Period Of Anesthesia Research Articles

Mass spectrometry monitoring of sevoflurane in the breathing circuit of an inhalation anesthesia machine

The results of controlling the amount of inhalation anesthetics sevoflurane in the patient breathing circuit of an inhalation anesthesia machine (IAM) by mass spectrometry are presented. A vacuum system with a differential chamber providing pressure difference in the range 1 × 105–1.5 ×10−4 Pa was used to inject the studied gas sample from the delivery circuit into the mass spectrometer. The concentrations of the anesthetic obtained using mass and IR spectrometry are compared. The potency of mass spectrometry for monitoring the anesthetic gas in the real time mode is demonstrated. The time dependences of the concentration of the anesthetic gas corresponding to different periods of anesthesia are given.

Cardiopulmonary effects of a new inspiratory impedance threshold device in acute hemorrhagic shock in dogs

To compare cardiovascular and respiratory effects of an inspiratory impedance threshold device (ITD) in dogs before and after induction of acute hemorrhagic shock. Prospective experimental randomized study. Eight healthy adult dogs. Dogs were anesthetized and maintained on spontaneous ventilation. Tidal volume (V(T)), systolic, mean and diastolic arterial blood pressure (SAP, MAP, DAP), central venous pressure (CVP), gastric P(CO2) (GBF) as an indicator of gastric perfusion, cardiac index (CI), systemic vascular resistance (SVR), oxygen delivery (DO(2)), and plasma lactate were monitored. To monitor respiratory compliance (RC) and respiratory resistance (ResR), animals were briefly placed on mechanical ventilation. Dogs were studied under 4 different conditions: (1) baseline (euvolemic state) (MAP > 60 mm Hg) with and without the ITD and (2) acute hemorrhagic shock (hypovolemic state) (target MAP of 40 mm Hg) with and without ITD. These 4 conditions were performed during one anesthetic period, allowing time for stabilization of parameters for each condition. Data were analyzed by ANOVA for repeated measure mixed models. No cardiovascular changes were detected between groups with and without use of ITD during euvolemic states. During acute hemorrhagic hypovolemic state, CI and DO(2) were higher with the ITD (2.9 ± 0.6 L/min/m(2)) and (326.5 ± 86.8 mL/min) compared with no ITD (1.8 ± 0.6 L/min/m(2)) and (191.3 ± 58.1 mL/min), respectively. The use of ITD during hypovolemia also increased SAP and MAP. There was an increase in ResR and decreased RC with the ITD in both euvolemic and hypovolemic states. The use of an ITD in dogs during acute hemorrhagic hypovolemic shock improved cardiovascular parameters but had negative effects on RC and ResR.

Deleterious Impact of a γ-Aminobutyric Acid Type A Receptor Preferring General Anesthetic When Used in the Presence of Persistent Inflammation

Experimental data suggest general anesthetics preferring γ-aminobutyric acid receptor type A may increase postoperative pain in patients with persistent inflammation. The current study was designed to begin to test this hypothesis. Groups of rats were defined by the presence of inflammation, surgical intervention, and/or the type of general anesthetic used for a 3-h period of anesthesia. Persistent inflammation was induced with complete Freund adjuvant. The surgical intervention was a plantar incision. Three mechanistically distinct general anesthetics were used: pentobarbital, ketamine/xylazine, and isoflurane. Ongoing pain and hypersensitivity were assessed with guarding behavior analysis and the von Frey test, respectively. There was no influence of general anesthetic type on the magnitude or time course of recovery from postoperative hypersensitivity in the absence of persistent inflammation. However, in the presence of persistent inflammation, recovery from hypersensitivity was significantly slower in the pentobarbital group than in the ketamine/xylazine or isoflurane groups. The pentobarbital effect was significant within 3 days of surgery and persisted through the remainder of the testing period. A comparable delay in recovery was observed in pentobarbital-anesthetized inflamed rats not subjected to hind paw incision. The time to 50% recovery in the pentobarbital-treated inflamed groups was almost double that in the other groups. No differences were observed between ketamine/xylazine and isoflurane. Pentobarbital exposure did not increase guarding scores. These results suggest that general anesthetics preferring γ-aminobutyric acid receptor type A may have deleterious consequences when used in the presence of persistent inflammation.

Alfaxalone anaesthesia in the green iguana (Iguana iguana)

ObjectiveTo characterise the anaesthetic effects of alfaxalone administered intramuscularly (IM) at 10, 20, and 30 mg kg−1. Study designProspective, randomized cross-over study. AnimalsTen juvenile green iguanas (Iguana iguana) of mean body weight (±SD) 480 ± 134 g. MethodsAlfaxalone was administered IM in the triceps of both thoracic limbs. Times for anaesthetic induction, plateau and recovery periods were recorded. Skeletal muscle tone of the jaw, neck, thoracic limbs, pelvic limbs, and tail was scored. The palpebral, corneal and righting reflexes, and the response to painful stimuli were also assessed. Pulse rate and respiratory rate were recorded. Comparisons between different dosages and over time were made using anova. ResultsTimes are given for 10, 20 and 30 mg kg−1 dosages respectively: mean time to maximal effect was 7.7 ± 2.2, 5.4 ± 1.7 and 3.9 ± 1.2 minutes; duration of the plateau phase was 11.3 ± 3.8, 22.1 ± 6.5 and 39.1 ± 11.5 minutes; recovery time was 10 ± 2.4, 17.5 ± 8.6 and 25 ± 7.1 minutes; and total anaesthetic duration was 29 ± 35.7, 45 ± 8.2 and 68 ± 9.8 minutes. Endotracheal intubation was possible in 40% of the subjects given 10 mg kg−1 and in 100% subjects given both 20 and 30 mg kg−1. Loss of response to a painful stimulus was seen in 0/10, 8/10 and 9/10 animals at 10, 20, and 30 mg kg−1 respectively. There was an initial dose-dependent depression of respiration followed by a significant increase in frequency over time. In contrast, pulse rates decreased by 20% over the duration of the anaesthetic events. Conclusions and clinical relevanceIntramuscular administration of alfaxalone is a simple, rapid and reliable means of achieving relatively brief sedation or anaesthesia in healthy green iguanas. A dosage of 10 mg kg−1 provides light sedation, appropriate for examination and venipuncture; 20 mg kg−1 provides a level suitable for minor procedures or for endotracheal intubation and supplementation with inhalational anaesthesia; 30 mg kg−1 produces an anaesthetic plane suitable for surgical procedures of limited duration (up to 40 minutes).

Comparative Study of 4% Articaine with 1:100,000 Adrenaline and 2% Lidocaine with 1:100,000 Adrenaline for Anesthetizing the Lingual, Oral and Labial Mucosas of the Mandible

Objetivo: Comparar a efetividade da Articaina e da Lidocaina em tecnica de anestesia infiltrativa supraperiostea em vestibulo bucal da mandibula em relacao a capacidade de insensibilizacao das mucosas lingual, jugal e labial. Metodo: O estudo foi classificado como duplo cego, cruzado e randomizado, onde foram selecionados 30 pacientes adultos, separados aleatoriamente por um primeiro examinador que marcou na ficha o numero 1 ou 2 correspondendo as solucoes anestesicas. O segundo examinador anestesiou de acordo com o numero e a seguir o terceiro examinador realizou os testes de sensibilidade atraves do teste pin-prick e a escala analogica visual de dor (EVA) nas mucosas lingual, jugal e labial. Apos anestesiado, a duracao da anestesia foi observada pelos mesmos testes no intervalo de 10 em 10 minutos. Na semana seguinte foram realizados os mesmos procedimentos com o outro anestesico de acordo com o grupo ao qual o paciente pertenceu. Os dados foram submetidos ao teste T-student (p<0,05). Resultados: Houve diferenca estatistica significante a favor da articaina em relacao a insensibilizacao das mucosas lingual e labial, assim como na duracao total de anestesia nas mucosas. Em relacao a mucosa jugal, nao houve diferenca estatistica significante entre as drogas Conclusao: A articaina apresentou melhores propriedades que a lidocaina, como melhor difusibilidade, menor tempo de latencia e maior duracao de anestesia. O estudo mostrou que pela infiltracao por bucal na mandibula, a articaina apresenta difusibilidade capaz de insensibilizar as mucosas lingual, jugal e labial, o que mostra ser possivel a realizacao de procedimentos localizados em pequenas regioes da mandibula pela tecnica infiltrativa.

Investigation of the Safety of Irreversible Electroporation in Humans

Purpose A single-center prospective nonrandomized cohort study was performed to investigate the safety of irreversible electroporation (IRE) for tumor ablation in humans. Materials and Methods Thirty-eight volunteers with advanced malignancy of the liver, kidney, or lung (69 separate tumors) unresponsive to alternative treatment were subjected to IRE under general anesthesia. Clinical examination, biochemistry, and computed tomography (CT) scans of the treated organ were performed before, immediately after, and at 1 month and 3 months after the procedure. Results No mortalities occurred at 30 days. Transient ventricular arrhythmia occurred in four patients, and electrocardiographically (ECG) synchronized delivery was used subsequently in the remaining 30 patients, with two further arrhythmias (supraventricular tachycardia and atrial fibrillation). One patient developed obstruction of the upper ureter after IRE. One adrenal gland was unintentionally directly electroporated, which produced transient severe hypertension. There was no other evidence of adjacent organ damage related to the electroporation. Other adverse events were not directly related to IRE, but two patients developed temporary neurapraxia as a result of arm extension during a prolonged period of anesthesia. Although not a primary aim of this preliminary study, complete target tumor ablation verified by CT was achieved in 46 of the 69 tumors treated with IRE (66%). Most treatment failures occurred in renal and lung tumors. Biopsy in three patients showed coagulative necrosis in the regions treated by IRE. Conclusions IRE appears to be safe for human clinical use provided ECG-synchronized delivery is used. Comparative evaluation with alternative ablative technologies is warranted.

Cardiac Arrhythmias Induced by Chloral Hydrate in Rhesus Monkeys

Chloral hydrate has been long used as a safe sedative and hypnotic drug in humans. However, reports on its cardiovascular adverse effects have been published from time to time. The present study was undertaken to use Rhesus monkeys as a model to define the dose regiment of chloral hydrate at which cardiac arrhythmias can be induced and the consequences of the cardiac events. Male Rhesus monkeys of 2-3years old were intravenously infused with chloral hydrate starting at 50mg/kg with an increasing increment of 25mg/kg until the occurrence of cardiac arrhythmias. In addition, a traditional up-and-down dosing procedure was applied to define a single dose level at which cardiac arrhythmias can be induced. The data obtained showed that when the sequentially escaladed dose reached 125mg/kg, cardiac arrhythmias occurred in all monkeys tested. The single effective dose to cause cardiac arrhythmias calculated from the crossover analysis was 143±4mg/kg. This value would be equivalent to 68.6±1.9mg/kg for children and 46.4±1.3mg/kg for adults in humans. Under either multiple or single dose condition, cardiac arrhythmias did not occur before 40min after the onset of anesthesia induced by chloral hydrate. Cardiac arrhythmias were recovered without help at the end of the anesthesia in most cases, but also continued after the regain of consciousness in some cases. The cardiac arrhythmias were accompanied with compromised cardiac function including suppressed fractional shortening and ejection fraction. This study thus suggests that cautions need to be taken when chloral hydrate is used above certain levels and beyond a certain period of anesthesia, and cardiac arrhythmias induced by chloral hydrate need to be closely monitored because compromised cardiac function may occur simultaneously. In addition, patients with cardiac arrhythmias induced by chloral hydrate should be monitored even after they are recovered from the anesthesia.

Comparison of pre- vs. post-incisional caudal bupivacaine for postoperative analgesia in unilateral pediatric herniorrhaphy: A double-blind randomized clinical trial

Introduction:This study was designed to evaluate the pre- vs. post-incisional analgesic efficacy of bupivacaine administered caudally in children undergoing unilateral hernia repair.Methods:Fifty children aged 6 months to 6 years were included in the study. Children were divided blindly between the two groups to receive pre- vs. post-incisional caudal bupivacaine. The preincisional group received 1 ml/kg of 0.125% bupivacaine caudally after induction of anesthesia and the postincisional group received the same dose caudally at the end of surgery. Heart rate, SaO2, end tidal CO2, and noninvasive arterial blood pressure were recorded every 10 min. The duration of surgery, extubation time, and duration of recovery period were also recorded. The pain scores were measured with using an Oucher chart in the recovery room, 2, 4, 6, 12, and 24 h after surgery. Time to first analgesia, numbers of supplementary analgesics required by each child in a 24-h period and total analgesic consumptions were recorded. Any local and systemic complications were recorded. Quantitative data were compared using a two-tailed t-test. Sex distribution and frequency of acetaminophen consumption were measured using χ2 test. P < 0.05 was considered statistically significant.Results:The Oucher pain scale at 4, 6, 12, and 24 h after surgery, the total analgesic consumption and the numbers of demand for supplemental acetaminophen were lower statistically in preincisional group (P < 0.05). Extubation time and duration were higher in preincisional group (P < 0.05). Mean changes of heart rates were statistically lower during the anesthesia period and recovery time in preincisional group (P < 0.05).Conclusion:Preincisional caudal analgesia with a single injection of 0.125% bupivacaine is more effective than the postincisional one for postoperative pain relief and analgesic consumption in unilateral pediatric herniorrhaphy.

Effects of propofol on isoflurane minimum alveolar concentration and cardiovascular function in mechanically ventilated goats

ObjectiveTo evaluate the effects of propofol, on isoflurane minimum alveolar concentration (MAC) and cardiovascular function in mechanically ventilated goats. Study designProspective, randomized, crossover experimental study. AnimalsSix goats, three does and three wethers. MethodsGeneral anaesthesia was induced with isoflurane in oxygen. Following endotracheal intubation, anaesthesia was maintained with isoflurane in oxygen. Intermittent positive pressure ventilation was applied. Baseline isoflurane MAC was determined, the noxious stimulus used being clamping a claw. The goats then received, on separate occasions, three propofol treatments intravenously: bolus of 0.5 mg kg−1 followed by a constant rate infusion (CRI) of 0.05 mg kg−1 minute−1 (treatment LPROP); bolus of 1.0 mg kg−1 followed by a CRI of 0.1 mg kg−1 minute−1 (treatment MPROP), bolus of 2.0 mg kg−1 followed by a CRI of 0.2 mg kg−1 minute−1 (treatment HPROP). Isoflurane MAC was re-determined following propofol treatments. Plasma propofol concentrations at the time of MAC confirmation were measured. Cardiopulmonary parameters were monitored throughout the anaesthetic period. Quality of recovery was scored. The Friedman test was used to test for differences between isoflurane MACs. Medians of repeatedly measured cardiovascular parameters were tested for differences between and within treatments using repeated anova by ranks (p < 0.05 for statistical significance). ResultsIsoflurane MAC [median (interquartile range)] was 1.37 (1.36–1.37) vol%. Propofol CRI significantly reduced the isoflurane MAC, to 1.15 (1.08–1.15), 0.90 (0.87–0.93) and 0.55 (0.49–0.58) vol% following LPROP, MPROP and HPROP treatment, respectively. Increasing plasma propofol concentrations strongly correlated (Spearman rank correlation) with decrease in MAC (Rho = 0.91). Cardiovascular function was not affected significantly by propofol treatment. Quality of recovery was satisfactory. Conclusions and clinical relevanceIn goats, propofol reduces isoflurane MAC in a dose-dependent manner with minimal cardiovascular effects.

Preoperative preparation of patients with infectious and restrictive respiratory diseases as comorbidities

In patients with respiratory pathology changes in respiratory physiology may lead to clinical problems during the conduct of anesthesia and the perioperative period. An understanding of the disease processes that can affect the lungs and pleura allows the anesthesiologist to account for the potential complications of these conditions and manage the anesthetic accordingly. This article describes the initial evaluation of a patient with respiratory problems. A thorough medical history, physical examination and some functional tests are the keys in decision-making in preparation for anesthesia and surgery. The burden of respiratory disease is reviewed, and some important areas of current interest are highlighted.

Post-operative nausea and vomiting after gynecologic laparoscopic surgery: comparison between propofol and sevoflurane

BackgroundWe compared the incidence and degree of post-operative nausea and vomiting (PONV) in patients who received general anesthesia with propofol or sevoflurane using the Rhodes index of nausea, vomiting, and retching (RINVR) to assess the degree of PONV quantitatively and objectively during the post-anesthetic period.MethodsWe performed a prospective study involving 38 patients who underwent gynecologic laparoscopic surgery in our hospital between September 2008 and August 2009. Nineteen patients were anesthetized with propofol during the entire anesthetic period and the other 19 patients received 2.0 mg/kg of propofol intravenously, followed by sevoflurane inhalation. Three patients who were anesthetized with sevoflurane were excluded from the analysis because they were omitted during the survey. We studied the patients who had PONV and RINVR scores 1, 6, and 24 hours post-operatively.ResultsThe propofol group had a statistically lower incidence of PONV and lower RINVR scores in the following subclasses within 1 hour of surgery: symptom occurrence; symptom distress; and symptom experience.ConclusionsPropofol at induction and during maintenance of anesthesia can be used to prevent PONV within 1 hour post-operatively in patients undergoing gynecologic laparoscopic surgery.

A comparison of acepromazine-buprenorphine and medetomidine-buprenorphine for preanesthetic medication of dogs

To assess sedative and cardiopulmonary effects of premedication with a medetomidine-buprenorphine or acepromazine-buprenorphine combination in dogs anesthetized with propofol and isoflurane. Randomized controlled clinical trial. 90 dogs undergoing routine surgical and diagnostic procedures. Dogs were randomly assigned to 1 of 3 premedication groups: group 1 (acepromazine, 0.03 mg/kg [0.014 mg/lb], IM; buprenorphine, 0.02 mg/kg [0.009 mg/lb], IM), 2 (medetomidine, 5 μg/kg [2.3 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM), or 3 (medetomidine, 10 μg/kg [4.5 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM). Anesthesia was induced with propofol and maintained with isoflurane in oxygen. Simple descriptive scores for sedation were assigned 15 minutes (groups 2 and 3) and 30 minutes (group 1) after premedication administration. Basic cardiopulmonary data were recorded throughout the anesthetic period. Times to recovery from anesthesia were recorded. Sedation scores did not differ significantly among groups. Mean and diastolic blood pressures were significantly lower and heart rate was significantly higher in group 1 than in the other groups. Mean end-tidal partial pressure of CO(2) was significantly lower and respiratory rate was significantly higher in group 1 than in the other groups. There were no significant differences in anesthetic recovery times between groups. Results suggested that either acepromazine or medetomidine could be used in combination with buprenorphine for premedication of dogs anesthetized with propofol and isoflurane for routine surgical and diagnostic procedures. Arterial blood pressure was better maintained with the medetomidine-buprenorphine combinations, but tissue perfusion was not investigated.

Risk factors for complications in the post anesthesia period in elderly patients

&#x0D; Objective. To identify the risk for complications in the post anesthesia recovery period in elderly patients. &#x0D; Methodology. Retrospective descriptive study. Data were collected from elderly patient’s medical records. &#x0D; Results. 110 patients were studied and had the following profile: male sex (56.4%, hypertensive (32.7%), and classified as ASA II (60.0%).With regard to the intraoperative: underwent abdominal surgery (53.6%), general anesthesia was given (50.9%), were in a supine position during the surgery (81.8%) and the intraoperative period was under three hours (62.7%). The most common complications were: Hypothermia (55.5%), pain (43.6%) and high blood pressure (36.4%). &#x0D; Conclusion. he preoperative visit importance to evaluate the risk factors that could influence in the surgical procedure was shown.

Descripción de los efectos anestesiológicos de un protocolo a base de etomidato en perro (Canis Familiaris)

In twenty six adult healthy dogs an anesthetic protocol with Etomidato (Hypnomidate) was studied. The effectsin the physiological parameters were described and the anesthesiological characteristics were determined. The animals were premedicated with atropine in dose of 0.04 mg/kg. IM, acepromazine, in dose of 0.04 mg/kg IM, and diazepam in dose of 0.33 mg/kg IV, to diminish the potencial adverse side effect of the anesthetic. Five minutes after the injection of each drug the physiological parameters were monitored.. The induction with Etomidato, was considered achieved when the patient was intubated without difficulty. The animals were monitorized once every 5 minutes, until the consciousness and motor function were complete regained. The dose of IV induction, was 1.71 ± 0.59 mg/kg, administered in 30.19 ± 7.03 seconds, providing a time of surgical anesthesia of 17.32 ± 7.96 minutes, followed by 18.27 ± 12.78 minutes of motor depression pos anesthesia. The total anesthesia period was 35.59 ± 16.63 minutes. Under the action of this protocol, the vital signs remained within the normal values, without demonstrating vital commitment in any of the individuals included in this assay.

Cortical Up State Activity Is Enhanced After Seizures: A Quantitative Analysis

In the neocortex, neurons participate in epochs of elevated activity, or Up states, during periods of quiescent wakefulness, slow-wave sleep, and general anesthesia. The regulation of firing during and between Up states is of great interest because it can reflect the underlying connectivity and excitability of neurons within the network. Automated analysis of the onset and characteristics of Up state firing across different experiments and conditions requires a robust and accurate method for Up state detection. Using measurements of membrane potential mean and variance calculated from whole-cell recordings of neurons from control and postseizure tissue, the authors have developed such a method. This quantitative and automated method is independent of cell- or condition-dependent variability in underlying noise or tonic firing activity. Using this approach, the authors show that Up state frequency and firing rates are significantly increased in layer 2/3 neocortical neurons 24 hours after chemoconvulsant-induced seizure. Down states in postseizure tissue show greater membrane-potential variance characterized by increased synaptic activity. Previously, the authors have found that postseizure increase in excitability is linked to a gain-of-function in BK channels, and blocking BK channels in vitro and in vivo can decrease excitability and eliminate seizures. Thus, the authors also assessed the effect of BK-channel antagonists on Up state properties in control and postseizure neurons. These data establish a robust and broadly applicable algorithm for Up state detection and analysis, provide a quantitative description of how prior seizures increase spontaneous firing activity in cortical networks, and show how BK-channel antagonists reduce this abnormal activity.

Maladie d’Alzheimer et anesthésie : relations potentielles et implications cliniques

Alzheimer's disease is the most common form of dementia. As the aging population increases, Alzheimer's disease is becoming a major concern of Public Health. Many molecular lesions have been detected in Alzheimer's disease, but physiopathology is still poorly understood. If the neurotoxicity of anaesthetics in human remains debatable, perioperative period is certainly a high-risk factor for cognitive impairment, especially in elderly population. Large clinical studies are required to develop new strategies for perioperative management in such patients, including the adjustment of anaesthesia techniques. Before that, information of patient and its relatives and a particular attention for elderly during anaesthesia and perioperative period should be considered.

Tetrahydrouridine Co-Administration Improves Oral Bioavailability and Dampens Inter-Individual Variability of Decitabine Pharmacokinetics In Baboons

AbstractAbstract 2081The cytosine analogue decitabine binds and depletes the chromatin modifying enzyme DNA methyl-transferase 1 (DNMT1), thereby modifying cellular epigenetics and differentiation. An oral formulation of decitabine would potentially increase the time-above-threshold concentration for depleting DNMT1 while avoiding high peak drug levels that cause DNA damage/cytotoxicity, facilitating outpatient epigenetic-differentiation therapy. The enzyme cytidine deaminase (CDA) is the major barrier to oral absorption and furthermore, causes significant inter-individual variability in decitabine pharmacokinetics. Since there is a narrow therapeutic window for depleting DNMT1 without causing cytotoxicity, decreasing inter-individual variability and improving the predictability of dose-pharmacokinetic relationships is important to the objective of non-cytotoxic epigenetic/differentiation therapy. Therefore, we examined if combining the CDA inhibitor tetrahydrouridine (THU) with decitabine could facilitate oral administration and furthermore, decrease inter-individual variability in decitabine pharmacokinetics. Drugs were administered under ketamine/xylazine anesthesia to normal female baboons by intravenous or subcutaneous injection or oral gavage. Blood samples for pharmacokinetic (PK) analysis were drawn at 7 time-points during anesthesia. Decitabine levels were measured using LC-MS/MS. The AUClast (the area under the curve from the time of dosing to the last measurable concentration) was calculated by the linear trapezoidal method. Oral bioavailability was estimated by the ratio of AUCoral to AUCIV, following adjustment of the AUC values for the different doses administered. Minimum doses of THU (400 mg/m2, oral gavage) and decitabine (100 mg/m2, oral gavage), and optimal timing between THU and decitabine administration (60 minutes), that achieved peak levels of decitabine associated with depletion of DNMT1 without cytotoxicity in normal hematopoietic cells (0.2 – 0.5 μM) were determined. Even with AUClast being calculated over a longer period of time for the decitabine alone group (240 versus 180 minutes), the increase in AUClast in the THU group was significant per mg/kg of decitabine administered (p=0.02, Wilcoxon test) (Table 1). Oral decitabine administered 60 minutes after THU produced area under the curve (AUClast) similar to that produced by decitabine alone at double the dose, with a decrease in the inter-individual variability in pharmacokinetics observed with decitabine alone (Table 1).Table 1:The largest increases in AUClast produced by co-administration of THU occurred in baboons which had the lowest AUClast with decitabine alone, thereby decreasing inter-individual variability in decitabine pharmacokineticsAUClast (min*ng/mL)Baboon NumberWeight (kg)Decitabine 10 mg/kg aloneDecitabine 5 mg/kg aloneTHU 20 mg/kg 60 mins before Decitabine 5 mg/kgPA748212.349.98Not doneNot donePA748411.5190.35252.735621.05PA725619.8299.02Not done760.27PA747210.7327.25Not done444.825PA725414.4463Not done2587PA725519.9807.8Not done533.47PA725812.62863.6Not done2284.48PA74709.66278.781219.987515.32Mean±SD1604 ± 22622821 ± 2749Median±IQR463 ± 25652284 ± 5088Median±IQR per mg of decitabine160 ± 226457 ± 1017Fold-variation~30-fold~14-foldCoefficient of Variation14197This is the first report of oral THU in combination with oral decitabine. The significant increase in decitabine bioavailability produced by preceding THU administration may actually be larger than reported here, since AUClast estimates for THU-decitabine were calculated over 180 minutes while AUClast estimates for decitabine alone were calculated over 240 minutes to accommodate the period of allowable anaesthesia. Furthermore, the concentration-time profiles suggested that decitabine levels may have continued to increase beyond the last sampling time in some animals, moreso in the THU-decitabine group. Preceding administration of THU could facilitate oral administration of decitabine and concurrently address other limitations of decitabine therapy, including the problem of inter-individual variability, to advance towards the objective of accessible non-cytotoxic epigenetic-differentiation therapy. Disclosures:Off Label Use: FDA approved decitabine for use in MDS, therefore, its use in thalassemia is off-label. Furthermore, the dose, schedule and route of administration used is also not on the label. Decitabine was used in a study to augment production of fetal hemoglobin in an NIH sponsored trial.

La anestesia epidural del perro realizada con hostacaina sola y premedicada con diazepam

Eighteen mixed bread males and females dogs, with abodyweight óf 12.9 ± 3.2 kg, were allocated into ttivo experimental groups, in order to study the effects of epidural anaesthesia with hostacain (2%) in a single dose of 0.5 ml / kg (Group 1). The group 2 was premedicated with diazepam in a dose of 1 mg/kg, intravenously 5 minutes before hostacain. Physiologycal values (arterial pressure, heart rate and respiratory cate) and anesthesiologycal values (latency} period, epidural anaesthetic period and recover'y period) were determined.The results sholved a decrease in the minimal and maximal arterial pressure and increase in the heart cate in both series, but these values viere no statistically sigrzificative. The respiratory rate showed a significant decrease between grorrps during the initial and medial transanaestetic period. The latency and anaesthetic period showed a significant increase in group 2, but this was not absorved during recovery anaesthetic period. The result suggests that the association diazepam hostacain should be useful due to the facility, of handling dogs and to the longer time of anaesthesia obtained, without disturb on the recovery period and physiologycal variables.

La anestesia epidural del perro realizada con hostacaina sola y premedicada con diazepam

Eighteen mixed bread males and females dogs, with abodyweight óf 12.9 ± 3.2 kg, were allocated into ttivo experimental groups, in order to study the effects of epidural anaesthesia with hostacain (2%) in a single dose of 0.5 ml / kg (Group 1). The group 2 was premedicated with diazepam in a dose of 1 mg/kg, intravenously 5 minutes before hostacain. Physiologycal values (arterial pressure, heart rate and respiratory cate) and anesthesiologycal values (latency} period, epidural anaesthetic period and recover'y period) were determined.The results sholved a decrease in the minimal and maximal arterial pressure and increase in the heart cate in both series, but these values viere no statistically sigrzificative. The respiratory rate showed a significant decrease between grorrps during the initial and medial transanaestetic period. The latency and anaesthetic period showed a significant increase in group 2, but this was not absorved during recovery anaesthetic period. The result suggests that the association diazepam hostacain should be useful due to the facility, of handling dogs and to the longer time of anaesthesia obtained, without disturb on the recovery period and physiologycal variables.

Emergence delirium after propofol anaesthesia

Dear Editor: Propofol is a commonly used anaesthetic agent. Recent findings suggest that low-dose propofol sedation reduces the risk of delirium in the elderly [1]. In children, emergence agitation was reported [2], even with convulsions, ataxia and hallucinations [3]. In addition to the rare complication of a propofol infusion syndrome, sexual hallucinations [4, 5], epileptic seizures and seizure-like phenomena [6, 7] were reported. We report a severe delirious and aggressive state during emergence after propofol anaesthesia. A 20-year-old female patient (175 cm, 75 kg) was passed to a gastroenterological service for nausea and vomiting. She had been suffering from Crohn’s disease, continuously treated with prednisolone 5 mg and azathioprine 150 mg for 3 years, adalimumab (TNF-α antagonist) for 3 months and pantoprazole and tropisetron for 2 weeks. The past medical history was negative for drug abuse, alcohol or nicotine abuse, metabolic diseases, allergic reactions or treatment with psychiatric drugs. EEG was normal and there was no history of epilepsy or neurological disorder in the patient or among her relatives. Cranial and abdominal MRI were regular. She had already undergone two gastroscopies under propofol anaesthesia without adverse effects. Anaesthesia was prepared with propofol (1%, 100 mg bolus, 180 mg continuously over 15 min). Sedation was delayed with minimal restlessness. Continuous monitoring showed no relevant hypotonia or hypoxia. During waking, restlessness increased, but the patient was not responsive, and her eyes were closed. She did not recognise her mother, who was present during the gastroscopy, and refused body contact by beating, scratching, biting and crying not to touch her. Here agitation increased and bed rails had to be attached. The patient received prednisolone 125 mg for a coughing fit and midazolam 2 mg for sedation, but without improvement. An epileptic seizure was deemed unlikely due to the intentioned and coordinated movement pattern and the lack of response to midazolam. Finally, after 25 min she received haloperidol 5 mg, which caused a decline of the agitation and aggression within a few minutes, followed by 1 h of sleep. After waking, she was fully orientated and reported dreamless sleep for the period of anaesthesia and complete amnesia regarding the delirious state. Muscle or bone pain or muscle rigidity did not appear. The patient was observed on the normal ward until the following day. Reports of severe or prolonged agitation are sparse [8]; other findings represent the adverse effects of sexual hallucinations or seizure-like phenomena (SLP). The latter is characterised by uncoordinated and tonic–clonic muscle movements [6, 7], opisthotonus and athetoid neck and limb movements [9]. Signs of SLP or grand mal epilepsy did not occur in our patient; rather, she showed intentional, coordinated movements, a purposeful defence reaction and anxiety, whilst being unresponsive. Complete amnesia and a dreamless sleep suggest the absence of sexual hallucinations [4, 5], despite there probably being delusions and anxiety. The sudden decline of all symptoms after haloperidol medication supports the diagnosis of delirium. It has to be discussed whether the new medication was responsible for the incident. Adalimumab may cause mood U. Palm (*) :M. Lieb Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany e-mail: ulrich.palm@med.uni-muenchen.de