Drug-induced respiratory depression: an integrated model of drug effects on the hypercapnic and hypoxic drive

Drug-induced respiratory depression is a common side effect of the agents used in anesthesia practice to provide analgesia and sedation. Depression of the ventilatory drive in the spontaneously breathing patient can lead to severe cardiorespiratory events and it is considered a primary cause of morbidity. Reliable predictions of respiratory inhibition in the clinical setting would therefore provide a valuable means to improve the safety of drug delivery. Although multiple studies investigated the regulation of breathing in man both in the presence and absence of ventilatory depressant drugs, a unified description of respiratory pharmacodynamics is not available. This study proposes a mathematical model of human metabolism and cardiorespiratory regulation integrating several isolated physiological and pharmacological aspects of acute drug-induced ventilatory depression into a single theoretical framework. The description of respiratory regulation has a parsimonious yet comprehensive structure with substantial predictive capability. Simulations relative to the synergistic interaction of the hypercarbic and hypoxic respiratory drive and the global effect of drugs on the control of breathing are in good agreement with published experimental data. Besides providing clinically relevant predictions of respiratory depression, the model can also serve as a test bed to investigate issues of drug tolerability and dose finding/control under non-steady-state conditions.

Can a novel web-based computer test predict poor simulated driving performance? A pilot study with healthy and cognitive-impaired participants

BACKGROUND Driving a car is a complex instrumental activity of daily living and driving performance is very sensitive to cognitive impairment. The assessment of driving-relevant cognition in older drivers is challenging and requires reliable and valid tests with good sensitivity and specificity to predict safe driving. Driving simulators can be used to test fitness to drive. Several studies have found strong correlation between driving simulator performance and on-the-road driving. However, access to driving simulators is restricted to specialists and simulators are too expensive, large, and complex to allow easy access to older drivers or physicians advising them. An easily accessible, Web-based, cognitive screening test could offer a solution to this problem. The World Wide Web allows easy dissemination of the test software and implementation of the scoring algorithm on a central server, allowing generation of a dynamically growing database with normative values and ensures that all users have access to the same up-to-date normative values. OBJECTIVE In this pilot study, we present the novel Web-based Bern Cognitive Screening Test (wBCST) and investigate whether it can predict poor simulated driving performance in healthy and cognitive-impaired participants. METHODS The wBCST performance and simulated driving performance have been analyzed in 26 healthy younger and 44 healthy older participants as well as in 10 older participants with cognitive impairment. Correlations between the two tests were calculated. Also, simulated driving performance was used to group the participants into good performers (n=70) and poor performers (n=10). A receiver-operating characteristic analysis was calculated to determine sensitivity and specificity of the wBCST in predicting simulated driving performance. RESULTS The mean wBCST score of the participants with poor simulated driving performance was reduced by 52%, compared to participants with good simulated driving performance (P<.001). The area under the receiver-operating characteristic curve was 0.80 with a 95% confidence interval 0.68-0.92. CONCLUSIONS When selecting a 75% test score as the cutoff, the novel test has 83% sensitivity, 70% specificity, and 81% efficiency, which are good values for a screening test. Overall, in this pilot study, the novel Web-based computer test appears to be a promising tool for supporting clinicians in fitness-to-drive assessments of older drivers. The Web-based distribution and scoring on a central computer will facilitate further evaluation of the novel test setup. We expect that in the near future, Web-based computer tests will become a valid and reliable tool for clinicians, for example, when assessing fitness to drive in older drivers.