Inhibition of ATP-sensitive potassium channels exacerbates anoxic coma in Locusta migratoria.

Under extreme environmental conditions, many insects enter a protective coma associated with a spreading depolarization (SD) of neurons and glia in the central nervous system (CNS). Recovery depends on the restoration of ion gradients by mechanisms that are not well understood. We investigated the effects of glybenclamide, an ATP-sensitive K+ (KATP) channel inhibitor, and pinacidil, a KATP activator, on the mechanisms involved in anoxic coma induction and recovery in Locusta migratoria. KATP channels allow for the efflux of K+ when activated, thereby linking cellular metabolic state to membrane potential. In intact locusts, we measured the time to enter a coma after water immersion and the time to recover the righting reflex after returning to normoxia. In semi-intact preparations, we measured the time to SD in the metathoracic ganglion after flooding the preparation with saline or exposing it to 100% N2 gas, and the time for the transperineurial potential to recover after removal of the saline or return to air. Glybenclamide decreased the time to coma induction, whereas pinacidil increased induction times. Glybenclamide also lengthened the time to recovery and decreased the rate of recovery of transperineurial potential after SD. These results were not the same as the effects of 10-2 M ouabain on N2-induced SD. We conclude that glybenclamide affects the CNS response to anoxia via inhibition of KATP channels and not an effect on the Na+/K+-ATPase.NEW & NOTEWORTHY We demonstrate the involvement of ATP-sensitive K+ (KATP) channels during recovery from spreading depolarization (SD) induced via anoxic coma in locusts. KATP inhibition using glybenclamide impaired ion homeostasis across the blood-brain barrier resulting in a longer time to recovery of transperineurial potential following SD. Comparison with ouabain indicates that the effects of glybenclamide are not mediated by the Na+/K+-ATPase but are a result of KATP channel inhibition.

Lateral Brain Displacement and Cerebral Autoregulation in Acutely Comatose Patients.

OBJECTIVES: Lateral displacement and impaired cerebral autoregulation are associated with worse outcomes following acute brain injury, but their effect on long-term clinical outcomes remains unclear. We assessed the relationship between lateral displacement, disturbances to cerebral autoregulation, and clinical outcomes in acutely comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Acutely comatose patients (Glasgow Coma Score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebral oximetry index, derived from near-infrared spectroscopy multimodal monitoring, was used to evaluate cerebral autoregulation. Associations between lateral brain displacement, global cerebral autoregulation, and interhemispheric cerebral autoregulation asymmetry were assessed using mixed random effects models with random intercept. Patients were grouped by functional outcome, determined by the modified Rankin Scale. Associations between outcome group, lateral displacement, and cerebral oximetry index were assessed using multivariate linear regression. Increasing lateral brain displacement was associated with worsening global cerebral autoregulation (p = 0.01 septum; p = 0.05 pineal) and cerebral autoregulation asymmetry (both p < 0.001). Maximum lateral displacement during the first 3 days of coma was significantly different between functional outcome groups at hospital discharge (p = 0.019 pineal; p = 0.008 septum), 3 months (p = 0.026; p = 0.007), 6 months (p = 0.018; p = 0.010), and 12 months (p = 0.022; p = 0.012). Global cerebral oximetry index was associated with functional outcomes at 3 months (p = 0.019) and 6 months (p = 0.013). CONCLUSIONS: During the first 3 days of acute coma, increasing lateral brain displacement is associated with worsening global cerebral autoregulation and cerebral autoregulation asymmetry, and poor long-term clinical outcomes in acutely comatose patients. The impact of acute interventions on outcome needs to be explored.

Glycated Hemoglobin is Associated with Glycemic Control and 6-Month Neurologic Outcome in Cardiac Arrest Survivors Undergoing Therapeutic Hypothermia.

BACKGROUND: Glucose control status after cardiac arrest depending on chronic glycemic status and the association between chronic glycemic status and outcome in cardiac arrest survivors are not well known. We investigated the association between glycated hemoglobin (HbA1c) and 6-month neurologic outcome in cardiac arrest survivors undergoing therapeutic hypothermia (TH) and whether mean glucose, area under curve (AUC) of glucose during TH, and neuron-specific enolase (NSE) are different between normal and high HbA1c groups. METHODS: This retrospective single-center study included adult comatose cardiac arrest survivors who underwent TH from September 2011 to December 2017. HbA1c and glucose were measured after return of spontaneous circulation (ROSC), and normal or high HbA1c was defined using cutoff value of 6.4% of HbA1c. Blood glucose was measured at least every 4 h and treated with a written protocol to maintain the range of 80-200 mg/dL. Hypoglycemia and hyperglycemia were defined with glucose < 70 or > 180 mg/dL. Mean glucose during induction and rewarming phase and AUC of glucose during every 6 h of maintenance were calculated, and NSE at 48 h after cardiac arrest was recorded. The primary outcome was unfavorable neurologic outcome, defined as Glasgow Pittsburgh Cerebral Performance Category scale 3-5 at 6 months after cardiac arrest. RESULTS: Of 384 included patients, 81 (21.1%) had high HbA1c and 247 (64.3%) had an unfavorable neurologic outcome. Patients with high HbA1c were more common in the unfavorable group than in favorable group (27.5% vs 9.5%, p < 0.001), and the unfavorable group had significantly higher HbA1c level (5.8% [5.4-6.8%] vs 5.6% [5.3-6.0%], p = 0.007). HbA1c level was independently associated with worse neurologic outcome (odds ratio 1.414; 95% confidence interval 1.051-1.903). High HbA1c group had higher glucose after ROSC, glucose AUC during maintenance, and rewarming phase than normal HbA1c group. High HbA1c group had significantly higher incidence of hyperglycemia throughout the TH, while normal HbA1c group had significantly higher incidence of normoglycemia. However, no glucose parameter remained as an independent predictor of neurologic outcome after adjustment, irrespective of HbA1c level. NSE showed good prognostic performance (area under curve 0.892; cutoff value 26.3 ng/mL). Although NSE level was not different between HbA1c groups, high HbA1c group had higher proportion of patient having NSE over cutoff. CONCLUSIONS: Higher HbA1c was independently associated with unfavorable neurologic outcome. Glycemic status during TH was different between normal and high HbA1c groups.

A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria.

BACKGROUND: Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital. METHODS: Children 24-83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects. The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken. RESULTS: Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 µg/mL) and all were above 6 µg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose. Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects. CONCLUSION: Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital. TRIAL REGISTRATION: NCT01660672 . NCT01982812 .

The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest.

OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 µg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17% (95% CI, 8.9-25%; p = 0.0004) and 21% (95% CI, 6.0-33%; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p < 0.0001). There was no effect of exenatide on other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac arrest patients, infusion with exenatide lowered blood glucose and resulted in increased clearance of lactate as well as increased heart rate. The clinical importance of these physiologic effects remains to be investigated.

Analysis of Risk Factors for Hypoglycemic Coma in 194 Patients with Type 2 Diabetes.

BACKGROUND The present study was conducted to analyze possible risk factors in patients with type 2 diabetes who are in hypoglycemic coma. MATERIAL AND METHODS A total of 194 patients with type 2 diabetic hypoglycemic coma who were admitted to our hospital between January 2010 and January 2016 were included. The patients were all in coma on admission, and their blood glucose levels were lower than 2.8 mmol/L. None of the patients had type I diabetes, specific types of diabetes, or gestational diabetes. Multiple linear regression analysis was used to determine possible factors associated with hypoglycemic coma. RESULTS Among the patients, 82 were male and 112 were female (mean age, 66.88±10.62 years). In addition, 72 patients lived in urban areas and 122 lived in rural areas. Occurrence of hypoglycemic coma was correlated with difference between urban and rural residence, glycosylated hemoglobin (HbA1c) level, combined hypertension, and combined neural complications. Self-purchased drugs resulted in significantly lower blood glucose level at the onset of hypoglycemic coma than insulin, secretagogue, or non-secretagogue drugs. Blood glucose level at onset was correlated with season. Patients living in rural areas or with combined macrovascular or microvascular complications had prolonged hospital stay and poor prognosis. CONCLUSIONS Our results demonstrate that rural residence, higher HbA1c level, combined hypertension, and combined neural complications increase the incidence of hypoglycemic coma. Use of self-purchased drugs and colder seasons may result in lower blood glucose levels in patients with hypoglycemic coma.

Pain-related Somato Sensory Evoked Potentials: a potential new tool to improve the prognostic prediction of coma after cardiac arrest.

INTRODUCTION: Early prediction of a good outcome in comatose patients after cardiac arrest still remains an unsolved problem. The main aim of the present study was to examine the accuracy of middle-latency SSEP triggered by a painful electrical stimulation on median nerves to predict a favorable outcome. METHODS: No- and low-flow times, pupillary reflex, Glasgow motor score and biochemical data were evaluated at ICU admission. The following were considered within 72 h of cardiac arrest: highest creatinine value, hyperthermia occurrence, EEG, SSEP at low- (10 mA) and high-intensity (50 mA) stimulation, and blood pressure reactivity to 50 mA. Intensive care treatments were also considered. Data were compared to survival, consciousness recovery and 6-month CPC (Cerebral Performance Category). RESULTS: Pupillary reflex and EEG were statistically significant in predicting survival; the absence of blood pressure reactivity seems to predict brain death within 7 days of cardiac arrest. Middle- and short-latency SSEP were statistically significant in predicting consciousness recovery, and middle-latency SSEP was statistically significant in predicting 6-month CPC outcome. The prognostic capability of 50 mA middle-latency-SSEP was demonstrated to occur earlier than that of EEG reactivity. CONCLUSIONS: Neurophysiological evaluation constitutes the key to early information about the neurological prognostication of postanoxic coma. In particular, the presence of 50 mA middle-latency SSEP seems to be an early and reliable predictor of good neurological outcome, and its absence constitutes a marker of poor prognosis. Moreover, the absence 50 mA blood pressure reactivity seems to identify patients evolving towards the brain death.

Effects of Experimental Coma on the Expression of Bcl-2 Protein and Caspases 3 and 9 in Rat Brain.

We performed immunohistochemical analysis of the expression of caspases 3, 9 and bcl-2 protein in rat brain at various terms after administration of LD50 of sodium thiopental. Expression of the specified apoptosis markers was found in the sensorimotor cortex and hippocampus (dentate gyrus and CA2 region).

Serum neuron-specific enolase levels from the same patients differ between laboratories: assessment of a prospective post-cardiac arrest cohort.

BACKGROUND: In comatose post-cardiac arrest patients, a serum neuron-specific enolase (NSE) level of >33 µg/L within 72 h was identified as a reliable marker for poor outcome in a large Dutch study (PROPAC), and this level was subsequently adopted in an American Academy of Neurology practice parameter. Later studies reported that NSE >33 µg/L is not a reliable predictor of poor prognosis. To test whether different clinical laboratories contribute to this variability, we compared NSE levels from the laboratory used in the PROPAC study (DLM-Nijmegen) with those of our hospital's laboratory (ARUP) using paired blood samples. METHODS: We prospectively enrolled cardiac arrest patients who remained comatose after resuscitation. During the first 3 days, paired blood samples for serum NSE were drawn at a median of 10 min apart. After standard preparation for each lab, one sample was sent to ARUP laboratories and the other to DLM-Nijmegen. RESULTS: Fifty-four paired serum samples from 33 patients were included. Although the serum NSE measurements correlated well between laboratories (R = 0.91), the results from ARUP were approximately 30% lower than those from DLM-Nijmegen. Therapeutic hypothermia did not affect this relationship. Two patients had favorable outcomes after hypothermia despite NSE levels measured by DLM-Nijmegen as >33 µg/L. CONCLUSIONS: Absolute serum NSE levels of comatose cardiac arrest patients differ between laboratories. Any specific absolute cut-off levels proposed to prognosticate poor outcome should not be used without detailed data on how neurologic outcomes correspond to a particular laboratory's method, and even then only in conjunction with other prognostic variables.

PET in coma and in vegetative state.

Advances in resuscitation and critical care management have resulted in the survival of many patients despite severe brain damage. These patients may remain in coma or in vegetative state. The probability of recovery of conscious function is dependent on the extent of structural brain damage, which is difficult to assess by clinical, laboratory or functional tests. Positron emission tomography (PET) of 18F-fluordeoxyglucose (FDG) can be used to investigate metabolic and functional impairment of the brain. In acute vegetative state (AVS, duration <1 month), overall glucose utilization was significantly reduced in comparison with age-matched controls. In a few cases with locked-in syndrome, cortical metabolism was in the normal range. 11C-Flumazenil (FMZ) measures the density of benzodiazepine receptors (BZRs) and thereby furnishes an estimate of neuronal integrity. PET with this tracer demonstrated a considerable reduction in BZRs in cortical areas, but indicated that the cerebellum was spared from neuronal loss. The comparison of FDG- and FMZ-PET findings in AVS demonstrates that alterations of cerebral glucose consumption do not represent mere functional inactivation, but also irreversible structural damage. In some cases with minimally conscious state, auditory stimuli with emotional valence induced more brain activation (investigated by H215O-PET) than meaningless noise; such studies can be used to detect residual cortical function. To improve prognostication of chances for recovery, a combination of functional activation studies and assessment of the extent of neuronal damage might be the optimal procedure and should be tested in larger cohorts of patients with comatose states of different severity.

Scleromyxedema and the dermato-neuro syndrome: case report and review of the literature.

Scleromyxedema is a generalized form of lichen myxedematosus which is characterized by a papular and sclerodermoid skin eruption resulting from dermal fibroblast proliferation and mucin deposition. The majority of patients with scleromyxedema have a monoclonal gammopathy, and other systemic manifestations are common. Herein we describe a case of the 'dermato-neuro syndrome', a rare and sometimes fatal neurologic manifestation of scleromyxedema which consists of fever, convulsions and coma, often preceded by a flu-like prodrome. In addition, we provide a comprehensive summary of previously published cases of the dermato-neuro syndrome and discuss the current etiopathogenic theories and treatment options for this rare disease.

Rapid cold hardening delays the onset of anoxia-induced coma via an octopaminergic pathway in Locusta migratoria.

Rapid cold hardening (RCH) is a short-term hormesis that occurs in many invertebrate species, especially in insects. Although RCH is best known as enhancing cold tolerance, it can also enhance anoxic tolerance. When exposed to prolonged anoxia, insects enter a reversible coma, which is associated with spreading depolarization (SD) in the central nervous system (CNS). In this study, we investigated the effects of RCH and octopamine (OA) on anoxia-induced SD in L. migratoria. OA is an insect stress hormone that has roles in many physiological processes. Thus, we hypothesized that OA is involved in the mechanism of RCH. First, we found that RCH affects the K+ sensitivity of the locust blood brain barrier (BBB) in a way similar to the previously described effects of OA. Next, using SD as an indicator of anoxia-induced coma, we took a pharmacological approach to investigate the effects of OA and epinastine (EP), an octopaminergic receptor (OctR) antagonist. We found that OA mimics, whereas EP blocks, the effect of RCH on anoxia-induced SD. This study demonstrates that OA is involved in the mechanism of RCH in delaying the onset of anoxia-induced locust coma and contributes to determining the mechanism of RCH that modulates insect stress tolerances.

Metabolic and neurologic sequelae in a patient with long-standing anorexia nervosa who presented with septic shock and deep hypoglycemia.

OBJECTIVE: To report the case of a 48-year female with chronic remitting anorexia nervosa who was found comatose at home and admitted to our hospital with a deep hypoglycemia (glucose level 0.6 mmol/L; 11 mg/dL) and septic shock secondary to a bilateral pneumonia. METHOD: Case report. RESULTS: After admission to the critical care unit, she further displayed a number of pronounced complications known to be associated with anorexia, including hypophosphatemia, disturbed liver functions and depression of all three hematological cell lines. The neurological recovery of the patient was complicated by encephalopathy and transient tetraparesis. With initial deep hypoglycemia at presentation and persisting coma, magnetic resonance imaging performed 5 days later did not demonstrate characteristic post-hypoglycemic abnormalities. Neuroradiological examination did however reveal the presence of extensive calcifications in the basal ganglia known as Fahr's syndrome. DISCUSSION: The potential relation between anorexia nervosa and Fahr syndrome has not been described before. The fact that this patient survived a glucose level that is usually associated with a very poor outcome is probably related to its special origin.

[Vegetative state (prolonged coma) as manifestation of stable pathological state].

Complex examination of 25 patients in vegetative state was performed before and after correction of secondary brain damage. Catamnesis over a period of at least 6 months was traced. Preliminary results showed that better recovery of consciousness and cognitive functions was observed if before treatment diffuse glucose hypometabolism was significantly more widespread than morphological changes. Minimal positive dynamics was detected in cases in which the reduction of glucose metabolism was minimal. This and other paradoxical results become explainable if to consider vegetative state as stable pathological state of the brain. This open new approaches to treatment of this group of patients.

Antidotal Effects of the Phenothiazine Chromophore Methylene Blue Following Cyanide Intoxication.

Our study was aimed at (1) determining the efficacy of the dye methylene blue (MB), following a rapidly lethal cyanide (CN) intoxication in un-sedated rats; (2) clarifying some of the mechanisms responsible for the antidotal properties produced by this potent cyclic redox dye. Sixty-nine awake rats acutely intoxicated by CN (IP, KCN 7 mg/kg) received saline, MB (20 mg/kg) or hydroxocobalamin (HyCo, 150 mg/kg) when in deep coma. Survival in this model was very low, reaching 9% at 60 min without any treatment. Methylene blue significantly increased survival (59%, p < .001) at 60 min, versus 37% with HyCo (p < .01). In addition, 8 urethane-anesthetized rats were exposed to a sublethal CN intoxication (KCN, 0.75 mg/kg/min IV for 4 min); they received MB (20 mg/kg, IV) or saline, 5 min after the end of CN exposure. All MB-treated rats displayed a significant reduction in hyperlactacidemia, a restoration of pyruvate/lactate ratio-a marker of NAD/NADH ratio-and an increase in CO2 production, a marker of the activity of the TCA cycle. These changes were also associated with a 2-fold increase in the pool of CN in red cells. Based on series of in vitro experiments, looking at the effects of MB on NADH, as well as the redox effects of MB on hemoglobin and cytochrome c, we hypothesize that the antidotal properties of MB can in large part be accounted for by its ability to readily restore NAD/NADH ratio and to cyclically re-oxidize then reduce the iron in hemoglobin and the electron chain complexes. All of these effects can account for the rapid antidotal properties of this dye following CN poisoning.

Recurrent moderate hypoglycemia exacerbates oxidative damage and neuronal death leading to cognitive dysfunction after the hypoglycemic coma.

Moderate recurrent hypoglycemia (RH) is frequent in Type 1 diabetes mellitus (TIDM) patients who are under intensive insulin therapy increasing the risk for severe hypoglycemia (SH). The consequences of RH are not well understood and its repercussions on neuronal damage and cognitive function after a subsequent episode of SH have been poorly investigated. In the current study, we have addressed this question and observed that previous RH during seven consecutive days exacerbated oxidative damage and neuronal death induced by a subsequent episode of SH accompanied by a short period of coma, in the parietal cortex, the striatum and mainly in the hippocampus. These changes correlated with a severe decrease in reduced glutathione content (GSH), and a significant spatial and contextual memory deficit. Administration of the antioxidant, N-acetyl-L-cysteine, (NAC) reduced neuronal death and prevented cognitive impairment. These results demonstrate that previous RH enhances brain vulnerability to acute hypoglycemia and suggests that this effect is mediated by the decline in the antioxidant defense and oxidative damage. The present results highlight the importance of an adequate control of moderate hypoglycemic episodes in TIDM.

Increased production of the TrkB protein tyrosine kinase receptor after brain insults.

The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults.

Truncation of the krebs cycle during hypoglycemic coma.

There is a misconception that hypoglycemic nerve cell death occurs easily, and can happen in the absence of coma. In fact, coma is the prerequisite for neuronal death, which occurs via metabolic excitatory amino acid release. The focus on nerve cell death does not explain how most brain neurons and all glia survive. Brain metabolism was interrogated in rats during and following recovery from 40 min of profound hypoglycemia using ex vivo (1)H MR spectroscopy to determine alterations accounting for survival of brain tissue. As previously shown, a time-dependent increase in aspartate was equaled by a reciprocal decrease in glutamate/glutamine. We here show that the kinetics of aspartate formation during the first 30 min (0.36 +/- 0.03 micromol g(-1) min(-1)) are altered such that glutamate, via aspartate aminotransferase, becomes the primary source of carbon when glucose-derived pyruvate is unavailable. Oxaloacetate is produced directly from alpha-ketoglutarate, so that reactions involving the six-carbon intermediates of the tricarboxylic acid cycle are bypassed. These fundamental observations in basic metabolic pathways in effect redraw the tricarboxylic acid cycle from a tricarboxylic to a dicarboxylic acid cycle during hypoglycemia. The basic neurochemical alterations according to the chemical equilibrium of mass action augments flux through a truncated Krebs cycle that continues to turn during hypoglycemic coma. This explains the partial preservation of energy charge and brain cell survival during periods of glucose deficiency.

[Coma: etiology, diagnosis, and treatment]. / Koma: priezastys, diagnostika, gydymas.

SUMMARY: Coma is the disorder of consciousness because of the damage to diffused bilateral cerebral hemisphere cortex or reticular activating system. Coma can be caused by neurogenic (head brain injury), metabolic (endogenic), and toxic (exogenic) factors. To determine the cause of metabolic and toxic coma, laboratory tests are performed; in case of neurogenic coma, the neurologic examination is essential, when five systems are evaluated: the level of consciousness (according to Glasgow Coma Scale or Full Outline of Unresponsiveness Scale), photoreaction of pupils and ophthalmoscopic examination, oculomotoric, motoric, and cardiopulmonary systems. For the treatment of coma, adequate oxygenation and correction of blood circulation disorders are important. The treatment of metabolic coma is guided by special schemes; antidotes often are needed in the treatment of toxic coma, and surgery helps if traumatic brain injury is present. The prognosis and outcomes of the comatose patient depend on the age and comorbid diseases of the patient, the underlying cause of coma, timely medical help and its quality, and intensive treatment and care of the patient in coma.