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Improved prediction of awakening or nonawakening from severe anoxic coma using tree-based classification analysis.

OBJECTIVE: To evaluate the utility of sensory and event-related evoked potentials for the prediction of awakening/nonawakening in severe anoxic coma and to design a decision tree helping decision for any patient in this condition. DESIGN: Prospective cohort study. SETTING: Clinical neurophysiology unit and intensive care unit of a French university hospital. PATIENTS: Sixty-two consecutive severe comatose patients after out-of-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We gathered clinical variables and recorded the somatosensory, auditory, and cognitive evoked potentials within an average period of 8 days after cardiac arrest. The patients were followed for 12 months and classified as awake or nonawake (permanent vegetative state or death). The statistical study included measurements of specificity, sensitivity, and positive and negative predictive value for each clinical and electrophysiologic variable recorded at the early stage of coma. Furthermore, a tree-based classification analysis was performed.All patients in whom somatosensory evoked potentials or middle-latency auditory evoked potentials were abolished did not awaken (100% specificity). All patients in whom mismatch negativity (MMN) was present awakened (100% specificity). MMN was superior to somatosensory evoked potentials for the prediction of awakening and had the best specificity and positive predictive value for awakening. On the decision tree, the awakening/nonawakening explicative variables were, by order of importance, MMN, pupillary reactivity, and somatosensory evoked potentials. CONCLUSIONS: There is a need to predict early and accurately awakening or nonawakening in postanoxic comas. Using sensory and cognitive evoked potentials to assess the functional condition of the brain, a prognostic tree for the prediction of awakening/nonawakening in severe anoxic coma has been designed. It is applicable to any patient in this condition and offers the possibility to predict with very high probability awakening when MMN, the earliest component of event-related potentials, is present and nonawakening when MMN and pupillary light reflex are absent or cortical components of somatosensory evoked potentials are abolished.

Adolescent↗

Brain death: a durable consensus?

Is it even conceivable that this global consensus [on the whole-brain definition of death] could, in time, be regarded as a very temporary and makeshift expedient, a momentary substitute for a resolution of some profoundly difficult issues which for a time, perhaps a brief time, fit with both the technical capacities and the legal needs of those who endorsed it? And that in the long run it could linger as a footnote, or perhaps a chapter heading, in the long history of man's conceptions of life and death? This suggestion is so far from conventional wisdom today that one who espouses it risks being regarded as a crank. Nevertheless, I believe that the argument in its favor, while not conclusive, is much stronger than the argument against it (and in favor of the prevailing consensus). I will state the argument briefly, with particular reference to the landmark report in 1982 in Washington of the President's Commission for the Study of Ethical Problems in Medicine, and will situate the argument in the context of trends in contemporary bioethics. I do not expect to win over, in this one pass, those who have been convinced of the validity of the conventional view. I do hope, however, to re-open the issue; in particular, to provide reasons to regard the issue as far from settled.

Advisory Committees↗

Making an advance directive.

The introduction in Britain of advance directives--which allow a person to state in advance of becoming incompetent that they wish to take part in treatment decisions when no longer mentally competent--has now been advocated by the medical and legal establishments. The practical application of directives relating to health care would be simplified by the adoption of a standard model document together with guidelines summarising the background clinical conditions and any subsequent acute events that may make it appropriate to trigger the use of a directive. As no specific legislation exists, good communication is needed at the various stages between the drafting and implementation of directives if the system of directives is to be successful.

Advance Directives↗

Survival and recovery of consciousness in anoxic-ischemic coma after cardiopulmonary resuscitation.

OBJECTIVE: In patients who remain unconscious after cardiopulmonary resuscitation (CPR) poor outcome may be predicted with several tests. To use these tests, knowledge of a priori chances of poor outcome after varying periods of unconsciousness is needed. This study is aimed at providing such data. DESIGN AND PATIENTS: Data regarding survival and recovery of consciousness were extracted from registry-based and prospective cohort studies of patients with anoxic-ischemic coma. A survival analysis was done using Kaplan-Meier estimates and 28-day outcomes were calculated for all patients unconscious after 24 h and 72 h, and 5 days, 7 days and 14 days after CPR. Patient characteristics and outcomes in our cohort were compared with those of published patient series. RESULTS: After 28 days, 27% of 172 patients from the two cohort studies were alive and conscious, 9% were still unconscious, and 64% had died. The proportion of patients who regained consciousness decreased from 34% of those unconscious within the first 6 h post-CPR to 13% of those still unconscious after 2 weeks. The proportion surviving in an unconscious state increased from 6% of patients who were unconscious initially to 33% of those still unconscious after 2 weeks. The chance of survival remained unchanged up to 7 days after CPR, irrespective of the duration of unconsciousness. Patient characteristics and outcomes in our cohort were comparable to data available from the literature. CONCLUSIONS: The a priori chances of (poor) outcome vary with the duration of unconsciousness after CPR. This study provides data for different time-intervals after CPR.

Adult↗

[Approach to the patient in vegetative state. Part III: prognosis].

To define a vegetative state (VS) as permanent is to declare its irreversibility. In 1994 a North-American multidisciplinary task force, by extensively analysing the literature, concluded that the recovery of consciousness from a post-traumatic or non-traumatic VS is unlikely after 12 and 3 months respectively. These conclusions did not obtain unanimous consent. The term permanent was in fact inappropriately used to define either the loss of consciousness or of function. Furthermore, patients with traumatic brain injury have been shown to recover the consciousness in a substantial greater percentage (6-7%) than previously appreciated (1.6%). This is hardly compatible with the peremptoriness of the term permanent, which should be used only in case of certainty. Ancillary tests are important in defining the prognosis. Patients in deep coma after an anoxic brain injury can be predicted as having a poor prognosis (death or permanent VS) with 100% specificity within one week of the insult. Magnetic resonance of the brain can predict patients at high risk of permanent VS within 6-8 weeks of a traumatic brain injury. In conclusion, the available evidence does not permit to define with certainty the patients who have irremediably lost their consciousness after a devasting brain insult. However, it seems possible to reliably define the risk of severe disability. Whether or not this knowledge might or should be used to titrate the intensity of therapeutic approach is to be defined. In this respect, it is central the definition of what an "acceptable outcome" is, certainly not an exclusive medical attribution.

Humans↗

The dead donor rule and the concept of death: severing the ties that bind them.

One goal of the transplant community is to seek ways to increase the number of people who are willing and able to donate organs. People in states between life and death are often medically excellent candidates for donating organs. Yet public policy surrounding organ procurement is a delicate matter. While there is the utilitarian goal of increasing organ supply, there is also the deontologic concern about respect for persons. Public policy must properly mediate between these two concerns. Currently the dead donor (dd) rule is appealed to as an attempt at such mediation. I argue that given the lack of consensus on a definition of death, the dd rule is no longer successful at mediating utilitarian and deontologic concerns. I suggest instead that focusing on a particular person's history can be successful.

Advance Directives↗

Early rehabilitative concepts in therapy of the comatose brain injured patients.

OBJECTIVES: To evaluate the changes of vegetative parameters and behavioural assessment in comatose patients after severe brain injury during the Multimodal-Early-Onset-Stimulation (MEOS) in early rehabilitation. MATERIAL AND METHODS: We studied 16 predominantly male (3:1) patients, age mean 43.6 (16-77) years. Mean coma duration was 22.2 (8-41) days, therapy duration (MEOS) 9.8 (1-30) days. The initial GCS was 6.6 (3-9), KRS 5.3 (0-15). Including criteria for therapy: Severe head trauma, coma for at least 48 hours (GCS < 8), vegetative stability, normal intracranial pressure, abandon of mechanical ventilation, sedation and severe infections. MEOS was finished in achieving GCS > 9, follow-up investigations were made after 2 years. RESULTS: We identified significant changes in two vegetative parameters (heart/respiratory frequencies), even in deep coma (GCS 3-4). Most significant changes were caused by tactile and acoustic stimulation. Standardized behavioural assessment turned out to be particularly advisable in cases of medium coma (GCS 5-7). Stimulation of tactile and acoustic senses resulted mainly in mimical, head and eye movements. Follow-up was possible in 14 patients: One remained in a vegetative state (GOS 2), two exhibited severe neurologic/neuropsychologic deficits, depending on care (GOS 3), six substained major functional deficits (GOS 4), at though they were able to perform the tasks of daily life on their own, three patients reached GOS 5. Two returned to their former jobs. DISCUSSION AND CONCLUSION: The present results indicate that stimulation therapy should be based on a close observation of patterns of behaviour, and, at least in deep coma stages, involve the registration of vegetative parameters. It may be sensitive to identify parameters predicting a favourable or unfavourable outcome. Preliminary data seem to support the hypothesis that the absence of any response to external stimuli is indicative of an unfavourable outcome.

Acoustic Stimulation↗

Vegetative state and minimally responsive patients--regional survey, long-term case outcomes and service recommendations.

A regional survey of Consultant level Neurology, Neurosurgical and Rehabilitation staff identified a retrospective estimate of patients in vegetative or minimally responsive states from their own clinical caseloads (October 1995--97). 35 patients were identified; the majority of whom were not currently placed in specialist brain injury facilities following acute hospital intervention. In addition, a retrospective review of referrals to this unit (1995--2001) was also undertaken. Of twelve patients referred as being in a vegetative or minimally responsive state, 4 were considered as having been misdiagnosed (emerged) at follow-up; 2 had been presumed to be vegetative for at least one year. All patients remained severely physically disabled (i.e., totally dependent for care) but four were nevertheless able to communicate their preference in quality of life issues, care decisions etc. either by verbal or non-verbal means. Vegetative-minimally responsive patients or those who are very severely and multiply disabled need skilled and frequently prolonged assessment. Appropriate management requires an experienced inter-disciplinary as opposed to multidisciplinary team working style, whose skill repertoire equips them to recognise often-subtle improvements in cognitive function and act to maximise individual patient's quality of life. The current paucity of service provision for this vulnerable group of patients is highlighted.

Activities of Daily Living↗

[Minimally conscious coma patients--patient positioning systems in general practice].

With a view to optimizing the positional management of patients with severe neurological damage, five positioning systems with different operating principles were submitted to suitability trials in a clinical neurological rehabilitation setting. The patients included were in the "Wachkoma", the minimally conscious state (i.e., in neurological early rehabilitation phase B). The experience collected by the various professions involved in positional management over a trial period of six months is summarized in the present report, indicating that none of the positioning systems used has been suitable for all patients alike. Hence, various items were compiled in a checklist to enable better estimation of each system's suitability in light of the individual patient, with muscle tone, body weight, skin condition, degree of mobilization and spontaneous movement the essential criteria in patient assessment. This checklist now permits identifying the positioning systems suitable for the individual patient in an economical manner, and lengthy positioning trials can be dispensed with to a large extent.

Beds↗

Predictors of outcome in prolonged posttraumatic disorders of consciousness and assessment of medication effects: A multicenter study.

OBJECTIVES: To develop predictive models of recovery from the vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury (TBI) and to gather preliminary evidence on the impact of various psychotropic medications on the recovery process to support future randomized controlled trials. Design Longitudinal observational cohort design, in which demographic information, injury and acute care history, neuroimaging data, and an initial Disability Rating Scale (DRS) score were collected at the time of study enrollment. Weekly follow-up data, consisting of DRS score, current psychoactive medications, and medical complications, were gathered until discharge from inpatient rehabilitation. SETTING: Seven acute inpatient rehabilitation facilities in the United States and Europe with specialized programs for treating patients in the VS and MCS. PARTICIPANTS: People with TBI (N=124) who were in the VS or MCS 4 to 16 weeks after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: DRS score at 16 weeks after injury and time until commands were first followed (among those participants demonstrating no command following at study enrollment). Results DRS score at enrollment, time between injury and enrollment, and rate of DRS change during the first 2 weeks of poststudy observation were all highly predictive of both outcomes. No variables related to injury characteristics or lesions on neuroimaging were significant predictors. Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed. More detailed analysis of the timing of functional improvement, with respect to the initiation of amantadine provided suggestive, but not definitive, evidence of the drug's causal role. CONCLUSIONS: These findings show the feasibility of improving outcome prediction from the VS and MCS using readily available clinical variables and provide suggestive evidence for the effects of amantadine and dantrolene, but these results require confirmation through randomized controlled trials.

Adult↗

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↗

Outcome of head injury in 2298 patients treated in a single clinic during a 21-year period.

Between 1968 and 1988, 2298 head-injured patients of all grades of severity were registered in the data bank of a single clinic. The majority of patients were admitted to a community hospital and transferred later to the neurosurgical clinic. The data included mechanism of injury and clinical status at admission, including the level of consciousness according to the Glasgow Coma Score (GCS) before and after resuscitation. After admission, nearly all patients below a score of 8 were intubated and treated with controlled ventilation until the patient awakened, died, or had remained in a steady state for approximately 3 weeks. Assessment of the final outcome was made according to the Glasgow Outcome Scale (GOS) both at discharge and again after the patient's status was stabilized. The results show a stable yearly outcome during the 21 years of recording but a significantly improved good recovery and mortality rate when compared with our previous results. Outcome was significantly correlated to age and type and severity of lesion, as judged by the postresuscitation GCS. The outcome of the 1264 most severely injured, comatose patients (GCS < 9) shows a good recovery rate of 55%, a severely disabled rate of 14%, a vegetative rate of 7%, and a mortality rate of 24%. We attribute these results, which compare favorably with others, to prompt airway control and controlled ventilation in unconscious patients.

Accidental Falls↗

Brain function in the vegetative state.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.

Cerebral Cortex↗

[Severely injured patients after the initial phase--vegetative state or remaining cognitive functions?].

BACKGROUND: We wanted to quantify improvements in the subacute rehabilitation phase in patients with severe brain injuries classified as vegetative or minimal brain consciousness. MATERIAL AND METHODS: Five patients were studied during a 12 months period using a method called Coma Recovery Scale (CRS) as described by Giacino et al. (1991). The parameters measured included visual and hearing functions, motor functioning, oromotor/verbal function, communication, and arousal. The observations of the patients and commandos given were standardised in a manual, and the responses achieved from the patients were recorded according to a scale for each parameter. RESULTS: This procedure for measuring closely the progress over time in these severely brain injured patients, was used for planning a realistic rehabilitation program. It was found to be very practical in communication with relatives of the patients and with the other therapists involved. INTERPRETATION: By decomposing the cognitive functions by this method using all the available possibilities for inputs, even minimal improvement in the cognitive functions mentioned could be uncovered and recorded.

Adolescent↗

Euthanasia and the quality of life debate.

Orthodox Christian ethics is grounded in the sacredness of life principle. Yet, it can accept a quality of life approach where "quality" refers not to capacities or states, but to the relationship between the patient's condition and the quest for transcendent life goals (Walter and Shannon, 1990). The true quality of human life derives from the vocation to stewardship, which enjoins an attitude of humble acceptance toward beneficial or "redemptive" suffering. The proper response to suffering in terminal cases is not active euthanasia or physician-assisted suicide but appropriate pain management and personal care. In cases of PVS or deep coma, only the determination of higher brain death can warrant the withholding or withdrawing of food and hydration. Yet, artificial maintenance of biological existence is also immoral. Death is to be accepted and embraced as a transition to eternal life.

Attitude to Death↗

Disability matters in medical law.

The British Parliament stated that health services would be covered by the Disability Discrimination Act 1995 (the act). However, when people with disabilities are at their most vulnerable, for example when in hospital or subject to medical procedures, the antidiscrimination law fails them. A review of cases indicates that when people with disabilities are subject to medical treatment, the legislative protections are allowed to vanish. Instead, medical decisions are justified on obscure notions such as "best interests", often with irreversible or even terminal results. This article examines the relevant provisions and limitations of the act, the features of notable non-treatment decisions, and the act's potential to guide future decision making. It argues that antidiscrimination legislation should be assertively applied to protect vulnerable people.

Decision Making↗

Can we predict poor outcome at presentation in patients with lobar hemorrhage?

OBJECTIVE: Supratentorial lobar hemorrhage can be devastating. Outcome prediction at presentation is important in triage and management decisions as well as appropriate resource utilization. We performed a decision tree analysis combining clinical and CT scan features to predict poor and hopeless outcome at initial presentation in patients with lobar hemorrhage. METHODS: We analyzed 81 patients with spontaneous lobar hemorrhage presenting within 48 hours of initial neurologic symptoms. In the first analysis, poor outcome was defined as Glasgow outcome score (GOS) of 1 (death), 2 (vegetative state) or 3 (dependence) at discharge. A second analysis was based on worst possible outcome (GOS 1-2). Binary recursive partitioning was fitted in a model, and odds ratios with 95% confidence intervals (CI) were calculated. RESULTS: Lobes involved were temporal (36%), parietal (33%), frontal (25%) and occipital (6%). Seventy-three percent of patients presented less than 17 h after initial ictus. The probability of poor outcome was 97% (CI 85-100%) in patients with hemorrhage greater than 40 cm(3). In the subset of patients with a volume less than 40 cm(3), time interval from ictus to presentation (< 17 h) together with a Glasgow coma score (GCS) less than or equal to 13 predicted poor outcome. Eighty-five percent (CI 42-99%) of those presenting early with GCS less than or equal to 13 had a poor outcome. In the second analysis, all patients with GCS less than or equal to 12 and septum pellucidum shift > 6 mm had GOS of 1 or 2 (CI 72-100%). CONCLUSION: Poor outcome in patients with lobar hemorrhage is associated with a hemorrhage size of more than 40 cm(3), GCS less than or equal to 13, but also dependent on time interval between ictus and presentation. This is consistent with prior studies demonstrating deterioration from enlargement may occur when patients present early on. Stupor and septum pellucidum shift greater than 6 mm on CT scan at presentation predict a hopeless outcome in conservatively treated patients. Ninety-one percent of patients were treated medically, thus these outcomes are largely a reflection of the natural history of spontaneous lobar hemorrhage. These signs may influence triage and management decisions.

Adolescent↗

Futility and unilateral decision making: a different view.

... Resuscitation of PVS patients is futile if the goal is to restore the patient to a cognitive or conscious state but not if the goal is restoration of respiratory function. The judgment of futility in either case is based on nonmedical (as well as medical) values or criteria, i.e., the value of cognitive life vs. the value of noncognitive life. If all of the affected parties concur that noncognitive recovery is a goal not worth achieving, a DNR order should be written. Lacking such concurrence, justification for a DNR order might be found in societal assessment of the burdens and benefits to others (besides the patient) of providing treatment in such circumstances. This is not a decision to be made unilaterally by a single physician, whose values are not necessarily reflective of those of the patient, family members, other physicians, or society at large.

Decision Making↗