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Critical Care (London, England) 2008In their article on the use of barbiturates for the treatment of intracranial hypertension after traumatic brain injury, Perez-Barcena and colleagues conclude that...
In their article on the use of barbiturates for the treatment of intracranial hypertension after traumatic brain injury, Perez-Barcena and colleagues conclude that thiopental was more effective than pentobarbital in decreasing intracranial pressure. Here we discuss the limitations of this study and review areas of controversy surrounding barbiturate use in neurocritical care.
Topics: Barbiturates; Brain Injuries; Humans; Intracranial Hypertension; Treatment Outcome
PubMed: 18983702
DOI: 10.1186/cc7020 -
British Medical Journal Mar 1974In a cross-over study of five hospitalized patients the half life of doxycycline was significantly shortened after 10 days' treatment with phenobarbitone. In five...
In a cross-over study of five hospitalized patients the half life of doxycycline was significantly shortened after 10 days' treatment with phenobarbitone. In five patients on continuous barbiturate therapy the half life of doxycycline was even shorter. Barbiturates or other agents inducing drug metabolism should be used cautiously in combination with doxycycline, since this might result in therapeutically inadequate serum concentrations of the antibiotic.
Topics: Adult; Aged; Amobarbital; Barbiturates; Carbamazepine; Doxycycline; Drug Interactions; Enzyme Induction; Female; Half-Life; Humans; Male; Middle Aged; Pentobarbital; Phenobarbital; Phenytoin
PubMed: 4817187
DOI: 10.1136/bmj.1.5907.535 -
Anesthesiology Aug 1971
Comparative Study Review
Topics: Anesthesia, Intravenous; Anesthetics; Barbiturates; Diazepam; Eugenol; Kinetics; Methohexital; Neuroleptanalgesia; Preanesthetic Medication; Thiopental
PubMed: 4936119
DOI: 10.1097/00000542-197108000-00009 -
The Cochrane Database of Systematic... May 2016Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury. Barbiturate therapy has been used for infants with perinatal asphyxia in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury. Barbiturate therapy has been used for infants with perinatal asphyxia in order to prevent seizures. However, barbiturate therapy may adversely affect neurodevelopment leading to concern regarding aggressive use in neonates.
OBJECTIVES
To determine the effect of administering prophylactic barbiturate therapy on death or neurodevelopmental disability in term and late preterm infants following perinatal asphyxia.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCT) and quasi-RCTs.
SELECTION CRITERIA
We included all RCTs or quasi-RCTs of prophylactic barbiturate therapy in term and late preterm infants without clinical or electroencephalographic evidence of seizures compared to controls following perinatal asphyxia.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected, assessed the quality of, and extracted data from the included studies. We assessed methodologic quality and validity of studies without consideration of the results. The review authors independently extracted data and performed meta-analyses using risk ratios (RR) and risk differences (RD) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI). For significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH).
MAIN RESULTS
In this updated review, we identified nine RCTs of any barbiturate therapy in term and late preterm infants aged less than three days old with perinatal asphyxia without evidence of seizures. Eight of these studies compared prophylactic barbiturate therapy to conventional treatment (enrolling 439 infants) and one study compared barbiturate therapy to treatment with phenytoin (enrolling 17 infants). Prophylactic barbiturate therapy versus conventional treatment: one small trial reported a decreased risk of death or severe neurodevelopmental disability for barbiturate therapy (phenobarbital) versus conventional treatment (RR 0.33, 95% CI 0.14 to 0.78; RD -0.55, 95% CI -0.84 to -0.25; NNTB 2, 95% CI 1 to 4; 1 study, 31 infants) (very low quality evidence).Eight trials comparing prophylactic barbiturate therapy with conventional treatment following perinatal asphyxia demonstrated no significant impact on the risk of death (typical RR 0.88, 95% CI 0.55 to 1.42; typical RD -0.02, 95% CI -0.08 to 0.05; 8 trials, 429 infants) (low quality evidence) and the one small trial noted above reported a significant decrease in the risk of severe neurodevelopmental disability (RR 0.24, 95% CI 0.06 to 0.92; RD -0.43, 95% CI -0.73 to -0.13; NNTB 2, 95% CI 1 to 8; 1 study, 31 infants) (very low quality evidence).A meta-analysis of the six trials reporting on seizures in the neonatal period demonstrated a statistically significant reduction in seizures in the prophylactic barbiturate group versus conventional treatment (typical RR 0.62, 95% CI 0.48 to 0.81; typical RD -0.18, 95% CI -0.27 to -0.09; NNTB 5, 95% CI 4 to 11; 6 studies, 319 infants) (low quality evidence). There were similar results in subgroup analyses based on type of barbiturate and Sarnat score. Prophylactic barbiturate therapy versus other prophylactic anticonvulsant therapy: one study reported on prophylactic barbiturate versus prophylactic phenytoin. There was no significant difference in seizure activity in the neonatal period between the two study groups (RR 0.89, 95% CI 0.07 to 12.00; 1 trial, 17 infants).
AUTHORS' CONCLUSIONS
We found only low or very low quality evidence addressing the use of prophylactic barbiturates in infants with perinatal asphyxia. Although the administration of prophylactic barbiturate therapy to infants following perinatal asphyxia did reduce the risk of seizures, there was no reduction seen in mortality and there were few data addressing long-term outcomes. The administration of prophylactic barbiturate therapy for late preterm and term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice. If used at all, barbiturates should be reserved for the treatment of seizures. The results of the current review support the use of prophylactic barbiturate therapy as a promising area of research. Future studies should be of sufficient size and duration to detect clinically important reductions in mortality and severe neurodevelopmental disability and should be conducted in the context of the current standard of care, including the use of therapeutic hypothermia.
Topics: Anticonvulsants; Asphyxia Neonatorum; Barbiturates; Humans; Infant; Infant, Newborn; Infant, Premature; Neurodevelopmental Disorders; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Seizures; Thiopental
PubMed: 27149645
DOI: 10.1002/14651858.CD001240.pub3 -
Journal of Neurotrauma Jan 2013The guidelines for management of traumatic brain injury (TBI) recommend that high-dose barbiturate therapy may be considered to lower intracranial pressure (ICP) that is... (Comparative Study)
Comparative Study
The guidelines for management of traumatic brain injury (TBI) recommend that high-dose barbiturate therapy may be considered to lower intracranial pressure (ICP) that is refractory to other therapeutic options. Lower doses of barbiturates may be used for sedation of patients with TBI, although there is no mention of this in the published guidelines. The goal of this study was to analyze the use of barbiturates in patients with severe TBI in the European centers where the International Neurotrauma Research Organization introduced guideline-based TBI management and to analyze the effects of barbiturates on ICP, use of vasopressors, and short- and long-term outcome of these patients. Data on 1172 patients with severe TBI were collected in 13 centers located in five European countries. Patients were categorized into three groups based on doses of barbiturates administered during treatment. Univariate and multivariate statistical methods were used to analyze the effects of barbiturates on the outcome of patients. Fewer than 20% of all patients with severe TBI were given barbiturates overall, and only 6% was given high doses. High-dose barbiturate treatment caused a decrease in ICP in 69% of patients but also caused hemodynamic instability leading to longer periods of mean arterial pressure <70 mm Hg despite increased use of high doses of vasopressors. The adjusted analysis showed no significant effect on outcome on any stage after injury.Thiopental and methohexital were equally effective. Low doses of thiopental and methohexital were used for sedation of patients without side effects. Phenobarbital was probably used for prophylaxis of post-traumatic seizures.
Topics: Adult; Austria; Barbiturates; Bosnia and Herzegovina; Brain Injuries; Croatia; Female; Humans; Injury Severity Score; Intracranial Pressure; Male; Middle Aged; Prospective Studies; Republic of North Macedonia; Slovakia; Young Adult
PubMed: 22950895
DOI: 10.1089/neu.2012.2554 -
Anaesthesia Mar 1980Experimental and clinical studies of the protective effect of barbiturates in cerebral ischaemia are reviewed. Their action in protecting the brain from the effects of... (Review)
Review
Experimental and clinical studies of the protective effect of barbiturates in cerebral ischaemia are reviewed. Their action in protecting the brain from the effects of ischaemia is related to their action as anaesthetic agents and probably to the depression of neuronal function and metabolism but is incompletely understood. Their effect is dose related. Early administration is likely to be crucial to the success of barbiturate therapy as secondary events following an episode of cerebral ischaemia can lead to irreversible brain damage within 2--3 h. A potential collateral circulation appears to be essential for the protective effect of barbiturates. There may be a possibility of partly overcoming time delays in administration by giving larger doses of barbiturates.
Topics: Animals; Barbiturates; Brain Ischemia; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypothermia, Induced; Pentobarbital; Thiopental; Time Factors
PubMed: 6994519
DOI: 10.1111/j.1365-2044.1980.tb05090.x -
European Journal of Medicinal Chemistry Nov 2022An amphipathic barbiturate mimic of the marine eusynstyelamides is reported as a promising class of antimicrobial agents. We hereby report a detailed analysis of the...
An amphipathic barbiturate mimic of the marine eusynstyelamides is reported as a promising class of antimicrobial agents. We hereby report a detailed analysis of the structure-activity relationship for cationic amphipathic N,N'-dialkylated-5,5-disubstituted barbiturates. The influence of various cationic groups, hydrocarbon linkers and lipophilic side chains on the compounds' antimicrobial potency and haemolytic activity was studied. A comprehensive library of 58 compounds was prepared using a concise synthetic strategy. We found cationic amine and guanidyl groups to yield the highest broad-spectrum activity and cationic trimethylated quaternary amine groups to exert narrow-spectrum activity against Gram-positive bacteria. n-Propyl hydrocarbon linkers proved to be the best compromise between potency and haemolytic activity. The combination of two different lipophilic side chains allowed for further fine-tuning of the biological properties. Using these insights, we were able to prepare both, the potent narrow-spectrum barbiturate 8a and the broad-spectrum barbiturates 11lG, 13jA and 13jG, all having low or no haemolytic activity. The guanidine derivative 11lG demonstrated a strong membrane disrupting effect in luciferase-based assays. We believe that these results may be valuable in further development of antimicrobial lead structures.
Topics: Amines; Anti-Bacterial Agents; Anti-Infective Agents; Barbiturates; Cations; Gram-Negative Bacteria; Hemolysis; Humans; Microbial Sensitivity Tests; Structure-Activity Relationship
PubMed: 36027613
DOI: 10.1016/j.ejmech.2022.114632 -
Journal of the American Association For... Mar 2023Barbiturate overdose is a common method for euthanizing pigs. However, barbiturates can cause tissue damage and may affect experimental results, so the minimal dose...
Barbiturate overdose is a common method for euthanizing pigs. However, barbiturates can cause tissue damage and may affect experimental results, so the minimal dose should be used. The minimal dose of barbiturate for euthanasia in pigs under isoflurane anesthesia has not yet been determined. In this study, we compared the effect of low and high doses of 2 barbiturates (pentobarbital, 30 or 60 mg/kg; thiopental, 20 and 40 mg/kg) on hemodynamic parameters and time to cardiac arrest in female pigs maintained on isoflurane. Acute decreases in blood pressure and end-tidal CO₂ occurred in all pigs shortly after administration of the barbiturate. However, these changes were not different between either of the high- and low dose groups. Cardiac arrest occurred significantly faster for high dose as compared with low dose thiopental groups, but this parameter was different between the 2 pentobarbital groups. The bispectral index fell immediately after dosing, in all pigs, but no significant differences were observed in the time needed to achieve 0 for the high or low-doses of either drug. In pigs maintained on isoflurane, a low dose of barbiturates is adequate for euthanasia and may result in less tissue damage.
Topics: Female; Animals; Swine; Pentobarbital; Thiopental; Isoflurane; Barbiturates; Anesthesia
PubMed: 36889741
DOI: 10.30802/AALAS-JAALAS-22-000093 -
Molecules (Basel, Switzerland) Sep 2022A concept of piezo-responsive hydrogen-bonded π-π-stacked organic frameworks made from Knoevenagel-condensed vanillin-barbiturate conjugates was proposed. Replacement...
A concept of piezo-responsive hydrogen-bonded π-π-stacked organic frameworks made from Knoevenagel-condensed vanillin-barbiturate conjugates was proposed. Replacement of the substituent at the ether oxygen atom of the vanillin moiety from methyl (compound ) to ethyl (compound ) changed the appearance of the products from rigid rods to porous structures according to optical microscopy and scanning electron microscopy (SEM), and led to a decrease in the degree of crystallinity of corresponding powders according to X-ray diffractometry (XRD). Quantum chemical calculations of possible dimer models of vanillin-barbiturate conjugates using density functional theory (DFT) revealed that π-π stacking between aryl rings of the vanillin moiety stabilized the dimer to a greater extent than hydrogen bonding between carbonyl oxygen atoms and amide hydrogen atoms. According to piezoresponse force microscopy (PFM), there was a notable decrease in the vertical piezo-coefficient upon transition from rigid rods of compound to irregular-shaped aggregates of compound (average values of coefficient corresponded to 2.74 ± 0.54 pm/V and 0.57 ± 0.11 pm/V), which is comparable to that of lithium niobate ( coefficient was 7 pm/V).
Topics: Barbiturates; Benzaldehydes; Hydrogen; Hydrogen Bonding; Models, Molecular; Oxygen
PubMed: 36080425
DOI: 10.3390/molecules27175659 -
The Journal of Biological Chemistry Feb 2017Barbiturates induce anesthesia by modulating the activity of anionic and cationic pentameric ligand-gated ion channels (pLGICs). Despite more than a century of use in...
Barbiturates induce anesthesia by modulating the activity of anionic and cationic pentameric ligand-gated ion channels (pLGICs). Despite more than a century of use in clinical practice, the prototypic binding site for this class of drugs within pLGICs is yet to be described. In this study, we present the first X-ray structures of barbiturates bound to GLIC, a cationic prokaryotic pLGIC with excellent structural homology to other relevant channels sensitive to general anesthetics and, as shown here, to barbiturates, at clinically relevant concentrations. Several derivatives of barbiturates containing anomalous scatterers were synthesized, and these derivatives helped us unambiguously identify a unique barbiturate binding site within the central ion channel pore in a closed conformation. In addition, docking calculations around the observed binding site for all three states of the receptor, including a model of the desensitized state, showed that barbiturates preferentially stabilize the closed state. The identification of this pore binding site sheds light on the mechanism of barbiturate inhibition of cationic pLGICs and allows the rationalization of several structural and functional features previously observed for barbiturates.
Topics: Animals; Bacterial Proteins; Barbiturates; Binding Sites; Crystallography, X-Ray; Cyanobacteria; Ion Channels; Models, Molecular; Protein Structure, Quaternary; Xenopus laevis
PubMed: 27986812
DOI: 10.1074/jbc.M116.766964