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PubMed1989

Reduction of highly elevated plasma levels of gamma-aminobutyric acid does not reverse hepatic coma.

The pathogenesis of coma in patients with fulminant hepatic failure is still unknown, but there is some evidence that decreased hepatic metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may be involved. If this hypothesis is true, reduction of increased GABA levels in patients with hepatic encephalopathy should reduce the depth of hepatic coma. In the case described here, highly elevated plasma GABA levels were reduced by cross-circulation with baboon liver. No amelioration of the coma was observed, thus suggesting that decreased hepatic metabolism of GABA is not critically involved in hepatic encephalopathy.

Adult↗
PubMed1978

Human cerebral free amino acids in hepatic coma.

Free amino acids and some related compounds in autopsy specimens of different human brain areas have been determined by column chromatography. Only in patients with hepatic coma could a significant difference in the contents of tyrosine and lysine between caudate nucleus and N. amygdalae be found. In comparison with control subjects the brains of patients with hepatic coma contained significantly higher concentrations of glutamine, isoleucine, histidine and ammonia. In patients with hepatic coma after complete parenteral nutrition plus L-valine administration, dying from other causes, the brain levels of alanine and valine were decreased, while the content of taurine was significantly increased. However, most of the amino acid levels in brain tended toward lower levels. A very significant reduction after treatment with L-valine could be observed in glutamine and ammonia concentration. It is suggested that L-valine has some beneficial action on ammonia detoxification and has also a competing action on amino acid uptake mechanism (specially with the large neutral amino acids).

Adult↗
PubMed1984

Effect of charcoal hemoperfusion on amino acid disturbance in experimental hepatic coma.

Using the galactosamine induced hepatic coma rat model, we studied the effects of coated charcoal hemoperfusion on amino acids in plasma and CSF in grade III hepatic coma. We found that 1 hour of hemoperfusion significantly reduced AAAs and BCAAs in plasma and increased the molar ratio of BCAA:AAA. When rats in grade III coma were treated with 2 consecutive 1-hour hemoperfusions, the substantial reduction of plasma AAAs resulted in a significant decrease of AAA levels in CSF.

Adsorption↗
PubMed1994

Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial.

Previous reports have suggested that "endogenous" benzodiazepines could contribute to neural inhibition in hepatic encephalopathy. RO 15-1788 (flumazenil), a specific antagonist of brain benzodiazepine receptors, could thus reverse the neurological symptoms of hepatic encephalopathy. To test this possibility, we conducted a double-blind, placebo-controlled crossover trial of the efficacy of flumazenil in cirrhotic patients in hepatic coma. Seventy-seven cirrhotic patients in hepatic coma were evaluated. Fifty-six were excluded from the trial because of multiorgan failure or because coma was precipitated by prior use of benzodiazepines, and 21 patients were randomly assigned to the flumazenil group (11 patients) or the placebo group (10 patients). Treatment was administered intravenously as a 20-ml solution (placebo or 2 mg flumazenil); seven patients were crossed over. Clinical status was assessed blindly by two observers, using a modified Glasgow scale, every 15 min for 6 hr. Electroencephalogram tracings obtained before and after drug administration were evaluated blindly by two independent observers. Serum concentrations of benzodiazepines before treatment were measured by means of a fluorescence polarization immunoassay. Improvement in neurological symptoms was observed in six patients treated with flumazenil, whereas none in the placebo group showed improvement (p < 0.05; Fisher's exact test). Improvements in electroencephalogram tracings were demonstrated in four patients treated with flumazenil, compared with two patients in the placebo group (p = NS). Benzodiazepines were found in the serum of four patients treated with flumazenil (two responders and two nonresponders); all of these patients had received pharmaceutical benzodiazepines 4 to 6 days before the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1976

[Parenteral nutrition in hepatic coma (author's transl)].

A special program of parenteral nutrition was established in 16 patients with genuine hepatic coma and in 24 patients with portal encephalopathy; this program involves stepwise addition of various nutritional components. On the day of admission water and electrolyte balance is normalized, on the following morning infusions with 40% glucose solutions are started, and the patient is adapted to glucose as the source of calories within the next 48 hours. After this period total parenteral nutrition is instituted comprising all essential ingredients of nutrition. Application of amino acids was especially adjusted to the situation of hepatic coma taking into account not only the typical derangements of metabolism in hepatic coma, but the essential complications of this disease as well. Serial determinations of plasma amino acids were done in order to assess the program of nutrition. Before the beginning of parenteral nutrition plasma levels of amino acids were altered in a manner typical for liver failure; these alterations could be normalized almost completely by total parenteral nutrition.

Adult↗
PubMed1976

Hemodialysis versus cross hemodialysis in experimental hepatic coma.

In this study, the effects of conventional hemodialysis on experimental hepatic coma have been compared with those of hemodialysis against blood from a normal donor which allows exchanges without mixing of blood. cuprophan and polyacrylonitrile membranes were compared. Cross hemodialysis with a donor resulted in rpompt but transient recovery of consciousness, whichever membrane was used. Cuprophan hemodialysis without donor had no effect. Polacrylonitrile hemodialysis without donor allowed progressive and prolonged improvement in the consciusness level and the electroencephalograms. Therefore, clearance of middle molecular weight substances was more effective than exchange with a donor. Preliminary results in man showed total recovery of consciousness in six of ten patients with acute liver failure and coma and partial recovery from complete grade IV coma to grade II encephalopathy in two patients. These two patients reacted when called by their name by opening their eyes and obeying simple orders.

Acrylic Resins↗
PubMed1998

Genotyping HIV-1 and HCV strains by a combinatorial DNA melting assay (COMA).

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) strains can be genetically classified into genetic lineages known as genetic types or subtypes according to phylogenetic analyses of complete or partial nucleotide sequences of their genomes. The genetic classification of HIV-1 and HCV strains has important implications for the development of globally effective vaccines and for the management of patients. MATERIALS AND METHODS: A new method, termed combinatorial DNA melting assay (COMA), allows rapid accessing of comparative genetic information between related DNA sequences, making it possible to rapidly and accurately genotype unknown HIV-1 and HCV strains. COMA is mainly based on the differential melting properties of long DNA heteroduplexes. Combinatorial arrays of DNA heteroduplexes are formed when captured PCR-amplified reference DNA with known nucleotide sequences are combined with solution-phase complementary and antigenically labeled DNA with unknown sequences. Genetic divergence between the known and the unknown sequences is inferred as the experimentally derived melting curves of the two strands of the DNA heteroduplexes increasingly diverge. RESULTS: COMA was successfully applied to the genetic classification of HIV-1 and HCV strains into phylogenetic lineages or subtypes. CONCLUSIONS: Use of this assay should accelerate current efforts to understand the global molecular epidemiology of HIV-1 and HCV and may extend to the genetic characterization of other genetically diverse infectious pathogens associated with numerous diseases.

Base Composition↗
PubMed1979

Hyperglycemic hyperosmolar coma in a 9-month-old child.

Hyperglycemic hyperosmolar coma is a life-threatening emergency with a mortality much higher than that of other forms of hyperosmolarity such as hypernatremia or diabetic ketoacidosis. Despite the differences in the three conditions, present evidence suggests that correction of hyperosmolarity should proceed slowly to avoid the seizures that may occur in all three conditions. This report describes a 9-month-old diabetic child who initially had hyperglycemic hyperosmolar coma and who is one of the youngest survivors of this syndrome in the American literature. This case report points out the limited understanding of the pathophysiology of this syndrome and the consequent problems of therapy.

Diabetic Coma↗
PubMed2005

Validation of a new coma scale: The FOUR score.

The Glasgow Coma Scale (GCS) has been widely adopted. Failure to assess the verbal score in intubated patients and the inability to test brainstem reflexes are shortcomings. We devised a new coma score, the FOUR (Full Outline of UnResponsiveness) score. It consists of four components (eye, motor, brainstem, and respiration), and each component has a maximal score of 4. We prospectively studied the FOUR score in 120 intensive care unit patients and compared it with the GCS score using neuroscience nurses, neurology residents, and neurointensivists. We found that the interrater reliability was excellent with the FOUR score (kappa(w) = 0.82) and good to excellent for physician rater pairs. The agreement among raters was similar with the GCS (kappa(w) = 0.82). Patients with the lowest GCS score could be further distinguished using the FOUR score. We conclude that the agreement among raters was good to excellent. The FOUR score provides greater neurological detail than the GCS, recognizes a locked-in syndrome, and is superior to the GCS due to the availability of brainstem reflexes, breathing patterns, and the ability to recognize different stages of herniation. The probability of in-hospital mortality was higher for the lowest total FOUR score when compared with the lowest total GCS score.

Aged↗
PubMed1996

Brainstem auditory evoked potentials and somatosensory evoked potentials in prediction of posttraumatic coma in children.

Follow-up brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP) studies were performed within 72 hours after admission in 127 children with severe head injury (Glasgow Coma Scale score of < or = 8) in order to predict quo ad vitam outcome of posttraumatic coma. Outcomes were categorised as brain death and survival. On first assessment 50 comatose children had normal BAEPs and SEPs. 78% of them survived and 22% deteriorated and died. 45 had abnormal findings. 69% of them improved and survived whilst 31% deteriorated and died. 32 children did not have recordable BAEPs and SEPs. All of them died. Thus, comatose children with normal EP studies have in 78% good prognosis and a bad outcome can be reliably predicted.

Acoustic Stimulation↗
PubMed2006

Intracranial pressure levels and single wave amplitudes, Glasgow Coma Score and Glasgow Outcome Score after subarachnoid haemorrhage.

OBJECT: To relate intracranial pressure (ICP) levels and single ICP wave amplitudes to the acute clinical state (Glasgow Coma Score, GCS) and final clinical outcome (Glasgow Outcome Score, GOS) in patients with subarachnoid haemorrhage (SAH). METHODS: Twenty-seven consecutive patients with severe SAH had their ICP and arterial blood pressure (ABP) continuously monitored during days 1-6 after SAH. The acute clinical state could be assessed in 11 non-sedated cases using the Glasgow Coma Scale, while outcome was assessed in all cases after 6 months using the Glasgow Outcome Scale. The ICP/ABP recordings were stored as raw data files and analyzed retrospectively. For every consecutive 6 seconds time window, mean ICP, mean cerebral perfusion pressure (CPP) and the mean ICP wave amplitude were computed. RESULTS: The GCS during days 1-6 after SAH was significantly related to the mean ICP wave amplitude, but not to the mean ICP or mean CPP. There was also a strong relationship between the mean ICP wave amplitude and GOS 6 months after SAH, with mean ICP wave amplitudes being significantly lower in those with moderate disability/good recovery, as compared with those with severe disability and death. Mean ICP was significantly higher in those who died than in the group with moderate disability/good recovery whereas mean CPP was not different between outcome groups. CONCLUSIONS: In this small patient group the mean ICP wave amplitude during days 1-6 after SAH was related to the acute clinical state (GCS) as well as to the clinical outcome (GOS) 6 months after SAH. Similar relationships were not found for mean ICP or the mean CPP, except for a higher mean ICP in those who died than in those with moderate disability/good recovery.

Aged↗
PubMed1996

The Glasgow Coma Scale: a critical appraisal of its clinimetric properties.

The Glasgow Coma Scale is a commonly used instrument in clinical practice. This article examines the published evidence to assess whether the scale possesses the requisite clinimetric properties. Articles describing and using the scale were located through a MEDLINE search. The clinimetric properties of the scale were appraised using the methodological principles of sensibility, reliability, validity, and responsiveness. The scale has a good sensibility and reliability (intraclass correlation coefficient, 0.8 to 1 for trained users). It has a well-established cross-sectional construct validity. Its predictive validity in traumatic coma, when combined with age and brainstem reflexes, is good in the generating sample (sensitivity, 79 to 97%; specificity, 84-97%) but has not been tested in an external validation sample. Its longitudinal construct validity has not been studied adequately. Thus, the scale is an established discriminative instrument but its validity as a predictive and an evaluative instrument has not yet been studied adequately.

Coma↗
PubMed2005

Late auditory and event-related potentials can be useful to predict good functional outcome after coma.

OBJECTIVE: To investigate whether late auditory and event-related potentials, and in particular N100 and mismatch negativity, together with clinical parameters, can help to predict good functional outcome in comatose patients. DESIGN: Prospective cohort study. SETTING: Hospital. PARTICIPANTS: Consecutively sampled comatose patients (N=346) whose etiologies of coma were stroke (125 patients), brain injury (96 patients), anoxia (64 patients), complication of neurosurgery (54 patients), and encephalitis (7 patients). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Glasgow Outcome Scale score at 1 year postonset. Patients in a minimally conscious state and those who awoke and died during the follow-up period were classified separately. RESULTS: Univariate analysis showed that all variables studied, except brainstem auditory evoked potentials, correlated significantly with functional outcome. Mismatch negativity showed the highest positive predictive value for good outcome. A validated model was obtained with multivariate logistic analysis, including pupillary light reflex, N100, mismatch negativity, etiology, and age. CONCLUSIONS: Late auditory and event-related potentials, and particularly N100 and mismatch negativity, provide strong prognostic factors for good functional outcome. Furthermore, these components may enhance the accuracy of prognosis when associated with other clinical parameters available at the early stage of coma.

Adolescent↗
PubMed2005

Prediction of 'awakening' and outcome in prolonged acute coma from severe traumatic brain injury: evidence for validity of short latency SEPs.

OBJECTIVE: To evaluate the prognostic value of somatosensory evoked potentials (SEPs) in severe traumatic brain injury (TBI) considering both 'awakening' and disability. METHODS: SEPs were recorded in 60 severe TBI with duration of acute coma>7 days. N20-P25 amplitudes, their side-to-side asymmetry and CCT were measured. SEPs on each hemisphere were classified as normal (N), pathological (P) or absent (A). 'Awakening' and disability were assessed after at least 12 months using Glasgow Outcome Scale (GOS). SEP predictive value was compared with GCS and EEG reactivity RESULTS: Seventy-five percent regained consciousness. 29/60 had a good outcome (GOS 4-5) and 31/60 had a bad outcome (GOS 1-3). According to the ROC curve, SEP findings were classified in 3 grades. Grade I (NN, NP) had PPV of 93.1% for 'awakening' and 86.2% for good outcome. Grade III (AA) had PPV of 100% for bad outcome and 72.7% for 'awakening'. Grade II (PP, NA, PA) was associated with the wider range of outcome. A multivariate analysis including SEP grading, GCS and EEG reactivity did not increase the percentage of cases prognosticated by SEP alone. CONCLUSIONS: We confirm the high predictive value of SEPs in TBI, which is greater than GCS and EEG reactivity. Indeed, SEP grades I and III were able to predict the correct prognosis in more than 80% of severe TBI. Therefore, SEPs should be used more widely in the prognosis of severe TBI. SIGNIFICANCE: Differently from post-anoxic, in post-traumatic coma the presence of normal SEPs has a favourable predictive value both for 'awakening' and disability. We think that in literature enough attention has still not been paid to this finding.

Adolescent↗
PubMed1998

Quantitative electroencephalographic evaluation of non-fatal and fatal traumatic coma.

Diffuse axonal injury (DAI) is an important cause of morbidity and mortality after traumatic brain injury (TBI), and its severity is therefore a major determinant of outcome. There have been suggestions that the extent of DAI may be reflected in quantitative measures of cerebral function, including the electroencephalogram (EEG) and brain-stem auditory evoked potentials (BAEPs). It has therefore been proposed that these quantitative methods of analysis may provide objective predictors of outcome following TBI. We prospectively investigated the relationship between quantitative EEG and BAEP measures and outcome, in 60 comatose patients (47 male and 13 female; age range 1-80 years, mean 36.4) after severe, closed head injury (post-resuscitation Glasgow Coma Scale (GCS) of 8). The Spearman correlation coefficients (rs) have been calculated for quantitative EEG measures (mean regional power and interhemispheric coherence) and BAEPs with patient outcome on the Glasgow Outcome and Disability Rating Scales at 6 months and 1 year. The measures most significantly correlated with outcome (P < 0.001) are over the left hemisphere, beta activity power (amplitude squared) in the fronto-central and centro-temporal regions, and alpha activity power in the centro-temporal region. We found no correlation between interhemispheric coherence (a statistical measure of cross-correlation in the frequency domain) and outcome at either 6 months or 1 year post-injury. In 10 fatalities, we examined the relationship between interhemispheric EEG coherence prior to deaths and the histopathological severity of DAI, in concordant regions. The only significant correlation between DAI and interhemispheric coherence is seen in the alpha band at the temporo-occipital site (rs = -0.79, P = 0.007). Our data indicate that there is regional information in EEG power spectra over the left hemisphere, which could be used in prognostic predictions for patients in coma after severe TBI. We were unable to demonstrate a correlation between interhemispheric coherence and outcome, or any clear and consistent evidence of a relationship between interhemispheric coherence and the severity of DAI.

Adolescent↗
PubMed1998

Auditory and somatosensory evoked potentials in coma following spontaneous cerebral hemorrhage: early prognosis and outcome.

The aim of this study was to check the prognostic power of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) in coma following spontaneous cerebral hemorrhage. Seventy patients comatose following subarachnoidal or hypertensive hemorrhage were submitted to ABR and SEP recordings during the acute phase of clinical course. Twenty-one patients survived (30%), two remained vegetative (2.9%) and 47 died (68.1%). The Glasgow Coma Score (GCS) was significantly related to the outcome (P < 0.001), but showed a low sensitivity, since about 50% of patients with GCS = 5-8 died or remained vegetative. ABRs and SEPs showed a much closer correlation with outcome (P < 0.001): their combined use allowed there to be a sensitivity of 96%, a specificity of 90% and a predictive power of 96%; the relative risk of poor outcome in patients with at least one abnormal modality was equal to 223 times the one for patients with normal evoked potentials. Moreover, in surviving patients a significant relationship appeared to exist between abnormalities of SEPs during the acute phase and the severity of disability. Our results confirm the prognostic effectiveness of short latency evoked potentials in cerebral hemorrhage: they are far superior to clinical data, being able to yield a marked decrease of falsely optimistic predictions.

Adult↗
PubMed1994

Relation between Glasgow coma score and cough reflex.

How unconscious does a patient need to be, to be intubated without drugs? In 76 comatose patients (Glasgow coma score [GCS] < or = 8) who were treated consecutively in an emergency department, the integrity of the cough reflex was not related to GCS. All comatose patients must be treated as if their airway is compromised but even at the lowest coma scores, there are many patients whose airway reflexes are sufficiently intact to make procedures such as endotracheal intubation difficult and dangerous without drugs. The state of the airway should be assessed independently of conscious level.

Coma↗
PubMed1998

Systematic review of early prediction of poor outcome in anoxic-ischaemic coma.

BACKGROUND: Studies to assess the prognostic value of early neurological and neurophysiological findings in patients with anoxic-ischaemic coma have not led to precise, generally accepted, prognostic rules. We did a systematic review of the relevant literature to assess whether such rules could be derived from the combined results of these studies. METHODS: From Medline and Embase databases we selected studies concerning patients older than 10 years with anoxic-ischaemic coma in which findings from early neurological examination, electroencephalogram (EEG), or somatosensory evoked potentials (SSEP) were related to poor outcome--defined as death or survival in a vegetative state. We selected variables with a specificity of 100% for poor outcome in all studies, and expressed the overall prognostic accuracy of these variables as pooled positive-likelihood ratios and as 95% CIs of the pooled false-positive test rates. FINDINGS: In 33 studies, 14 prognostic variables were studied, three of which had a specificity of 100%: absence of pupillary light reflexes on day 3 (pooled positive-likelihood ratio 10.5 [95% CI 2.1-52.4]; 95% CI pooled false-positive test rate 0-11.9%); absent motor response to pain on day 3 (16.8 [3.4-84.1]; 0-6.7%); and bilateral absence of early cortical SSEP within the first week (12.0 [5.3-27.6]; 0-2.0%). EEG recordings with an isoelectric or burst-suppression pattern had a specificity of 100% in five of six relevant studies (pooled positive-likelihood ratio 9.0 [2.5-33.1]; 95%CI pooled false-positive test rate 0.2-5.9%). These characteristics were present in 19%, 31%, 33%, and 33% of pooled patient populations, respectively. For the 11 SSEP studies, results did not significantly differ between studies in which the treating physicians were or were not masked from the test result, prospective and retrospective studies, studies with short and long follow-up periods, and studies with high or low overall poor outcome. INTERPRETATION: SSEP has the smallest CI of its pooled positive-likelihood ratio and its pooled false-positive test rate. Because evoked potentials are also the least susceptible to metabolic changes and drugs, recording of SSEP is the most useful method to predict poor outcome.

Adolescent↗