Cognitive Performance and Sleep Quality Following Caffeinated Chewing Gum in Night-shift Emergency Physicians: A Double-blind Randomized Crossover Controlled Trial

Methods 2.1. Design This experiment was a double-blind, repeated-measures, crossover design according to the guidelines of CONSORT 2010 and was divided into either a caffeine trial (CAF) or a placebo trial (PL). To eliminate the impact of individual physical differences, a crossover trial was conducted with the same group of subjects. Randomized groups were created using Microsoft 365-Excel (Microsoft, Redmond, Washington, United States), and allocation was randomized and unpredictable. Each trial was separated by at least four weeks to avoid interactive effects. This study compared CAF and PL trial to determine the effects of caffeinated chewing gum on cognitive performance in emergency physicians engaged in night shift work., and subjective, objective sleep quality. Caffeinated chewing gum and placebo chewing gum are very similar in appearance, color, size, shape, and flavor and are difficult to distinguish. The randomization was carried out by a research assistant, with another resident performing the experiment, and neither the subjects themselves nor the resident experimenting knew which group the subjects were assigned to or what type of gum they were assigned. Once the data has been collected, it will be forwarded to the group's statistical analyst for statistical analysis, who was also unaware of the group assignments. At least one week before the formal experiment, all subjects participated in three to five familiarization tests for the cognitive function tests. Sleep quality was also assessed subjectively by a single question score, and objectively by ActiGraph for one night on the off day and the last sleep before the first night shift. The primary outcome was the results of cognitive function tests, and the secondary outcome was the sleep quality.

2.2. Participants Fourteen healthy male emergency physicians were recruited in this study and based on previous research on caffeine in e-sport athletes, we used the G*power 3.1 software 24 to achieve an alpha value of 5% and a power of 0.8, which was sufficient for the study with only six subjects. However, due to the lack of relevant studies on the effects of caffeine and caffeinated chewing gum on cognitive functioning in night-shift healthcare workers, reference was made to a recent study that examined the cognitive performance of emergency physicians after 24 consecutive hours of on-call duty, which included 13 subjects. Therefore, it should be adequate to interpret the data derived and statistics from the study.

All participants had experience working regular rotating shifts on the emergency clinical front line and regularly accepted night shift assignments each month. The inclusion criteria were: (i) healthy male adults, those individuals who are free of pain, insomnia, or other injuries recently, without any medication used in recent 2 months, (ii) underwent rotating shifts on the emergency clinical front line with regularly accepted night shift more than two years. The exclusion criteria were: (i) allergy to caffeine, (ii) experience of adverse effects of caffeine, (iii) with cardiovascular diseases or any disease that made subjects feel ill. Two weeks before the main trial, all the participants were asked to avoid ingestion of more than 80 mg of caffeine a day. Before the experiment, all participants were fully informed of the experimental procedures and risks and provided informed consent. This study received approval from the Institutional Review Board of China Medical University Hospital (CMUH111-REC2-169). This study was conducted following the Declaration of Helsinki.

2.3. Protocol 2.3.1. Experimental procedure The entire study was conducted in the office of the emergency department of China Medical University Hospital, and the indoor ambient temperature was set at 22°C. Participants' diet and mealtimes were recorded for the 3 days before the first formal experiment, and the participants were required to follow the same diet 3 days before the next formal experiment. They were also required to avoid food and beverages with caffeine (e.g., coffee, energy drinks, chocolate, chocolate drink, and tea) 3 days before the formal experiment.

On the day of the formal experiment, participants had breakfast and lunch at 08:00 and 12:00, respectively. The participants arrived at the office at approximately 23:20 for the experiment. A brief explanation was given and the cognitive test was administered at 23:30, which took about 20 minutes to complete, after which the subjects were ready to go to work. At 03:30, according to the randomized results, the subjects were given two pieces of caffeinated chewing gum at an absolute dose of 200 mg (Military Energy Gum®, Ford Gum and Machine Go, Akron, NY, USA) (CAF trial) or two pieces of similar looking and tasting placebo gum that did not contain caffeine (xylitol, lime mint, green; Lotte, Saitama, Japan) (PLA trial). After 10 minutes of chewing, cognitive function tests were administered. Finally, the last cognitive function tests were performed after duty at 08:20. All subjects used a dedicated computer with a screen frame rate of at least 240 Hz and a mouse response rate of 1ms.