Discharge Readiness After Propofol With or Without Dexmedetomidine for Colonoscopy

A Randomized Controlled Trial

Leonard U. Edokpolo, M.D.; Daniel J. Mastriano, M.D.; Joanna Serafin, Ph.D.; Jeremy C. Weedon, Ph.D.; Maryam T. Siddiqui, M.D.; Dennis P. Dimaculangan, M.D.

Disclosures

Anesthesiology. 2019;131(2):279-286. 

In This Article

Discussion

The primary finding of this study is that adding a single, low-dose bolus of dexmedetomidine (0.3 μg/kg) to propofol at the beginning of colonoscopy for ambulatory patients delays discharge readiness compared with propofol alone. We did not find any previous publications that used validated discharge criteria to assess the effects of this anesthesia modification for outpatient colonoscopies. Ji et al.[12] compared the effects of a similar regimen on vital signs and anesthetic depth. As a secondary outcome, they reported that recovery time was less in the group of patients who received the combined regimen compared with the group who received only propofol.[12] However, the definition of recovery in that report was not based on validated discharge criteria. Our study implemented the Aldrete scoring system[19] and the Modified Post Anesthetic Discharge Scoring System scale[16,17] to assess, respectively, recovery from the immediate effects of anesthetics (Phase 1 recovery), and home-readiness (Phase 2 recovery).

Phase 1 recovery was assessed at the end of the procedure in the endoscopy suite, and again upon arrival in the PACU, by a score of greater than or equal to 9 on the Aldrete scale. Phase 2 recovery was evaluated using the Modified Post Anesthetic Discharge Scoring System every 10 min from the end of the endoscopy procedure through the PACU stay, until home-readiness was attained.

The Modified Post Anesthetic Discharge Scoring System criteria objectively determines that a patient is ready to be discharged to home by incorporating assessments of pain control, nausea and ability to ambulate.[17] We found that recovery from the effects of anesthesia, as well as home-readiness, were delayed in the group of subjects who received dexmedetomidine as an adjunct. The median Aldrete score upon arrival in the PACU was 8 in subjects receiving propofol–dexmedetomidine, compared with 10 in those receiving propofol only (Table 2). Similarly, only an aggregate of 51% of subjects receiving propofol–dexmedetomidine were ready for discharge to home after 30 min from the procedure end time, compared with 88% of subjects receiving propofol. The value for those receiving propofol-dexmedetomidine is well outside the probability range of 70 to 90% for discharge to home within 30 min from end of procedure that we defined as indicative of noninferiority.

The total propofol consumption was also considerably lower in subjects receiving propofol–dexmedetomidine (140 μg · kg−1 · min−1) compared with those receiving propofol (180 μg · kg−1 · min−1). These values include the initial bolus dose of 1 mg/kg administered to each subject at the beginning of the procedure to allow passage of the endoscope. This result is consistent with findings by Ji et al.[12] and is likely due to the α2-adrenoceptor agonist-mediated sedative and analgesic effects of dexmedetomidine[8] having an additive effect with the hypnotic effects of propofol to achieve the desired level of sedation.

Subjects receiving propofol–dexmedetomidine had a larger decrease in MAP, from their preprocedure baseline to the lowest value observed during the procedure, compared with subjects receiving propofol. In those receiving propofol–dexmedetomidine, the MAP decreased by 30%, from a median baseline value of 99 mmHg, to 70 mmHg during the procedure. In subjects receiving propofol, the decrease was only 21%, from a median baseline value of 99 mmHg, to 78 mmHg during the procedure. Although the effect on MAP was statistically significant (P = 0.003), the clinical implications of this decrease in blood pressure are likely less relevant because recent studies suggest that maintaining a MAP of 65 is equally good as the classic "20%" rule of keeping the blood pressure within 20% of preoperative values. A recent retrospective analysis found no clinically important interaction between preoperative blood pressure and intraoperative blood pressure targets.[24]

Although dose-dependent bradycardia is a known side effect of dexmedetomidine, and significant bradycardia has been reported with the use of dexmedetomidine alone for sedation,[15,25] we found no statistically significant difference in the occurrence of either sustained bradycardia or apnea between the two groups. These findings are consistent with our expectations and are similar to the results of other studies that used a low dose of dexmedetomidine as an analgesic adjunct. While some of these studies found a lower heart rate in subjects receiving dexmedetomidine, the values were generally above 50 beats/min and, as such, typically did not require administration of medications to counteract bradycardia.[9,10,12,13]

If a lower dose of propofol had been used in this study, we would expect similar results because the delay in discharge readiness seems clearly related to the addition of dexmedetomidine to the anesthesia regimen. While it is difficult to speculate if the results would have been different if dexmedetomidine was administered as an infusion rather than a bolus dose, we would expect that similar effects would be observed although the onset of such effects may be delayed with an infusion as the time to peak effect of the drug would be longer.

Our study had several limitations. First, we did not assess variables that may have been advantageous for the subjects receiving dexmedetomidine, such as the incidence of patient movements that could affect the endoscopy procedure. Anecdotally, several anesthesiologists at our institution have reported that adjunctive administration of dexmedetomidine seemed to decrease patient movement and improve the endoscopist's satisfaction with the procedure. Ji et al. reported significantly less body activity affecting the colonoscopy procedure in patients who received dexmedetomidine as an adjunct.[12] Similarly, in a randomized trial, Wang et al. reported a lower requirement for rescue fentanyl in a group of patients having ambulatory inguinal hernia repairs who were sedated with dexmedetomidine versus those sedated with propofol.[13]

A second limitation of this study is that we measured anesthesia depth using BIS monitors instead of standard methods such as the Modified Observer Assessment of Alertness/Sedation, which defines sedation levels according to patient response. However, BIS monitor values have been shown to correlate significantly with the Richmond Agitation Sedation Scale and Observer Assessment of Alertness and Sedation.[26,27]

Another limitation of this study is our definition of apnea as oxygen desaturation requiring intervention with positive pressure ventilation. This form of apnea is a rare event during anesthesia for endoscopic procedures,[22] and did not occur in either of our study groups. Studies that have used less stringent definitions for respiratory issues, such as transient hypoxemia and occurrence of airway obstruction, reported advantages for subjects sedated with propofol plus dexmedetomidine compared with propofol only.[13,15] Furthermore, we evaluated the effects of only one dose (0.3 μg/kg) of dexmedetomidine. It is possible that a lower dose would yield more favorable hemodynamic results and reduce the effect on the duration of recovery. Future investigations using lower doses of dexmedetomidine may be warranted.

From a statistical perspective, this study is also limited by our use of a per protocol analysis without performing an intention to treat analysis. An intention to treat approach was not used because this study was designed as a non-inferiority trial, thus we did not collect outcome data for the excluded cases. Recommendations vary on whether to use an intention to treat or per-protocol approach for noninferiority trials. Some authors recommend using the intention to treat approach for all randomized controlled trials including noninferiority trials.[28] Others have showed that there is potentially no benefit to using the intention to treat approach for noninferiority trials.[29,30]

This study may also be limited by the subjective use of 20% as the noninferiority margin of clinical importance, based on our institutional experience. However, these results are strengthened by the finding that discharge was significantly delayed (convincingly outside our selected noninferiority margin) in subjects receiving propofol–dexmedetomidine (51% ready for discharge within 30 min) compared to subjects receiving propofol (88% ready for discharge within 30 min).

Finally, while our results might be generalizable to adults of all races and ethnicities undergoing ambulatory colonoscopy, it is important to note that our medical center serves a predominantly black population. While minorities were not specifically targeted for recruitment, over 80% of subjects included in this study identified as black. We are not aware of any overall consensus regarding a variable response to anesthesia based on race. However, variability with race in response to sedation has been reported by some investigators.[31,32]

In conclusion, combining a low dose of dexmedetomidine with propofol for anesthesia decreased propofol consumption in adults having ambulatory colonoscopy, with no effect on the incidence of sustained bradycardia. However, using only propofol for colonoscopy provided more stable hemodynamics, allowed for faster recovery from anesthesia, and faster attainment of discharge readiness, compared with using propofol–dexmedetomidine.

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