaine associated with dexmedetomidine. METHODS: Forty patients scheduled for hernia repair or varicose vein surgeries under epidural anesthesia participated in this study. They were assigned to: Control Group (n = 20), 0.75 percent ropivacaine, 20 ml (150 mg); and Dexmedetomidine Group (n = 20), 0.75 percent ropivacaine, 20 ml (150 mg), plus dexmedetomidine, 1 mg.kg-1. The following variables were studied: total analgesic block onset time, upper level of analgesia, analgesic and motor block duration time, intensity of motor block, state of consciousness, hemodynamics, postoperative analgesia and incidence of side-effects. RESULTS: Epidural dexmedetomidine did not affect onset time or upper level of anesthesia (p > 0.05) however it prolonged sensory and motor block duration time (p < 0.05) and postoperative analgesia (p < 0.05), and also resulted in a more intense motor block, l (p < 0.05). Values of bispectral index were lower in Dexmedetomidine Group (p < 0.05). There was no difference in incidence of hypotension and bradycardia (p > 0.05). Occurrence of side-effects (shivering, vomiting and SpO2 < 90 percent) was low and similar between groups (p > 0.05). CONCLUSION: There is clear synergism between epidural dexmedetomidine and ropivacaine, further this drug association does not bring about additional morbidity.