Systematic Review and Meta-analysis of the Effects of Caffeine in Fatigued Shift Workers: Implications for Emergency Medical Services Personnel

Figures & data

Figure 1. PRISMA Flow Diagram PICO#3 PROSPERO 2016:CRD42016040101.

Table 1. Synthesis of findings of the impact of caffeine as a countermeasure to mitigate fatigue, fatigue related risk, and or improve sleep for selected outcomes

EXPERIMENTAL STUDIES
			Critical Outcome	Important Outcomes
Author, Year	Distiller RefID^* PMID^*	Study Design	Personnel Safety	Patient Safety^†	Personnel Performance^*	Acute Fatigue^‡	Sleep and Sleep Quality^§	Long-Term Health^║
Kamimori	RefID-587	Double-blind, placebo	—	—	Favorable	—	Unfavorable	—
et al., 2015 (31)	PMID-25527035	controlled – caffeine (800 mg) vs. placebo
Kamimori	RefID N/A	Double-blind, randomized,	—	—	Favorable	No	—	—
et al., 2005 (33)	PMID-16313140	counterbalanced design: effects of 0, 50, 100, or 200 mg of caffeine on psychomotor vigilance				impact
Schweitzer	RefID-1104	Cross-over design with	—	—	Favorable	Favorable	Unfavorable	—
et al., 2006 (32) (field study only)	PMID-16453980	participants randomized to study order. Two conditions: caffeine (all nights) + evening nap vs. placebo (all nights) and no nap
Ronen et al.,	RefID-1053	Within-subjects crossover	Favorable	—	Favorable	Favorable	—	—
2014 (34)	PMID-24913484	design comparing control, energy drink, and energy drink + rest
McLellan,	RefID N/A	Double-blind, placebo	—	—	Favorable	—	—	—
Kamimori, Voss, et al., 2005 (29)	PMID-16018347	controlled design comparing placebo vs. caffeine
McLellan,	RefID N/A	Double-blind, placebo	—	—	Favorable	—	—	—
Kamimori, Bell, et al., 2005 (30)	PMID-15672985	controlled comparison of placebo vs. caffeine
McLellan,	RefID-818	Double-blind, placebo	—	—	Favorable	—	—	—
2004 (36)	PMID-15328782	controlled comparison of placebo vs. caffeine
Doan et al.,	RefID-329	Double-blind, placebo	Favorable	—	Favorable	Favorable	—	—
2006 (35)	PMID-17042248	controlled comparison of placebo vs. caffeine

Findings are classified as favorable, unfavorable, mixed/inconclusive, or no impact.

^* Includes external objective and subjective ratings of the study subject's performance including perceived satisfaction with the subject's performance.

^† Includes quality of care.

^‡ Includes acute states of fatigue, sleepiness, and alertness.

^§ includes sleep latency, total sleep time, recovery, and related measures.

^║ General wellness or well-being measures included.

Figure 2. Forest plots for Standardized Mean Difference between placebo and caffeine reaction time and lapses on the PVT test. a) Reaction time at end of shift. b) Reaction time change/delta from start-to-end of shift. c) Lapses at end of shift. d) Lapses change/delta from start-to-end of shift. Figures 2a–2d Notes: report the standardized mean difference (SMD) for reaction time (a and b) and lapses (c and d) on the psychomotor vigilance test in participants receiving caffeine or placebo. The mean ± SD reaction time (ms) was calculated using data presented in each of the manuscripts and entered into RevMan to generate forest plots. All of the studies defined lapses as responses that were made after a specified amount of time had passed (500 ms – 5 seconds). The mean ± SD number of lapses were available for the 2 McLellan manuscripts, but only the mean number of lapses was available for the Kamimori et al. manuscript (29, 30, 33). In order to estimate the SD for this measure, we used a conservative approach of doubling the mean, which was a significantly greater proportion of the mean than either of the other studies. In order to generate data, we relied on means and standard deviations/errors reported in each manuscript. We estimated the means and standard errors presented in graphs when means and standard deviations/errors were not reported. In all cases, we selected all time points after caffeine administration and averaged them across placebo and caffeine conditions. Data for PVT lapses were collected as follows: For the Kamimori et al. 2005 manuscript, data were found in Figure 1 (33). Caffeine administration was indicated with dashed lines. All points after the first caffeine administration (305) were averaged up until time point 1100 hours for placebo and 200 mg of caffeine. The final time point was considered too long after caffeine administration, given a half-life of approximately 4.5 hours. For the McLellan, Kamimori, Voss, et al. 2005 paper, means and standard deviations were reported in the manuscript (29). For the McLellan, Kamimori, Bell, et al., 2005 paper, data were extracted from Figure 4b from the referenced manuscript (30). Caffeine was administered on Day 2 at 2130. We averaged the number of lapses for all time points on Day 3 for the placebo and caffeine conditions. We obtained PVT reaction time data as follows: For the Kamimori et al. 2015 manuscript, data were taken from Figure 1 and converted to reaction times (31). We averaged data from all time points after the initial caffeine dose at 2100 hours, excluding the time points 1815 and 2100 on Days 3 and 4, as those were too long after the previous caffeine administration to be considered relevant. For the McLellan, Kamimori, Voss, et al. 2005 manuscript, data were taken from Figure 4 from the referenced manuscript (29). We averaged all time points on Day 3 after the initial caffeine administration at 0140 hours for both placebo and caffeine. For the McLellan, Kamimori, Bell, et al. 2005 manuscript, data were extracted from Figure 4a from the referenced manuscript (30). Caffeine was administered on Day 2 at 2130 hours. We averaged the reaction time for all time points on Day 3 for the placebo and caffeine conditions. For the Schweitzer et al. 2006 manuscript, data were taken from Figure 5 in the referenced manuscript and converted to reaction time (32). We used the second time point, as the first time point on each night was prior to caffeine administration.

Kamimori GH, McLellan TM, Tate CM, Voss DM, Niro P, Lieberman HR. Caffeine improves reaction time, vigilance and logical reasoning during extended periods with restricted opportunities for sleep. Psychopharmacology (Berl). 2015;232(12):2031–42. https://doi.org/10.1007/s00213-014-3834-5.

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Schweitzer PK, Randazzo AC, Stone K, Erman M, Walsh JK. Laboratory and field studies of naps and caffeine as practical countermeasures for sleep-wake problems associated with night work. Sleep. 2006;29(1):39–50. https://doi.org/10.1093/sleep/29.1.39.

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McLellan TM, Kamimori GH, Bell DG, Smith IF, Johnson D, Belenky G. Caffeine maintains vigilance and marksmanship in simulated urban operations with sleep deprivation. Aviat Space Environ Med. 2005;76(1):39–45.

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McLellan TM, Bell DG, Kamimori GH. Caffeine improves physical performance during 24 h of active wakefulness. Aviat Sace Environ Med 2004;75(8): 666–72.

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Doan BK, Hickey PA, Lieberman HR, Fischer JR. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat Space Environ Med. 2006;77(10):1034–40.

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