Acute impairing effects of morphine related to driving: A systematic review of experimental studies to define blood morphine concentrations related to impairment in opioid-naïve subjects

ABSTRACT

Objective: The objective of this study was to look for dose– and concentration–effect relationships in experimental studies on single-dose administration of morphine on traffic-relevant behavioral tests by a systematic literature review and possibly to see whether a dose/concentration could be defined below which few or no tests would be affected.

Methods: Searches for corresponding literature were conducted using MEDLINE, EMBASE, and PsycINFO, throughout March of 2016. The search strategy consisted of words colligated to cognitive and psychomotor functions of relevance to driving, in relation to morphine administration. The tests were arranged in main groups, and tests showing impairment were categorized by doses as well as calculated plasma concentrations.

Results: Fifteen studies were included in the review. Impairment after the administration of a single intravenously dose of morphine was found in some of the tests on reaction time, attention, and visual functions. No impairment was observed in tests on psychomotor skills and en-/decoding. Tests on reaction time appeared to be less sensitive to the morphine administration, whereas tests on visual functions and attention appeared to be the most sensitive to the morphine administration. Single-dose administration of morphine with dosages up to 5 mg appeared to cause very few effects on traffic-relevant performance tasks. At higher dosages, impairment was found on various tasks but with no clear dose–effect relationship. Plasma morphine concentrations less than 50 nmol/L are most probably accompanied by few effects on traffic-relevant performance tasks.

Conclusions: A plasma morphine concentration of 50 nmol/L (approximately 14.3 ng/mL) could represent an upper level, under which there is little accompanying road traffic risk. A single dose of 5 mg morphine IV and analgetic equivalence doses of fentanyl, hydromorphone, oxycodone, and oxymorphone are presented with the suggestion that few traffic-relevant effects will appear after such doses.

KEYWORDS:

• Morphine
• driving
• impairment
• performance
• review

Acknowledgments

We thank Wenche Jacobsen for her literature search. In addition, we thank Dr. Liliana Bachs, Dr. Eirin Bakke, Dr. Ingebjørg Gustavsen, Dr. Marte Handal, Dr. Knut Hjelmeland, Dr. Cecilie Thaulow, and Dr. Merete Vevelstad for their invaluable assistance in evaluating the primary search of titles, with corresponding abstracts.

For the development of pharmacokinetic models for the morphine concentrations in plasma, we thank Dr. Sticht (Institute of Legal Medicine, University of Cologne, Germany).

Funding

The presented review was partly funded by the DRUID project (2009; BASt, D-51427 Bergisch Gladbach, Germany).