The superiority of ketofol and etomidate against propofol or thiopental anesthesia for ECT.

OBJECTIVES: Most anesthetic drugs used for electroconvulsive therapy (ECT) have dose-dependent anticonvulsive effects, counter-acting seizure induction, lowering seizure quality. However, a consummate drug for ECT anesthesia has not yet been established. Therefore, in this study, we aimed to investigate the effects of etomidate, thiopental, propofol and co-administration of ketamine-propofol (ketofol) on seizure quality and hemodynamic safety. METHODS: Registries of 121 patients (1077 sessions) were retrospectively evaluated. The effects of anesthetics on ECT-related parameters (stimulation charge, central seizure duration, number of failed stimulation trials, mean arterial pressure, and peak heart rate) were analyzed via linear mixed-effects models. RESULTS: Overall, the seizure duration decreased, and the stimulation charge increased in time with continuing sessions within a course of ECT. The decrease in seizure duration and the increase in required stimulation charge was significantly lower with etomidate and ketofol. Additionally, ketofol was significantly related to a lower number of failed stimulation trials compared to propofol. Ketofol and propofol use was associated with a significantly lower postictal mean arterial pressure. CONCLUSION: Ketofol and etomidate were equivalently superior in the rate of decrease in seizure duration and the required elevation in stimulus charge, which would interpret into valuable clinical guidance, especially for "seizure resistant" patients, and their use may potentially lower ECT related cognitive side effects.

Frequently applied ketamine, medetomidine and thiopental anaesthesia induces high mortality in Wistar rats.

OBJECTIVE: Fatal reactions to the combination of ketamine-medetomidine and thiopental in Wistar rats are described in two different models of orthodontic tooth movement. MATERIALS AND METHODS: Thirty male rats were divided into two groups that required repeated anaesthesia during a 42-day study period, once a week or more frequently depending on the experimental group. The combination of ketamine [50 mg/kg body weight (b.w.)] and medetomidine (67 µg/kg b.w.) was administered intraperitoneally. Thiopental (8.3 mg/kg b.w.) was administered intraperitoneally 5 minutes later, barring any observable adverse reactions to the anaesthesia. RESULTS: Twelve animals died, though none during the first two procedures. Three animals died shortly after the administration of a ketamine-medetomidine combination, and the remainder died 10-25 minutes later. Only four of the affected animals received thiopental before their death on a particular day. As ten rats died in the more frequently anaesthetized group, repeated anaesthesia was suspected to be the cause of the increased mortality. CONCLUSIONS: Obstruction of the respiratory airways by saliva with subsequent suffocation may have been one of the causes of death, as it appeared in all the affected animals. Although the combination of ketamine and an alpha-2 adrenergic agonist is generally considered to be safe in rats, we propose that studies utilizing protocols requiring repeated anaesthesia adhere to a minimum safety period of 8.5 days between anaesthesia events. Alternative anaesthetic protocols should be employed if adherence to this is not possible due to the nature of the study.

[Establishing Evidence for Use of Appropriate Medicines in the Operating Room].

Various issues related to clinical use of medicines remain unclear, and pharmacists are expected to establish evidence for appropriate use of medicines. The present review summarizes our findings from three areas of research regarding the use of medicines in the operating room: 1) We evaluated the extent of extravasation injury due to thiopental (2.5 mg/100 µL) and propofol (1.0 mg/100 µL) at the macroscopic and histopathologic levels in a rat model. Thiopental, which causes tissue necrosis, can be classified as a "vesicant", and propofol can be classified as an "irritant". Moreover, warming strongly exacerbated the degeneration or necrosis induced by extravasation of thiopental. 2) The cytotoxicity of povidone-iodine solution (PVP-I) for ophthalmic use and that of polyvinyl alcohol-iodine solution (PAI) was compared using a human corneal epithelial cell line. Despite exhibiting equivalent antiseptic effects, the cytotoxicity of PVP-I diluted 16-fold was greater than that of PAI diluted 6-fold. After inactivation of iodine, the cytotoxicity of PVP-I persisted; therefore, to avoid corneal damage, antisepsis should be achieved with PAI. 3) The stability of 1 µg/mL adrenaline when used as an intraocular irrigating solution to maintain pupil dilation was evaluated. After mixing for 6 h, the adrenaline concentration was 65.2% (pH 8.0) of the initial concentration. Moreover, the low concentration of sodium bisulfite in the irrigating solution could have caused adrenaline reduction. Our results strongly suggest that intraocular irrigation solution containing adrenaline should be prepared just prior to use in surgery.

Safety of Triple Neuroprotection with Targeted Hypothermia, Controlled Induced Hypertension, and Barbiturate Infusion during Emergency Carotid Endarterectomy for Acute Stroke after Missing the 24 Hours Window Opportunity.

BACKGROUND: The aim of this study is to establish the initial safety of triple neuroprotection (TNP) in an acute stroke setting in patients presenting outside the window for systemic tissue plasminogen activator (tPA). METHODS: Over 12,000 patients were referred to our vascular services with carotid artery disease, of whom 832 had carotid intervention with a stroke rate of 0.72%. Of these, 25 patients presented (3%), between March 2015 and 2019, with acute dense stroke. These patients had either failed tPA or passed the recommended timing for acute stroke intervention. Fifteen (60%) had hemi-neglect with evidence of acute infarct on magnetic resonance imaging of the brain and a Rankin score of 4 or 5. Ninety-six percent had an 80-99% stenosis on the symptomatic side. Mean ABCD3-I score was 11.35. All patients underwent emergency carotid endarterectomy (CEA) with therapeutically induced hypothermia (32-34°C), targeted hypertension (systolic blood pressure 180-200 mm Hg), and brain suppression with barbiturate. RESULTS: There were no cases of myocardial infarction, death, cranial nerve injury, wound hematoma, or procedural bleeding. Mean hospital stay was 8.4 (±9.5) days. All cases had resolution of neurological symptoms, except 3 who had failed previous thrombolysis. Eighty percent had a postoperative Rankin score of 0 on discharge and 88% of patients were discharged home with 3 requiring rehabilitation. CONCLUSIONS: Positive neurological outcomes and no serious adverse events were observed using TNP during emergency CEA in patients with acute brain injury. We recommend TNP for patients who are at an increased risk of stroke perioperatively, or who have already suffered from an acute stroke beyond the recommended window of 24 hr. Certainly, the positive outcomes are not likely reproducible outside of high-volume units and patients requiring this surgery should be transferred to experienced surgeons in appropriate tertiary referral centers.

Thiopental Does Not Produce Hyperalgesia: A Laboratory Study Using Two Human Experimental Pain Models.

OBJECTIVE: Past investigations assessing the effects of thiopental on pain are conflicting. Although several studies demonstrate hyperalgesia as a result of barbiturate administration, others show analgesia. Our objective was to assess the effects of an infusion of the GABAA agonist thiopental, compared with placebo, in healthy participants on two subjective experimental pain paradigms: noxious electrical stimulation and intradermal capsaicin. METHODS: For electrical stimulation, the milliamps required to achieve pain threshold and tolerance were recorded, and the percent change from baseline was determined for each infusion condition. In the intradermal capsaicin condition, the area of hyperalgesia was determined by von Frey technique pre- and postinfusion, and the percent change in the area of hyperalgesia was calculated. RESULTS: Though thiopental infusion resulted in an increase in the electrical stimulation current required to elicit pain threshold or reach pain tolerance when compared with baseline, this finding was not statistically significant. In the intradermal capsaicin condition, there was a statistically significant difference in overall pre- and postinfusion pain interpretation, as measured by the McGill Pain Questionnaire (P < 0.05), but there was no significant difference in area of hyperalgesia. CONCLUSIONS: In this human study of thiopental's effects on two experimental pain models, our results show that thiopental does not induce hyperalgesia.

[An Autopsy Case of Death After Deep Sedation of Thiopental].

The victim was a morbidly obese and bull-necked woman in her twenties. She had the disorders, due to Down's syndrome, including severe mental retardation, advanced hearing loss, congenital cataract surgery, and amblyopia at postoperative glaucoma. She was deeply sedated for rest with an intravenous drip infusion of 350 mg of thiopental (TP) for 5 minutes during an intraocular pressure examination with secondary glaucoma at a hospital. The examination was finished within 10 minutes after the TP injection, but her respiratory condition deteriorated rapidly when the doctor left the patient. Although immediate artificial respiration was carried out, she was declared dead about 20 hours after the examination. Medical malpractice was suspected for her death. At autopsy, no fatal disease or injury was observed in the victim. The serum TP level was 0.80 µg /ml. TP is an ultra-short-acting intravenous anesthetic, and usually only the smallest amount should be administered by frequent additions after pre-anesthesia administration while maintaining contact with patients. Although contact with patients with a disability can be difficult, it was diagnosed that the death was caused by both respiratory arrest due to a single dose of TP and delay in resuscitation due to the absence of a doctor.

Thiopental versus propofol on the outcome of the newborn after caesarean section: An impact study.

BACKGROUND: In 2011, the company that produced thiopental in France and in the United States stopped its marketing. Because of limited evidences, the choice of the best induction agent for caesarean section remains controversial, especially in emergency. The objective of this study was to compare the effects of propofol versus thiopental on the Apgar score of the newborn. METHODS: Newborns delivered by elective or emergency caesarean section under general anaesthesia in a university hospital were included from January 2009 to December 2013. Two periods, according to the hypnotic drug used, were compared in this before-and-after comparative study: thiopental before May 2011 and propofol after. The primary outcome was to compare the proportion of newborns with a 5-minute Apgar Score < 7 between both groups. RESULTS: 367 newborns were enrolled, 178 in thiopental group and 189 in propofol group. Demographic and clinical characteristics were similar in both groups. The occurrence of a 5-minute Apgar Score less than 7 was not influenced by the use of propofol (OR 1.40 [CI 95% 0.90-2.20] P = 0.135). Blood gas analyses and admission's rate in neonatal intensive care unit were similar in both groups. CONCLUSIONS: Thiopental and propofol do not appear to present significant difference in term of outcome of the newborn after caesarean section. In this situation, propofol may probably be a reliable alternative to the supply reduction of thiopental imposed by forces. Prospective studies are required to confirm the safety of propofol, particularly in the long term.

New evidence for refinement of anesthetic choice in procedures preceding the forced swimming test and the elevated plus-maze.

Previous studies indicated that some general anesthetics induce long-term antidepressant and/or anxiolytic-like effects. This raises the concern about the use of anesthesia in surgeries that precede psychopharmacological tests, since it may be a potential bias on results depending on the experimental design used. Thus, we evaluated whether general anesthetics used in surgeries preceding psychopharmacological tests would affect rats behavior in tests predictive of antidepressant or anxiolytic-like effects. We tested if a single exposure to sub-anesthetic or anesthetic doses of tribromoethanol, chloral hydrate, thiopental or isoflurane would change rats behavior in the forced swimming test (FST) or in the elevated plus-maze (EPM) test, at 2 h or 7 days after their administration. We also evaluated whether prior anesthesia would interfere in the detection of the antidepressant-like effect of imipramine or the anxiolytic-like effect of diazepam. Previous anesthesia with the aforementioned anesthetics did not change rats behaviors in FST per se nor it changed the antidepressant-like effect induced by imipramine treatment. Rats previously anesthetized with tribromoethanol or chloral hydrate exhibited, respectively, anxiogenic-like and anxiolytic-like behaviors in the EPM. Prior anesthesia with thiopental or isoflurane did not produce any per se effect in rats behaviors in the EPM nor disturbed the anxiolytic-like effect of diazepam. Our results suggest that, in our experimental conditions, tribromoethanol and chloral hydrate are improper anesthetics for surgeries that precede behavioral analysis in the EPM. Isoflurane or thiopental may be suitable for anesthesia before evaluation in the EPM or in the FST.

Evaluation of Propofol in Comparison with Other General Anesthetics for Surgery in Children Younger than 3 Years: a Systematic Review and Meta-Analysis.

BACKGROUND: Despite well-known advantages, propofol remains off-label in many countries for general anesthesia in children under 3 years of age due to insufficient evidence regarding its use in this population. This study aimed to evaluate the efficacy and safety of propofol compared with other general anesthetics in children under 3 years of age undergoing surgery through a systematic review and meta-analysis of existing randomized clinical trials. METHODS: A comprehensive literature search was conducted of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to find all randomized clinical trials comparing propofol with another general anesthetic that included children under 3 years of age. The relative risk or arcsine-transformed risk difference for dichotomous outcomes and the weighted or standardized mean difference for continuous outcomes were estimated using a random-effects model. RESULTS: A total of 249 young children from 6 publications were included. The children who received propofol had statistically significantly lower systolic and diastolic blood pressures, but hypotension was not observed in the propofol groups. The heart rate, stroke volume index, and cardiac index were not significantly different between the propofol and control groups. The propofol groups showed slightly shorter recovery times and a lower incidence of emergence agitation than the control groups, while no difference was observed for the incidence of hypotension, desaturation, and apnea. CONCLUSION: This systematic review and meta-analysis indicates that propofol use for general anesthesia in young healthy children undergoing surgery does not increase complications and that propofol could be at least comparable to other anesthetic agents.

Anesthesia may alter mRNA expression of certain wound healing-associated genes in dermal wound environment of the rats.

Some anesthetics including ketamine/xylazine and thiopental have been shown to alter the expression of genes related with inflammatory cytokines and chemokines in previous studies unassociated with wound healing, arising the question of whether commonly used anesthetics in wound healing models could interfere with the transcriptional responses of the genes associated with skin wound healing. The gene expression profile in wound biopsies of rats who received widely used anesthetics doses of intraperitoneal ketamine/xylazine (50 mg/kg and 10 mg/kg) or thiopental (50 mg/kg) in comparison with control rats was analyzed by monitoring the expression of genes effective on various phases of wound healing. The expression levels of 84 genes were determined on 3rd, 7th and 14th days of post-wounding using a qPCR array system. Of the genes either up or downregulated fivefolds or more, three (Egf, Col5a1 and Cxcl3) and two (Tgfa and Il2) genes were found to be the most responsive ones to ketamine/xylazine or thiopental anesthesia respectively in a period of 14 days after correction for multiple testing. However, up to 22 and 24 genes for ketamine/xylazine and thiopental were found to be differentially expressed in the same period without correction for multiple-comparisons testing (p < 0.05). In conclusion, our data suggest that ketamine/xylazine and thiopental may alter the transcriptional responses of some genes associated with wound healing in rats. We strongly suggest to consider the possible alteration effect of these anesthetics on gene expression in animal models of dermal wound healing.

Hypnotic agents for induction of general anesthesia in cesarean section patients: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: An ideal induction drug for cesarean section (CS) must have quick action, with minimum side effects such as awareness, hemodynamic compromise, and neonatal depression. Thiopentone is frequently used; however, no reliable evidence is available to support its use as a dedicated hypnotic agent in this setting. DESIGN: A systematic review and meta-analysis, using PRISMA methodology, of randomized controlled trials (RCTs), comparing women undergoing CS using thiopentone with those undergoing CS with propofol, ketamine, or benzodiazepines as hypnotic agents. DATA SOURCES: Comprehensive search without language restrictions of MEDLINE, EMBASE, and the Cochrane Controlled Trials Registers until May 2015, with an update in January 2017. Included trials must have reported at least one of the following variables: neonatal arterial or venous umbilical blood gas, maternal systolic blood pressure pre- and post-intubation, or Apgar score. MAIN RESULTS: A total of 911 patients from 18 RCTs were eligible for quantitative analysis. The increase in maternal systolic blood pressure was smaller in patients administered propofol, compared with those administered thiopentone (weighted mean difference [WMD]: -11.52 [-17.60, -5.45]; p = 0.0002). Induction with propofol also resulted in a significantly lower umbilical arterial pO2 (WMD: -0.12 [-0.20, -0.04]; p = 0.004) than induction with thiopentone. A comparison between propofol and thiopentone revealed no significant differences in other umbilical blood gas parameters or in Apgar scores. In contrast, when comparing ketamine with thiopentone, the number of neonates with a lower Apgar score (<7) at 1 and 5 min was significantly higher in the ketamine group than in the thiopentone group (p = 0.004). CONCLUSION: The evidence, based on sparse and relatively old trials, indicates that propofol and thiopentone are equally suited for CS. After 1 and 5 min, ketamine yields lower Apgar scores than thiopentone. Additional well-designed trials are needed to reach firmer conclusions.

Thiopental versus ketofol in paediatric sedation for magnetic resonance imaging: A randomized trial.

OBJECTIVE: To compare the efficiency of intravenous thiopental against intravenous ketamine-propofol combination in paediatric sedation for magnetic resonance imaging. METHODS: This prospective study was conducted at Ondokuz Mayis University Hospital, Samsun, Turkey, from July 1, 2014, to January 1, 2015, and comprised children aged 1 month to 12 years undergoing elective magnetic resonance imaging who were randomly assigned to two equal groups. Group I received thiopental 3 mg/kg intravenously followed by an additional dose of thiopental 1 mg/kg to achieve a Ramsay sedation score of 4. Group II received ketofol, a 1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL, in a single syringe intravenously at a dose of 0.5 mg/kg at 1 minute intervals and titrated to reach a Ramsay sedation score of 4. The groups were compared for total drug dose, time to sedation, recovery time, total sedation time, and adverse effects. Data was analysed using SPSS 22. RESULTS: There were 120 children in the study; 60(50%) in each group. The time to sedation was significantly longer with ketofol than thiopental (p<0.01). The mean recovery time was significantly shorter with thiopental than with ketofol (p<0.01). Total sedation time was significantly longer with ketofol than thiopental (p<0.01). Overall, 17(28.3%) ketofol patients had adverse events, whereas no thiopental patients had adverse events (p<0.0001). CONCLUSIONS: Thiopental had a comparable effectiveness with shorter anaesthesia inductions and recovery times than ketofol. Intravenous thiopental can be an effective and safe alternative drug in sedating children undergoing magnetic resonance imaging.

A review of anaesthetic outcomes in patients with genetically confirmed mitochondrial disorders.

Mitochondrial disorders are a clinically and biochemically diverse group of disorders which may involve multiple organ systems. General anaesthesia (GA) poses a potential risk of decompensation in children with mitochondrial disorders, and there is little guidance for anaesthetists and other clinicians regarding the optimal anaesthetic agents and perioperative management to provide to patients with mitochondrial disease[15]. The aim of this review was to document adverse events and perioperative complications from GA in patients with genetically confirmed mitochondrial disorders. A retrospective chart review of patients with genetically confirmed mitochondrial disorders who had undergone GA was undertaken. The indication for GA, anaesthetic agents utilised, length of admission and post anaesthetic complications were documented and analysed. Twenty-six patients with genetically proven mitochondrial disease underwent 65 GAs. Thirty-four (52%), received propofol as their induction agent. Thirty-three (51%) patients received sevoflurane for the maintenance of anaesthesia, while 8 (12%) received isoflurane and 24 (37%) received propofol. The duration of most GAs was short with 57 (87%) lasting less than 1 h. Perioperative complications occurred in five patients while under GA including ST segment depression, hypotension and metabolic acidosis in one. All five patients were stabilised successfully and none required ICU admission as a consequence of their perioperative complications. The duration of hospital stay post GA was <24 h in 25 (38%) patients. CONCLUSION: No relationship between choice of anaesthetic agent and subsequent perioperative complication was observed. It is likely that individual optimisation on a case-by-case basis is more important overall than choice of any one particular technique. What is Known: • General anaesthesia (GA) poses a potential risk of decompensation in children with mitochondrial disorders. • There is a great diversity in the anaesthetic approaches undertaken in this cohort, and little guidance exists for anaesthetists and other clinicians regarding the optimal anaesthetic agents and perioperative management to provide to patients with mitochondrial disease. What is New: • In this study of 26 patients with genetically confirmed mitochondrial disease who underwent 65 GAs, no relationship between choice of anaesthetic agent and subsequent perioperative complication was observed • It is likely that individual optimisation on a case-by-case basis is more important overall than choice of any one particular technique.

Refractory and severe status epilepticus in a patient with ring chromosome 20 syndrome.

Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder that is characterized by the development of refractory epilepsy during childhood with gradual declines in cognitive performance and behavior. Although the prognoses of seizures and intellectual disability associated with this condition are poor, life-threatening complications have rarely been described. We herein presented a case of a 17-year-old female with [r(20)] syndrome who developed recurrent status epilepticus (SE) at 14years of age that evolved into unremitting SE in spite of vigorous antiepileptic treatments. She was administered thiopental anesthesia for 1year, and was subsequently left in severe neurological sequelae. It is important to note that patients with this syndrome not only have severe epileptic encephalopathy persisting into adulthood, but are also at risk of fatal SE.

Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety.

Current management guidelines for refractory status epilepticus (RSE) recommend the use of intravenous continuous anesthetic therapy, but there is little evidence to guide the selection of the most efficacious and safest drug. We conducted a retrospective study to evaluate the efficacy and safety of midazolam versus thiopental for treatment of RSE. Retrospective case-control series of prospectively identified patients treated with midazolam or thiopental for RSE between January 2007 and December 2014. The primary outcome was control of RSE. Secondary outcomes included the rate of adverse events, intensive care unit (ICU) and hospital length of stay, hospital mortality and long-term neurological outcome, assessed with the extended Glasgow outcome scale (GOS-E) at discharge and at six 6 months. A total of 33 patients were included, 19 treated with midazolam and 14 with thiopental. Groups were similar for demographic data, clinical variables, comorbidity and the underlying cause of RSE. The rate of control of SE did not differ between groups (63 vs. 64 %). Adverse events including hypotension (mean arterial pressure <70 mmHg) requiring vasopressors, infections, anemia requiring red blood cells transfusion, leucopenia (<4000/mm(3)), and hyponatremia (<130 mEq/l) were more frequent during thiopental infusion. Furthermore, patients treated with midazolam had a shorter median ICU length of stay (6 vs. 15 days; p = 0.02) and better GOS-E at 6 months (8 [8] vs. 4 [4, 5]; p = 0.01). These findings suggest that continuous midazolam administration is as efficacious as thiopental infusion for the treatment of RSE; however, midazolam was associated with a significantly lower number of adverse events. These findings should be confirmed in larger multicenter trials.