Effect of chronic opioid therapy on actual driving performance in non-cancer pain patients.

RATIONALE: Chronic non-cancer pain (CNCP) is a major health problem. Patients are increasingly treated with chronic opioid therapy (COT). Several laboratory studies have demonstrated that long-term use of opioids does not generally impair driving related skills. But there is still a lack of studies investigating on-the-road driving performance in actual traffic. OBJECTIVES: The present study assessed the impact of COT on road-tracking and car-following performance in CNCP patients. METHODS: Twenty CNCP patients, long-term treated with stable doses of opioid analgesics, and 19 healthy controls conducted standardized on-the-road driving tests in normal traffic. Performance of controls with a blood alcohol concentration (BAC) of 0.5 g/L was used as a reference to define clinically relevant changes in driving performance. RESULTS: Standard Deviation of Lateral Position (SDLP), a measure of road-tracking control, was 2.57 cm greater in CNCP patients than in sober controls. This difference failed to reach statistical significance in a superiority test. Equivalence testing indicated that the 95% CI around the mean SDLP change was equivalent to the SDLP change seen in controls with a BAC of 0.5 g/L and did not include zero. When corrected for age differences between groups the 95% CI widened to include both the alcohol reference criterion and zero. No difference was found in car-following performance. CONCLUSIONS: Driving performance of CNCP patients did not significantly differ from that of controls due to large inter-individual variations. Hence in clinical practice determination of fitness to drive of CNCP patients who receive opioid treatments should be based on an individual assessment.

Hepatic encephalopathy and fitness to drive.

BACKGROUND & AIMS: Low-grade hepatic encephalopathy (HE) may impair fitness to drive. Driving deficits have not yet been characterized, and their relation to psychometric test results is unclear. METHODS: Fifty-one cirrhotic patients and 48 age-matched controls underwent real driving in a multiple sensor and camera-equipped car, laboratory and "in-car" computer psychometry, and driving instructor's assessment. RESULTS: Ten cirrhotic patients had no hepatic encephalopathy (HE0); 27 and 14 patients suffered from minimal HE (mHE) and overt HE grade I (oHE), respectively. During real driving, mHE and oHE patients showed significantly more violations of in-lane keeping, reduced break use, prolonged reaction times, and diminished stress tolerance compared with control or cirrhotic HE0 patients. In a self-evaluation questionnaire, mHE and oHE, but not the HE0, patients strongly overestimated their driving abilities. According to the driving instructor's assessment, 75%, 48%, and 39% of the patients with HE0, mHE, and oHE, respectively, were fit to drive, compared with 87% in the control group. Driving deficits in oHE patients were largely due to cognitive defects and prolonged reaction times, whereas, in mHE patients, mistakes and attention deficits predominated. Computer psychometric test results worsened with HE severity and age, whereas real driving was age independent. In 25 out of 94 patients, discordant results for driving fitness were obtained (driving instructor's assessment vs computer psychometry); in mHE and oHE patients, the concordance rates were only 62% and 64%, respectively. CONCLUSIONS: Despite significant driving deficits, HE patients overestimate their driving abilities. The presence of mHE does not necessarily predict driving unfitness, and computer-based testings cannot reliably predict driving fitness.

Aminergic control of high-frequency (approximately 200 Hz) network oscillations in the hippocampus of the behaving rat.

Hippocampal high-frequency (200 Hz, 'ripple') oscillations were recorded in the CA1 area of behaving rats. The histamine H1-receptor antagonist pyrilamine facilitated while the H2-antagonist zolantidine (5 mg/kg i.p) transiently decreased ripple occurrence. Thioperamide, an H3 antagonist, had no effect. The 5-HT1A-receptor antagonist WAY100635 (50 microg i.c.v.) reduced the occurrence and the intrinsic frequency of ripples. The 5-HT3-receptor antagonist Y-25130 (i.c.v.) increased the number but reduced the amplitude of ripples. All the treatments affected sharp-waves and ripple oscillations to the same extent. Changes of ripple occurrence were not secondary to alterations of behavior. In the light of these divergent actions via different receptor subtypes the net effect of aminergic innervations will be determined by their state-dependent activities and mutual interactions as well as receptor localizations.