Barbiturate coma therapy (BCT) is a choice treatment for refractory intracranial hypertension after all surgical or medical managements have failed to control the intracranial pressure (ICP). It helps to reduce cerebral blood flow, cerebral metabolic rate of oxygen consumption and ICP. However, this therapy can also cause many complications. One of the underreported, but life-threatening complications is refractory hypokalemia, which can lead to subsequent rebound hyperkalemia after sudden cessation. We report our experience of managing unusual complication of refractory hypokalemia during BCT with thiopentone in postdecompressive craniectomy patient.
Barbiturate coma therapy (BCT) is a treatment option that is used for refractory intracranial hypertension after all other options have been exhausted. Although BCT is a brain protection treatment, it also has several side effects such as hypotension, hepatic dysfunction, renal dysfunction, respiratory complications and electrolyte imbalances. One less concerning but potentially life-threatening complication of BCT is dyskalaemia. This complication could present as severe refractory hypokalaemia during the therapy with subsequent rebound hyperkalaemia after cessation of the therapy. Judicious potassium replacement during severe refractory hypokalaemia and gradual cessation of the therapy to prevent rebound hyperkalaemia are recommended strategies to deal with this complication, based on previous case series and reports. In this case report, we show that these strategies were applicable in improving severe hypokalaemia and preventing sudden, life-threatening rebound hyperkalaemia. However, even with use of these strategies, BCT patients could still present with mild, asymptomatic hyperkalaemia.
GABAA receptors are members of the Cys-loop family of ligand-gated ion channels which mediate most inhibitory neurotransmission in the central nervous system. These receptors are pentameric assemblies of individual subunits, including α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3. The majority of receptors are comprised of α, β and γ or δ subunits. Depending on the subunit composition, the receptors are located in either the synapses or extrasynaptic regions. The most abundant receptors are α1βγ2 receptors, which are activated and modulated by a variety of pharmacologically and clinically unrelated agents such as benzodiazepines, barbiturates, anaesthetics and neurosteroids, all of which bind at distinct binding sites located within the receptor complex. However, compared to αβγ, the binary αβ receptors lack a benzodiazepine α-γ2 interface. In pentameric αβ receptors, the third subunit is replaced with either an α1 or a β3 subunit leading to two distinct receptors that differ in subunit stoichiometry, 2α:3β or 3α:2β. The consequence of this is that 3α:2β receptors contain an α-α interface whereas 2α:3β receptors contain a β-β interface. Apart from the replacement of γ by α1 or β3 in binary receptors, the incorporation of ε subunit into GABAA receptors might be more complicated. As the ε subunit is not only capable of substituting the γ subunit, but also replacing the α/β subunits, receptors with altered stoichiometry and different pharmacological properties are produced. The different subunit arrangement of the receptors potentially constructs novel binding sites which may become new targets of the current or new drugs.
GABAA receptors are the major inhibitory neurotransmitter receptor in the human brain. The receptors are assembled from combination of protein subunits in pentameric complex which may consist of α1-6, β1-3, γ1-3, ρ1-3, δ, ε, θ, or π subunits. There are a theoretical > 150,000 possible assemblies and arrangements of GABAA subunits, although only a few combinations have been found in human with the most dominant consists of 2α1, 2β2, and 1γ2 in a counterclockwise arrangement as seen from the synaptic cleft. The receptors also possess binding sites for various unrelated substances including benzodiazepines, barbiturates, and anesthetics. The α5-containing GABAARs only make up ≤ 5% of the entire receptor population, but up to 25% of the receptor subtype is located in the crucial learning and memory-associated area of the brain-the hippocampus, which has ignited myriads of hypotheses and theories in regard to its role. As well as exhibiting synaptic phasic inhibition, the α5-containing receptors are also extrasynaptic and mediate tonic inhibition with continuously occurring smaller amplitude. Studies on negative-allosteric modulators for reducing this tonic inhibition have been shown to enhance learning and memory in neurological disorders such as schizophrenia, Down syndrome, and autism with a possible alternative benzodiazepine binding site. Therefore, a few α5 subunit-specific compounds have been developed to address these pharmacological needs. With its small population, the α5-containing receptors could be the key and also the answer for many untreated cognitive dysfunctions and disorders.
The brain is considered the most eloquent organ in the human body as its activities impacts on all other systems. Though protected physically (in a bony covering), physiologically through the blood-CSF barrier (from invading organisms and toxins) and hemodynamically through the phenomenon of cerebral autoregulation; the brain is open to insults of various kinds which can critically damage this structure. Intracellular Ca++ accumulation, excessive activation of excitatory amino acid receptors, lipid peroxidation and free radical releaserelated damage are but a few of the pathological processes that occur at the neuronal level leading to damage. The mechanism by which the brain can be provided protection when it is in a compromised state or likely to be compromised is known as cerebral protection. There are various modalities of pharmacologic (use of barbiturates, etomidate, isoflurane, steroids, Ca++, corticosteroids etc) and non-pharmacologic therapies (hypothermia, hyperventilation, induced hypotension, electrophysiologic monitoring, endovascular management etc) available for cerebral protection which finds place in the armamentarium of clinicians managing the critically injured brain. Our knowledge of the functioning of the brain at the molecular level and the various biochemico-pathological processes that are set into motion during critical states continues to evolve. This review article attempts to explain present understanding of the biochemical and pathological processes involved in neuronal damage while also looking at current available therapies (pharmacologic & nonpharmacologic) being utilized in different clinical settings.
The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13C-NMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis.
A field survey, based on a representative sample of children aged 12 to 16 years was carried out in three different areas of Malaysia. The data derived from the study have revealed that 10.5 per cent of them used drugs for non-medical reasons. Drug use was more common among boys (11.9 per cent) than girls (8.6 per cent). The highest frequency of drug was found in the youngest group--12-year-old children (13.5 per cent). The use of barbiturate and/or non-barbiturate sedatives (5.5 per cent) ranked first. This was followed in descending order by tranquillizers (4.5 per cent), simultants/amphetamines (3.9 per cent), heroin (3.6 per cent), morphine and/or opium (3.9 per cent), the hallucinogens (3.1 per cent) and cannabis (2.7 per cent).