Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology

OBJECTIVES: To evaluate the use of single-dose flumazenil in the diagnosis of coma of unknown etiology, and of continuous flumazenil infusion in the treatment of benzodiazepine-induced coma. DESIGN: Prospective study. SETTING: Emergency room and general medicine ward of a teaching hospital. PATIENTS: A total of 42 comatose adults in whom metabolic, neurologic, or traumatic causes of coma were excluded. INTERVENTIONS: a) Intravenous bolus injections of 0.25 mg flumazenil were given at 1-min intervals, either until improvement by two coma grades or a total dose of 2.0 mg was reached. b) Loading doses as in (a) followed by a maintenance infusion administered as long as indicated by repeated coma grade evaluation. MEASUREMENTS AND MAIN RESULTS: a) Of 34 patients, 28 received only the flumazenil loading dose responded promptly. Twenty-one of 25 available urine samples of the responding patients contained only benzodiazepine metabolites. Four urine samples contained benzodiazepines in combination with other drugs. Six patients did not respond to the flumazenil loading dose. The urine of three patients contained a combination of benzodiazepines and another coma-exerting drug; the remaining three were negative. A total of 24 patients, who initially responded to flumazenil loading, deteriorated to their previous coma state and were admitted to the general medical ward. Six (25%) patients developed complications related to hospitalization and their bedridden state. b) Eight other patients, who deteriorated after an initial loading dose, received a second iv bolus of flumazenil, followed by maintenance infusions over 5 to 24 hrs. Their hospital course was uneventful. CONCLUSIONS: These findings indicate that flumazenil is safe and effective in the diagnosis of benzodiazepine-induced coma. Furthermore, the use of continuous flumazenil maintenance infusion is of considerable therapeutic value in patients who exhibit deterioration after initial response to the single loading dose.     

Prognostic value of myoclonus status in comatose survivors of cardiac arrest

Generalized myoclonus status is common in comatose patients after cardiac resuscitation, but its prognostic value is uncertain. We studied the clinical, radiologic, and pathologic findings in 107 consecutive patients who remained comatose after cardiac resuscitation. Myoclonus status was present in 40 patients (37%). Features more prevalent in patients with myoclonus status were burst suppression on electroencephalograms, cerebral edema or cerebral infarcts on computed tomography scans, and acute ischemic neuronal change in all cortical laminae. All patients with myoclonus status died. Of 67 patients without myoclonus, 20 awakened. We conclude that myoclonus status in postanoxic coma should be considered an agonal phenomenon that indicates devastating neocortical damage. Its presence in comatose patients after cardiac arrest must strongly influence the decision to withdraw life support.     

Prediction of posttraumatic stress disorder by immediate reactions to trauma: a prospective study in road traffic accident victims

Road traffic accidents often cause serious physical and psychological sequelae. Specialists of various medical faculties are involved in the treatment of accident victims. Little is known about the factors which might predict psychiatric disorders, e.g. Posttraumatic Stress Disorder (PTSD) after accidents and how psychological problems influence physical treatment. In a prospective study 179 unselected, consecutively admitted road traffic accident victims were assessed a few days after the accident for psychiatric diagnoses, severity of injury and psychopathology. All were inpatients and had to be treated for bone fractures. At 6-months follow-up assessment 152 (85%) of the patients were interviewed again. Of the patients, 18.4% fulfilled the criteria for Posttraumatic Stress Disorder (DSM-III-R) within 6 months after the accident. Patients who developed PTSD were injured more severely and showed more symptoms of anxiety, depression and PTSD a few days after the accident than patients with no psychiatric diagnosis. Patients with PTSD stayed significantly longer in the hospital than the other patients. Multiple regression analysis revealed that the length of hospitalization was due mainly to a diversity of factors such as severity of injury, severity of accident, premorbid personality and psychopathology. Posttraumatic stress disorder is common after road traffic accidents. Patients with PTSD at follow-up can be identified by findings from early assessment. Untreated psychological sequelae such as PTSD cause longer hospitalization and therefore more costs than in non-PTSD patients.     

Diagnosis of death in comatose patients under resuscitation treatment: a critical review of the Harvard report

In this Article, which draws primarily on continental West European views on death and dying, the author contends that the Harvard criteria for irreversible coma (1968) are not reliable for diagnosing death in comatose patients under resuscitation treatment. The Article suggests that use of the Harvard Criteria to diagnose death leaves such patients legally unprotected against surgical assaults such as organ removal and biomedical experiments while they still may be living and capable of perception, possibly including the perception of pain and the spoken word. An alternative to the Harvard Criteria--angiography--is offered, and several additional issues related to the definition and diagnosis of death are discussed. Finally, the author suggests that even prior to death, termination of resuscitation treatment of irreversibly comatose patients, though followed by death, should be lawful.     

Correlation of cerebral blood flow with outcome in head injured patients

In order to determine the relationship of cerebral blood flow (CBF) to the clinical outcome of head injury, serial determinations of CBF were performed by the intravenous Xenon technique in 24 patients. The patients were of mixed injury severity and were classified into four groups depending on the neurological exam at the time of each CBF study. All eight patients who were lethargic on admission demonstrated increases in their minimally depressed CBF as they improved to normal status. Eleven patients in deep stupor or coma ultimately recovered. Ten of these patients initially had moderate to profound decreases in CBF which improved as recovery occurred. The single exception was an adolescent whose initial CBF was high but became normal at recovery. Five comatose patients died. In four of these, already depressed CBF fell even lower, while one adolescent with initially increased CBF developed very low CBF preterminally. The data presented in this report demonstrated a good correlation between CBF and clinical outcome. In every one of the adult survivors, depressed CBF increased as the patient recovered to normal status. All adults who died showed a deterioration of CBF as the neurological status worsened. The only exceptions were two adolescents who initially showed high CBF values. In the adolescent who died, CBF dropped to low levels while in the survivor a normal CBF was achieved. Thus in adults a traumatic brain injury was associated with depressed CBF which increased with recovery or decreased further with deterioration while the reaction to injury was quite different in the younger brain.     

Serum neuron-specific enolase as early predictor of outcome after cardiac arrest

OBJECTIVE: To examine the prognostic value of serum neuron-specific enolase for early prediction of outcome in patients at risk for anoxic encephalopathy after cardiac arrest. DESIGN: Prospective study. SETTING: Coronary intensive care unit of the University of Heidelberg. PATIENTS: Forty-three patients (66.8 +/- 12.7 [SD] yrs, range 33 to 85) who had had either primary or secondary cardiac arrest, followed by cardiopulmonary resuscitation (CPR). INTERVENTIONS: Serial blood samples and clinical examinations. MEASUREMENTS AND MAIN RESULTS: Serum neuron-specific enolase concentrations were determined after CPR on 7 consecutive days. Twenty-five patients remained comatose and subsequently died; 18 patients survived the first 3 months and had no relevant functional deficit at 3-month follow-up. Neuron-specific enolase concentrations were correlated with neurologic outcome. Concentrations of >33 ng/mL predicted persistent coma with a high specificity (100%) and a positive predictive value of 100%. Overall sensitivity was 80%, with a negative predictive value of 78%. Serum concentrations of neuron-specific enolase exceeded this cutoff value no more than 3 days after cardiac arrest in 95% of patients in whom these concentrations had exceeded 33 ng/mL. CONCLUSIONS: In patients who have been resuscitated after cardiac arrest, serum neuron-specific enolase concentrations of >33 ng/mL predict persistent coma with a high specificity. Values below this cutoff level do not necessarily indicate complete recovery, because this method has a sensitivity of 80%.     

Hypoglycaemia in spinal muscular atrophy

Repeated episodes of hypoglycaemia were observed in two girls with spinal muscular atrophy. During a 12 h fast blood glucose fell to 3.4 and 2.7 mmol/L, respectively. One girl developed hypoglycaemia and ketonuria. Reduced gluconeogenesis was probably the cause of hypoglycaemia in these patients who had a muscle mass of about 10% of bodyweight (normal 30-40%). Hypoglycaemia must be suspected and treated when patients with severe muscle wasting due to chronic neuromuscular disorders are admitted comatose. In our experience this condition is often regarded as respiratory insufficiency.     

A Canadian survey of cancer patients' experiences: are their needs being met?

Cancer patients (n = 913) who received treatment within the previous 2 years were interviewed to quantify reports of symptoms associated with cancer, measure the impact of symptoms on lifestyles, document experiences with accessing information and treatment for cancer and its symptoms, and record attitudes about the level of care received. Cancer patients were primarily recruited through newspaper ads placed throughout Canada and asked to complete a self-report questionnaire. Patients called a toll-free number and were interviewed to ensure eligibility. Most respondents were female (66%) with breast cancer (64%). Prostate cancer (40%) was the most common diagnosis among males. Almost all respondents (94%) reported experiencing one or more symptoms. Fatigue and anxiety were the most frequently reported symptoms (78% and 77%, respectively). Fatigue was most likely to be self-rated as moderate to severe and was most likely to interfere in normal daily activities. Respondents who experienced fatigue reported a more frequent use of healthcare services (including complementary therapies) than those who did not experience fatigue. Half of the respondents reported trying to find information on fatigue, but only half of these said they had obtained information. The most helpful sources of information were nurses, specialists, and other cancer patients. Respondents were more likely to be dissatisfied with their treatments for their symptoms than for their cancer. This survey indicates that most cancer patients experience symptoms related to the disease and its treatment. The most prevalent symptoms are fatigue and anxiety; fatigue is the most debilitating.     

Fatal traffic accidents in Denmark. Survival time and factors of importance for the prehospital phase]

The aim of the study was to determine the length of time of survival, and which factors affected the length of the prehospital phase/treatment-free period for persons who died as a result of a traffic accident in the County of Southern Jutland during the period from 1 January 1986 to 31 December 1991. The study was conducted as a retrospective investigation based on police reports and medical records. Two hundred and ninety-nine traffic victims were included. One hundred and nineteen were still alive when the ambulance reached the scene of the accident. Thirty-five of these died within one hour of the accident occurring, and 24 of the 35 died before reaching the hospital. The number of patients who died days to weeks after the trauma was lower than expected. In 80.2% of the traffic accidents (comprising 229 people killed and 193 wounded) there were other factors than distance from accident site to hospital that had a negative effect on the length of the prehospital phase and treatment-free period. It is concluded that the time that elapses between the accident occurring and the patient arriving at hospital must be better utilized, and that when evaluating the length of the prehospital phase/treatment-free period there are other factors than distance to hospital that must be taken into account.     

The koala has claws: applications of the shifting perspectives model in research of chronic illness

The Shifting Perspectives Model of Chronic Illness was recently developed in the metasynthesis of more than 250 qualitative research reports about chronic illness. The model proposes that people with chronic illness view living with their disease in accordance with how much wellness or illness is in the foreground of their experience. It also identifies a number of circumstances and situations that can prompt a shift from wellness or illness in the foreground to wellness or illness in the background. One such situation is being interviewed or observed as a participant in research about the experience of living with a chronic disease. The author reviews the model, providing excerpts from an interview with a key informant with a chronic illness to substantiate the model and to identify a number of implications of the model for researchers. She highlights some of the difficulties and limitations encountered when researchers attempt to define the experience of living with chronic illness through the lens of a single perspective.     

Development of the human fetal visceral pleura. An ultrastructural study

OBJECTIVE: To develop a method to predict long-term outcome after head injury and determine if outcome can be accurately predicted 24 hours after injury. DESIGN: A retrospective review was performed on a study cohort of 672 head-injured patients admitted in coma (Glascow Coma Scale score < or = 8) who remained comatose for at least 6 hours, survived more than 24 hours, and had 6-month outcome data available. Stepwise logistic regression analysis was used to determine which clinical variables predicted 6-month outcome. Statistically significant clinical predictors were combined into a single examination variable (MPX score), which reflected a rank-ordering of examinations from worst to best, which was then further weighted by patient age. The relation between 6-month outcome and MPX score at admission and 24 hours was plotted and analyzed. MEASUREMENT AND MAIN RESULTS: Age, best motor score, and pupillary reactivity at admission and 24 hours were significant predictors of outcome; extraocular motility was predictive at 24 hours only. Age was the most important independent predictor, followed by best motor score, pupillary reactivity, and extraocular motility. Combining these predictors into MPX score resulted in a set of graphs that reliably predicted long-term outcome. The 24-hour MPX data were better predictors of 6-month outcome and were more specific in predicting negative outcomes than admission data. CONCLUSIONS: The method is simple to use, relying on bedside neurologic examination and a single graph, but appears to predict long-term outcome accurately as early as 24 hours after head injury. If validated on other large series of patients, this method could provide an objective and practical basis for terminating care in patients unlikely to survive a head injury.     

Identifying illness: pitfalls and discoveries

A 63-year-old woman presented with a comatose state after a fall. Results of cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans were normal. An EEG recorded 5 h after admission was very severely attenuated and slowed. Consciousness and EEG were improved the next day. No cause was detected initially. After sleep deprivation, the patient had a generalized seizure followed by a similar coma and EEG. Even a single seizure may cause a prolonged coma with a very severely attenuated and slowed EEG.     

Characteristic clinical features in a case of fulminant subacute sclerosing panencephalitis

A 12-year-old girl with fulminant subacute sclerosing panencephalitis (SSPE) without myoclonic jerk and periodic EEG complexes is reported. She presented with blurred vision, fell into a coma after 2 weeks and died within 4 months. Magnetic resonance image (MRI) disclosed high intensity lesions in the lateral geniculate bodies, when the patient initially complained of blurred vision. Reviewing the cases of fulminant SSPE in the literature, more than half of the patients showed blurred vision or visual agnosia as an initial symptom. Most of those patients were female and rapidly deteriorated to a comatose state within 2 weeks. Based on the MRI study of the present patient, we speculate that the initial visual impairment in such patients can be attributed to the involvement of the lateral geniculate body.     

Fine-needle aspiration cytology of metastatic small cell carcinoma of the colon: a report of three cases

In an effort to understand the effect of cancer diagnosis and treatment in children and adolescents, and to identify issues that should be addressed with newly diagnosed patients, 85 patients with Ewing's sarcoma family tumors (ESFT) were interviewed about their experience of having cancer. This represents 90% of all eligible patients who survived at least 3 years since their diagnosis and who were treated for ESFT at the National Cancer Institute (NCI) from 1965-1993. The mean age of patients at the time of diagnosis was 15.8 +/- 5.3 years, and mean time since diagnosis was 13.6 +/- 6.4 years. Patients from this cohort had a disease usually related to poor outcome. Patients answered five open-ended written questions. Negative experiences that they described included transient and permanent discomfort and disabilities related to cancer; disruption of life or relationships; and emotional aspects of cancer diagnosis or treatment. Positive aspects of having cancer included changed attitudes about self and life, improved relationships with others, or better job performance. Advice for newly diagnosed patients most often dealt with the emotional aspects of cancer. The importance of patient-to-patient support was frequently described. Overall, having cancer was not an entirely negative experience, and it may result in introspection and improved relationships with others.     

Familial predisposition for degenerative disc disease. A case-control study

STUDY DESIGN: This case-control study was undertaken to determine if relatives of patients who had been admitted for surgery for degenerative disc disease-related problems were at increased risk for lower back pain or sciatica. OBJECTIVES: To determine if familial factors play a role in placing a person at risk for development of degenerative disc disease of the lumbar spine. SUMMARY OF BACKGROUND DATA: It is known that smoking and various occupational factors can place a person at risk for degenerative disc disease problems. It is not known if a familial predisposition may also exist. METHODS: The family members and relatives of 65 patients who had undergone surgery for lumbar degenerative disc disease were interviewed with a standardized questionnaire and compared with a control group of 67 patients who had been admitted to hospital for non-spine-related orthopedic procedures. The same interview and standardized questionnaire was used for both groups by a single observer. RESULTS: In the study group of 65 patients who had undergone surgery for degenerative disc disease, 44.6% were noted to have a positive family history, whereas 25.4% of the patients in the control group had a positive family history. Eighteen and one-half percent of relatives in the study group had a history of having spinal surgery, compared with only 4.5% of the control group. CONCLUSIONS: The results indicate that a familial predisposition to degenerative disc disease can exist along with other risk factors.     

Observation of lipid profile and lipoproteins in viral hepatitis and hepatic coma

Lipid profile and lipoprotein levels were estimated in 35 patients of viral hepatitis, 15 patients of viral hepatitis with coma and in age and sex match 35 healthy controls. The values were compared in different groups. Levels of triglycerides were significantly raised (145.00 +/- 30.70 mg/dl) in viral hepatitis as compared to viral hepatitis with coma (111.40 +/- 16.80 mg/dl) which were similar to controls (110.8 +/- 20.6 mg/dl). Patients who recovered had higher levels of triglycerides (136.0 +/- 30.8 mg/dl) as compared to those who expired (110 +/- 15.72 mg/dl). Total serum cholesterol remained statistically unaltered in both groups. HDLc was significantly decreased in both groups, viral hepatitis (2.23 +/- 6.7 mg/dl) and viral hepatitis with coma (16.52 +/- 2.27 mg/dl) in comparison to controls (62.21 +/- 18.04 mg/dl). The levels were much lower in patients with coma than without coma. Furthermore the values were still lower in patients who expired (15.82 +/- 2.27 mg/dl) than in patients who recovered (24.13 +/- 7 mg/dl). The levels of LDLc were significantly raised in both groups, as compared with each other and in relation to mortality. VLDLc levels were significantly decreased in patients of viral hepatitis (22.13 +/- 5.8 mg/dl) as well as on viral hepatitis with coma (21.89 +/- 4.3 mg/dl). However, no significant difference was observed when compared with each other and in relation to mortality. Thus it may be concluded that isolated low value of HDLc in viral hepatitis may be used as a prognostic indicator.     

Protective effect of intravenously administered cefuroxime against nosocomial pneumonia in patients with structural coma

In comatose patients admitted to an ICU, particularly those with head injury, the incidence of early onset pneumonia is exceedingly high. We performed an open, prospective, randomized, and controlled clinical trial aiming at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation. One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study (n = 50) received cefuroxime intravenously (two 1,500-mg doses 12 h apart after intubation) (the cefuroxime group) and 50 patients not receiving cefuroxime formed the control group. In the former group patients did not receive any other antibiotics before the end-point determination, whereas in the latter, 17 patients received prophylactic antibiotics as prescribed by the attending physician. The global incidence of microbiologically confirmed pneumonia was 37% (n = 37); 12 (24%) belonged to the cefuroxime group, and 25 (50%) belonged to the control group (p = 0.007). Early-onset pneumonia accounted for 70% of all the pneumonia episodes (n = 26), eight (67%) belonging to the cefuroxime group, and 18 (72%) belonging to the control group (p = 0.02). In the control group, four of 17 (23%) patients receiving prior antibiotics developed pneumonia, whereas 21 of 33 (64%) patients who did not receive antibiotics developed pneumonia (p = 0.016). The multivariate analysis revealed that the duration of mechanical ventilation (per each day) was an independent risk factor significantly associated to the development of pneumonia. Furthermore, the use of cefuroxime and/or prior antibiotics in the control group, before the pneumonia episode, had a protective effect against its development. No differences were found with regard to mortality and morbidity when comparing the study population with the control group. Nevertheless, when comparing patients with pneumonia (from both study and control groups) with those without it, there was a decrease in total hospital stay (35 +/- 13 versus 25 +/- 14 d, p = 0.048) and ICU stay (20 +/- 11 versus 11 +/- 7 d, p = 0.001). The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia.     

Disorders of the calcium-sensing receptor

From 1990 to 1995, 12 patients with cavo-atrial renal cell carcinoma underwent resection of the tumor. Circulatory arrest was employed in 11/12 cases. The neoplasm extended to the inferior vena cava in two patients and to the intrahepatic veins or right atrium in five cases. Two severely cardiac compromised patients died perioperatively. Of five patients who showed preoperative suspicion of isolated metastases, 3 patients died postoperatively because of relapsing disease after a mean period of 10.8 months. Five patients are alive and doing well after a mean follow-up of 14.8 months. In our experience myocardial dysfunction determined poor immediate survival. Mid-term survival was influenced by preoperative metastases and lymph-node involvement, but not by intracaval extension. Circulatory arrest appears to be a relatively safe technique to remove renal carcinoma with cavo-atrial extension and should be indicated whenever there are no metastases.     

Influence of breastfeeding and complementary food on growth between 5 and 10 months

OBJECTIVE: To evaluate the effectiveness of single proton emission tomography (SPECT) with 99mTc-HMPAO in the diagnosis of brain death (BD). DESIGN: Prospective study in comatose and brain-dead patients. SETTING: Neurologic ICU. PATIENTS AND METHODS: Fifty comatose patients (age range: 10 days-75 years) were submitted to SPECT study. In 21 of them (42%) reversible factors (e.g., influence of drugs affecting the central nervous system) were present. Thirty-eight patients were clinically brain-dead, while the remaining 12 were tested both in pre-terminal conditions and after the clinical onset of BD. INTERVENTIONS: Brain SPECT following i.v. injection of 99mTc-HMPAO (300-1100 MBq), using a 4-headed gamma-camera (20 min, 360 degrees, 88 images). MEASUREMENTS AND RESULTS: All patients tested in pre-terminal conditions showed preserved brain perfusion. Two of them had flat EEGs despite the absence of any reversible cause of coma; three patients survived, but remained in persistent vegetative states. SPECT confirmed the diagnosis of BD in 45 out of 47 patients (95.7%), clearly showing the arrest of brain perfusion (picture of "empty skull"); in two clinically brain-dead children (aged 10 days and 12 months, respectively) weak perfusion of the basal ganglia, thalamus and/or brain stem was still present, precluding the diagnosis of BD; both of them died a few days later. CONCLUSIONS: Our results confirm the reliability of SPECT in the diagnosis of BD. A problem arises about its effectiveness in brain-dead children, but this seems to be a matter of definition of BD and cerebral viability, rather than a limit of SPECT.     

Analysis of the T cell receptor repertoire in rheumatoid arthritis

BACKGROUND AND AIMS OF THE STUDY: Valve repair, where suitable, is the preferred option in patients who require mitral surgery. A number of studies have shown excellent long-term results, but most were undertaken in tertiary referral centers with a high throughput of patients. METHODS: We present our experience in 60 patients, aged 60 +/- 14 years, undergoing repair between 1984 and 1993. Most patients (83%) were in New York Heart Association (NYHA) class II or III at the time of surgery; 27% had concomitant ischemic heart disease. Almost all (98%) had posterior leaflet repair and 18% had anterior leaflet repair. Eight surgeons each performed a mean of 7.5 operations during this period. RESULTS: The 30-day mortality rate was 3.3%. There were seven late deaths. Five patients underwent reoperation for mitral regurgitation (two early, three late). At six years, 60% of patients were alive, or free of stroke or reoperation. Late follow up was obtained in 45 of 47 surviving patients: 95% were in NYHA class I or II; one-third were on anticoagulants for atrial fibrillation; 90% had mild (or less) mitral regurgitation on echocardiography. CONCLUSIONS: These data show that most patients have a very good outcome from valve repair surgery and encourage the trend towards operating earlier in the course of the disease. Adverse outcomes occurred mainly in patients who were highly symptomatic at the time of surgery. The high proportion of patients on postoperative anticoagulants underscores the importance of operating before atrial fibrillation becomes permanent.