Acetaminophen improves tardive akathisia induced by dopamine D2 receptor antagonists.

Tardive akathisia is a movement disorder characterized by internal restlessness with an uncontrollable urge to move, leading to repetitive movements. It is a common side effect of long-term treatment with dopamine D2 receptor antagonists. In the present study, we analyzed the FDA Adverse Event Reporting System and IBM MarketScan Research Database to find a drug that can be used concomitantly with dopamine D2 receptor antagonists and still reduce the risk of akathisia. Acetaminophen was determined to be the most effective akathisia-suppressing drug. In an experimental validation of the hypothesis, chronic treatment of rats with haloperidol caused akathisia symptoms, including increased stereotyped behavior and locomotor activity, and decreased immobility time. Acute treatment with acetaminophen significantly attenuated haloperidol-induced akathisia. In the ventral striata of these rats, acetaminophen prevented haloperidol-induced decrease in the number of c-Fos+ preproenkephalin+ neurons. These results suggest that acetaminophen is effective in suppressing tardive akathisia by activating indirect-pathway medium spiny neurons.

Reassessment of amphetamine- and phencyclidine-induced locomotor hyperactivity as a model of psychosis-like behavior in rats.

Locomotor hyperactivity induced by psychotomimetic drugs, such as amphetamine and phencyclidine, is widely used as an animal model of psychosis-like behaviour and is commonly attributed to an interaction with dopamine release and N-methyl-D-aspartate (NMDA) receptors, respectively. However, what is often not sufficiently taken into account is that the pharmacological profile of these drugs is complex and may involve other neurotransmitter/receptor systems. Therefore, this study aimed to assess the effect of three antagonists targeting different monoamine pathways on amphetamine- and phencyclidine-induced locomotor hyperactivity. A total of 32 rats were pre-treated with antagonists affecting dopaminergic, noradrenergic and serotonergic transmission: haloperidol (0.05 mg/kg), prazosin (2 mg/kg) and ritanserin (1 mg/kg), respectively. After 30 min of spontaneous activity, rats were injected with amphetamine (0.5 mg/kg) or phencyclidine (2.5 mg/kg) and distance travelled, stereotypy and rearing recorded in photocell cages over 90 min. Pre-treatment with haloperidol or prazosin both reduced amphetamine-induced hyperactivity although pre-treatment with ritanserin had only a partial effect. None of the pre-treatments significantly altered the hyperlocomotion effects of phencyclidine. These findings suggest that noradrenergic as well as dopaminergic neurotransmission is critical for amphetamine-induced locomotor hyperactivity. Hyperlocomotion effects of phencyclidine are dependent on other factors, most likely NMDA receptor antagonism. These results help to interpret psychotomimetic drug-induced locomotor hyperactivity as an experimental model of psychosis.

Adult Emergence Agitation: A Veteran-Focused Narrative Review.

Emergence agitation (EA) is a self-limited state of psychomotor excitement during awakening from general anesthesia. EA is confined to the emergence period as consciousness is restored, which sharply distinguishes it from other postoperative delirium states. Sporadic episodes of EA may become violent with the potential for harm to both patients and caregivers, but the long-term consequences of such events are not fully understood. Current literature on EA in adults is limited to small-scale studies with inconsistent nomenclature, variable time periods that define emergence, a host of different surgical populations, and conflicting diagnostic criteria. Therefore, true incidence rates and risk factors are unknown. In adult noncardiac surgery, the incidence of EA is approximately 19%. Limited data suggest that young adults undergoing otolaryngology operations with volatile anesthetic maintenance may be at the highest risk for EA. Currently suggested EA mechanisms are theoretical but might reflect underblunted sympathetic activation in response to various internal (eg, flashbacks or anxiety) or external (eg, surgical pain) stimuli as consciousness returns. Supplemental dexmedetomidine and ketamine may be utilized for EA prevention. Compared to the civilian population, military veterans may be more vulnerable to EA due to high rates of posttraumatic stress disorder (PTSD) manifesting as violent flashbacks; however, confirmatory data are limited. Nonetheless, expert military medical providers suggest that use of patient-centered rapport tactics, PTSD trigger identification and avoidance, and grounding measures may alleviate hyperactive emergence phenomena. Future research is needed to better characterize EA in veterans and validate prophylactic measures to optimize care for these patients. This narrative review provides readers with an important framework to distinguish EA from delirium. Furthermore, we summarize current knowledge of EA risk factors, mechanisms, and adult management strategies and specifically revisit them in the context of veteran perioperative health. The anesthesiology care team is ideally positioned to further explore EA and develop effective prevention and treatment protocols.

Effect of ancillary drugs on sevoflurane related emergence agitation in children undergoing ophthalmic surgery: a Bayesian network meta-analysis.

BACKGROUND: The comparative efficacy of ancillary drugs on sevoflurane related emergence agitation (EA) in children undergoing ophthalmic surgery remains controversial. METHODS: The databases were retrieved in an orderly manner from the dates of their establishment to October, 2018, including PubMed, The Cochrane Library and Web of Science, to collect randomized controlled trials (RCT) of different anesthetic drugs combined with sevoflurane for ophthalmic surgery. Then a network meta-analysis was conducted using R and Stata 12.0 softwares. RESULTS: The meta-analysis showed that, in reducing sevoflurane related EA, dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil and clonidine were superior to placebo (P < 0.05). The network meta-analysis showed that the effects of ancillary drugs combine with sevoflurane in reducing risk of EA in children undergoing ophthalmic surgery was superior to placebo: dexmedetomidine (OR = 0.17, 95% CrI 0.12-0.22), ketamine (OR = 0.30, 95% CrI 0.11-0.49), propofol (OR = 0.24, 95% CrI 0.09-0.63), fentanyl (OR = 0.16, 95% CrI 0.08-0.56), midazolam (OR = 0.20, 95% CrI 0.09-0.40), sufentanil (OR = 0.27, 95% CrI 0.14-0.41), remifentanil (OR = 0.18, 95% CrI 0.08-0.54) and clonidine (OR = 0.14, 95% CrI 0.07-0.41). The SUCRA of placebo, dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil, clonidine were respectively 0.26, 77.93, 27.71, 42.8, 69.43, 52.89, 59.83, 57.62 and 61.53%. CONCLUSIONS: The effects of dexmedetomidine combine with sevoflurane in reducing risk of emergence agitation in children undergoing ophthalmic surgery was superior to other drugs.

Comparison of the effects of 0.03 and 0.05 mg/kg midazolam with placebo on prevention of emergence agitation in children having strabismus surgery.

BACKGROUND: Midazolam has been widely studied for preventing emergence agitation. The authors previously reported that in children with sevoflurane anesthesia, intravenous administration of midazolam (0.05 mg/kg) before the end of surgery reduced the incidence of emergence agitation but prolonged the emergence time. This study was designed to test the hypothesis that a lower midazolam dose could suppress emergence agitation with minimal disturbance of the emergence time in children with sevoflurane anesthesia. METHODS: In this randomized, double-blind, placebo-controlled trial, 90 children (1 to 13 yr of age) having strabismus surgery were randomized to 1:1:1 to receive 0.03 mg/kg of midazolam, 0.05 mg/kg of midazolam, or saline just before the end of surgery. The primary outcome, the incidence of emergence agitation, was evaluated by using the pediatric anesthesia emergence delirium scale and the four-point agitation scale. The secondary outcome was time to emergence, defined as the time from sevoflurane discontinuation to the time to extubation. RESULTS: The incidence of emergence agitation was lower in patients given 0.03 mg/kg of midazolam (5 of 30, 16.7%) and patients given 0.05 mg/kg of midazolam (5 of 30, 16.7%) compared with that in patients given saline (13/of 30, 43.3%; P = 0.036 each). The emergence time was longer in patients given 0.05 mg/kg of midazolam (17.1 ± 3.4 min, mean ± SD) compared with that in patients given 0.03 mg/kg of midazolam (14.1 ± 3.6 min; P = 0.0009) or saline (12.8 ± 4.1 min; P = 0.0003). CONCLUSION: Intravenous administration of 0.03 mg/kg of midazolam just before the end of surgery reduces emergence agitation without delaying the emergence time in children having strabismus surgery with sevoflurane anesthesia.

Effects of sevoflurane versus other general anaesthesia on emergence agitation in children.

BACKGROUND: Sevoflurane is an inhaled volatile anaesthetic that is widely used in paediatric anaesthetic practice. Since its introduction, postoperative behavioural disturbance known as emergence agitation (EA) or emergence delirium (ED) has been recognized as a problem that may occur during recovery from sevoflurane anaesthesia. For the purpose of this systematic review, EA has been used to describe this clinical entity. A child with EA may be restless, may cause self-injury or may disrupt the dressing, surgical site or indwelling devices, leading to the potential for parents to be dissatisfied with their child's anaesthetic. To prevent such outcomes, the child may require pharmacological or physical restraint. Sevoflurane may be a major contributing factor in the development of EA. Therefore, an evidence-based understanding of the risk/benefit profile regarding sevoflurane compared with other general anaesthetic agents and adjuncts would facilitate its rational and optimal use. OBJECTIVES: To compare sevoflurane with other general anaesthetic (GA) agents, with or without pharmacological or non-pharmacological adjuncts, with regard to risk of EA in children during emergence from anaesthesia. The primary outcome was risk of EA; secondary outcome was agitation score. SEARCH METHODS: We searched the following databases from the date of inception to 19 January 2013: CENTRAL, Ovid MEDLINE, Ovid EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost), Evidence-Based Medicine Reviews (EBMR) and the Web of Science, as well as the reference lists of other relevant articles and online trial registers. SELECTION CRITERIA: We included all randomized (or quasi-randomized) controlled trials investigating children < 18 years of age presenting for general anaesthesia with or without surgical intervention. We included any study in which a sevoflurane anaesthetic was compared with any other GA, and any study in which researchers investigated adjuncts (pharmacological or non-pharmacological) to sevoflurane anaesthesia compared with no adjunct or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently searched the databases, decided on inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved differences between their results by discussion. Data were entered into RevMan 5.2 for analyses and presentation. Comparisons of the risk of EA were presented as risk ratios (RRs) with 95% confidence intervals (CIs). Sevoflurane is treated as the control anaesthesia in this review. Sensitivity analyses were performed as appropriate, to exclude studies with a high risk of bias and to investigate heterogeneity. MAIN RESULTS: We included 158 studies involving 14,045 children. Interventions to prevent EA fell into two broad groups. First, alternative GA compared with sevoflurane anaesthesia (69 studies), and second, use of an adjunct with sevoflurane anaesthesia versus sevoflurane without an adjunct (100 studies). The overall risk of bias in included studies was low. The overall Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) assessment of the quality of the evidence was moderate to high. A wide range of EA scales were used, as were different levels of cutoff, to determine the presence or absence of EA. Some studies involved children receiving potentially inadequate or no analgesia intraoperatively during painful procedures.Halothane (RR 0.51, 95% CI 0.41 to 0.63, 3534 participants, high quality of evidence) and propofol anaesthesia were associated with a lower risk of EA than sevoflurane anaesthesia. Propofol was effective when used throughout anaesthesia (RR 0.35, 95% CI 0.25 to 0.51, 1098 participants, high quality of evidence) and when used only during the maintenance phase of anaesthesia after sevoflurane induction (RR 0.59, 95% CI 0.46 to 0.76, 738 participants, high quality of evidence). No clear evidence was found of an effect on risk of EA of desflurane (RR 1.46, 95% CI 0.92 to 2.31, 408 participants, moderate quality of evidence) or isoflurane (RR 0.76, 95% CI 0.46 to 1.23, 379 participants, moderate quality of evidence) versus sevoflurane.Compared with no adjunct, effective adjuncts for reducing the risk of EA during sevoflurane anaesthesia included dexmedetomidine (RR 0.37, 95% CI 0.29 to 0.47, 851 participants, high quality of evidence), clonidine (RR 0.45, 95% CI 0.31 to 0.66, 739 participants, high quality of evidence), opioids, in particular fentanyl (RR 0.37, 95% CI 0.27 to 0.50, 1247 participants, high quality of evidence) and a bolus of propofol (RR 0.58, 95% CI 0.38 to 0.89, 394 participants, moderate quality of evidence), ketamine (RR 0.30, 95% CI 0.13 to 0.69, 231 participants, moderate quality of evidence) or midazolam (RR 0.57, 95% CI 0.41 to 0.81, 116 participants, moderate quality of evidence) at the end of anaesthesia. Midazolam oral premedication (RR 0.81, 95% CI 0.59 to 1.12, 370 participants, moderate quality of evidence) and parental presence at emergence (RR 0.91, 95% CI 0.51 to 1.60, 180 participants, moderate quality of evidence) did not reduce the risk of EA.One or more factors designated as high risk of bias were noted in less than 10% of the included studies. Sensitivity analyses of these studies showed no clinically relevant changes in the risk of EA. Heterogeneity was significant with respect to these comparisons: halothane; clonidine; fentanyl; midazolam premedication; propofol 1 mg/kg bolus at end; and ketamine 0.25 mg/kg bolus at end of anaesthesia. With investigation of heterogeneity, the only clinically relevant changes to findings were seen in the context of potential pain, namely, the setting of adenoidectomy/adenotonsillectomy (propofol bolus; midazolam premedication) and the absence of a regional block (clonidine). AUTHORS' CONCLUSIONS: Propofol, halothane, alpha-2 agonists (dexmedetomidine, clonidine), opioids (e.g. fentanyl) and ketamine reduce the risk of EA compared with sevoflurane anaesthesia, whereas no clear evidence shows an effect for desflurane, isoflurane, midazolam premedication and parental presence at emergence. Therefore anaesthetists can consider several effective strategies to reduce the risk of EA in their clinical practice. Future studies should ensure adequate analgesia in the control group, for which pain may be a contributing or confounding factor in the diagnosis of EA. Regardless of the EA scale used, it would be helpful for study authors to report the risk of EA, so that this might be included in future meta-analyses. Researchers should also consider combining effective interventions as a multi-modal approach to further reduce the risk of EA.

Comparison of propofol and fentanyl administered at the end of anaesthesia for prevention of emergence agitation after sevoflurane anaesthesia in children.

BACKGROUND: Propofol and fentanyl can be administered at the end of sevoflurane anaesthesia to decrease the incidence and severity of emergence agitation (EA), although it has not been determined which agent has superior efficacy. The purpose of this study was to compare the effects of propofol and fentanyl on EA. METHODS: In this prospective, randomized, double-blind study, 222 children, 18-72 months of age, undergoing sevoflurane anaesthesia were randomly assigned to one of the three groups receiving either propofol 1 mg kg(-1) (Group P), fentanyl 1 µg kg(-1) (Group F), or saline (Group S) at the end of anaesthesia. The incidence and severity of EA were evaluated with the paediatric anaesthesia emergence delirium (PAED) scale. Time to recovery and incidence of nausea/vomiting were assessed. RESULTS: The mean PAED score was 4.3 in Group P and 4.9 in Group F (P=0.682), which were lower than 9.0 in Group S (P<0.001). Nausea and vomiting were significantly more frequent in Group F than Groups P and S (adjusted P=0.003 and adjusted P<0.001). Group F had also longer stay in the post-anaesthesia care unit (PACU) than Group S (P<0.001), while Group P did not. However, the differences in PACU stays between the P and F groups were considered clinically insignificant. CONCLUSION: Small doses of propofol or fentanyl at the end of sevoflurane anaesthesia comparably reduced EA. Propofol was better than fentanyl due to a lower incidence of nausea and vomiting.

A trial of midazolam vs diphenhydramine in prophylaxis of metoclopramide-induced akathisia.

STUDY OBJECTIVE: The study aimed to evaluate the effects of midazolam and diphenhydramine for the prevention of metoclopramide-induced akathisia. METHODS: This randomized, double-blind, and controlled trial aimed to investigate coadministered midazolam vs diphenhydramine in the prophylaxis of metoclopramide-induced akathisia. Patients 18 to 65 years of age who presented to the emergency department with primary or secondary complaints of nausea and/or moderate to severe vascular-type headache were eligible for this study. Patients were randomized to one of the fallowing 3 groups: (1) metoclopramide 10 mg + midazolam 1.5 mg; (2) metoclopramide 10 mg + diphenhydramine 20 mg; (3) metoclopramide 10 mg + placebo. Metoclopramide was administered as a 2-minute bolus infusion. Midazolam, diphenhydramine, and normal saline solution were administered as a 15-minute slow infusion. The whole procedure was observed; and akathisia and sedation scores and vital changes were recorded. RESULTS: There were significant differences among groups with respect to akathisia (P = .016) and sedation (P < .001). The midazolam group showed the lowest mean akathisia score but the highest mean sedation score. Akathisia scores of the diphenhydramine group were not different from placebo. There were significant differences among groups in terms of changes in mean vital findings such as respiration rates, pulse rates, and systolic blood pressures (P < .05). There were no significant difference among groups in terms of changes in mean diastolic blood pressures (P = .09). CONCLUSION: Coadministered midazolam reduced the incidence of akathisia induced by metoclopramide compared to placebo but increased the rate of sedation. No difference was detected from diphenhydramine. Routine coadministered 20 mg diphenhydramine did not prevent metoclopramide-induced akathisia.

Improvement of tardive dyskinesia and dystonia associated with aripiprazole following a switch to quetiapine: case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. CASE SUMMARY: We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. WHAT IS NEW AND CONCLUSION: There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear.

Slow infusion metoclopramide does not affect the improvement rate of nausea while reducing akathisia and sedation incidence.

OBJECTIVE: To compare the effects of metoclopramide infusion in emergency department (ED) patients complaining of nausea to determine the changes in its therapeutic effect and prevention of side effects such as akathisia and sedation. METHODS: A prospective, randomised, double blind trial, from 1 March 2007 to 1 May 2008 in the ED of Pamukkale University Faculty of Medicine. Patients with moderate to severe nausea were randomised and divided into two groups: group 1 received 10 mg metoclopramide as a slow intravenous infusion over 15 min plus placebo (SIG); group 2 received 10 mg metoclopramide as an intravenous bolus infusion over 2 min plus placebo (BIG). The whole procedure was observed, and nausea scores, akathisia and vital changes were recorded. RESULTS: 140 patients suffering from moderate to severe nausea in the ED were included in the study. There was no significant difference between the groups in terms of mean nausea scores during follow-up (p=0.97). A significant difference in akathisia incidence was observed between the groups (18 (26.1%) in the BIG and 5 (7%) in the SIG) (p=0.002). There was also a significant difference in sedation incidence between the groups (19 (27.5%) in the BIG and 10 (14.5%) in the SIG) (p=0.05). CONCLUSION: Even though slowing the rate of infusion of metoclopramide does not affect the rate of improvement in nausea, it may be an effective strategy for reducing the incidence of akathisia and sedation in patients with nausea.

Accidental intoxication with high dose of methoxetamine (MXE)--a case report.

UNLABELLED: Methoxetamine (MXE) is an analogue of ketamine. CASE REPORT: We present a 25-year-old male who, after getting an information from the Internet, started to use MXE to avoid the excitement connected with recreational codeine abuse. For about 8 - 10 months he injected about 100 mg of MXE intramuscularly. On the day of admission the patient decided to take much higher dose of 750 mg of MXE. For the first 3-4 hours of hospitalization the profound agitation, which demanded the usage of high doses of benzodiazepines, was observed every several minutes. After 6-7 hours of supportive treatment the patient returned to his baseline mental status. CONCLUSION: MXE presents the new healthcare threat because of easy accessibility via Internet, and lack of legal restrictions in many countries. The low dose of MXE can cause "peace and serenity", however, higher dose may act opposite.

Effects of hydroxyzine-midazolam premedication on sevoflurane-induced paediatric emergence agitation: a prospective randomised clinical trial.

BACKGROUND AND AIM: Anaesthesia with sevoflurane leads to a high prevalence of emergence agitation in paediatric patients. This study investigates the effects of combining hydroxyzine and midazolam on sevoflurane-induced emergence agitation in paediatric patients undergoing infraumbilical surgery with a caudal block. PATIENTS AND METHODS: Eighty-four children 1-7 years of age undergoing general anaesthesia with sevoflurane and caudal block were assigned to two groups. Children in group M (n = 42) were premedicated with 0.5 mg kg oral midazolam and children in group MH (n = 42) were premedicated with 0.5 mg kg oral midazolam and 1 mg kg hydroxyzine given 30 min before anaesthesia induction. A caudal epidural block was performed following anaesthesia induction. Induction quality, parental separation scores and emergence agitation were evaluated. Emergence agitation was evaluated with the PAED score (Paediatric Anesthesia Emergence Delirium) every 5 min during the first 30 min after admission to recovery room. Induction quality and parental separation were assessed with 4-point scores. Postoperative pain was evaluated with the 10-point Children's and Infants' Postoperative Pain Scale. RESULTS: Median parental separation (3 vs. 2; P = 0.01), induction quality (2 vs. 2; P = 0.03) and sedation scores (3 vs. 2; P = 0.003) were significantly better in the MH group compared to the M group. Median PAED score of group M (15) was higher than that of group MH (11; P < 0.001) and the number of children with PAED scores more than 16 was also higher in group M (n = 16) compared to group MH (n = 2; P < 0.001). None of the children had a pain score more than 3 throughout the study period. CONCLUSION: The incidence of sevoflurane-induced emergence agitation was significantly lower in children premedicated with a midazolam and hydroxyzine combination compared to those premedicated with midazolam only. Furthermore, the midazolam and hydroxyzine combination provided better premedication quality than midazolam alone.

A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department.

STUDY OBJECTIVE: Intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients presenting to the emergency department (ED). METHODS: In this randomized, double-blind, placebo-controlled trial, after providing written informed consent, patients presenting to the ED with a chief complaint of migraine received a 500-mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg diphenhydramine IV plus saline solution placebo subcutaneously or saline solution placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with 100-mm visual analog scales (visual analog scale at baseline and every 20 minutes for 80 minutes). The primary outcome was change in pain intensity from baseline to 80 minutes or time of ED discharge if subjects remained in the ED for fewer than 80 minutes after treatment. Sedation and nausea were assessed every 20 minutes with visual analog scale scales, and subjects were contacted within 72 hours to assess headache recurrence. RESULTS: Sixty-eight subjects entered the trial, with complete data for 66 subjects. Baseline pain scores were similar for the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm). Sedation, nausea, and headache recurrence rates were similar. CONCLUSION: IV prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine.

Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies.

BACKGROUND: Emergence agitation (EA) in children is increased after sevoflurane anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of this study was to provide a meta-analysis of the studies of the pharmacological prevention of EA in children. METHODS: A comprehensive literature search was conducted to identify clinical trials that focused on the prevention of EA in children anaesthetized with sevoflurane, desflurane, or both. The data from each trial were combined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95% confidence interval. I(2) statistics were used to assess statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess bias. RESULTS: Thirty-seven articles were found which included a total of 1695 patients in the intervention groups and 1477 in the control ones. Midazolam and 5HT(3) inhibitors were not found to have a protective effect against EA [OR=0.88 (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21 (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], alpha(2)-adrenoceptors [OR=0.23 (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup analysis according to the peroperative analgesia given does not affect the results. CONCLUSIONS: This meta-analysis found that propofol, ketamine, fentanyl, and preoperative analgesia had a prophylactic effect in preventing EA. The analgesic properties of these drugs do not seem to have a role in this effect.

Effects of fentanyl infusion on tracheal intubation and emergence agitation in preschool children anaesthetized with sevoflurane.

BACKGROUND: Sevoflurane can be used as a sole agent for intubation in children, but studies have suggested that it is associated with emergence agitation. Fentanyl infusions can be used both to facilitate intubation and decrease emergence agitation. We investigated the effects of fentanyl on conditions at intubation and on emergence from sevoflurane anaesthesia without confounding nitrous oxide or premedication. METHODS: IRB approval and informed consent were obtained. Subjects comprised 150 ASA physical status I or II (age, 2-6 yr). Anaesthesia was induced with sevoflurane in oxygen and maintained using a predetermined concentration of sevoflurane. Subjects were randomly allocated to receive one of three doses of fentanyl: vehicle only (control group), a bolus dose of 1 microg kg(-1) followed by a continuous infusion of 0.5 microg kg(-1) h(-1) (F1 group), or a bolus dose of 2 microg kg(-1) followed by a continuous infusion of 1 microg kg(-1) h(-1) (F2 group). Sevoflurane minimum alveolar concentration for tracheal intubation (MAC(TI)) and emergence agitation score were assessed. RESULTS: MAC(TI) values were 2.49%, 1.61%, and 1.16% in control, F1, and F2 groups, respectively (P<0.05). Agitation scores were 11.5, 7.0, and 2.6 in control, F1, and F2 groups, respectively (P<0.05). CONCLUSIONS: Fentanyl infusion consisting of a bolus dose of 2 microg kg(-1) followed by a continuous infusion of 1 microg kg(-1) h(-1) facilitates tracheal intubation and smooth emergence in children anaesthetized using sevoflurane. CLINICAL TRIAL REGISTRATION: this study was started in 2000 and was finished in 2008. We had no registration number. IRB approval was obtained.

Potential adverse effects of discontinuing psychotropic drugs. Part 3: Antipsychotic, dopaminergic, and mood-stabilizing drugs.

Abrupt discontinuation of antipsychotic drugs in patients with schizophrenia is associated with earlier, and often more severe, illness episodes than are seen with gradual discontinuation. Antipsychotic drugs can cause various abnormal motor syndromes, but abruptly stopping them has been associated with the seemingly paradoxical development of similar motor syndromes, such as withdrawal dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome. Dopamine-releasing and dopamine-agonist drugs are used to treat some of the motor syndromes caused by antipsychotic drugs, but their abrupt discontinuation can also be associated with abnormal syndromes. When antipsychotic drugs, lithium, or certain anticonvulsant drugs are used for treatment of bipolar disorder, rapid versus gradual discontinuation is more likely to lead to greater mood instability and manic relapse. If necessary, these medications should be gradually tapered to minimize all types of adverse discontinuation effects. Patients should be educated about the possible adverse effects of abrupt medication discontinuation.

[Postanesthetic agitation syndrome after inhalation anesthesia with sevofluorane in children].

The paper analyzes the publications dedicated to the problem of agitation after inhalation anesthesia with sevofluorane. A brief explanation of the conception "agitation" is given in the context of interpretation of explanatory and psychological dictionaries. According to most of the analyzed papers, it is concluded that the incidence of the postanesthetic agitation syndrome occurs after anesthesia with sevofluorane than after that with halothane. The leading risk factors of agitation are preschool age, significant psychoemotional lability in the preoperative period (difficult parting with parents), fear. The efficiency of the preventive measures given in the analyzed paper is disputable. These include opioids (fentanyl), benzodiazepines (midasolam), clonidine, ketamine, dexmedotomidine, nitrous oxide, propofol, etc. The authors conclude that this problem is of no high significance in the aspect of priority, the width and safety of sevofluorane use in the anesthetic maintenance of children although it by far needs further more detailed study.

A randomized trial of diphenhydramine as prophylaxis against metoclopramide-induced akathisia in nauseated emergency department patients.

STUDY OBJECTIVE: Akathisia, an adverse effect observed at times after administration of parenteral metoclopramide, is an unpleasant symptom complex characterized by restlessness and agitation. Some try to limit the development of akathisia by coadministering diphenhydramine when using parenteral metoclopramide. The goal of this investigation is to determine whether concomitant administration of diphenhydramine 25 mg decreased the rate of development of akathisia after administration of 10 mg or 20 mg of intravenous metoclopramide. METHODS: This was a randomized, double-blind, factorial design trial. Patients who presented to our emergency department with a primary or secondary chief complaint of nausea were randomized to one of the following 4 groups: (1) metoclopramide 10 mg+diphenhydramine 25 mg; (2) metoclopramide 10 mg+placebo; (3) metoclopramide 20 mg+diphenhydramine 25 mg; (4) metoclopramide 20 mg+placebo. The medications were inserted into a 50-mL bag of normal saline solution and administered as an intravenous drip during 15 minutes. Primary outcome was development of akathisia within 60 minutes of medication administration, as measured by blinded assessors using a short akathisia instrument, or use of rescue medication for treatment of akathisia by blinded clinical staff. Patients were also asked at baseline and 30 minutes later whether they felt restless. RESULTS: Two hundred eighty-nine patients were randomized and 286 patients were included in the final analysis. Within 1 hour of medication administration, 17 of 143 patients randomized to diphenhydramine (12%; 95% confidence interval [CI] 8% to 18%) and 17 of 143 (12%; 95% CI 8% to 18%) randomized to placebo developed akathisia (95% CI for difference of 0%: -8% to 8%). Thirteen of 143 patients randomized to metoclopramide 10 mg (9%; 95% CI 5% to 15%) and 21 of 143 randomized to metoclopramide 20 mg (15%; 95% CI 10% to 22%) developed akathisia (95% CI for difference of 6%: -2% to 14%). In those administered prophylactic diphenhydramine, odds of akathisia relative to placebo were 1.0 (95% CI 0.5 to 2.0). Odds of akathisia in those administered 20 mg of metoclopramide relative to the 10-mg dose were 1.7 (95% CI 0.8 to 3.6). Among patients who received 20 mg of metoclopramide, subjective restlessness was reported by 7 of 72 (9.7%) patients who received diphenhydramine and 14 of 71 (19.7%) patients who received placebo (95% CI for difference of 10%: -2% to 22%). CONCLUSION: Routine prophylaxis with diphenhydramine to prevent akathisia is unwarranted when intravenous metoclopramide is administered over 15 minutes. For patients administered 20 mg of metoclopramide, prophylactic diphenhydramine may decrease subjective restlessness.