Dear Editor,
With guidelines recommending an analgosedation approach to the management of mechanically ventilated intensive care unit (ICU) patients, use of continuous infusion fentanyl has become common practice. 1 , 2 Analgosedation is a delicate balance, targeting patient comfort while avoiding oversedation which may lead to prolonged intubation and length of stay (LOS). 3 Fentanyl continuous infusions can be dosed based on weight or fixed intervals. Being lipophilic, fentanyl accumulates in adipose tissue, prolonging duration of action. In addition, obesity has been shown to increase fentanyl concentrations in critically ill and one study found that dosing with actual body weight overestimates fentanyl dose requirements in obese patients. 4 , 5 Therefore, the aim of this study was to compare weight-based and fixed-interval fentanyl infusion dosing to explore differences in medication utilization, with assessment by body mass index (BMI) category.
Our study institution switched from weight-based (titrated by 0.5 μg/kg/h; max 10 μg/kg/h) to fixed-interval (titrated by 50 μg/h; max 500 μg/h) dosing strategies for fentanyl continuous infusions in late 2016. We randomly selected adult patients receiving a fentanyl continuous infusion for at least 24 hours between January 1, 2016 and December 31, 2016. Patients were excluded if they underwent targeted temperature management, experienced status epilepticus, or had concomitant use of ketamine or barbiturates during their admission. Parametric data were analyzed using a 2-sided t test and nonparametric data were analyzed using the Mann-Whitney U test.
Two-hundred patients were included for evaluation, with 100 patients in both weight-based and fixed-interval dosing strategies. Baseline characteristics were balanced between groups with no statistical difference in patient age or weight. Overall, no difference was observed in average dose of fentanyl administered between the fixed-interval and weight-based group (1.20 μg/kg/h [0.66-2.27] vs 1.17 μg/kg/h [0.56-1.90]; P = .255; see Table 1). In nonobese patients (BMI < 30 kg/m2), there was a larger average quantity of fentanyl infused for the fixed-interval dosing group (1.59 μg/kg/h [0.77-2.95] vs 1.16 μg/kg/h [0.56-1.76]; P = .019). In the BMI ≥ 40 kg/m2 group, the average dose of fentanyl administered was 94% higher in the weight-based compared with the fixed-interval group, although not statistically significant. There were no statistical differences in patient outcomes for ICU LOS or duration of mechanical ventilation.
Table 1.
Main Outcomes.
| Overall and subgroups a | Weight-based dosing(n = 100) | Fixed-interval dosing(n = 100) | P value |
|---|---|---|---|
| Fentanyl (μg/kg/h) average | |||
| Overall | 1.17 [0.56–1.90] | 1.20 [0.66–2.27] | .255 |
| <30 kg/m2 | 1.16 [0.56–1.76] | 1.59 [0.77–2.95] | .019 |
| <20 kg/m2 | 0.35 [0.08–1.08] | 2.26 [0.78–4.43] | .007 |
| 20–24.99 kg/m2 | 1.57 [1.13–2.12] | 1.87 [0.53–2.95] | .904 |
| 25–29.99 kg/m2 | 1.03 [0.59–1.33] | 1.25 [1.00–2.94] | .051 |
| ≥30 kg/m2 | 1.29 [0.59–2.33] | 0.90 [0.54–1.83] | .478 |
| 30–34.99 kg/m2 | 1.00 [0.42–1.49] | 1.04 [0.62–1.81] | .345 |
| 35–39.99 kg/m2 | 1.62 [0.71–2.50] | 1.27 [0.70–2.18] | .639 |
| ≥40 kg/m2 | 1.34 [0.63–1.88] | 0.69 [0.35–1.31] | .243 |
| Intensive care unit length of stay, d | |||
| Overall | 6.90 [4.01–13.00] | 7.50 [4.13–11.98] | .984 |
| <30 kg/m2 | 6.35 [3.22–11.30] | 7.25 [3.89–10.92] | .556 |
| <20 kg/m2 | 5.62 [2.58–10.99] | 8.02 [5.55–10.92] | .247 |
| 20–24.99 kg/m2 | 6.74 [3.17–7.91] | 6.74 [4.32–7.69] | .717 |
| 25–29.99 kg/m2 | 6.13 [3.40–12.11] | 7.16 [2.50–11.96] | .647 |
| ≥30 kg/m2 | 10.11 [6.44–15.39] | 7.82 [4.51–12.39] | .198 |
| 30–34.99 kg/m2 | 9.12 [6.35–10.89] | 6.93 [4.69–12.15] | .977 |
| 35–39.99 kg/m2 | 13.83 [6.89–17.21] | 10.11 [5.34–15.90] | .368 |
| ≥40 kg/m2 | 8.55 [6.71–22.59] | 7.82 [4.52–12.16] | .570 |
| Mechanical ventilation duration, d | |||
| Overall | 4.99 [2.30–10.58] | 5.35 [2.39–9.83] | .924 |
| <30 kg/m2 | 3.81 [2.02–7.57] | 4.57 [2.11–8.16] | .780 |
| <20 kg/m2 | 3.70 [1.35–6.28] | 4.95 [2.24–9.96] | .315 |
| 20–24.99 kg/m2 | 3.20 [2.06–6.78] | 4.03 [1.75–6.96] | .989 |
| 25–29.99 kg/m2 | 4.11 [2.06–9.95] | 4.18 [2.11–9.98] | .874 |
| ≥30 kg/m2 | 9.00 [2.99–13.27] | 5.90 [3.49–10.00] | .421 |
| 30–34.99 kg/m2 | 5.67 [3.31–10.37] | 5.61 [2.96–10.00] | .932 |
| 35–39.99 kg/m2 | 10.78 [5.64–12.54] | 5.90 [4.41–15.97] | .898 |
| ≥40 kg/m2 | 8.92 [2.63–17.51] | 6.06 [3.68–9.79] | .570 |
Note. ICU = intensive care unit.
Subgroups are broken down by body mass index (BMI).
Our study is limited based on the retrospective nature of the study design, sample size, and the lack of assessment for the effect on pain or sedation scales. However, our study highlights the fact that both dosing protocols may increase opioid exposure in select patients based on weight. For example, a 0.5 μg/kg/h titration in 50- and 200-kg patients represents a 25 and 100 μg/h titration, respectively, whereas a 50 μg/h titration represents a 1 and 0.25 μg/kg/h adjustment in the same respective patients. This highlights the challenge of determining an optimal fentanyl dosing strategy. From this review, a change was made to our fixed-interval dosing titration to reduce the titration intervals to 25 μg/h. Future evaluations of fentanyl utilization may provide greater insight on opioid exposure and dosing strategies.
Footnotes
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iD: Michael J. Peters https://orcid.org/0000-0002-2652-5724
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