Achieving higher safety standards for sedation in routine endoscopy has been a priority over the last few years. In keeping with this objective, the present study showed that patients undergoing colonoscopy under sedation developed relative hypoventilation (as reflected by retention of CO
2) that persisted for a significantly longer period in patients sedated with midazolam than in patients sedated with propofol. The results support the findings of a meta-analysis that suggested that propofol sedation during colonoscopy is associated with a lower risk of complications when compared with traditional sedative agents[
21].
Although the use of oxygen saturation monitoring during sedation is routinely used by most gastroenterologists and the administration of supplemental oxygen has become a widely accepted practice, little attention has been paid to the development of alveolar hypoventilation[
17]. Because of the buildup of CO
2 in the patient’s alveoli and blood, hypoventilation can be effectively detected by capnography, which has recently become a focus of interest as an additional monitoring parameter during gastrointestinal procedures. This procedure has become relevant as the use of newer anesthetic drugs such as propofol has increased[
15].
Several studies to date have evaluated the importance of CO
2 buildup during endoscopic procedures[
14-16,22]. Freeman et al[
15] were the first to show that profound hypoventilation may frequently occur undetected during a gastrointestinal endoscopy, especially if additional oxygen is given and the decline of oxygen saturation is thus prevented; we observed a similar effect in our study. Freeman et al[
15] also found that the degree of hypoventilation was more closely related to the sedative drug dose than to the underlying medical illness. In 30 colonoscopies, with 90% receiving fentanyl and 37% additionally receiving midazolam, Freeman et al[
15] recorded a mean PCO
2 increase of 6.4 ± 3.8 mmHg, whereas during ERCP with a higher rate of deeper sedation, the mean values were 14.2 ± 10.2 mmHg. Our results showed a mean increase in PcCO
2 of 8.6 ± 3.7 mmHg despite a continuous SpO
2 above 90%; these results are similar to the experience of Freeman et al[
15].
The pattern of the registered PcCO2 readings differed noticeably in our study according to the pharmacological properties of the administered drugs. The pattern of the initial rise of PcCO2 was similar, but the PcCO2 level decreased much earlier after the administration of propofol than after the administration of midazolam. Although propofol had to be administered more often in a repeated fashion to maintain the desired sedation level, its effect ceased much faster than the effect of midazolam. This pharmacologic pattern seems to be reflected by the shape of the PcCO2 curve.
We did not observe severe hypoxemia or apnea in either of the study groups; the increase in CO
2 could, however, indicate silent risk during poor sedative practice. In the study by Freeman et al[
15]. We did not observe severe hypoxemia or apnea in either of the study groups; the increase in CO
2 could, however, indicate silent risk during poor sedative practice. In the study by Freeman et al[
15], one case demonstrated an increase of the PcCO
2 curve above 80 mmHg prior to respiratory arrest. Nelson et al[
16] showed that the monitoring of PcCO
2 may be useful for the endoscopist to guide sedation using midazolam and fentanyl and that this monitoring can help to prevent severe carbon dioxide retention. Thus, we believe that determining the PcCO
2 level can be helpful for the endoscopist when deciding whether to administer a further incremental dose of the sedative.
The combination used in this study of alfentanil, which is a potent opioid with a rapid onset of action, and midazolam is uncommon. Typically, this substance alfentanil is administered in combination with propofol for patient-controlled sedation or for short sedoanalgesia in emergency medicine[
23]. The rationale to use this substance alfentanil as a single bolus at the beginning of the procedure was (1) to provide the patients with optimal analgesia during the most painful passage of the sigmoid colon; and (2) to determine whether differences in alveolar hypoventilation at the end of the procedure can be completely attributed to the pharmacologic effect of the sedatives. Furthermore, if propofol is used in outpatient procedures, alfentanil may be an ideal drug to use in combination because of its pharmacokinetic properties and analogous profile of action. Because alfentanil (similarly to all opioids) can induce or enhance alveolar hypoventilation, our protocol prescribed a single low dose of 4 μg/kg per BW of alfentanil and a strict time interval of administration one minute before the first titration dose of the sedative was given.
Alveolar hypoventilation exists when the arterial PaCO2 increases above 45 mmHg, which can occur as the result of various underlying factors. Sedation directly or indirectly influences alveolar hypoventilation by a predominant central effect, thereby causing an increase in the PaCO2. Therefore, recognition and adequate monitoring of this physiological change through indirect means such as transcutaneous monitoring of PcCO2 could play an important role during sedation. The peak PcCO2 value may not be clinically relevant; however, the time period during which reduced ventilation occurs may represent a period of increased risk for some patients. Because of the S-shape of the oxygen dissociation-curve, hypoventilation accompanied by a decrease in PaO2 may remain unnoticed over time. Although a patient would have adequate arterial saturation with the administration of supplemental oxygen, an adverse physiologic trend that may be reflected by changes in the PaCO2 may go unnoticed.
Transcutaneous CO2 monitoring in adults has yielded conflicting results because of technological limitations, such as the time required for calibration, the need to warm the skin to 42 degrees, the effect of sweating and the influence of skin metabolism and thickness. Technical problems precluded an accurate interpretation of the data in 7 of the 97 patients and thus represent a limitation in our study.
A predominant central effect, thereby causing an increase in the PaCO2. Therefore, recognition and adequate monitoring of this physiological change through indirect means such as transcutaneous monitoring of PcCO2 could play an important role during sedation. The peak PcCO2 value may not be clinically relevant; however, the time period during which reduced ventilation occurs may represent a period of increased risk for some patients. Because of the S-shape of the oxygen dissociation-curve, hypoventilation accompanied by a decrease in PaO2 may remain unnoticed over time. Although a patient would have adequate arterial saturation with the administration of supplemental oxygen, an adverse physiologic trend that may be reflected by changes in the PaCO2 may go unnoticed.
Transcutaneous CO2 monitoring in adults has yielded conflicting results because of technological limitations, such as the time required for calibration, the need to warm the skin to 42 degrees, the effect of sweating and the influence of skin metabolism and thickness. Technical problems precluded an accurate interpretation of the data in 7 of the 97 patients and thus represent a limitation in our study.
The main focus of this study was to evaluate the impairment of ventilation induced by midazolam or propofol during colonoscopies. Most trials comparing the use of propofol and midazolam in the endoscopy suite have focused on differences in recovery time (assessed using a discharge scoring system, for example)[
24]. The present study suggests that there is also a significant difference in the duration of hypoventilation during the post-procedural period. Although alveolar hypoventilation is generally well tolerated by most patients, it may nevertheless be of clinical relevance in patients with compromised health. Iber et al[
25] showed that in 4% of patients sedated with midazolam, a relevant decrease of oxygen saturation below 89% occurred during the 30 min after the endoscopic procedure, which is contrast to our practical experience with propofol, where the effect occurs exclusively during the time when the attention on the patient is greatest. During the endoscopic procedure, the PcCO
2 monitoring indicated no increased hypoventilation risk for propofol when compared with midazolam.
Insufflation of the colon with carbon dioxide (CO
2) rather than air has been shown to reduce pain and discomfort because CO
2 is rapidly absorbed by the intestinal lining. In previous studies, measurement of end tidal CO
2 (ETCO
2) and the mean pCO
2 demonstrated these procedures to be safe. However, no studies have used transcutaneous continuous pCO
2 monitoring, which could be valuable given the increasing use of this insufflation technique for pain relief during colonoscopies[
26].
A metanalysis by Qadeer et al[
21] showed that propofol sedation had a lower rate of cardiopulmonary complications than traditional agents used during colonoscopy procedures. This current study highlights another physiological mechanism that may be detrimental when propofol is used in larger cohorts. Therefore, assessing the PcCO
2 during sedation could serve as an added safety measure to detect alveolar hypoventilation.
In conclusion, hypoventilation occurs frequently during sedation for colonoscopy and is often undetected during routine pulse oximetry. A significantly higher number of patients sedated with propofol had normalized PcCO2 values five minutes after sedation when compared with patients sedated with midazolam. Understanding the role of CO2 retention will be important in increasing the further safety standards of sedation during endoscopy. More studies are required to identify and prevent hypercapnia and thus ensure the safe practice of sedation during routine gastrointestinal endoscopies.