In the controlled studies included in these analyses there were 1436 patients who were treated with fentanyl ITS. These phase 3 studies were designed to be inclusive of a broad range of weights, with no maximum BMI specified in the inclusion/exclusion criteria. The distribution of patients across BMIs was expectedly not even, reflective of the surgical population; however, there were a sizeable number of patients in the higher BMI categories (138 with a BMI ≥35 kg/m2 and ≤40 kg/m2, and 86 with a BMI >40 kg/m2). Overall, treatment success, as assessed with the PGA of the method of pain control, with fentanyl ITS was 76.5% in the highest BMI group (>40 kg/m2) group, which was consistent with the results in the lower BMI categories. Similar results were seen with the IGA. Therefore, it appears that fentanyl ITS is equally effective in the high and low BMI categories. The comparison of fentanyl ITS to morphine IV PCA by each BMI category showed overall consistency between the two treatments as assessed using either the PGA or IGA, further supporting efficacy in high BMI patients.
Fentanyl and morphine are powerful opioids; therefore, it is expected that the pain control is similar between these two modalities (fentanyl ITS and morphine IV PCA). However, the additional benefits of fentanyl ITS relating to the validated instruments of physical therapy ease-of-care , nurse ease-of-care , and patient ease-of-care  have been evaluated and published in other analyses of the full phase 3 dataset. In addition, postoperative mobility is important for every patient undergoing surgery and especially so for obese patients. Early patient mobilization has been shown to reduce the cost of care and improve patient outcomes, whereas immobility is associated with increased complications, length of stays, and costs [17,18,19]. Fentanyl ITS is an effective analgesic in the postoperative period and also does not require an IV line and associated equipment (pumps, IV poles). Fentanyl ITS has demonstrated in a double-blind clinical trial that patients find it easier to mobilize when compared to morphine IV PCA . A previous analysis evaluated mobility with fentanyl ITS and morphine IV PCA and found that patients treated with fentanyl ITS were better able to mobilize in the postoperative period than those treated with morphine IV PCA across high and low BMI ranges that were assessed: <25 kg/m2; 25 kg/m2 to <30 kg/m2; 30 kg/m2 to <40 kg/m2; and >40 kg/m2 .
Intravenous access can be challenging to obtain and maintain in obese patients . Notably, patients with poor venous access may experience interruption of standard IV PCA. One of the features of fentanyl ITS is that it reduces the need for a separate IV line for PCA administration in patients and therefore can be advantageous to utilize in the obese patient population.
The mean number of doses of fentanyl ITS utilized in the first 24 h did not differ between the BMI categories. One research group has previously shown that the G allele of the OPRM1 gene encoding the mu receptor is more common in patients who are obese . This polymorphism has been associated with an increase in the requirement for morphine and fentanyl for pain relief. However, this was not evident in these analyses. Neither fentanyl ITS nor morphine IV PCA showed differences in doses used between the BMI categories. However, it is informative to note that as with other PCA systems, the fentanyl ITS system allows the patient to individualize their pain management regimen; therefore, patients requiring more fentanyl may take up to 80 doses in a 24-h period and those requiring less can take less.
Overall, the safety profile was generally similar across the high and low BMI categories. The TEAEs observed most often in the fentanyl ITS group and morphine IV PCA group are common to all opioids and include nausea, pyrexia, vomiting, and headache. Nausea, vomiting, and dizziness were all slightly less common in the BMI >40 kg/m2 group compared to the BMI <35 kg/m2 group, while headache was slightly more common in the >40 kg/m2 group compared to the BMI <35 kg/m2 and the 35–40 kg/m2 groups.
Respiratory depression is of particular importance in an obese population and needs to be carefully evaluated and monitored when using opioids. In this analysis, in the fentanyl ITS groups, hypoxia was reported in 3.3% of patients with a BMI <35 kg/m2, in 2.2% of patients with a BMI ≥35 kg/m2 to ≤40 kg/m2, and in 1.2% of patients with a BMI >40 kg/m2. In a meta-analysis that was performed using the active-comparator trials, opioid-related adverse events (including respiratory depression and sedation) were assessed in the aggregate study population . During the development program with more than 2500 patients treated with fentanyl ITS, there were no patients treated with fentanyl ITS who experienced clinically relevant respiratory depression (CRRD), and there were five patients in the morphine IV PCA group who did experience CRRD . However, despite the low rates of CRRD in the clinical studies, it is still important to closely monitor patients being treated with any opioid, including fentanyl ITS, for signs of sedation and respiratory depression. This is especially true for patients who are obese and may be more predisposed to these adverse events.
One limitation of these analyses is that none of the studies were designed to specifically look at BMI and therefore the population is not evenly distributed between the categories. However, this is a reasonably large sample of patients who are obese or morbidly obese. Another limitation is the selection of the BMI categories. These categories were chosen for their clinical relevance to reflect the categories that are commonly used to assess for bariatric surgery eligibility ; however, it is reassuring that there was a great deal of consistency across the BMI categories in terms of safety and efficacy. The main purpose of these analyses was to evaluate the safety and efficacy of fentanyl ITS in the high and low BMI categories; however, we also compared the efficacy and safety to morphine IV PCA as there were fairly large sample sizes available from the clinical trial database. Another limitation of these studies, and therefore these analyses, is that they do not factor in multimodal analgesia treatment. It is important to remember that the primary purpose of the studies included was to evaluate the safety and efficacy of fentanyl ITS for regulatory submissions and ultimately drug approval and therefore multimodal analgesia was not included in the methodology. There were some additional endpoints that would have been useful to have measured, such as time to first bowel movement, time to getting up from bed etc.; however, these were not included in the design of the trials and therefore there is no information contained to specifically address these issues within the database. Further research in patients with high BMI using fentanyl ITS in multimodal treatment would be useful to confirm and extend the findings of this paper.