Abstract

Background

Sedation/analgesia (S/A) is widely used to relieve patients’ anxiety and discomfort during colonoscopy. Their effects on abdominal pain after colonoscopy have never been fully investigated.

Methods

The prospective study consecutively recruited 494 healthy patients having a screen colonoscopy examination as part of their health checkup. They were divided into two groups based on individuals’ decision to receive sedation and analgesia or not. In the S/A group, 374 patients received midazolam and alfentanil during colonoscopy with standard monitoring , while in the non-sedation/analgesia (NSA) group, 120 patients received no analgesics. Severity and duration of abdominal pain (ordinal scale: 1 = none, 4 = severe) were assessed at the end of stay in the postanesthetic care unit (the S/A group) or examination room (the NSA group) and before discharge. Side effects S/A during (hypotension, hypoxemia) and after (nausea, vomiting, dizziness) colonoscopy were also recorded. All patients were closely monitored during the whole course of the health check-up package.

Results

The mean doses of midazolam and alfentanil were 4.06 mg and 813.12 μg, respectively. Patients in the NSA group had two-fold risks of moderate to severe abdominal pain compared to those in the S/A group (16.67% vs. 9.36%, odds ratio = 1.937, 95% confidence interval: 1.010–3.625). The NSA group also had a higher incidence of abdominal pain 120 minutes after examination (33.33% vs. 16.04%, P < 0.001). Duration of abdominal pain in those patients who did have abdominal pain was longer in the S/A group than in the NSA group (153.3 ± 49.9 vs. 118.7 ± 47.5 minutes, P < 0.001). The incidence of hypotension and hypoxemia in the group S/A was 5.6% and 2.9%, respectively. More patients in the S/A group felt dizzy or sleepy than those in the NSA group (14.7% vs. 3.3%, P < 0.001). The incidence of nausea and vomiting was similar between the two groups.

Conclusion

Optimal S/A with midazolam and alfentanil decreases the severity and duration of postcolonoscopic abdominal pain.

Keywords

abdominal pain, colonoscope, sedation/analgesia

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Introduction

Colonoscopy is commonly used as a diagnostic and screening method for colorectal neoplasms. However, gas insufflation and intraluminal instrumentation during colonoscopy cause colonic distension and abdominal pain. The abdominal pain may persist for more than 24 hours ¹ and even lead to admission ² and unplanned absence from work. ³ Its incidence ranges from 5.3% to 45.0% in different studies, depending on their design, definition of abdominal discomfort, and which time patients were asked. It may also decrease patients’ satisfaction and their willingness to accept another colonoscopy if it is necessary in the future.

Several methods, including using CO ₂ instead of air for insufflation ⁴ or total colonic decompression after colonoscopy ⁵ , were tried to decrease abdominal discomfort with different degrees of success. On the other hand, although sedation and analgesia have been widely used to decrease patients’ anxiety and discomfort during colonoscopy, their effect on abdominal pain after colonoscopy, including severity, incidence, and duration, has not been clarified yet. In the current study, we test the hypothesis that among patients undergoing colonoscopy, those who received optimal sedation/analgesia (S/A) will suffer from less severe and shorter-lived postcolonoscopic abdominal pain.

Methods

Study Design and Population

After obtaining approval from the Ethics Committee of our hospital and written informed consent, asymptomatic healthy patients who received total colonoscopic examination as part of their self-paid medical health check-up were recruited consecutively in this prospective study. They were all provided with the information about S/A during colonoscopy, including its benefits and possible adverse effects. Then, they decided whether to receive S/A or not by themselves. Exclusion criteria include irritable bowel syndrome by Rome II criteria, known colorectal pathologies, and other potential causes of abdominal pain before colonoscopy. Patients were further excluded if any therapeutic procedure, for example, polypectomy, was performed during examination. Patients were divided into two groups: S/A group, in which patients received S/A; non-sedation/analgesia (NSA) group, in which patients refused to have S/A. Their demographic characteristics and medical histories were reviewed by physicians not involved in this study.

S/A and Colonoscopy

In the examination suite, monitors were provided to patients of the S/A group with continuous electrocardiogram, periodic noninvasive blood pressure measurement, and pulse oxymetry. After obtaining a baseline hemodynamic profile, patients were put in the lateral decubitus position for colonoscopy. For patients receiving S/A, supplemental oxygen 3 L per minute via nasal cannula was given after entering the examination suite. They were also encouraged to take deep breaths as preoxygenation. Induction of S/A with intravenous midazolam 0.05 mg/kg and alfentanil 10 μg/kg was given by staff anesthesiologists. After confirming patients’ loss of consciousness, endoscopists performed rectal digital examination first, then colonoscopy. During examination, a supplemental bolus of midazolam 0.5 mg with alfentanil 100 μg was given whenever the patient expressed nocifensive behavior such as withdrawal, facial grimacing, or verbal complaints about discomfort. Hypoxemia (SpO ₂ < 90%) or hypotension (systolic blood pressure drops > 25% of baseline value) were treated with an oxygen face mask (6 L/min) or mask ventilation, and a bolus of intravenous ephedrine (8 mg), respectively. Major complications were defined as severe cardiopulmonary compromise for which endotracheal intubation or continuous inotropic support were necessary, unplanned admission, or mortality.

After examination, patients receiving S/A stayed in the postanesthetic care unit until, and they were fully awake, had stable vital signs without oxygen or other medication, and were able to ambulate without help.

The colonoscopy was performed in the morning by one of the four experienced endoscopists. Each of them had performed at least 1,500 colonoscopies before this study (Lee YC, Chiu HM, Huang SP, Lai YP). The one-man method was used to insert the endoscope, shorten the gut, and minimize loop formation. Air was used for insufflation. All patients had the same colon preparation regimen prior to examination.

Assessment of Abdominal Pain

One trained nurse who wasn’t involved in colonoscopic examination assessed the severity of abdominal pain in the patients of the NSA group at the end of their stay in the examination room, and in the patients of the S/A group at the end of their stay in the postanesthetic care unit. The degree of abdominal pain was graded on a 4-point ordinal scale: none, mild, moderate, or severe. Before discharge, usually in the afternoon after patients finished a battery of tests, patients were evaluated again for overall severity and duration of postcolonoscopic abdominal pain, and S/A-associated side effects, including nausea, vomiting, and dizziness. All subjects were closely monitored during this period (about 4 to 6 hours). The onset and duration of postcolonoscopic abdominal pain were recorded. In addition to the duration reported by individual patients before discharge, the duration between leaving the examination room and being able to report abdominal pain for the first time at postanesthesia care unit was added to calculate the total duration of abdominal pain in group S/A.

Statistical Analysis

Quantitative data were summarized as mean ± standard deviation (SD) and categorical variables as percentages and absolute count. Chi-square test for categorical variable, Student t test for interval/ratio variable are used to calculate differences in different variables between the S/A and NSA groups. Kaplan–Meier survival curve was used to express postcolonoscopic abdominal pain time course among those who suffered from abdominal pain. Differences were considered significant when the P value was less than 0.05. Statistical analyses were performed with the statistical software package STATA version 8.0.

Results

Patients Analysis

A total of 494 patients were recruited in this prospective study, 120 in the NSA group and 374 in the S/A group. Their demographic characteristics are listed in Table 1. There was no statistically significant difference between the two groups with respect to age and body mass index. The male/female ratio was higher in the NSA group than in the S/A group. In other words, fewer male patients chose to receive S/A than female patients (71% vs. 82%, P = 0.0054).

S/A

Among patients receiving S/A, mean total doses (induction and bolus doses) of midazolam and alfentanil were 4.06 ± 0.70 mg (0.067 ± 0.015 mg/kg) and 813.12 ± 139.90 μg (13.31 ± 3.04 μg/kg), respectively. Hypoxemia occurred in 11 patients (2.9%), and hypotension occurred in 21 patients (5.6%). The incidence of nausea and vomiting wasn’t significantly different between the NSA and S/A groups. More patients in the S/A group felt dizzy or sleepy than in the NSA group (14.7% vs. 3.3%, P < 0.001). No patients needed endotracheal intubation or inotropics support. No patient was admitted for any reason. No mortality and no major complications were noted during the study period.

Abdominal Pain

During their health checkup course after colonoscopy and before discharge, 16.67% of patients in the NSA group and 9.36% of patients in the S/A group experienced moderate to severe abdominal pain ( P = 0.026) (Table 2). S/A made a 44% decrease in the risk of moderate to severe abdominal pain (Figure 1). In those patients who suffered from abdominal pain (mild to severe), S/A also made a difference in the duration of abdominal pain (153.3 ± 49.9 min in the NSA group vs. 118.7 ± 47.5 min in the S/A group, P < 0.001). Figure 2 shows that the proportion of patients having abdominal pain decreased more rapidly in the S/A group than in the NSA group. The greatest difference was observed approximately 120 minutes after colonoscopy, when S/A was associated with a 52% decrease in the risk of abdominal pain (33.33% in the NSA group vs. 16.03% in the S/A group, Table 2 and Figure 3).

Discussion

To date, this is the first study demonstrating that with optimal sedation and analgesia, patients will experience less discomfort not only during colonoscopy but also after examination. We’ve shown that S/A caused a 44% decrease in the incidence of moderate to severe abdominal pain, which might affect patients’ willingness to return for subsequent examination more likely. ⁶ Besides incidence, patients who did have abdominal pain had a more rapid recovery with S/A than those who refused it.

Although colonoscopy is a relatively non-traumatic procedure, it causes noxious stimulation by instrumentation and colorectal distension. Colorectal distension has been proved to be a noxious visceral stimulus and used as a model of visceral pain. ^7,8 In animal studies, adrenoreceptor, 5-HT, GABA, NMDA, and opioid receptors located in the spinal cord are found to be involved in the processing of visceral pain caused by colorectal distension. ^9-12 The mechanisms of anti-visceral pain behind the combination of midazolam and alfentanil have been proven by numerous animal studies that GABA agonists would increase the antinociceptive effect of opioids in the colorectal distension model ¹⁰ . The synergism between two distinct pharmacodynamic medicines, i.e., midazolam and alfentanil, could thus prolong the duration of action and thereby reduce the incidence and duration of postcolonoscopic abdominal pain. Figure 2 shows that, instead of 2 parallel lines, the recovery curve of the S/A group has a steeper slope than that of the NSA group. The greatest difference lies about 120 minutes after colonoscopy, far beyond the duration of action of midazolam and alfentanil. It may be explained by the prevention of visceral hyperalgesia. Visceral hyperalgesia, meaning that previous exposure to colorectal distension or irritant made subjects more sensitive and produced more severe responses to subsequent colorectal distension, was found in the rat model. ^13-15 Midazolam and alfentanil, given before gas insufflation, may prevent or decrease the occurrence of visceral hyperalgesia. In humans, gas insufflation during colonoscopy is a unique clinical scenario most similar to the colorectal distension model. The clear cause-effect relationship can be established not only between gas insufflation and abdominal pain but also between treatment and pain relief. In this study, colonoscopy is a part of a health checkup program, not a single exam. Our patients did not need to stay in the hospital much longer than patients having a common outpaient colonoscopy. Thus, time spent on close follow-up and direct contact via phone communication will be markedly reduced.

In addition to gas insufflation, instrumentation and manipulation during colonoscopy may also be possible causes of postcolonoscopic abdominal pain. Thinner and more flexible endoscopes were found to be associated with less discomfort. ¹⁶ Another study showed that most pain episodes during colonoscopy coincided with the looping or straightening of the colonoscope shaft. ¹⁷ The question of whether more looping is associated with more postcolonoscopic abdominal pain still needs to be clarified.

Shah et al. ¹⁷ also found that looping was more frequent and less well tolerated in women than in men. In our study, more women chose S/A than men. The unequal gender distribution meant women might be more anxious about possible discomfort and might express a higher degree of abdominal pain. Therefore, the real benefit of S/A may be more than what our study can reveal because patients in the S/A group, although with more female patients, expressed less abdominal pain. We also have performed logistic regression analysis to control for the possible effect of gender difference. After controlling for gender, the odds ratio for the overall incidence of moderate to severe abdominal pain is 0.50 (the S/A group vs. the NSA group, P = 0.025). Odds ratio for the incidence of persistent abdominal pain 120 minutes after colonoscopy is 0.39 (the S/A group vs. the NSA group, P < 0.001). So, after controlling for the possible confounding effect of gender difference, S/A still has a significant effect on postcolonoscopic abdominal pain.

The incidence of complications related to S/A in our study, especially hypotension and hypoxemia, was comparable to other studies. ^18-20 The consumption dose of midazolam and opioid (in equipotent dose) was also similar. We chose midazolam and alfentanil, instead of propofol, which is associated with faster recovery of cognitive function ^18,19 because our patients regarded injection pain caused by propofol as a major side effect, and they had to stay in the hospital after colonoscopy for other health checkup exams. Early recovery and discharge are not a chief goal in this circumstance. Other minor complications, such as nausea, vomiting, and dizziness, didn’t cause much disturbance. Patients in the S/A group didn’t have more nausea or vomiting than in the NSA group. The short duration of action of alfentanil may explain that. Although S/A caused more dizziness, most was well tolerated (mild: 12.3%; moderate to severe: 2.4%).

Further study about postcolonoscopic abdominal pain may include ketamine or opioids with a longer duration of action. The former, as an NMDA receptor antagonist, may reduce abdominal pain because NMDA receptor antagonists could attenuate visceral hyperalgesia in animal models. ^13,21 Prolonged abdominal pain and persistent colon distension ¹ explain the possible role of opioids with the duration of action long enough to cover the recovery phase, not just the examination period.

In conclusion, our study demonstrates that intravenous midazolam 0.05 mg/kg and alfentanil 10 μg/kg can produce nearly half decrease in the incidence of abdominal pain after colonoscopy and shorten its duration. Building on the present investigation, our results highly recommend that combining sedation and analgesia medications—such as ultra-short-acting remifentanil and remimazolam—will serve as a better combination choice in the future study design.

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References