Publications by authors named "Lars Slørdal"

115 Publications

Legemiddelavvik hos pasienter innlagt i sykehus.

Tidsskr Nor Laegeforen 2021 Mar 16;141(5). Epub 2021 Mar 16.

Background: Errors in the use and administration of medicinal drugs are not uncommon. There is little up-to-date information available on medication errors in Norwegian hospitals.

Material And Method: It is compulsory to report all adverse events internally at St Olav's Hospital via an electronic form. For the three-year period 2015-2017 we have reviewed all medication errors in the database where the reports are stored and compared them with figures from a similar study conducted in the period 2002-2006.

Results: Altogether 1604 medication errors were registered, distributed among 1587 reports. Dosing errors were most common (n=1070; 67 %), followed by administration of another drug than prescribed (n=175; 11 %). Most errors were of an insignificant or low degree of severity. There was a preponderance of reporting among the youngest and the oldest patients. 79 % of the errors were reported by nurses. Inattention/forgetfulness (15 %), stress/high workload (12 %), sloppy documentation in drug charts (10 %) and erroneous/unclear prescribing (10 %) were reported as the most frequent causes.

Interpretation: The number of reports of medication errors is increasing, but the extent of underreporting is uncertain. The types of errors and their distribution are similar to previous studies. The underlying causes are also well known; the challenge is to prevent these situations from arising.
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http://dx.doi.org/10.4045/tidsskr.20.0664DOI Listing
March 2021

Recognising madness.

Tidsskr Nor Laegeforen 2020 11 23;140(17). Epub 2020 Nov 23.

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http://dx.doi.org/10.4045/tidsskr.20.0184DOI Listing
November 2020

Severe Neurological Sequelae after a Recreational Dose of LSD.

J Anal Toxicol 2020 Oct 8. Epub 2020 Oct 8.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim.

A young man with an unremarkable medical history suffered a seizure with subsequent cardiorespiratory arrest and severe neurological sequelae after ingesting a blotter. Analysis of a similar blotter and a serum sample obtained 3 hours after the event detected lysergic acid diethylamide (LSD) at the amount of 300 μg in the blotter and at a concentration of 4.0 ng/mL (12.4 nmoles/L) in serum. No other drugs were present in concentrations which may confer significant effects. In addition, no individual traits which would make the patient particularly susceptible to adverse LSD effects have subsequently been identified. This suggests that LSD may confer toxic effects in previously healthy individuals.
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http://dx.doi.org/10.1093/jat/bkaa145DOI Listing
October 2020

Quetiapine for the people?

Tidsskr Nor Laegeforen 2020 09 28;140(13). Epub 2020 Sep 28.

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http://dx.doi.org/10.4045/tidsskr.20.0704DOI Listing
September 2020

Post mortem tissue distribution of quetiapine in forensic autopsies.

Forensic Sci Int 2020 Oct 24;315:110413. Epub 2020 Jul 24.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Clinical Pharmacology, St. Olav University Hospital, NO-7006, Trondheim, Norway.

The antipsychotic drug quetiapine is widely used, and increasingly prescribed off-label. Furthermore, quetiapine use has been linked to increased mortality rates, most likely due to a range of cardiovascular and metabolic adverse effects. This makes quetiapine a relevant substance in forensic toxicology casework. Quetiapine is believed to undergo significant post mortem redistribution. Herein, we present tissue distribution and concentration levels of quetiapine in post mortem whole blood, brain tissue, skeletal muscle, and liver tissue in a series of 14 quetiapine-implicated forensic autopsy cases along with the quetiapine concentrations determined in femoral whole blood in conjunction with the autopsies. Quantification was performed using liquid-liquid extraction and a validated UPLC-MSMS method. Six deaths were attributed to intoxication with quetiapine in combination with other substances; there were no quetiapine monointoxications. In eight cases, death was attributed to other causes than drug toxicity. In a majority of the cases, liver tissue contained the highest quetiapine concentrations, while whole blood levels were the lowest. Central (heart) blood concentrations were generally higher than peripheral (femoral) blood levels. Quetiapine concentrations in femoral blood correlated most strongly with concentrations in skeletal muscle. Otherwise, there was no consistent hierarchy of quetiapine tissue concentrations, and the tissue distribution showed no clear relationship with the length of the post mortem interval.
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http://dx.doi.org/10.1016/j.forsciint.2020.110413DOI Listing
October 2020

Retrospective screening of synthetic cannabinoids, synthetic opioids and designer benzodiazepines in data files from forensic post mortem samples analysed by UHPLC-QTOF-MS from 2014 to 2018.

Forensic Sci Int 2020 Jun 3;311:110274. Epub 2020 Apr 3.

Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden; National Forensic Centre, Drug Unit, Linköping, Sweden.

The introduction of new psychoactive substances (NPS) on the illicit drug market has led to major challenges for the analytical laboratories. Keeping screening methods up to date with all relevant drugs is hard to achieve and the risk of missing important findings in biological samples is a matter of concern. Aiming for an extended retrospective data analysis, diagnostic fragment ions from synthetic cannabinoids (n=251), synthetic opioids (n=88) and designer benzodiazepines (n=26) not included in our original analytical method were obtained from the crowdsourced database HighResNPS.com and converted to a personalized library in a format compatible with the analytical instrumentation. Data files from the analysis of 1314 forensic post mortem samples with an Agilent 6540 ultra high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in our laboratory from January 2014 to December 2018 were retrieved and retrospectively processed with the new personalized library. Potentially positive findings were grouped in two: The most confident findings contained MS/MS data for library match (category 1) whereas the less confident findings lacked such data (category 2). Five new category 1 findings were identified: Flubromazepam in two data files from 2015 and 2016, respectively, phenibut (4-amino-3-phenylbutyric acid) in one data file from 2015, fluorofentanyl in one data file from 2016 and cyclopropylfentanyl in one data file from 2018. Retention time matches with reference standards further strengthened these findings. A list of 35 presumably positive category 2 findings was generated. Of these, only one finding of phenibut was considered plausible after checking retention times and signal-to-noise ratios. This study shows that new compounds can be detected retrospectively in data files from QTOF-MS using an updated library containing diagnostic fragment ions. Automatic screening procedures can be useful, but a manual re-evaluation of positive findings will always be necessary.
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http://dx.doi.org/10.1016/j.forsciint.2020.110274DOI Listing
June 2020

A Validated Method for the Simultaneous Determination of Quetiapine, Clozapine and Mirtazapine in Postmortem Blood and Tissue Samples.

J Anal Toxicol 2020 Apr;44(5):440-448

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway.

Psychotropic drugs are regularly present in cases of sudden, unexpected death. Such drugs also tend to express significant postmortem redistribution. To facilitate further investigation of this phenomenon, reliable quantitative methods applicable to multiple biological matrices are needed. We present a validated ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of quetiapine, clozapine and mirtazapine in postmortem whole blood, skeletal muscle, brain tissue and liver tissue using high-performance liquid chromatography-tandem mass spectrometry. Sample preparation was performed using liquid-liquid extraction. The validated ranges were 3.8-1534, 16-1960 and 13-1060 μg/L for quetiapine, clozapine and mirtazapine, respectively. Within-run and between-run accuracy (87.4-122%) and precision (CV 1.5-8.9%), matrix effects (95-101%) and recovery (35.7-92%) were validated at two concentration levels; 5.8 and 1227 μg/L for quetiapine, 25 and 1568 μg/L for clozapine and 20 and 849 μg/L for mirtazapine. Stability in a 10°C environment was assessed for treated samples of brain, liver and muscle tissue, showing deviations in analyte concentrations ranging from -8% to 9% after 3 days. The analyte concentrations in treated samples of whole blood stored at 4°C deviated by <5% after 5 days. The method was applied in three forensic autopsy cases implicating quetiapine, clozapine and mirtazapine, respectively, in supratherapeutic concentrations.
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http://dx.doi.org/10.1093/jat/bkaa002DOI Listing
April 2020

Safety with use of long-acting β₂-selective agonists for asthma.

Tidsskr Nor Laegeforen 2019 Nov 18;139(17). Epub 2019 Nov 18.

Background: Since their introduction more than 50 years ago, use of β-agonists for inhalation has been associated with increased mortality. Since the turn of the century, particular concern has been voiced regarding long-acting β2-selective agonists. Our purpose was to investigate the evidence from recently published randomised trials of possible increased risks of death and serious adverse events related to exposure to these drugs.

Material And Method: A PubMed search identified ten clinical trials which fulfilled predefined inclusion criteria.

Results: The ten trials encompassed 66 664 patients. A total of 16 asthma-related deaths after exposure to long-acting β2-selective agonists were recorded among 33 043 actively treated patients, whereas four such deaths were recorded among the 33 621 patients in the control groups. A single, large, pragmatic trial accounts for a majority of these fatalities.

Interpretation: Exposure to long-acting β2-selective agonists is associated with a small increase in mortality. Whether concomitant use of inhalation steroids fully reverses this effect is not clear.
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http://dx.doi.org/10.4045/tidsskr.19.0032DOI Listing
November 2019

E. Ulvestad and L. Slørdal respond.

Tidsskr Nor Laegeforen 2019 08 19;139(11). Epub 2019 Aug 19.

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http://dx.doi.org/10.4045/tidsskr.19.0442DOI Listing
August 2019

E. Ulvestad and L. Slørdal respond.

Tidsskr Nor Laegeforen 2019 08 19;139(11). Epub 2019 Aug 19.

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http://dx.doi.org/10.4045/tidsskr.19.0444DOI Listing
August 2019

The interaction between rifampicin and lamotrigine: A case report.

Br J Clin Pharmacol 2019 08 29;85(8):1859-1860. Epub 2019 May 29.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

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http://dx.doi.org/10.1111/bcp.13973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624381PMC
August 2019

An anniversary to reflect on.

Tidsskr Nor Laegeforen 2019 May 27;139(9). Epub 2019 May 27.

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http://dx.doi.org/10.4045/tidsskr.19.0299DOI Listing
May 2019

A Wolf in Sheep's Clothing.

J Anal Toxicol 2019 03;43(2):e7-e8

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.

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http://dx.doi.org/10.1093/jat/bky080DOI Listing
March 2019

Overgangen fra digitoksin til digoksin i årene 2011–13.

Tidsskr Nor Laegeforen 2018 10 1;138(15). Epub 2018 Oct 1.

Background: The withdrawal of digitoxin and subsequent substitution with digoxin around 2012 may have led to an increased health risk for patients. The aim of this study was to follow individual patients during the switch.

Material And Method: Serum concentrations of digitoxin and digoxin, measured at the Department of Clinical Pharmacology at St Olavs University Hospital in the period 1 January 2011-31 December 2013 were reviewed. Patients who had switched from digitoxin to digoxin and whose serum concentrations of both drugs had been measured during this period were included.

Results: A total of 304 patients, 1686 samples and 1858 serum concentration analyses were included in the study. Therapeutic serum concentrations were measured in 171 patients (56.3 %) before the switch and 176 (57.9 %) after this had taken place. Altogether 108 patients (35.5 %) had therapeutic concentrations both before and after the change. For 58.9 % of the patients, the change resulted in a reduction in serum concentration of digitalis, calculated as digoxin equivalents. The proportion of patients with assumed supratherapeutic concentrations fell from 43.1 % to 33.9 %; however, the proportion of patients with toxic serum concentrations rose from 0.3 % to 3.0 %.

Interpretation: Although the switch led to a reduction in dose and serum concentration for many, a significant number of patients may have been put in harm's way.
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http://dx.doi.org/10.4045/tidsskr.18.0093DOI Listing
October 2018

Læringsmål, eksamen og legers virkelighet.

Tidsskr Nor Laegeforen 2018 09 17;138(14). Epub 2018 Sep 17.

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http://dx.doi.org/10.4045/tidsskr.18.0666DOI Listing
September 2018

Kvetiapin brukes for mye.

Tidsskr Nor Laegeforen 2018 09 3;138(13). Epub 2018 Sep 3.

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http://dx.doi.org/10.4045/tidsskr.18.0535DOI Listing
September 2018

[An alternative trinity].

Authors:
Lars Slørdal

Tidsskr Nor Laegeforen 2018 05 18;138(9). Epub 2018 May 18.

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http://dx.doi.org/10.4045/tidsskr.18.0284DOI Listing
May 2018

[Can you patent the sun?].

Authors:
Lars Slørdal

Tidsskr Nor Laegeforen 2018 04 16;138(7). Epub 2018 Apr 16.

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http://dx.doi.org/10.4045/tidsskr.18.0253DOI Listing
April 2018

Corrigendum to "Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases" [Forensic Sci. Int. 281 (2017) 127-133].

Forensic Sci Int 2018 02 30;283:219. Epub 2017 Dec 30.

Department of Forensic Sciences, Oslo University Hospital, Post Box 4950, Nydalen, N-0424 Oslo, Norway; Norwegian Centre of Addiction Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Post Box 1039, Blindern, N-0315 Oslo, Norway.

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http://dx.doi.org/10.1016/j.forsciint.2017.12.040DOI Listing
February 2018

Pillevarslende!

Authors:
Lars Slørdal

Tidsskr Nor Laegeforen 2018 01 8;138(1). Epub 2018 Jan 8.

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http://dx.doi.org/10.4045/tidsskr.17.0886DOI Listing
January 2018

Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases.

Forensic Sci Int 2017 Dec 6;281:127-133. Epub 2017 Nov 6.

Department of Forensic Sciences, Oslo University Hospital, Post Box 4950, Nydalen, N-0424 Oslo, Norway; Norwegian Centre of Addiction Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Post Box 1039, Blindern, N-0315 Oslo, Norway.

Background: In toxicology, international classification systems focus on single intoxicants as the cause of death. It is, however, well known that very few drug related deaths are caused by a single substance and that information concerning the drug concentrations as well as the combinations of drugs are essential in order to ascertain the cause of death. The aim of the study was to assess whether those prone to fatal intoxications differ significantly from chronic drug users - in terms of demographics and drug exposure patterns.

Material And Methods: Fatal psychoactive drug intoxications in Norway during 2012, where a forensic autopsy including toxicological analysis were performed, were included. Analytical findings in blood were compared with concentrations in blood from apprehended drivers under the influence of drugs and ethanol (DUID) during the same time period. The opioid and benzodiazepine concentrations were assessed as morphine and diazepam equivalents, respectively, in order to compare concentrations across the different groups.

Results: A total of 194 autopsy cases and 4811 DUID cases were included. Opioids were detected in around 90% of the drug intoxication cases, but in only 16% of the DUID cases. The number of substances detected in fatal intoxications was 4.9 compared to 2.6 in the DUID cases. The total opioid concentrations were significantly higher in the fatal intoxication cases compared to DUID cases (229ng/mL versus 56.9ng/mL morphine equivalents, respectively). Benzodiazepines were detected in 90% of the fatal cases. Only one fatal opioid mono-intoxication was found; a case with a very high methadone concentration (1238ng/mL).

Discussion: Mono-intoxication with heroin was not seen in any of the fatal intoxications in Norway, and single drug intoxications were rare (1.5%). Fatal intoxications were caused by a combination of drugs with significantly more substances as well as higher total drug concentrations among the fatal cases compared to the DUID cases. The combination of opioids and benzodiazepines seemed to represent an increased risk of death.

Conclusion: The total load of drugs influence the degree of intoxication and the total concentration level must be considered, including the total number of substances. Our findings imply that international statistics regarding an opioid being the main intoxicant should have a shift in focus towards combinations of drugs (especially opioids and benzodiazepines) as a major risk factor for fatal drug overdoses.
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http://dx.doi.org/10.1016/j.forsciint.2017.10.045DOI Listing
December 2017

Conversion factors for assessment of driving impairment after exposure to multiple benzodiazepines/z-hypnotics or opioids.

Forensic Sci Int 2017 Dec 20;281:29-36. Epub 2017 Oct 20.

Oslo University Hospital, Department of Forensic Medicine, Oslo, Norway; Center of Drug and Addiction Research, Faculty of Medicine, University of Oslo, Norway. Electronic address:

Aims: Norway has introduced legal concentration limits in blood for 28 non-alcohol drugs in driving under the influence cases. As of 2016 this legislation also regulates the assessment of combined effects of multiple benzodiazepines and opioids. We herein describe the employed methodology for the equivalence tables for concentrations of benzodiazepines/z-hypnotics and opioids implemented in the Norwegian Road Traffic Act.

Methods: Legislative limits corresponding to impairment at blood alcohol concentrations (BAC) of 0.02%, 0.05% and 0.12% were established for 15 different benzodiazepines and opioids. This was based on a concept of a linear relationship between blood drug concentration and impairment in drug naïve users. Concentration ratios between these drugs were used to establish conversion factors and calculate net impairment using diazepam and morphine equivalents.

Results: Conversion factors were established for 14 benzodiazepines/z-hypnotics (alprazolam, bromazepam, clobazam, clonazepam, etizolam, flunitrazepam, lorazepam, nitrazepam, nordiazepam, oxazepam, phenazepam, temazepam, zolpidem and zopiclone) and two opioids (methadone and oxycodone).

Conclusions: Conversion factors to calculate diazepam and morphine equivalents for benzodiazepines/z-hypnotics and selected opioids, respectively, have been operative in the Norwegian Road Traffic Act as of February 2016. Calculated equivalents can be applied by the courts to meter out sanctions.
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http://dx.doi.org/10.1016/j.forsciint.2017.10.022DOI Listing
December 2017

Innsiktsfullt om rus.

Authors:
Lars Slørdal

Tidsskr Nor Laegeforen 2017 Oct 16;137(19). Epub 2017 Oct 16.

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http://dx.doi.org/10.4045/tidsskr.17.0562DOI Listing
October 2017

Two Hospitalizations and One Death After Exposure to Ortho-Fluorofentanyl.

J Anal Toxicol 2017 Oct;41(8):708-709

Department of Clinical Pharmacology, St. Olav University Hospital.

Two young males were hospitalized with miosis and respiratory dysfunction after exposure to a white powder obtained from a foreign source by mail. A few days later, one of the males was found dead at his home. A serum sample from one of the hospitalized patients and a blood sample from the deceased contained ortho-fluorofentanyl in concentrations of 2.5 and 2.4 ng/mL, respectively. It was concluded that death was caused by ortho-fluorofentanyl.
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http://dx.doi.org/10.1093/jat/bkx050DOI Listing
October 2017

[The expert rule].

Authors:
Lars Slørdal

Tidsskr Nor Laegeforen 2017 09 4;137(16). Epub 2017 Sep 4.

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http://dx.doi.org/10.4045/tidsskr.17.0618DOI Listing
September 2017

Erratum to: Analgesic use in a Norwegian general population: change over time and high-risk use - The Tromsø Study.

BMC Pharmacol Toxicol 2017 06 27;18(1):51. Epub 2017 Jun 27.

Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.

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http://dx.doi.org/10.1186/s40360-017-0158-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485670PMC
June 2017

The antipsychotic agent quetiapine is increasingly not used as such: dispensed prescriptions in Norway 2004-2015.

Eur J Clin Pharmacol 2017 Sep 16;73(9):1173-1179. Epub 2017 Jun 16.

Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

Purpose: The antipsychotic agent quetiapine was introduced in Norway in 2003. We have assessed changes in dispensed prescriptions, including dosing, of quetiapine in Norway from 2004 to 2015.

Methods: Data on the sales of antipsychotics and antidepressants were drawn from the Norwegian Prescription Database. A total of 47,474 outpatients filled 195,622 prescriptions of quetiapine. Reimbursement codes, use of antipsychotics or antidepressants 12 months prior to the first prescription of quetiapine and estimated mean volume used measured as defined daily doses (DDDs) per day were used as proxies for diagnoses. We conducted a regression analysis with DDD per day as a function of possible explanatory variables.

Results: The number of users filling at least two prescriptions of quetiapine per year increased from 584 in 2004 to 8506 in 2015 and the mean dose declined from 1.58 DDD per day (SD 8.00) to 0.48 DDD per day (SD 2.27). The latter is much lower than recommended for treatment of psychoses. In 2015, 60.1% of the 8506 quetiapine users did not seek reimbursement for the treatment of a major psychiatric disorder and only 2.6% of the patients were prescribed 1 DDD or more per day and reimbursed in accordance with the drug's primary indication, psychosis. A reported diagnosis of psychosis was not associated with higher quetiapine doses.

Conclusions: In 2015, the pattern of quetiapine dispensing in Norway most likely reflects predominant off-label use. This is unsettling considering poorly documented effects in non-psychotic disorders, profound side effects, significant toxicity and growing concern regarding abuse.
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http://dx.doi.org/10.1007/s00228-017-2281-8DOI Listing
September 2017

[Digitization ad modum the Norwegian Medicines Agency].

Tidsskr Nor Laegeforen 2016 11 8;136(20):1700. Epub 2016 Nov 8.

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http://dx.doi.org/10.4045/tidsskr.16.0810DOI Listing
November 2016

Driving simulator sickness: Impact on driving performance, influence of blood alcohol concentration, and effect of repeated simulator exposures.

Accid Anal Prev 2016 Sep 17;94:180-7. Epub 2016 Jun 17.

Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.

Simulator sickness is a major obstacle to the use of driving simulators for research, training and driver assessment purposes. The purpose of the present study was to investigate the possible influence of simulator sickness on driving performance measures such as standard deviation of lateral position (SDLP), and the effect of alcohol or repeated simulator exposure on the degree of simulator sickness. Twenty healthy male volunteers underwent three simulated driving trials of 1h's duration with a curvy rural road scenario, and rated their degree of simulator sickness after each trial. Subjects drove sober and with blood alcohol concentrations (BAC) of approx. 0.5g/L and 0.9g/L in a randomized order. Simulator sickness score (SSS) did not influence the primary outcome measure SDLP. Higher SSS significantly predicted lower average speed and frequency of steering wheel reversals. These effects seemed to be mitigated by alcohol. Higher BAC significantly predicted lower SSS, suggesting that alcohol inebriation alleviates simulator sickness. The negative relation between the number of previous exposures to the simulator and SSS was not statistically significant, but is consistent with habituation to the sickness-inducing effects, as shown in other studies. Overall, the results suggest no influence of simulator sickness on SDLP or several other driving performance measures. However, simulator sickness seems to cause test subjects to drive more carefully, with lower average speed and fewer steering wheel reversals, hampering the interpretation of these outcomes as measures of driving impairment and safety. BAC and repeated simulator exposures may act as confounding variables by influencing the degree of simulator sickness in experimental studies.
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http://dx.doi.org/10.1016/j.aap.2016.05.008DOI Listing
September 2016