Sleep-Aids Derived from Natural Products

Although drugs such as barbiturates and benzodiazepines are often used for the treatment of insomnia, they are associated with various side effects such as habituations, tolerance and addiction. Alternatively, natural products with minimal unwanted effects have been preferred for the treatment of acute and/or mild insomnia, with additional benefits of overall health-promotion. Basic and clinical researches on the mechanisms of action of natural products have been carried out so far in insomnia treatments. Recent studies have been focusing on diverse chemical components available in natural products, with an interest of developing drugs that can improve sleep duration and quality. In the last 15 years, our co-workers have been actively looking for candidate substances from natural products that can relieve insomnia. This review is, therefore, intended to bring pharmacological data regarding to the effects of natural products on sleep duration and quality, mainly through the activation of GABAA receptors. It is imperative that phytochemicals will provide useful information during electroencephalography (EEG) analysis and serve as an alternative medications for insomnia patients who are reluctant to use conventional drugs.

Current clinical application of dexmedetomidine for sedation and anesthesia

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.

Current clinical application of dexmedetomidine for sedation and anesthesia

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.

Thiamylal sodium increased inflammation and the proliferation of vascular smooth muscle cells / 대한마취과학회지

BACKGROUND: Thiamylal sodium is a common anesthetic barbiturate prepared in alkaline solution for clinical use. There is no previously reported study on the effects of barbiturates on the inflammation and proliferation of vascular smooth muscle cells (VSMCs). Here, we examined the effects of clinical-grade thiamylal sodium solution (TSS) on the inflammation and proliferation of rat VSMCs. METHODS: Expression levels of interleukin (IL)-1α, IL-1β, IL-6, and toll-like receptors in rat VSMCs were detected by quantitative reverse transcription-polymerase chain reaction and microarray analyses. The production of IL-6 by cultured VSMCs or ex vivo-cultured rat aortic segments was detected in supernatants by enzyme-linked immunosorbent assay. VSMC proliferation and viability were determined by the water-soluble tetrazolium-1 assay and trypan blue staining, respectively. RESULTS: TSS increased expression of IL-1α, IL-6, and TLR4 in VSMCs in a dose-dependent manner, and reduced IL-1β expression. Ex vivo TSS stimulation of rat aorta also increased IL-6. Low concentrations of TSS enhanced VSMC proliferation, while high concentrations reduced both cell proliferation and viability. Expression of IL-1 receptor antagonist, which regulates cell proliferation, was not increased by TSS stimulation. Exposure of cells to the TSS additive, sodium carbonate, resulted in significant upregulation of IL-1α and IL-6 mRNA levels, to a greater extent than TSS. CONCLUSIONS: TSS-induced proinflammatory cytokine production by VSMCs is caused by sodium carbonate. However, pure thiamylal sodium has an anti-inflammatory effect in VSMCs. TSS exposure to VSMCs may promote vascular inflammation, leading to the progression of atherosclerosis or in-stent restenosis, resulting in vessel bypass graft failure.

Meloxicam-induced Erythema Multiforme / 대한정형외과연구학회지

Erythema multiforme is an acute cutaneous reaction which manifests as macular patches and edematous papules commonly involving the hands, feet, forearm and mucous membranes. It is thought to be caused by viral and bacterial infections, neoplasms, autoimmune diseases such as rheumatoid arthritis, and also by pharmaceuticals such as sulfonamides, phenytoin, barbiturates, penicillins, carbamazepines. Nonsteroidal antiinflammatory drugs (NSAIDs) have been also reported as a possible cause. However, meloxicam that is a kind of cyclooxygenase-2 selective inhibitor has not been rarely reported as a cause of erythema multiforme. Therefore, we report a case with a review of the literature.

Práticas alimentares no primeiro ano de vida: representações sociais de mães adolescentes / Eating habits in the first year of life: social representations of young mothers / Los hábitos de alimentación en el primer año de vida: las representaciones sociales de las madres adolescentes

Trata-se de pesquisa qualitativa exploratória, que buscou analisar as representações sociais de mães adolescentes sobre as práticas alimentares do filho no primeiro ano de vida. Teve como sujeitos 10 mães adolescentes, cujos filhos encontravam-se na faixa etária de sete a doze meses de vida. Os dados foram coletados por meio de entrevista semi-estruturada, além da utilização de material visual. A análise seguiu a técnica de análise de conteúdo, apoiando-se no referencial da Teoria das Representações Sociais. Dessa análise, emergiram quatro temas: conflito do amamentar versus consagração do mingau; estabelecendo a alimentação complementar do filho; discurso cristalizado: "danoninho vale mais que um bifinho"; a (in)definição dos hábitos alimentares maternos: implicações para a alimentação infantil. As representações que conduzem as práticas maternas na escolha, preparo e oferta dos alimentos seguem uma lógica particular, onde as adolescentes reinterpretam os discursos técnicos nos termos da sua cultura.

This is qualitative research that investigates the social representations of adolescent mothers on child eating habits in the first year of life. Its subjects were 10 adolescent mothers, whose children were aged seven to twelve months. Data were collected through semi-structured interview, besides the use of visual material. The analysis followed the technique of content analysis, relying on the framework of Social Representations Theory. That analysis revealed four themes: the conflict of breastfeeding versus consecration of porridge; establishing complementary feeding of the child; crystallized speech: "yogurt is better than a little steak"; the (un)definition of maternal eating habits: implications for infant feeding. The representations that drive maternal practices in selecting, preparing and offering food follow a particular logic, where adolescents reinterpret technical speeches in terms of their culture.

Esta es una investigación cualitativa que investiga las representaciones sociales de madres adolescentes en las prácticas de alimentación infantil en el primer año de vida. El estudio incluyó a 10 madres adolescentes cuyos hijos tenían entre siete a doce meses. Los datos fueron obtenidos mediante entrevista semiestructurada, además de la utilización de material visual. El análisis se realizó por la técnica de análisis de contenido, basándose en el marco de la teoría de las representaciones sociales. Ese análisis revelo cuatro temas: el conflicto de la lactancia materna frente a la consagración de la papilla; el establecimiento de alimentación complementaria del niño; discurso cristalizado "el yogur es mejor que un filete"; la dieta materna sin definición: implicaciones para la alimentación infantil. Las representaciones que impulsan prácticas maternas en la selección, preparación y oferta de alimentos siguen una lógica particular, donde las adolescentes reinterpretan intervenciones técnicas en términos de su cultura.

Clinical Efficacy of Acute Monitoring Cortical Activity Using Subdural Strip Electrode after Decompressive Craniectomy / 대한신경손상학회지

OBJECTIVE: Decompressive craniectomy is widely used in cases of uncontrolled intracranial hypertension, including traumatic brain injury or acute stroke. Physiological monitorings, such as intracranial pressure or electroenecephalography (EEG) are critical for patients in the acute phase. We retrospectively reviewed our experience of continuous electrocorticography (ECoG) monitoring by subdural strip electrode in patients who performed decompressive craniectomy and assessed its clinical efficacy. METHODS: Patients who underwent decompressive craniectomy because of severe intracranial hypertension were included. 4 Channel strip electrodes were inserted on the frontal cortex before closure. 24-hour continuous monitoring of ECoG was done to identify abnormal electrical activity. The level of consciousness was assessed according to Glasgow Coma Scale (GCS). In patients with malignant intracranial hypertension, barbiturate coma therapy was considered. RESULTS: Fifteen patients (9 men and 6 women) were included and the mean age was 55.7 years (from 17 to 80). The initial mean GCS score was 7.9 (from 3 to 14). In six out of fifteen patients, abnormal spike activities were identified, and one of these six patients was diagnosed as nonconvulsive status epilepticus (NCSE). Cortical spreading depression (CSD) was suspected in five. Three patients underwent barbiturate coma therapy and ECoG monitoring of these patients showed typical burst suppression pattern, which was used for indicator of therapeutic level. The mean duration of strip electrode and ECoG monitoring was 3.5 days, and there was no complication. CONCLUSION: Continuous ECoG monitoring using subdural strip electrode was useful to detect abnormal brain activity in the acute period after decompressive craniectomy.

Inadvertent intrathecal dobutamine administration and barbiturate induced nystagmus: A case report

Medication errors remain an unsolved problem in medicine. Some factors have been found to contribute to drug errors, and among them, the incorrect administration of drugs is a major factor. In this case report, 2 ml of dobutamine was inadvertently injected intrathecally instead of bupivacaine owing to ampoule confusion during spinal anesthesia, followed by the induction of general anesthesia with sodium thiopental-sevoflurane. It was uneventful during perioperative period, however, nystagmus was observed in post anesthesia care unit (PACU), about 1 h after induction of general anesthesia. There were no other neurologic abnormalities except nystagmus and vital sign were stable during PACU stay. Nystagmus subsided spontaneously and it was confirmed there was no evidence of any central nervous system lesion on imaging study. The patient was discharged 5 days later without any complications.

Redistribuição postmortem de barbitúricos em tecidos biológicos humanos / Postmortem redistribution of barbiturates in human biological tissues

Os barbitúricos são fármacos com atividade depressora do sistema nervoso central e estão relacionados com elevados números de casos de intoxicações e uso não-médico em vários países. No Brasil, a droga antiepiléptica mais encontrada em casos de intoxicação é o fenobarbital, pois os pacientes relatam que "essa é uma substância com ação forte no cérebro". De fato, os barbitúricos estão altamente relacionados com tentativa de suicídio e homicídio. Nesses casos existe a necessidade da quantificação dessas substâncias para correlacionar com a causa mortis. No entanto, as análises toxicológicas postmortem são de difícil execução e interpretação, pois a concentração de agentes tóxicos encontrados é bastante complexa e afetada não só pela condição de deterioração do corpo, mas também por um processo conhecido como redistribuição postmortem. Em geral, concentrações mais elevadas são encontradas no sangue situado nos sítios centrais (como o sangue coletado da cavidade cardíaca) em comparação aos níveis verificados nos vasos periféricos (como a veia femoral). Em outros casos, o tempo entre a morte e o exame postmortem é suficiente para que algumas substâncias que normalmente estariam presentes no sangue não estejam mais disponíveis neste fluido biológico. Há ainda um agravante, pois não existem valores de referências para a maioria das amostras biológicas não-convencionais, dificultando assim a interpretação dos resultados. Os exames toxicológicos devem ser realizados em amostras biológicas e tem como objetivo a avaliação da intoxicação como circunstância qualificadora do delito, como causa de periculosidade ou imputabilidade. O objetivo deste trabalho foi o desenvolvimento e aplicação de métodos de identificação de barbitúricos (butalbital, secobarbital, pentobarbital e fenobarbital) em amostras postmortem (sangue cardíaco, sangue femoral e fígado). Os analitos foram extraídos das amostras utilizando a micro extração em fase líquida (LPME), identificados...

Barbiturates are a class of drugs that act as central nervous system depressant and are associated with high numbers of poisoning cases and non-medical use in several countries. In Brazil, phenobarbital is the most related antiepileptic drug involved in intoxication cases. Patients report that "this drug is a substance with strong action in the brain." In fact, barbiturates are highly related to attempted suicide and homicide cases, in which quantification of these substances to correlate with the possible cause of death is necessary. However, postmortem toxicological analyses are difficult to perform and interpret, because the concentration of toxic agents found is quite complex and affected not only by deterioration condition of the body but also by a process known as postmortem redistribution. In general, higher concentrations are found in the blood located in central sites (e.g. heart cavity) compared with the levels found in peripheral vessels (such as the femoral vein). In other cases, the time between death and postmortem examination is enough for some substances that would normally be present in the blood are no longer available in this biological fluid. Besides, there are few reference values for most non-conventional biological samples, making it difficult to interpret the results. The objective of this work was the development and application of methods for identification of barbiturates (butalbital, secobarbital, pentobarbital and phenobarbital) in postmortem samples (heart blood, femoral blood and liver). The analytes were extracted by using liquid-phase micro extraction (LPME) and quantified by gas chromatography-mass spectrometry (GC-MS). After the development and validation, analytical methods were applied in real cases of eleven corpses autopsied by Death Verification Service of São Paulo City (USP-SVO), with suspected of barbiturates involvement. Nine cases were positive for phenobarbital. The mean ratio of blood femoral / cardiac blood was...

Ultrastructure and electrophysiology of astrocytes differentiated from adult adipose-derived stromal cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adipose-derived stromal cell (ADSC) differentiation into neural cells in vitro is becoming widely studied. However, there are few reports on astrocytes following differentiation, and particularly on maturation and electrophysiology. In this study, we used various methods to determine ADSC-derived astrocyte maturity.</p><p><b>METHODS</b>Chemical induction with isobutylmethylxanthine (IBMX) was used to differentiate adult ADSCs into astrocytes followed by hematoxylin-eosin (HE) staining to observe morphology and transmission electron microscopy for cellular ultrastructure assessment. Immunofluorescence was used to detect expression of neural stem cell marker nestin as well as glial markers glial fibrillary acidic protein (GFAP) and S-100. In addition, we measured membrane potentials in bis-(1,3-dibarbituric acid) trimethine oxanol-labeled ADSCs and astrocytes by stimulation with a high potassium solution under an inverted fluorescence microscope. Finally, cell cycle distribution was detected by flow cytometry.</p><p><b>RESULTS</b>Typical astrocyte morphology was shown by HE staining after 48-hour differentiation. Glial fibril was observed with transmission electron microscopy. GFAP and S-100 were not expressed in the control group, but were expressed within 24-hour differentiation and reached a maximum at day 14 with no change up to day 28. Nestin was weakly expressed in control cells and also reached a maximum at day 14 with the percentage of positive cells constant until day 21 followed by a decrease. Differentiated cell membrane potentials after stimulation with potassium were slightly increased, and then gradually declined over time. There was no significant membrane potential change in the control group. Flow cytometry showed that the percentage of cells in G0/G1 phase was 93% and only 5% in S phase.</p><p><b>CONCLUSION</b>ADSCs were differentiated into mature astrocytes with typical characteristics including morphology, ultrastructure, marker protein expression, mature potassium channels and mitotic capacity.</p>

Comparative Study of Brain Protection Effect between Thiopental and Etomidate Using Bispectral Index during Temporary Arterial Occlusion

OBJECTIVE: This study was conducted to compare the effect of etomidate with that of thiopental on brain protection during temporary vessel occlusion, which was measured by burst suppression rate (BSR) with the Bispectral Index (BIS) monitor. METHODS: Temporary parent artery occlusion was performed in forty one patients during cerebral aneurysm surgery. They were randomly assigned to one of two groups. General anesthesia was induced and maintained with 1.5-2.5 vol% sevoflurane and 50% N2O. The pharmacological burst suppression (BS) was induced by a bolus injection of thiopental (5 mg/kg, group T) or etomidate (0.3 mg/kg, group E) according to randomization prior to surgery. After administration of drugs, the hemodynamic variables, the onset time of BS, the numerical values of BIS and BSR were recorded at every minutes. RESULTS: There were no significant differences of the demographics, the BIS numbers and the hemodynamic variables prior to injection of drugs. The durations of burst suppression in group E (11.1+/-6.8 min) were not statistically different from that of group T (11.1+/-5.6 min) and nearly same pattern of burst suppression were shown in both groups. More phenylephrine was required to maintain normal blood pressure in the group T. CONCLUSION: Thiopental and etomidate have same duration and a similar magnitude of burst suppression with conventional doses during temporary arterial occlusion. These findings suggest that additional administration of either drug is needed to ensure the BS when the temporary occlusion time exceed more than 11 minutes. Etomidate can be a safer substitute for thiopental in aneurysm surgery.

Cerebral Hemorrhage after Endovascular Treatment of Bilateral Traumatic Carotid Cavernous Fistulae with Covered Stents

Bilateral traumatic carotid-cavernous fistulae (TCCFs) is rarely encountered neurovascular disease. For treatment of TCCF, detachable balloons have been widely used. Nowadays, transarterial and/or transvenous coil embolization with placement of covered stents is adopted as another treatment method. We experienced a patient with a bilateral TCCFs who was successfully treated with covered stents. However, cerebral hemorrhage occurred in the bed of previous infarction one day after treatment. Hyperperfusion syndrome was considered as a possible cause of the hemorrhage, so that barbiturate coma therapy was started and progression of hemorrhage was stopped. We emphasize that cerebral hyperperfusion hemorrhage can occur even after successful endovascular treatment of TCCF.

Análise da ocorrência de hipertensão intracraniana refratária e da resposta ao tratamento de crianças com traumatismo crânio-encefálico grave / Analysis of the incidence of refractory intracranial hypertension and the response of children with severe head trauma to the treatment

Introdução: o traumatismo crânio-encefálico (TCE) grave é frequente em pediatria, mas as recomendações para seu tratamento têm baixo nível de evidência. Objetivo: analisar a ocorrência de hipertensão intracraniana (HIC) refratária e a resposta ao tratamento em crianças com TCE grave. Métodos: coorte incluindo pacientes com pontuação abaixo de nove na Escala de Coma de Glasgow (ECG) entre setembro de 2005 e agosto de 2008. Aprovado pelo Comitê de Ética em Pesquisa da Fhemig. Resultados: analisados 156 pacientes, 116 masculinos (74,4%), idades entre três meses e 18 anos, média nove, mediana 11. Mediana da pontuação na ECG: 6. Atropelamento: 54 pacientes (34,6%); lesões em ocupantes de veículos: 34 (21,8%); queda: 21 (13,5%); e lesões em ciclistas: 18 (11,5%). Tomografia alterada: 133 pacientes (85,3%); hemorragia intracraniana: 105 (67,3%); swelling: 66 (42,3%); lesão axonal difusa: (28,8%). A monitorização da pressão intracraniana foi realizada em 73 pacientes (46,8%). Foi encontrada HIC com necessidade de tratamento em 56 (76,7%) e refratária em 30 (41%) pacientes. Destes pacientes, 10 receberam barbitúrico e sete morreram. A craniectomia descompressiva foi realizada em nove pacientes, sendo que dois faleceram. O risco relativo de morte com barbitú- rico: 3,9 (IC 95%: 1,1 a 14,1; p=0,02), com significância estatística. O risco relativo de morte com craniectomia descompressiva: 0,3 (IC95%: 0,1 a 1,0, p=0,02). Ocorreram 33 óbitos (21,1%), 59% de redução em relação a estudo anterior da Instituição. Conclusões: HIC refratária foi muito frequente em crianças com TCE grave. O uso de coma barbitúrico para seu tratamento aumentou o risco de morte em quatro vezes.(AU)

Background: Severe head trauma is common in children, but there is a lack of evidence for the intracranial hypertension treatment in the literature. Objectives: To analyze the occurrence of refractory intracranial hypertension and the response of children and adolescents with severe head trauma to the treatment. Method: Cohort study between September 2005 and August 2008 involving pediatric patients with Glasgow coma scale (GCS) from 3 to 8 points. This study was approved by the ethical committee of FHEMIG. Results: From the 156 patients, 116 were male (74,4%). The range of age varied from tree months to 18 years, mean age 9, and median 11. Median of GCS score: 6. Running over crash: 54 patients (34,6%), car occupants injuries: 34 (21,8%), falls: 21 (13,5%) e cyclist´s injuries: 18 (11,5%). Abnormalities in computed tomography: 133 patients (85,3%), intracranial hemorrhage: 105 (67,3%), swelling: 66 (42,3%), diffuse axonal injury: (28,8%). Seventy three patients received intracranial pressure monitoring (46,3%); 56 had had intracranial hypertension that needed treatment (76,7%), and 30 had had refractory intracranial hypertension (41%). From the patients with refractory hypertension, 10 received barbiturates as treatment, seven died. Nine underwent decompressive craniectomy, two died. Relative risk of death with barbiturates: 3,9 (CI 95%: 1,1 a 14,1; p=0,02). Relative risk of death with decompressive craniectomy: 0,3 (IC95%: 0,1 a 1,0, p=0,02). Total mortality rate was 21,1% (33 patients). This showed a decrease of 59% in mortality comparing to previous study done in the same hospital. Conclusion: refractory intracranial hypertension were very common in pediatric patients with severe head injury. The use of barbiturates for its treatment increased the risk of death four times.(AU)

Micellar liquid chromatography and its application in toxicological analysis / 法医学杂志

Micellar liquid chromatography (MLC) is a reversed phase liquid chromatography with mobile phases containing surfactant above its critical micellar concentration (CMC). The basic mechanism and advantages of MLC in physicochemical analysis were reviewed, and its applications in analysis of drugs, barbiturates, benzodiazepines were chiefly introduced in this paper. MLC is a potential method to toxicological analysis due to strong selectivity, wide application scope and easy biological samples, etc.

Development of a Critical Pathway of Barbiturate Coma Therapy in the Management for Severe Brain Damage / 간호행정학회지

PURPOSE: This study is a descriptive research to analyze prognostic factors of barbiturate coma therapy (BCT) for severe brain damage patients, to develop a critical pathway (CP) based on the results of analysis and to examine the effect of its clinical application. METHOD: We analyzed medical records of 76 patients who received BCT for more than three days between January 1999 to July 2005. Based on the results of the analysis, we developed a CP and applied it to 12 people during August-December of 2005. RESULT: By application of BCT CP, the mortality rate decreased from 31.6% to 16.7%. It was found that the period of staying at ICU and total period of hospitalization were shortened by 2.78 (13.9%) days and 16.43 (29.4%) days, respectively. The Glasgow coma scale of the recovery group by CP application was 9.03 (4.64) at 72 hours post of BCT and 14.28 (1.82) at discharge from hospital, and DRS was 6.62 (6.38) points. CONCLUSION: By verifying clinical validity of the suggested CP, we believe that we have obtained visible effects standardizing the treatment pathway of BCT for brain damage patients.

Comparison of the effects of propofol and pentobarbital on hydrogen peroxide-stimulated hepatic SNU761 cells / 대한마취과학회지

BACKGROUND: Propofol and barbiturates are both known to protect cells of several organs against ischemia/reperfusion injury, but there are few reports on any possible protective effects on human hepatocytes. We investigated the activities of both agents on human hepatic SNU761 cells under hydrogen peroxide (H2O2)-induced oxidative stress. METHODS: To determine whether propofol and pentobarbital protect hepatocytes from H2O2-induced toxicity, we used SNU761 cells, a human hepatocellular carcinoma (HCC) cell line. Cells were pretreated with different dosages (1, 10, 50 micrometer) of propofol or pentobarbital (1, 10, 50, 100, 400 micrometer) 30 min before H2O2 application. Lactate dehydrogenase (LDH) was measured to assess and quantify cell death. To determine the nature of cell death, treated hepatocytes were doubly stained with fluorescein isothiocyanate (FITC)-labeled Annexin V and propidium iodide (PI), and analyzed by flow cytometry. RESULTS: Pretreatment with propofol, but not pentobarbital, suppressed H2O2-induced LDH release. In Annexin V-FITC/PI binding analysis, propofol decreased the number of necrotic and late apoptotic cells, but no significant decreases in such cell numbers were seen when pentobarbital was used. CONCLUSIONS: Unlike pentobarbital, propofol, at clinical concentrations, protected SNU-761 HCC cells against oxidative stress.

Development of a Critical Pathway of Barbiturate Coma Therapy in the Management for Severe Brain Damage / 간호행정학회지

PURPOSE: This study is a descriptive research to analyze prognostic factors of barbiturate coma therapy (BCT) for severe brain damage patients, to develop a critical pathway (CP) based on the results of analysis and to examine the effect of its clinical application. METHOD: We analyzed medical records of 76 patients who received BCT for more than three days between January 1999 to July 2005. Based on the results of the analysis, we developed a CP and applied it to 12 people during August-December of 2005. RESULT: By application of BCT CP, the mortality rate decreased from 31.6% to 16.7%. It was found that the period of staying at ICU and total period of hospitalization were shortened by 2.78 (13.9%) days and 16.43 (29.4%) days, respectively. The Glasgow coma scale of the recovery group by CP application was 9.03 (4.64) at 72 hours post of BCT and 14.28 (1.82) at discharge from hospital, and DRS was 6.62 (6.38) points. CONCLUSION: By verifying clinical validity of the suggested CP, we believe that we have obtained visible effects standardizing the treatment pathway of BCT for brain damage patients.

Efficacy of Low Dose Barbiturate Coma Therapy for the Patients with Intractable Intracranial Hypertension Using the Bispectral(TM) Index Monitoring

OBJECTIVE: Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with Bispectral(TM) index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring. METHODS: We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing. RESULTS: The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were 0.63 +/- 0.26 in low dose group, and 1.31 +/- 0.48 in high dose group. The treatment durations were 4.89 +/- 1.68 days and 3.38 +/- 1.24 days in low dose BCT and high dose BCT, respectively. CONCLUSION: It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP.

Management of intracranial hypertension.

Raised intracranial pressure (ICP) is a life threatening condition that is common to many neurological and non-neurological illnesses. Unless recognized and treated early it may cause secondary brain injury due to reduced cerebral perfusion pressure (CPP), and progress to brain herniation and death. Management of raised ICP includes care of airway, ventilation and oxygenation, adequate sedation and analgesia, neutral neck position, head end elevation by 200 -300, and short-term hyperventilation (to achieve PCO2 32- 35 mm Hg) and hyperosmolar therapy (mannitol or hypertonic saline) in critically raised ICP. Barbiturate coma, moderate hypothermia and surgical decompression may be helpful in refractory cases. Therapies aimed directly at keeping ICP <20 mmHg have resulted in improved survival and neurological outcome. Emerging evidence suggests that cerebral perfusion pressure targeted therapy may offer better outcome than ICP targeted therapies.

Medical managements of intracranial hypertension

Normal intracranial pressure (ICP) is below 10?15 mmHg.It may increase as a result of traumatic brain injury, stroke, neoplasm or other pathologies. When ICP is pathologically elevated it needs to be lowered. Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate intracranial hypertension.It is important to rule out space occupying lesion that should be surgically removed.Medical managements of intracranial hypertension include maintenance of proper oxygenation and cerebral perfusion pressure and osmotheraphy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical treatment, profound hyperventilation, barbiturate coma or hypothermia should be considered. Steroids are not indicated and maybe harmful in the treatment of intracranial hypertension caused by traumatic brain injury.