Mivazerol inhibits intrathecal release of glutamate evoked by halothane withdrawal in rats

Background : Mivazerol is a new and selective α₂-adrenergic receptor agonist devoid of hypotensive effects (1, 2). Previous studies have demonstrated that mivazerol prevents hemodynamic instability during emergence from halothane anesthesia in rats (3). The present study was to determine whether glutamate and aspartate are involved in this action of mivazerol, at the second to third thoracic segments (T2–T3) of the spinal cord.
Methods : In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed in the study. Blood pressure (BP) and heart rate (HR) were recorded along with intrathecal (i.t.) microdialysis perfusion.
Results : BP, HR and i.t. release of glutamate (GLU, pmol/μl) were stable in the rats under 1.1% halothane anesthesia. However, halothane withdrawal immediately increased BP, HR, and i.t. release of GLU, and remained elevated for at least 2 h after withdrawal of halothane. Thirty minutes prior to halothane withdrawal, intravenous (i.v.) infusion of mivazerol (15 μg · kg^–l · h^–) almost completely prevented the increases in HR (Δ18±7 vs Δ79±7 beats/min), and in the i.t. release of GLU (Δ10.3±3.7 vs Δ30.6±5.9; 112% vs 167%). Local i.t. microinjection of mivazerol (2.5 μg/kg) 2 min prior to withdrawal of halothane also blocked the HR responses, as well as on the i.t. release of GLU following halothane withdrawal.
Conclusion : The present study demonstrates that emergence from halothane anesthesia increases i.t. release of GLU, and that mivazerol has an inhibitory effect on the above, through its direct action on the spinal cord.     

Hemodynamic effects of dexmedetomidine sedation for CT imaging studies

Background: Dexmedetomidine sedation for radiological imaging studies is a relatively recent application for this drug. Previous studies have demonstrated some haemodynamic effects of dexmedetomidine, however, the effects remain poorly described in children. The aim of this study was to better define the effect of age on heart rate (HR) and blood pressure changes in children sedated for CT imaging with dexmedetomidine. Methods/materials: At our institution dexmedetomidine is given for sedation for CT imaging as a bolus of 2 mcg·kg⁻¹ over 10 min followed by an infusion of 1 mcg·kg⁻¹·h⁻¹ with a second bolus if required. Detailed quality assurance data sheets document patient demographics, sedation outcomes, adverse events, and hemodynamic data are recorded for each patient. Results: A total of 250 patients (range 0.1–10.6 years) received dexmedetomidine. anova revealed strong evidence for changes in HR and mean arterial blood pressure during bolus and infusion relative to presedation values (P < 0.001). These changes were apparent in each age group and similar between groups. During the first bolus and during infusion, 82% and 93% of patients respectively were within the age-based normal range for HR. For mean arterial blood pressure, 70% of patients were within the normal range during first bolus and 78% during infusion. Conclusion: In the pediatric population studied, intravenous dexmedetomidine sedation was associated with modest fluctuations in HR and blood pressure. Hemodynamic changes were independent of age, required no pharmacologic interventions and did not result in any adverse events. By anticipating these possible hemodynamic effects and avoiding dexmedetomidine in those patients who may not tolerate such fluctuations in HR and blood pressure, dexmedetomidine is an appropriate sedative for children undergoing CT imaging.     

High-dose dexmedetomidine sedation for pediatric MRI

Objectives: To test the hypothesis that high‐dose dexmedetomidine can be successfully used for pediatric magnetic resonance imaging (MRI) sedation without significant hemodynamic compromise. Background: The dexmedetomidine dose required to achieve optimal sedation is often higher than its recommended dose. High doses of dexmedetomidine can lead to significant hemodynamic side effects. Methods: Dexmedetomidine use for pediatric MRI over a 1‐year period was retrospectively reviewed. A dexmedetomidine bolus of 2 μg·kg^?1 intravenous followed by 1 μg·kg^?1·h^?1 infusion was used. Dexmedetomidine efficacy, side effects, timing of side effects, and additional use of medications were analyzed. Data were compared by t‐test, Mann–Whitney rank‐sum test, Fisher’s exact test, and anova . Results: High‐dose dexmedetomidine was used in 77 patients, and MRI was completed in 76 (99%) patients. A second bolus of dexmedetomidine was required in 28 (36%) patients, and 22 (29%) patients required additional medications (midazolam, fentanyl, or ketamine) for adequate sedation. A 25% decrease in blood pressure (BP) was observed in 10.5%, a transient increase in BP in 3.9%, and a heart rate <60 min^?1 in 7.9% of cases. These side effects resolved spontaneously. There were no apneas or respiratory depression. Vital sign changes, recovery time, and discharge time were not significantly different in subgroups of patients receiving one or two boluses of dexmedetomidine with or without additional medications. Transient hypertension was more common in patients receiving two boluses of dexmedetomidine (P = 0.048). Conclusions: High‐dose dexmedetomidine can be successfully used for pediatric MRI sedation, but a significant number of children require additional medications for optimal control. Hemodynamic side effects resolved spontaneously. High‐dose dexmedetomidine did not result in respiratory depression.     

Comparison of heart rate changes after neostigmine-atropine administration during recovery from propofol-N2O and isoflurane-2O anesthesia

Purpose. Propofol augments the reduction of heart rate (HR) in combination with cholinergic agents and attenuates the HR response to atropine. We examined whether propofol anesthesia was associated with an increased incidence and extent of bradycardia after neostigmine-atropine administration compared with the effects of isoflurane anesthesia. Methods. Thirty-six adult patients were randomly assigned to two groups (n = 18 each): the propofol group patients were anesthetized with propofol (5–10 mg·kg⁻¹·h⁻¹)-₂O-fentanyl, and the isoflurane group patients were anesthetized with isoflurane (0.5%–1.0%)-₂O-fentanyl. When surgery was completed, anesthetics were discontinued, and then a mixture of neostigmine 0.05 mg·kg⁻¹ and atropine 0.02 mg·kg⁻¹ was injected intravenously over 20 s. Blood pressure (BP) and HR were measured noninvasively at 1-min intervals for 10 min. Results. At the completion of the surgery, the average infusion rate of propofol was 6.2 ± 1.7 mg·kg⁻¹·h⁻¹, and the average inspired concentration of isoflurane was 0.73 ± 0.15%. Immediately before the neostigmine-atropine injections, HR and mean BP were similar in the two groups. The maximum increase in HR after the neostigmine-atropine injections was significantly less in the propofol group than in the isoflurane group (16 ± 9 and 34 ± 6 beats·min⁻¹, respectively, P < 0.01). The subsequent maximum decrease in HR was greater in the propofol group than in the isoflurane group (−9 ± 4 and −5 ± 4 beats·min⁻¹, respectively; P < 0.01). The incidence of bradycardia (HR < 50 beats·min⁻¹) after neostigmine-atropine injection was greater in the propofol group than in the isoflurane group (61% and 28%, respectively; P < 0.01). Conclusion. We conclude that propofol anesthesia attenuates the initial increases in HR, enhances the subsequent decreases in HR, and increases the incidence of bradycardia after neostigmine-atropine injections compared with the effects of isoflurane anesthesia. Received: May 21, 2001 / Accepted: August 29, 2001     

Dexmedetomidine attenuates tourniquet-induced hyperdynamic response in patients undergoing lower limb surgeries: A randomized controlled study

BackgroundActivation of sympathetic nervous system has a crucial role in mediating the pneumatic tourniquet inflation induced hyperdynamic response. Dexmedetomidine, a selective α₂-adrenergic receptor agonist, has potent sympatholytic effects. We conducted this prospective, randomized, placebo-controlled, double-blinded study to elucidate the effects of dexmedetomidine on attenuating the tourniquet-induced hyperdynamic response during general anesthesia.Materials and methodsWe included a total of 72 healthy adult patients undergoing elective lower limb surgery. Under general anesthesia, patients were randomized to the dexmedetomidine or the control group (n = 36 in each group). The dexmedetomidine group received a loading dose of dexmedetomidine (0.8 μg·kg^?1 over 10 min) followed by continuous infusion of dexmedetomidine (0.4 μg·kg^?1.h^?1) until tourniquet deflation. The control group received normal saline instead. We compared tourniquet-induced changes in hemodynamic parameters between groups to elucidate the effects of dexmedetomidine.ResultsTourniquet inflation induced significant increases in hemodynamic parameters, including heart rate, systolic arterial pressure, mean arterial pressure, diastolic arterial pressure, rate pressure product, cardiac output, and stroke volume in the control group. The effects of tourniquet inflation on increasing hemodynamic parameters were significantly attenuated by dexmedetomidine: heart rate (P < 0.001), systolic arterial pressure (P = 0.002), mean arterial pressure (P = 0.042), diastolic arterial pressure (P = 0.012), rate pressure product (P < 0.001), and cardiac output (P = 0.001) of the dexmedetomidine group were significantly lower than those of the control group. However, the stroke volume of these groups was comparable.ConclusionsDexmedetomidine attenuates tourniquet-induced hyperdynamic response in general anesthesia patients undergoing lower limb surgeries.     

Effects of dexmedetomidine on intraoperative motor and somatosensory evoked potential monitoring during spinal surgery in adolescents

Background: Dexmedetomidine may be a useful agent as an adjunct to an opioid–propofol total intravenous anesthesia (TIVA) technique during posterior spinal fusion (PSF) surgery. There are limited data regarding its effects on somatosensory (SSEPs) and motor evoked potentials (MEPs). Methods: The data presented represent a retrospective review of prospectively collected quality assurance data. When the decision was made to incorporate dexmedetomidine into the anesthetic regimen for intraoperative care of patients undergoing PSF, a prospective evaluation of its effects on SSEPs and MEPs was undertaken. SSEPs and MEPs were measured before and after the administration of dexmedetomidine in a cohort of pediatric patients undergoing PSF. Dexmedetomidine (1 μg·kg^?1 over 20 min followed by an infusion of 0.5 μg·kg^?1·h^?1) was administered at the completion of the surgical procedure, but prior to wound closure as an adjunct to TIVA which included propofol and remifentanil, adjusted to maintain a constant depth of anesthesia as measured by a BIS of 45–60. Results: The cohort for the study included nine patients, ranging in age from 12 to 17 years, anesthetized with remifentanil and propofol. In the first patient, dexmedetomidine was administered in conjunction with propofol at 110 μg·kg^?1·min^?1 which resulted in a decrease in the bispectral index from 58 to 31. Although no significant effect was noted on the SSEPs (amplitude or latency) or the MEP duration, there was a decrease in the MEP amplitude. The protocol was modified so that the propofol infusion was incrementally decreased during the dexmedetomidine infusion to achieve the same depth of anesthesia. In the remaining eight patients, the bispectral index was 52 ± 6 at the start of the dexmedetomidine loading dose and 49 ± 4 at its completion (P = NS). There was no statistically significant difference in the MEPs and SSEPs obtained before and at completion of the dexmedetomidine loading dose. Conclusion: Using the above‐mentioned protocol, dexmedetomidine can be used as a component of TIVA during PSF without affecting neurophysiological monitoring.     

Autonomic activity during dexmedetomidine or fentanyl infusion with desflurane anesthesia

Study ObjectiveTo evaluate autonomic activity with dexmedetomidine or fentanyl infusion and desflurane anesthesia during laparoscopic gastric banding.Study DesignRandomized, single-blinded, open-label study.SettingOperating rooms at a university hospital.Subjects40 patients scheduled for laparoscopic gastric banding with a mean body mass index of 50 kg/m².InterventionsPatients received either dexmedetomidine (0.5 μg/kg given intravenously over 10 minutes, 0.4 μg · kg⁻¹ · h⁻¹, n = 20) or fentanyl (0.5 μg · kg⁻¹ bolus, 1 μg · kg⁻¹ · h⁻¹, n = 20) during anesthesia. Response entropy of the electroencephalogram was maintained at 45 ± 5 by adjusting end-tidal desflurane concentration.MeasurementsIn the operating room, blood pressure, heart rate (HR), response entropy, end-tidal desflurane concentration, tone entropy, and power-spectral analysis of HR were measured with the patient awake; 20, 40, and 60 minutes from intubation and the start of drug infusion; and at extubation.Main ResultsThe mean end-tidal desflurane concentration during anesthesia was 4.0% ± 0.6% with dexmedetomidine and 4.1% ± 0.7% with fentanyl, indicating a similar anesthetic requirement in both groups. Autonomic activity, determined by tone entropy and spectral analysis of HR, decreased by 50% during anesthesia in both groups. The dexmedetomidine group showed a greater decrease in sympathovagal balance during anesthesia.ConclusionBoth dexmedetomidine and fentanyl facilitated anesthesia and attenuated autonomic activity. Dexmedetomidine produced a greater decrease in sympathovagal balance than fentanyl.     

The effect of dexmedetomidine during myringotomy and pressure-equalizing tube placement in children

Background: Bilateral myringotomy (BMT) is a commonly performed otolaryngologic procedure in children. Objectives: To examine the effects of intranasal dexmedetomidine, an α₂‐adrenoceptor agonist, on time‐averaged pain scores, pain control, need for rescue analgesia, and agitation scores in children undergoing BMT. Methods: We designed a trial to enroll 160 children randomized to one of four groups: two study groups, dexmedetomidine (1 or 2 μg·kg^?1), or two control groups representing our institutional standards of practice (intranasal fentanyl‐2 μg·kg^?1 or acetaminophen as needed postoperatively). Results: After 101 children were enrolled, patient caregivers observed that some enrollees were excessively sedated and required prolonged postanesthesia care unit (PACU) stay. This observation led to an unplanned interim analysis and early trial termination. After data were collected, severe nonnormality of pain and agitation scores necessitated a switch of the outcome to assess repeated measurements of the proportion of patients with pain, severe pain, and agitation. Demographics, time to emergence, and agitation were similar among all groups. The risk of requiring acetaminophen rescue (P < 0.0001) and proportion of patients having pain (P = 0.016) was significantly higher in one control group (rescue analgesia only) compared with fentanyl or dexmedetomidine groups. Importantly, length of stay in the PACU was significantly longer in dexmedetomidine‐2 μg·kg^?1‐treated compared with dexmedetomidine‐1 μg·kg^?1‐treated, fentanyl‐treated, or the control group, P = 0.0037. Conclusions: In this trial, we were unable to answer the original question as to the role of dexmedetomidine on time‐averaged pain and agitation scores after BMT. However, our findings clearly demonstrate that in children undergoing BMT, at higher doses, dexmedetomidine significantly prolongs length of stay in the PACU.     

Dexmedetomidine disposition in children: a population analysis

Background: There are few data describing dexmedetomidine population pharmacokinetics (PK) in children (0–15 years) despite increasing use. Methods: An open‐label study was undertaken to examine the PK of i.v. dexmedetomidine 1–4 μg·kg^?1 bolus in children after cardiac surgery (n = 45). A population PK analysis of dexmedetomidine time–concentration profiles (148 observations) was undertaken using nonlinear mixed effects modeling. Estimates were standardized to a 70‐kg adult using allometric size models. Results: Children had a mean age of 3.38 years (range 4 days to 14 years) and weight 15.1 kg (range 3.1–58.9 kg). A two‐compartment disposition model with first order elimination was superior to a one‐compartment model. Population parameter estimates (between subject variability) were clearance (CL) 39.2 (CV 30.36%) l·h^?1 per 70 kg, central volume of distribution (V1) 36.9 (69.49%) l per 70 kg, inter‐compartment clearance (Q) 68.2 (37.6%) l·h^?1 per 70 kg and peripheral volume of distribution (V2) 69.9 (48.6%) l per 70 kg. Clearance at birth was 15.55 l·h^?1 per 70 kg and matured with a half‐time of 46.5 weeks to reach 87% adult rate by 1 year of age. Simulation of an infusion of 1 μg·kg^?1 over 10 min followed by an infusion of 0.7 μg·kg^?1·h^?1 for 50 min suggested that children arouse from sedation at a plasma concentration of 0.304 μg·l^?1. Conclusions: Clearance in neonates is approximately one‐third of that described in adults, consistent with immature elimination pathways. Maintenance dosing, which is a function of clearance, should be reduced in neonates and infants when using a target concentration approach.     

Dexmedetomidine infusion as a supplement to isoflurane anaesthesia for vitreoretinal surgery

Background: We explored the sympatholytic property of dexmedetomidine, especiallyits role in intraocular pressure (IOP) reduction, haemodynamicstability, and attenuation of extubation response. Method: In this double-blind, randomized, controlled trial approvedby the Hospital Ethics Committee, 60 patients undergoing electivevitreoretinal surgery were allocated to two groups, receivingeither placebo or dexmedetomidine. A loading dose of dexmedetomidine2.5 µg kg^–1 h^–1 (or placebo in same volume)was infused for 10 min immediately before induction of anaesthesiawith propofol, followed by a maintenance dexmedetomidine orplacebo infusion at 0.4 µg kg^–1 h^–1 till 30min before the end of the operation. Anaesthesia was maintainedwith isoflurane, oxygen, and air mixture. IOP was measured beforethe loading dose and 1 min after tracheal intubation. The meanarterial pressure (MAP) and heart rate (HR) during loading,induction, maintenance, extubation, and recovery period weremeasured. The degree of strain on extubation was graded from0 to 5. Results: The use of vasopressor/labetalol/atropine and the reductionin IOP were comparable between the two groups. There was a significantvariation in MAP and HR over time within group, but not betweengroups. The median degree of strain was significantly lower(P = 0.049), and the time to reach Aldrete score of 10 shorter(P = 0.031) in the dexmedetomidine group. Conclusion: Dexmedetomidine can be used without undue haemodynamic fluctuationand can decrease the excitatory response during extubation.The reduction in IOP with dexmedetomidine was comparable withplacebo.     

Effects of dexmedetomidine on propofol and remifentanil infusion rates during total intravenous anesthesia for spine surgery in adolescents

Introduction: Total intravenous anesthesia with propofol and a synthetic opioid is a frequently chosen anesthetic technique for posterior spinal fusion. Despite its utility, adverse effects may occur with high or prolonged propofol dosing regimens including delayed awakening. The current study investigated the propofol‐sparing effects of the concomitant administration of the α₂‐adrenergic agonist, dexmedetomidine, during spinal fusion surgery in adolescents. Methods: The surgical database of the department of orthopedic surgery was searched and patients (12–21 years of age) were identified who had undergone spinal fusion for either idiopathic or neuromuscular scoliosis during the past 24 months. Patients were assigned to two groups. Group 1 included patients anesthetized with propofol and remifentanil and group 2 included patients anesthetized with dexmedetomidine, propofol, and remifentanil. In the latter group, dexmedetomidine was administered as a continuous infusion of 0.5 μg·kg^?1·h^?1 started after the induction of anesthesia without a loading dose. Propofol was adjusted to maintain the bispectral index (BIS) number at 40–50 and remifentanil was adjusted to maintain the mean arterial pressure (MAP) at 50–65 mmHg. Labetolol or hydralazine was used if the MAP could not be maintained at 50–65 mmHg with remifentanil up to a maximum dose of 0.6 μg/kg/min. Statistical analysis included a nonpaired t‐test for parametric data (age, weight, remifentanil/propofol infusion requirements, and heart rate/blood pressure values). A nonparametric statistical analysis (Dunn) was used to compare BIS numbers. Parametric data are presented as the mean ± sd while nonparametric data are presented as the median and the 95th percentile confidence intervals. Results: Twelve patients received propofol–remifentanil–dexmedetomidine and 24 received propofol–remifentanil. There were no differences in the demographic data, BIS numbers or hemodynamic parameters between the two groups. There was a reduction in the propofol infusion requirements in patients who also received dexmedetomidine (71 ± 11 μg·kg^?1·min^?1) compared with those receiving only propofol–remifentanil (101 ± 33 μg·kg^?1·min^?1, P = 0.0045). No difference was noted in the remifentanil infusion requirements or the use of supplemental agents (hydralazine and labetolol) to maintain controlled hypotension. Conclusion: The concomitant use of dexmedetomidine in patients undergoing spinal fusion reduces propofol infusion requirements when compared with those patients receiving only propofol and remifentanil.     

Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results

Background. We evaluated the sedative, haemodynamic and respiratoryeffects of dexmedetomidine and compared them with those of midazolamin children undergoing magnetic resonance imaging (MRI) procedures. Methods. Eighty children aged between 1 and 7 yr were randomlyallocated to receive sedation with either dexmedetomidine (groupD, n=40) or midazolam (group M, n=40). The loading dose of thestudy drugs was administered for 10 min (dexmedetomidine 1 µgkg^–1 or midazolam 0.2 mg kg^–1) followed by continuousinfusion (dexmedetomidine 0.5 µg kg^–1 h^–1or midazolam 6 µg kg^–1 min^–1). Inadequatesedation was defined as difficulty in completing the procedurebecause of the child's movement during MRI. The children whowere inadequately sedated were given a single dose of rescuemidazolam and/or propofol intravenously. Mean arterial pressure(MAP), heart rate (HR), peripheral oxygen saturation (     

Comparação dos efeitos de sulfato de magnésio e da dexmedetomidina sobre a qualidade da visibilidade em cirurgia endoscópica sinusal: estudo clínico randomizado

Background and objectivesEven a small amount of bleeding during endoscopic sinus surgery can corrupt the endoscopic field and complicate the procedure. Various techniques, including induced hypotension, can minimize bleeding during endoscopic sinus surgery. The aim of this study was to compare the surgical vision quality, haemodynamic parameters, postoperative pain, and other effects of magnesium, a hypotensive agent, with that of dexmedetomidine, which was initially developed for short‐term sedation in the intensive care unit but also is an alpha 2 agonist sedative.Method60 patients between the ages of 18 and 45 years were divided into either the magnesium group (Group M) or the dexmedetomidine group (Group D). In Group M, magnesium sulphate was given at a pre‐induction loading dose of 50 mg kg⁻¹ over 10 min and maintained at 15 mg kg⁻¹ h⁻¹; in Group D, dexmedetomidine was given at 1 mcg kg⁻¹ 10 min before induction and maintained at 0.6 mcg kg⁻¹ h⁻¹. Intraoperatively, the haemodynamic and respiratory parameters and 6‐point intraoperative surgical field evaluation scale were recorded. During the postoperative period, an 11‐point numerical pain scale, the Ramsay sedation scale, the nausea/vomiting scale, the adverse effects profile, and itching parameters were noted.ResultsGroup D showed a significant decrease in intraoperative surgical field evaluation scale scale score and heart rate. The average operation time was 50 min, and Group M had a higher number of prolonged surgeries. No significant difference was found in the other parameters.ConclusionsDue to its reduction of bleeding and heart rate in endoscopic sinus surgery and its positive impacts on the duration of surgery, we consider dexmedetomidine to be a good alternative to magnesium.     

Fentanyl attenuates cardiovascular responses to tracheal extubation

We carried out a controlled, randomized, double-blind study to examine the effects of intravenous fentanyl (1 or 2 μg kg^?1) on hemodynamic changes during tracheal extubation and emergence from anesthesia in 60 ASA physical status I or II patients undergoing elective gynecological surgery. Anesthesia was maintained with 0.5%–1.5% isoflurane and 60% nitrous oxide (N₂O) in oxygen. Muscle relaxation was achieved with vecuronium. The patients were randomly assigned to three group (each, n = 20), and fentanyl (1 or 2 μg kg^?1), or saline (as a control) was given at the time of peritoneal closure. Changes in heart rate (HR) and blood pressure (BP) were measured during and after tracheal extubation. Adverse effects, including postoperative sedation and respiratory depression, were also assessed. The HR, systolic BP, and diastolic BP increased significantly during tracheal extubation in the control group (P<0.05). Fentanyl 2 μg kg^?1 attenuated the increases in these variables more effectively than fentanyl 1 μg kg^?1. The time interval from the study drug to extubation was similar in each group. Postoperative somnolence and respiratory depression were not observed in any patients in any of the three groups. We concluded that a bolus dose of intravenous fentanyl 2 μg kg^?1 given at the time of peritoneal closure was of value in attenuating the cardiovascular changes associated with tracheal extubation and emergence from anesthesia, and that this treatment did not prolong the recovery. However, further studies are required to assess this technique in patients with cardiovascular or cerebrovascular diseases.     

Effects of dexmedetomidine on cerebral circulation and systemic hemodynamics after cardiopulmonary resuscitation in dogs

Purpose Our purpose was to examine the effect of dexmedetomidine, when used with phenylephrine during cardiopulmonary resuscitation (CPR), on the cerebral and systemic circulations. Methods In pentobarbital-anesthetized, mechanically ventilated dogs, we evaluated pial vessel diameters, cerebral oxygen extraction, and systemic hemodynamics before and after cardiac arrest (5 min) and resuscitation, in the presence or absence of dexmedetomidine (n = 7 each; dexmedetomidine or control group). Results In both groups: (a) pial arterioles were dilated at 5 and 15 min after CPR, and had returned to baseline diameters at 30 min; (b) sagittal sinus pressure was significantly raised at 5 and 15 min after CPR; and (c) cerebral oxygen extraction was decreased at 5, 15, and 30 min after CPR, and had returned to baseline level at 60 min after CPR. We could find no differences between the two groups in the cerebral circulation after CPR. However, the number of defibrillation electric shocks required to restore spontaneous circulation (5.5 vs 3.6; P < 0.05), the dose of phenylephrine used for CPR (1193 μg vs 409 μg; P < 0.01), and the number of postresuscitation ventricular ectopic beats observed during the first 120 min after successful resuscitation (1606 vs 348; P < 0.05) were all significantly lower in the dexmedetomidine group. Conclusion Although intravenous dexmedetomidine, as used for CPR, does not have a beneficial effect on either cerebral vessels or cerebral oxygen extraction, it may reduce the number of defibrillation shocks needed and the number of postresuscitation ventricular ectopic beats, and help to bring about stable systemic circulation after CPR.     

Anaesthesia for coronary artery bypass grafting: opioid-analgesia combined with either flunitrazepam,propofol or isoflurane

This is a prospective, open, randomized study comparing three different anaesthetic regimens with respect to haemodynamic stability (cardiac index and pressure measurements), ischaemia (ECG), and loss of awareness (midlatency auditory evoked potentials) in 58 patients undergoing coronary artery surgery. Anaesthesia was based on fentanyl 0.01 mg kg^-1 bw for induction and 0.8-2.0 mg h^-1 in combination with nitrous oxide for maintenance before cardiopulmonary bypass and 0.2-0.6 mg h^-1 without nitrous oxide during and after cardiopulmonary bypass. Eighteen patients were anaesthetised with flunitrazepam 0.01 mg kg^-1 bw for induction and received thereafter 1–2 mg h^-1 for maintenance (group F). In 40 patients anaesthesia was induced with etomidate and maintained with either isoflurane 0.4-1.2 vol% (group I) or propofol 4–10 mg kg^-1 bw h^-1 (group P). Vasodilators and inotropes were used for haemodynamic control when needed. Haemodynamic variables and ECG were studied at five timepoints (awake; after induction before surgery; after sternotomy; before cardiopulmonary bypass; and 20 min after separation from bypass). During surgical stimulation, vasodilators were needed significantly more frequently in group F, than in groups I and P. Surgery and sternotomy caused an increase in SVI and APs/SV in all groups. Differences between the groups were only found for systemic pressures, which after sternotomy were lowest in group I and before cardiopulmonary bypass were highest in group F. After termination of bypass all groups showed an increase in HR and a decrease in SVI, SVR, and LVSWI compared to the awake state, while CI remained unchanged. The only differences noted between the groups were a lower PCWP and a smaller reduction in SVR with propofol compared to the others and higher APs/SV with propofol compared to isoflurane. Concerning ST segment changes (> 0.1 mV, leads II and/or V5) at the five measurement times, significant differences were found comparing groups F and P after sternotomy (P < 0.10) and comparing groups F and I after separation from CPB (P <0.05), group F showing the highest incidences of ischaemic events. A blinded evaluation of auditory evoked potentials demonstrated more reduced midlatency auditory potentials after sternotomy during isoflurane and propofol anaesthesia than during flunitrazepam. The authors conclude that fentanyl supplemented with isoflurane or propofol was unequivocally superior to supplementation with flunitrazepam.     

Dexmedetomidine pharmacokinetics in pediatric intensive care – a pooled analysis

Background: Published dexmedetomidine pharmacokinetic studies in children are limited by participant numbers and restricted pathology. Pooling the available studies allows investigation of covariate effects. Methods: Data from four studies investigating dexmedetomidine pharmacokinetics after i.v. administration (n = 95) were combined to undertake a population pharmacokinetic analysis of dexmedetomidine time–concentration profiles (730 observations) using nonlinear mixed effects modeling (NONMEM). Estimates were standardized to a 70‐kg adult using allometric size models. Results: Children had a mean age of 3.8 (median 3 years, range 1 week–14 years) and weight of 16.0 kg (median 13.3 kg, range 3.1–58.9 kg). Population parameter estimates (between subject variability) for a two‐compartment model were clearance (CL) 42.1 (CV 30.9%) l·h^?1·70 kg^?1, central volume of distribution (V1) 56.3 (61.3%) l·70 kg^?1, inter‐compartment clearance (Q) 78.3 (37.0%) l·h^?1·70 kg^?1 and peripheral volume of distribution (V2) 69.0 (47.0%) l·70 kg^?1. Clearance maturation with age was described using the Hill equation. Clearance increases from 18.2 l·h^?1·70 kg^?1 at birth in a term neonate to reach 84.5% of the mature value by 1 year of age. Children given infusion after cardiac surgery had 27% reduced clearance compared to a population given bolus dose. Simulation of published infusion rates that provide adequate sedation for intensive care patients found a target therapeutic concentration of between 0.4 and 0.8 μg·l^?1. Conclusions: The sedation target concentration is similar to that described for adults. Immature clearance in the first year of life and a higher clearance (when expressed as l·h^?1·kg^?1) in small children dictate infusion rates that change with age. Extrapolation of dose from children given infusion in intensive care after cardiac surgery may not be applicable to those sedated for noninvasive procedures out of intensive care.     

The comparison of the effects of dexmedetomidine and midazolam sedation on electroencephalography in pediatric patients with febrile convulsion

Background: When electroencephalogram (EEG) activity is recorded for diagnostic purposes, the effects of sedative drugs on EEG activity should be minimal. This study compares the sedative efficacy and EEG effects of dexmedetomidine and midazolam. Subjects and methods: EEG recordings of 60 pediatric subjects with a history of simple febrile convulsions were performed during physiologic sleep. All of these patients required sedation to obtain follow‐up (control) EEGs. Subjects in Group D received 0.5 μg·kg^?1 of dexmedetomidine, and those in Group M received 0.1 mg·kg^?1 of midazolam. For rescue sedation, the same doses were repeated to maintain a Ramsey sedation score level of between 4 and 6. Results: The mean doses that were required for sedation were 0.76 μg·kg^?1 of dexmedetomidine and 0.38 mg·kg^?1 of midazolam. Diastolic blood pressure and HR were lower in Group D than in Group M (P < 0.05). Hypoxia was observed in 11 (36.7%) subjects in Group M and none in Group D; this was statistically significant (P < 0.001). Frontal and parieto‐occipital (PO) EEG frequencies were similar during physiologic sleep and dexmedetomidine sedation. However, EEG frequencies in these areas (P < 0.001) and PO EEG amplitude (P = 0.030) were greater during midazolam sedation than during physiologic sleep. Conclusions: Dexmedetomidine is a suitable agent to provide sedation for EEG recording in children. There is less change in EEG peak frequency and amplitude after dexmedetomidine than after midazolam sedation.     

The influence of isoflurane on a continuous infusion of mivacurium

Sixty surgical patients were studied to evaluate the neuromuscular effects of mivacurium 0.l5 mg.kg^-1 (2 × ED₉₅)for tracheal intubation. After intubation the patients were randomly allocated to receive alfentanil with either propofol (starting with 9mg.kg^-1 h^-1, reducing to 6mg.kg^-1 h^-1 after 20min) or isoflurane (0.5% end-tidal). In addition, all the patients were given a continuous infusion of mivacurium 10 μg.kg^-1 min^-1 after tracheal intubation which was adjusted to maintain 90% depression of T₁. Following mivacurium 0.15 mg.kg^-1 T₁ decreased below 25% in all but four patients. Mean (SD) percentage maximum block attainedwas 92.9% (12.5) after 309 (89)s. Tracheal intubation was completed 232 (155) s after administration of the relaxant and intubating conditions were graded as‘excellent’ or‘good’ in 56 patients. Although the mean (SD) mivacurium infusion rate for maintaining T₁ at 10% was higher in the propofol group, 4.8 (2.1) compared with 4.4 (2.0) μg.kg^-1 min^-1 in the isoflurane group, this was not significantly different (p > 0.05). The mean (SD) recovery index was prolonged in the isoflurane patients, 757 (508)s, compared to those receiving propofol, 466 (219)s (p < 0.05).     

Bupivacaine Mandibular Nerve Block Affects Intraoperative Blood Pressure and Heart Rate in a Yucatan Miniature Swine Mandibular Condylectomy Model: A Pilot Study

Purpose/Aim: The primary objective was to evaluate the effect of a bupivacaine mandibular nerve block on intraoperative blood pressure (BP) and heart rate (HR) in response to surgical stimulation and the need for systemic analgesics postoperatively. We hypothesized that a mandibular nerve block would decrease the need for systemic analgesics both intraoperatively and postoperatively. Materials and Methods: Fourteen adult male Yucatan pigs were purchased. Pigs were chemically restrained with ketamine, midazolam, and dexmedetomidine and anesthesia was maintained with isoflurane inhalant anesthesia. Pigs were randomized to receive a mandibular block with either bupivacaine (bupivacaine group) or saline (control group). A nerve stimulator was used for administration of the block with observation of masseter muscle twitch to indicate the injection site. Invasive BP and HR were measured with the aid of an arterial catheter in eight pigs. A rescue analgesic protocol consisting of fentanyl and lidocaine was administered if HR or BP values increased 20% from baseline. Postoperative pain was quantified with a customized ethogram. HR and BP were evaluated at base line, pre-rescue, 10 and 20 min post-rescue. Results: Pre-rescue mean BP was significantly increased (p = .001) for the bupivacaine group. Mean intraoperative HR was significantly lower (p = .044) in the bupivacaine versus saline group. All other parameters were not significant. Conclusion: Addition of a mandibular nerve block to the anesthetic regimen in the miniature pig condylectomy model may improve variations in intraoperative BP and HR. This study establishes the foundation for future studies with larger animal numbers to confirm these preliminary findings.