Propofol and methohexital as anesthetic agents for electroconvulsive therapy: a randomized, double-blind comparison of electroconvulsive therapy seizure quality, therapeutic efficacy, and cognitive performance

BACKGROUND: Propofol is often used as an anesthetic agent for electroconvulsive therapy (ECT). Whether the relatively short seizure duration, resulting from the medication, deteriorates the seizure quality and therapeutic outcomes, or whether propofol might be associated with small but significant post-ECT cognitive impairments, is still a subject of controversy. The purpose of our study was to test these hypotheses in comparison with methohexital. MATERIALS AND METHODS: In a double-blind, controlled study, 50 patients with severe major depression who were to be treated with ECT were randomly assigned to anesthesia with propofol (120.9 +/- 50.0 mg) or methohexital (83 +/- 26.3 mg) and were observed for 2 months. The 2 drugs were compared on the basis of electroencephalography-registered seizure duration, mean blood pressure, as well as pulse frequency, seizure efficacy index, and postictal suppression. Systolic and diastolic blood pressure, and seizure duration and quality were recorded consecutively during ECT treatments. Changes in depressive symptoms and cognitive functions were measured at 5 time points, pre-ECT, after the third to fifth ECT, post-ECT treatment, and at a follow-up examination 2 and 8 weeks after the last ECT treatment. RESULTS: Patients on propofol showed a significantly lower increase in blood pressure post-ECT (P < 0.001), their seizure duration was comparable to patients on methohexital (P = 0.072), and seizure quality was significantly superior, as was measured by the Postictal Suppression Index (P = 0.020), and comparable to the methohexital group as measured by the Seizure Efficacy Index (P = 0.160). The improvement of depressive symptoms and the improvement in cognitive functions were similar in both groups (with the exception of the results from 2 cognition tests). CONCLUSIONS: Propofol, as compared with methohexital, results in a more moderate increase in blood pressure and shorter seizure duration. The seizure quality did not differ significantly between the 2 groups. We detected a tendency toward improved cognitive performance after anesthesia with propofol as compared with methohexital, but with statistical significance in only 2 cognition trials. Therefore, propofol is a safe and efficacious anesthetic for ECT treatment.     

Assessment of salivary cortisol as stress marker in ambulance service personnel: comparison between shifts working on mobile intensive care unit and patient transport ambulance

Purpose  

The aim of this study was to describe and compare salivary cortisol of ambulance personnel on days with different work demands as well as to correlate the individual perception of demands to the physiological outcome cortisol.     

Rats with hippocampal lesion show impaired learning and memory in the ziggurat task: a new task to evaluate spatial behavior

Spatial tasks are widely used to determine the function of limbic system structures in rats. The present study used a new task designed to evaluate spatial behavior, the ziggurat task (ZT), to examine the performance of rats with widespread hippocampal damage induced by N-methyl-d-aspartic acid (NMDA). The task consisted of an open field containing 16 identical ziggurats (pyramid shaped towers) arranged at equal distances. One of the ziggurats was baited with a food reward. The task required rats to navigate through the open field by using a combination of distal and/or proximal cues in order to locate the food reward. The ability to acquire and recall the location of the goal (baited) ziggurat was tested in consecutive training sessions of eight trials per day for 10 days. The location of the goal ziggurat was changed every second day, requiring the rats to learn a total of five different locations. Several parameters, including latency to find the target, distance traveled, the number of visits to non-baited ziggurats (errors), and the number of returns were used as indices of learning and memory. Control rats showed a significant decrease in distance traveled and reduced latency in locating the goal ziggurat across trials and days, suggesting that they learned and remembered the location of the goal ziggurat. Interestingly, the hippocampal-damaged group moved significantly faster, and traveled longer distances compared to the control group. Significant differences were observed between these groups with respect to the number of errors and returns on test days. Day 11 served as probe day, in which no food reward was given. The controls spent more time searching for the food in the previous training quadrant compared to the hippocampal group. The findings demonstrate that the ZT is a sensitive and efficient dry task for measuring hippocampus-dependent spatial performance in rats requiring little training and not associated with some of the disadvantages of water tasks.     

Stress accelerates neural degeneration and exaggerates motor symptoms in a rat model of Parkinson's disease

The causes of most cases of Parkinson's disease (PD) are still poorly understood. Here we show that chronic stress and elevated corticosterone levels exaggerate motor deficits and neurodegenerative events in a Parkinson's disease rat model. Animals were tested in skilled and non-skilled movement while being exposed to daily restraint stress or oral corticosterone treatment. Stress and corticosterone compromised normal motor function and exaggerated motor deficits caused by unilateral 6-hydroxydopamine lesion of the nigrostriatal bundle. Moreover, stress and corticosterone treatments diminished the ability to acquire compensatory strategies in limb use during skilled reaching and skilled walking. In contrast, lesion control animals were able to significantly improve in the ability of skilled limb use during the repeated test sessions. The exaggerated motor impairments in stress-treated animals were related to accelerated loss of midbrain dopamine-producing neurons during the first week postlesion. Correlation analysis revealed a significant connection between loss of tyrosine hydroxylase-positive cells and increase in Fluoro-Jade-positive cells only in stress- and corticosterone-treated animals. Furthermore, stress and elevated corticosterone levels caused greater permanent loss of midbrain neurons than found in non-treated lesion animals. These findings demonstrate that stress and elevated corticosterone levels can exaggerate nigral neuronal loss and motor symptoms in a rat analogue of PD. It is therefore possible that stress represents a key factor in the pathogenesis of human PD by impeding functional and structural compensation and exaggerating neurodegenerative processes.     

Advantages of a steady-state crossover design in assessment of bioequivalence of highly variable drugs: propafenone

Bioequivalence of highly variable drugs (i.e. high clearance drugs) is difficult to assess by means of conventional study designs. This paper reports a study on bioequivalence of two immediate release formulations of the antiarrhythmic drug propafenone in which a steady-state crossover design was used. The decision on bioequivalence was made with regard to the data of propafenone. Bioavailability data of the active metabolite, 5-hydroxypropafenone, and circadian pharmacokinetics of both analytes are also discussed. Following 5 days of administration (300 mg twice daily) to 20 volunteers, all parameters measured for estimating bioequivalence (AUC, C_max and PTF) were determined for both propafenone and 5-hydroxypropafenone during two consecutive dosage intervals. All target parameters obtained after administration of the test formulation were within the defined limits of bioequivalence when compared to reference for both parent compound and active metabolite for both dosage intervals. Basing on the calculated 90% confidence intervals it can be concluded that the two formulations are bioequivalent. Moreover, the steady-state study design may be applicable to other compounds with similar pharmacokinetic behaviour and seems to be generally advantageous for bioequivalence studies of highly variable drugs.     

A torque-controlled device to measure passive abduction of the thumb carpometacarpal joint.

The primary aim of this study was to design and then test the intrarater reliability of a torque-controlled method of measuring passive abduction of the thumb carpometacarpal (CMC) joint. A secondary aim was to quantify passive CMC abduction in patients with and without contracture. Initially, clinicians used subjective feel (without range of motion measurements) to identify 52 people with loss of passive thumb CMC abduction. All subjects had a neurological condition. Passive thumb CMC abduction was measured in both hands of these 52 people and the hands of another 20 healthy able-bodied individuals (total of 72 people and 144 hands). Passive thumb CMC abduction was measured using a newly designed torque-controlled device and the previously recommended caliper method. Repeat measurements were taken with both devices, two to three days later, by blinded assessors on a subgroup of 12 patients (24 hands). Median (interquartile range) CMC angle of thumbs deemed by clinicians to have contracture was 45 degrees (41-52 degrees) and that of subjects without contractures was 56 degrees (53-60 degrees). The intraclass correlation coefficient for the repeat measures attained with the torque-controlled device was 0.78 (95% confidence interval, 0.56-0.90). The torque-controlled device provides a way of standardizing torque when measuring passive thumb CMC abduction. The clear difference between passive CMC abduction of subjects with and without contracture confirms the ability of clinicians to use feel and subjective assessment to identify patients with contracture.     

Alcoholism and somatic comorbidity among homeless people in Mannheim,Germany

Aims  To assess the prevalence of alcoholism and somatic codisorders of homeless people.
Design  Epidemiological cross-sectional field study in a sample of the homeless in the area.
Setting  The study was conducted from 1997 to 1999 in the inner-city area of Mannheim, Germany (approximately 320 000 inhabitants).
Participants  One hundred and two single homeless people (15–16% of the estimated total population of single homeless people in the city).
Measurement  Alcoholism, substance abuse and mental disorders were diagnosed with the SCID. Medical examinations were performed by an experienced physician. Blood samples were taken and urine samples collected. Further assessments were conducted for factors potentially correlating with mental or physical state.
Findings  Of the study probands, 63.7% presented with the alcohol dependence syndrome or harmful use, 61.7% had current somatic problems or disorders. Probands with alcohol dependence had significantly more frequent somatic disorders in total, more cerebral degeneration, liver disease or alcoholic polyneuropathies. Multiple stepwise regression identified alcoholism, life-satisfaction, duration of homelessness and lacking social support as significant explanatory factors for having a somatic disorder. Alcoholism increased the risk of physical ill-health more than fourfold.
Conclusion  Alcoholism is a major contributor to the physical ill-health of homeless people. Treatment or rehabilitation of addictive behaviour among the homeless should be of major concern for adequate service planning or provision.