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Background: Caudal epidural anesthesia is often used as an adjunct to general anesthesia and for postoperative pain relief in children. In anesthetized children, epinephrine and isoproterenol are reliable indicators to detect accidental intravascular injection of a test dose. Oral clonidine, a useful premedicant in pediatric anesthesia, modifies hemodynamic responses to sympathomimetics, including catecholamines. The aim of the current study was to determine whether oral clonidine premedication alters the efficacy of a simulated intravascular test dose containing epinephrine or isoproterenol in sevoflurane-anesthetized children., Methods: One hundred twenty children (aged 1-7 yr) were randomly divided into six groups; control-saline, control-epinephrine, control-isoproterenol, clonidine-saline, clonidine-epinephrine, and clonidine-isoproterenol. The three clonidine groups received oral clonidine 4 microg/kg [DOSAGE ERROR CORRECTED] as premedication, whereas the three control groups did not receive any premedication. Anesthesia was maintained with sevoflurane at a level of 1.2 minimum alveolar concentration. After hemodynamics were stable, 0.1 ml/kg of 1% lidocaine containing epinephrine 0.5 mg/kg or isoproterenol 75 ng/kg was intravenously given to the two epinephrine or isoproterenol groups, respectively, to simulate intravascular injection of a test dose. The saline groups received saline alone instead of the test dose. Heart rate, blood pressure, and T-wave amplitude of electrocardiogram were recorded before and after administration of study drugs for subsequent analysis., Results: Test solution containing epinephrine increased heart rate, systolic blood pressure, and T-wave amplitude. Oral clonidine had no effect on elevation of these variables in response to epinephrine. The isoproterenol-containing test dose produced a prominent increase in heart rate and a less pronounced increase in systolic blood pressure and T-wave amplitude. Oral clonidine also failed to modify isoproterenol-induced hemodynamic and T-wave changes. Calculated sensitivity and specificity of epinephrine or isoproterenol were all 100% based on a new heart rate criterion (positive if >/= 10 beats/min) and were unaltered by oral clonidine premedication., Conclusions: Epinephrine or isoproterenol is a reliable marker to detect accidental intravascular injection of a test dose with 100% sensitivity and specificity based on a new heart rate criterion in sevoflurane-anesthetized children. These data suggest that oral clonidine premedication does not alter the efficacy of a simulated epidural test dose containing epinephrine or isoproterenol.

We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.

Unlabelled: Neutrophil functions are inhibited by various anesthetics. Clonidine and dexmedetomidine, alpha2-agonists, are often used as adjuncts to anesthesia. Thus, we conducted the current study to determine the effect of clonidine, dexmedetomidine, and xylazine at clinically (or veterinary anesthetically) relevant concentrations (and 10 and 100 times these concentrations) on several aspects of human neutrophil functions using an in vitro system. The three alpha2-agonists had no effects on chemotaxis, phagocytosis, or superoxide anion (O2-) production of neutrophils, except that the highest concentration of clonidine inhibited chemotaxis. Increases in intracellular calcium concentrations in neutrophils stimulated by chemotaxin were not influenced by clonidine, dexmedetomidine, or xylazine. Unchanged calcium concentrations may contribute to failure to modulate the neutrophil functions. In addition, these drugs did not scavenge O2- generated by the cell-free (xanthine-xanthine oxidase) system. This is the first report concerning the effect of clonidine or dexmedetomidine on human neutrophil functions. Our findings suggest that we may not have to take extra precautions in using the alpha2-agonists in patients with infection, but that we cannot expect these drugs to be prophylaxis against autotissue injuries whose pathogenesis includes activation of neutrophils., Implications: Neutrophils are involved in the antibacterial host defense system and autotissue injury. We found that clinically relevant concentrations of clonidine and dexmedetomidine do not affect chemotaxis, phagocytosis, or superoxide production by human neutrophils. These findings indicate that it may not be necessary to take special care in using alpha2-agonists in patients with infection, sepsis, or systemic inflammation.

Background: Oral clonidine may influence plasma glucose and lipid homeostasis by modulating endocrinologic responses to surgical stress. The effect of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion were investigated in children undergoing minor surgery., Methods: Otherwise healthy children (n, 120; aged 3-13 yr) were assigned randomly to six groups according to the glucose concentration of the intravenous solution (0%, 2%, or 5%, at a rate of 6 ml kg(-1) x h(-1)) and the preoperative medications (4 microg/kg clonidine or placebo given 100 min before anesthesia) they were to receive. The plasma concentrations of glucose, nonesterified fatty acid, ketone bodies, epinephrine, norepinephrine, and cortisol were determined., Results: Infusion of 5% glucose caused hyperglycemia (mean glucose concentration >200 mg/dl) in six children receiving placebo and two receiving clonidine. Although the mean plasma glucose concentration increased in three placebo groups, it was unchanged and the plasma concentrations of total ketone bodies and nonesterified fatty acid were increased in children receiving clonidine and glucose-free solution. The plasma epinephrine, norepinephrine, and cortisol levels in children receiving placebo increased in response to surgery. Clonidine attenuated the increase in catecholamines and cortisol., Conclusions: Oral clonidine premedication attenuated the hyperglycemic response, probably by inhibiting the surgical stress-induced release of catecholamines and cortisol. Infusion of 2% of glucose maintained plasma glucose concentrations within physiologic ranges in children receiving clonidine.

Background: Sevoflurane is a useful anesthetic for inhalational induction in children because of its low solubility in blood and relatively nonpungent odor. Clonidine has sedative and anxiolytic properties and reduces the requirement for inhalation agents. Nitrous oxide (N2O) also decreases the requirement of inhaled anesthetics, but the effect is variable. The minimum alveolar concentration for tracheal intubation (MAC(TI)) of sevoflurane was assessed with and without N2O and clonidine premedication., Methods: Seventy-two patients, aged 3-11 yr, were assigned to one of six groups (n = 12 each). They received one of three preanesthetic medications (two groups for each premedication): placebo (control), 2 microg/kg oral clonidine or 4 microg/kg oral clonidine. In one group of each premedication, anesthesia was induced with sevoflurane in oxygen; in the other group, anesthesia was induced with sevoflurane in the presence of 60% N2O. Each concentration of sevoflurane at which tracheal intubation was attempted was predetermined according to Dixon's up-and-down method and held constant for at least 20 min before the trial, Results: The MAC(TI) of sevoflurane in the absence of N2O (mean +/- SEM) was 3.2 +/- 0.2%, 2.5 +/- 0.1%, and 1.9 +/- 0.2% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups, respectively. Nitrous oxide (60%) decreased the MAC(TI) of sevoflurane by 26%, 24%, and 27% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups., Conclusions: Oral clonidine premedication decreased the MAC(TI) of sevoflurane. Nitrous oxide also decreased the MAC(TI). The combination of clonidine and N2O lessened the MAC(TI) of sevoflurane more than did either drug alone.

Background: Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children., Methods: In a prospective, randomized, double-blind, controlled clinical trial, 60 children (ASA I) aged 5-11 yr, received placebo (control), 2 micrograms kg-1 clonidine, or 4 micrograms kg-1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end-tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed., Results: Higher inspired concentrations of halothane (%) were required in the control and 2 micrograms kg-1 clonidine-treated groups (mean SD: 1.1 +/- 0.2 and 1.0 +/- 0.2, respectively) than in the 4 micrograms kg-1 clonidine-treated group (0.6 +/- 0.1) for haemodynamic stability (P < 0.05). Clonidine, 4 micrograms kg-1, significantly reduced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens., Conclusion: Oral clonidine premedication at a dose of 4 micrograms kg-1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.

Clonidine is an effective preanesthetic medication in children, providing a preoperative sedative effect. The analgesic properties of the drug have been well documented in adults. The current study was designed to investigate the effect of oral clonidine given preoperatively on postoperative pain in children undergoing minor surgery. In a prospective, randomized, controlled clinical trial, 90 children aged 5-12 yr undergoing elective ophthalmic, urologic, and otologic surgery received placebo (control), clonidine 2 micrograms/kg, or clonidine 4 micrograms/kg. These drugs were administered 105 min before the estimated time of induction of anesthesia and followed by treatment with oral atropine 0.03 mg/kg 60 min before anesthesia. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). Clonidine 4 micrograms/kg provided lower OPS (highest) scores during 12 h after surgery and reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. These data suggest that oral clonidine premedication (4 micrograms/kg) is a possible approach to facilitating postoperative analgesia in children undergoing minor surgery.

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.

We conducted a prospective, randomized, double-blind , controlled clinical trial to examine (1) whether plasma catecholamine (CA) concentrations increased in response to tracheal intubation in children, and (2) the effects of clonidine on the CA responses. Sixty children (ASA physical status I) aged 7-13 yr were allocated to one of three groups (n = 20 for each group): diazepam 0.4 x kg(-1) (active control), clonidine 2 micrograms x kg(-1), or clonidine 4 micrograms x kg(-1) po. These agents were administered 105 min before induction of anaesthesia followed by oral atropine 0.03 mg x kg(-1) given 60 min before anaesthesia which was induced with thiamylal 5 mg x kg(-1) and tracheal intubation was facilitated with vecuronium 0.2 mg x kg(-1). Laryngoscopy, lasting 30 sec, was attempted two minutes after administration of the induction agents. Serial values for blood pressure, heart rate, and venous plasma CA concentrations were compared among the three groups and with the respective preinduction measurements. Children receiving diazepam or clonidine 2 micrograms x kg(-1) showed remarkable increases in systolic and diastolic blood pressures, heart rate, and plasma CA concentrations in response to tracheal intubation (P < 0.05). The increases were similar for the two regimens. These haemodynamic and CA changes were smaller in children receiving clonidine 4 micrograms x kg(-1) (P < 0.005). The haemodynamic responses were positively correlated with the CA responses. These findings indicate that tracheal intubation following rapid sequence induction of anaesthesia in children provokes a reflex increase in sympathetic activity characterized by increased plasma CA concentrations, and that attenuation of the cardiovascular changes with a high oral dose of clonidine may be due to suppression of the increase in sympathetic activity evoked by the intubation.

Background: Clonidine, which is known to have analgesic and sedative properties, has recently been shown to be an effective preanesthetic medication in children. The drug may cause side effects, including bradycardia and hypotension. This study was conducted to evaluate the ability of intravenous atropine to increase the heart rate (HR) in awake children receiving clonidine preanesthetic medication., Methods: We studied 96 otherwise healthy children, 8-13 yr old, undergoing minor surgery. They received, at random, oral clonidine 2 or 4 micrograms.kg-1 or placebo 105 min before scheduled induction of anesthesia. Part I (n = 48, 16 per group): When hemodynamic parameters after insertion of a venous catheter had been confirmed to be stable, atropine was administered in incremental doses of 2.5, 2.5, and 5 micrograms.kg-1 every 2 min. The HR and blood pressure were recorded at 1-min intervals. Part II (n = 48, 16 per group): After the recording of baseline hemodynamic values, successive doses of atropine (5 micrograms.kg-1 every 2 min, to 40 micrograms.kg-1), were administered until HR increased by 20 beats.min-1. The HR and blood pressure were recorded at 1-min intervals., Results: Part I: The increases in HR in response to a cumulative dose of atropine 10 micrograms.kg-1 were 33 +/- 3%, 16 +/- 3%, and 8 +/- 2% (mean +/- SEM) in children receiving placebo, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1, respectively (P < 0.05). Part II: The HR in the control group increased by more than 20 beats.min-1 in response to atropine 20 micrograms.kg-1 or less. In two patients in the clonidine 4 micrograms.kg-1 group, HR did not increase by 20 beats.min-1 even after 40 micrograms.kg-1 of atropine., Conclusions: Oral clonidine premedication (4 micrograms.kg-1) blunted the increase in HR after intravenous atropine in awake children, although clonidine 2 micrograms.kg-1 did not. A larger dose of atropine was required to increase the HR by 20 beats.min-1 in children receiving the premedicant in the larger dose.

Clonidine is a useful drug to give preoperatively because it produces anxiolysis, sedation, and hemodynamic stability, and reduces intravenous and volatile anesthetic requirements. Several premedicants, including midazolam and diazepam, have been shown to reduce the induction dose of intravenous anesthetics, such as thiopental, ketamine, or propofol. A randomized, double-blind controlled study was conducted to evaluate the effect of premedication with oral clonidine on thiamylal requirement for the induction of anesthesia and on associated hemodynamic changes in children. Sixty children (ASA grades I-II, 7-12 yr old) were assigned randomly to receive one of three treatments (n = 20, for each group): placebo (control), clonidine 2 micrograms/kg, or clonidine 4 micrograms/kg 105 min before the induction of anesthesia. Thiamylal was injected at a dose of 1 mg/kg every 15 s until loss of the eyelash reflex and the dose was recorded. Blood pressure (BP), heart rate (HR), and arterial oxygen saturation were recorded every minute from the beginning of injection of thiamylal for 5 min. Significant decreases in thiamylal dose were observed in patients receiving clonidine. The induction dose of thiamylal (mean +/- SD) was 5.4 +/- 0.9, 4.5 +/- 1.1, and 3.4 +/- 0.9 mg/kg for patients receiving placebo, clonidine 2 micrograms/kg, and clonidine 4 micrograms/kg, respectively (P < 0.05). Systolic BP decreased by 6.8%, 5.6%, and 6.6% and HR increased by 5.7%, 4.8%, and 4.1% after administration of thiamylal in the control (placebo) group and the clonidine 2 micrograms/kg and clonidine 4 micrograms/kg groups, respectively (P > 0.05). Premedication with oral clonidine reduced the dose of intravenous thiamylal required for the induction of anesthesia in children.

Background: Clonidine, an alpha 2-adrenoceptor agonist, has been shown to be effective as a preanesthetic medication in adults. The current study was designed to investigate the efficacy of two doses of oral clonidine as a premedicant preceding oral atropine in children., Methods: In a prospective, randomized, double-blind, controlled clinical trial, 105 children, aged 4-12 yr, undergoing elective ophthalmologic surgery received 0.4 mg/kg diazepam, 2 micrograms/kg clonidine, or 4 micrograms/kg clonidine orally. These agents mixed with apple juice were administered 105 min before the estimated time of induction of anesthesia, and were followed by treatment with 0.03 mg/kg oral atropine 60 min before anesthesia. A blinded observer noted the children's level of sedation, quality of separation from parents, and degree of acceptance of mask application during inhalation of nitrous oxide used for establishment of venous access. Anesthesia was induced with 5 mg/kg thiamylal, and tracheal intubation was facilitated with 0.2 mg/kg vecuronium. Hemodynamic changes after tracheal intubation were compared among the three groups., Results: Clonidine produced significant sedation, and the effect was dose related. Clonidine, 4 micrograms/kg, provided better quality of separation and acceptance of mask than the two other regimens. This dose of clonidine attenuated the increases in blood pressure and heart rate after tracheal intubation. No clinically significant perioperative hypotension or bradycardia was observed., Conclusions: These data indicate that, even in pediatric surgery, the combination of 4 micrograms/kg and 0.03 mg/kg oral clonidine is an effective premedication. However, the safety and optimal dose of clonidine in this setting remain to be determined.

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Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)