A single bolus 7.5 μg/kg intravenous alfentanil results in a clinically relevant reduction in maximum pain during colonic insufflation required for CT colonography. Importantly, alfentanil also reduced the total pain and burden of the complete CT colonography procedure. Alfentanil did not influence the procedure time and with alfentanil fewer patients considered colonic insufflation the most burdensome aspect of CT colonography. Dizziness and desaturations were the most common side effects of alfentanil, though recovery times were short.
The reduction of maximum pain was more than the 1.3 points on an 11-point numeric rating scale as we hypothesised and which is considered the minimum clinically relevant difference
[26–28]. For this scale, a pain score reduction of 2–2.4 points or 33-35% may be of even greater clinical importance
[26, 27, 42]. Both these criteria are also met with the reduction we observed. Pain scores during the prone scan acquisition position was 3.0 in the placebo group and thus lower than during the left decubitus position, likely due to decreased pressure after initial insufflation or habituation to the insufflated colon
Importantly, also the pain and burden of the total CT colonography procedure were reduced. The effect of alfentanil was more evident on the most burdensome aspect, than on the most painful aspect. This is likely because patients experience the bowel preparation as burdensome, but not as painful. With alfentanil, the insufflation becomes less burdensome and therefore the burden of the bowel preparation becomes relatively more important.
The observed dizziness and desaturations are known side effects of alfentanil. The desaturation in the placebo group may indicate that some patients experience spontaneous desaturations during the day. Importantly, all desaturations were not clinically relevant, because they were short and self-limiting we did not had to perform any intervention.
Although we found desaturations with alfentanil, we did not find a SpO2 reduction at 5 and 10 minutes after alfentanil injection. Conti et al. observed a significant saturation reduction with a 10 μg/kg bolus intravenous alfentanil in ASA 1 patients during minor surgery or endoscopy
In colonoscopy opioids are commonly used in combination with a benzodiazepine to induce amnesia. We did not consider this mandatory for CT colonography while this combination leads to a greater respiratory depressant effect than opioids only. The benzodiazepine-induced drowsiness may complicate the CT colonography procedure and recovery facilities may be required.
A number of limitations have to be acknowledged. The dizziness caused by alfentanil may have partly affected the double blind character of the trial. We had anticipated this however, to our knowledge no substance is available that causes dizziness in an equal number of patients as alfentanil and that does not affect the outcomes. We chose to use 0.9% saline solution for the placebo group because it was the solvent for alfentanil and the viscosity and colour was similar to that of alfentanil. Importantly, patients were not aware that dizziness would be more likely related to alfentanil administration than placebo. Pain was assessed in prone scan acquisition position only, as we wanted to limit the number of questions and the pressure is higher in prone position
. The time of prone scan acquisition differed some minutes between studies with and without intravenous contrast medium. The influence of prone score on the maximum pain was negligible as these were much lower compared with left decubitus. We chose to use an 11-point numeric rating scale, which is a commonly used scale
[26, 44]. The visual analogue scale
 is also commonly used, however this scale is less practical during colonic insufflation on a narrow table, while having colonic cramps and being monitored. Additionally, we have experience with the 11-point numeric rating scale during CT colonography. For the Aldrete score, we chose as reference values blood pressure and heart rate measurements, recorded 1½ minute after injection of the spasmolytic agent. Most patients received butylscopalamine bromide, which increases the heart rate
. As the effect of the spasmolytic decreases over time, the heart rate also decreases. Furthermore, most patients are nervous at the beginning of a medical procedure and calm down in the course of the procedure. Both factors might have influenced Aldrete score negatively, although all patients had a normal heart rate and blood pressure after the procedure. Despite the fact the side effects of alfentanil were of minor clinical relevance and the benefit-risk ratio seems to favour alfentanil, a safety profile cannot be made based on 45 patients. Although other studies also have shown safe use of a single bolus low-dose alfentanil
[43, 45], more data on patient safety is warranted.
When alfentanil is used it is important to realise that monitoring and airway intervention equipment and sufficient knowledge about the pharmacology of opioids and airway interventions should be present. This means that the attendance of a physician is required. For institutions were a technician is performing the CT colonography procedure, adjustments will have to be made in the procedure. All patients receiving intravenous alfentanil require an intravenous cannula, so emergency medication can be given. The above mentioned issues may lead to an increase in costs. Furthermore, when using alfentanil the patients need to arrange transportation, because driving after alfentanil injection is not allowed for 12–24 hours minimum; this can be a large hurdle for implementation of alfentanil
. Patients who receive butylscopalamine bromide during CT colonography are already advised not to drive just after the procedure, as this may affect the ability to drive. Because of disadvantages such as the inability to drive, the lack of analgesia has been mentioned as one of the advantages of CT colonography