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Abstract

Objectives

To investigate the efficacy and safety of sedation with dexmedetomidine in upper gastrointestinal endoscopy.

Methods

Patients with ASA physical status I–II undergoing elective upper gastrointestinal endoscopy were randomly allocated to receive dexmedetomidine or midazolam for conscious sedation. Continuous peripheral oxygen saturation (SpO₂), heart rate, mean arterial pressure (MAP), Ramsay Sedation Scale (RSS) and numeric rating scale pain scores were recorded before, during and after the procedure. Patients completed a post-procedure satisfaction questionnaire.

Results

Patients in the midazolam group (n = 30) experienced a significant decrease in MAP during sedation compared with pre-sedation values. Patients in the dexmedetomidine group (n = 30) had significantly higher SpO₂ and RSS scores during sedation than those in the midazolam group. Overall satisfaction was higher in the dexmedetomidine group than the midazolam group. There were no clinically significant complications in either group.

Conclusion

Dexmedetomidine has a good safety profile and is an effective sedative for use in upper gastrointestinal endoscopy.

Keywords

Dexmedetomidine sedation gastrointestinal endoscopy

Introduction

Upper gastrointestinal endoscopy is a commonly performed diagnostic and therapeutic procedure. Patients may experience anxiety regarding potential discomfort and pain, and are generally unable to tolerate the procedure with topical pharyngeal anaesthesia alone. Conscious sedation enables patients to maintain their response to verbal and tactile stimuli without losing cardiovascular and ventilatory function.¹ This form of sedation combines an opioid analgesic and a benzodiazepine, and is commonly used in upper gastrointestinal endoscopy.^2,3 The α-adrenoceptor agonist dexmedetomidine dose-dependently reduces arterial blood pressure and heart rate, and decreases haemodynamic and plasma catecholamine responses. It is used as a sedative, anaesthetic adjuvant, premedicant and anxiolytic, and has minimal adverse effects on respiratory function.^4–7 The aim of this study was to investigate the use of dexmedetomidine compared with midazolam in conscious sedation for upper gastrointestinal endoscopy, and examine its effects on perioperative haemodynamics, sedation, pain and patient satisfaction.

Patients and methods

Study population

This retropective randomized study recruited patients with ASA physical status I–II⁸ who were scheduled to undergo elective upper gastrointestinal endoscopy between January 2012 and December 2012 at Union Hospital, Fujian Medical University, Fuzhou, China. Exclusion criteria were: inability or unwillingness to participate or to give consent; ASA status ≥III; coexisting cardiac anomalies; aged <20 years or >60 years; allergy to study drugs (midazolam, dexmedetomidine or opioids); history of chronic alcoholism, sedative or narcotic analgesic drug abuse; advanced or decompensated liver or renal disease; uncooperative; and any serious illness.

The study was approved by the ethics committee of Fujian Medical University, China and adhered to the tenets of the Declaration of Helsinki. All subjects provided written informed consent prior to enrolment.

Anaesthesia

Using a computer generated randomization schedule, patients were assigned to undergo conscious sedation with either dexmedetomidine or midazolam and were taken into the operating room without any premedication. Patients in the dexmedetomidine group received 0.3 µg/kg dexmedetomidine bolus injection and 1 µg/kg fentanyl citrate intravenous infusion 10 min before endoscopy, followed by 0.2–0.3 µg/kg per h dexmedetomidine continuous infusion until an appropriate level of sedation was achieved.¹ Patients in the midazolam group received 0.05 mg/kg midazolam bolus injection and 1 µg/kg fentanyl citrate intravenous infusion 10 min before endoscopy, followed by 0.01 mg/kg midazolam at intervals of approximately 2–5 min until a satisfactory level of sedation was achieved.¹ Additional 0.01 mg/kg midazolam boluses were available for rescue sedation, if required. In both groups, additional and 1 µg/kg fentanyl boluses were available for rescue analgesia.

Standard monitoring (electrocardiogram, pulse oximetry and noninvasive blood pressure) was performed and antecubital venous access for intravenous fluids was achieved with a 20G intravenous cannula. All patients received prophylactic oxygen (1–2 l/min) via a nasal cannula during the procedure. A physician was present throughout the procedure and provided direct supervision of the endoscopist. All endoscopies were performed using standard techniques^1,2 and were carried out by the same endoscopist.

Data collection

All patients were observed in the recovery room until Aldrete post-anaesthesia recovery score reached ≥9 (full recovery from sedation).⁹ The time to full sedation and full recovery were recorded for all patients. Complications occurring during and after endoscopy, including apnoea, SpO₂ < 85%, decreased blood pressure (<80% of basal value), HR <50 beats/min, cough or abnormal body movements were noted. Patients’ overall satisfaction was assessed via questionnaire immediately following discharge from the procedure room.¹⁰

Continuous peripheral oxygen saturation (SpO₂), heart rate (HR) with telemetry and mean arterial pressure (MAP) were recorded at the following time-points: 1, before sedation; 2, full sedation, before endoscopy; 3, 5 min after beginning of endoscopy; and 4, after completion of endoscopy and discontinuance of drugs. Ramsay Sedation Scale (RSS)¹¹ and numeric rating scale for pain (NRS)¹² scores were recorded at time-points 2 (full sedation, before endoscopy) and 3 (5 min after beginning of endoscopy).

Statistical analyses

Continuous data were presented as mean ± SD and range. Between-group comparisons were made using Student’s t-test for normally distributed data or Mann–Whitney U test for non-normally distributed data. Within-group comparisons were made using paired t-test for independent variables or Wilcoxon test for dependent variables. P-values <0.05 were defined as statistically significant.

Results

The study recruited 60 patients (35 male/25 female; mean age 35.9 ± 10.9 years; age range 20–60 years), who were randomly assigned to receive either midazolam or dexmedetomidine (n = 30/group). Demographic and clinical data on the patients are shown in Table 1. There were no statistically significant between-group differences in sex distribution, age, weight or time to full sedation or recovery.

Table 1.

Demographic and clinical characteristics of patients included in a study to compare the use of dexmedetomidine and midazolam for conscious sedation in upper gastrointestinal tract endoscopy (n = 60).

Characteristic	Dexmedetomidine group n = 30	Midazolam group n = 30
Sex, male/female	16/14	17/13
Age, years	35.3 ± 10.6	36.6 ± 11.4
Weight, kg	61.1 ± 7.3	59.4 ± 8.4
Time to full sedation, min	8.5 ± 1.2	7.6 ± 1.8
Time to full recovery, min	8.9 ± 6.2	10.3 ± 5.3

Data presented as n or mean ± SD.

No statistically significant between-group differences (P ≥ 0.05; Student’s t-test).

Data on clinical parameters at each time-point are shown in Table 2. In the midazolam group, mean arterial pressure was significantly lower at time-points 2 and 3 compared with time-point 1 (P < 0.05 for both comparisons). SpO₂ and RSS scores were significantly higher in the dexmedetomidine group than the midazolam group at time-points 2 and 3 (P < 0.05 for all comparisons).

Table 2.

Pre-, intra- and post-procedure clinical parameters of patients undergoing upper gastrointestinal endoscopy under conscious sedation with dexmedetomidine or midazolam.

Parameter	Dexmedetomidine group n = 30				Midazolam group n = 30
	Time-point				Time-point
	1	2	3	4	1	2	3	4
Heart rate, beats/min	80.4 ± 14.4	75.6 ± 12.6	72.5 ± 13.2	78.5 10.7	82.4 ± 14.9	78.5 ± 15.3	74.1 ± 13.9	78.3 ± 10.7
Mean arterial pressure, mmHg	115.3 ± 12.5	108.5 ± 10.1	105.2 ± 9.3	110.8 ± 8.7	120.6 ± 12.3	100.5 ± 14.1^a	98.7 ± 13.5^a	110.3 ± 14.1
Pulse oximetry, SpO₂	99.8 ± 0.4	98.4 ± 1.1^b	98.3 ± 0.7^b	99.7 ± 0.5	99.7 ± 0.4	91.4 ± 1.4	92.4 ± 1.2	99.3 ± 0.6
RSS score¹¹	NR	4.2 ± 0.8^b	4.5 ± 1.2^b	NR	NR	3.2 ± 1.1	3.5 ± 1.5	NR
NRS score¹²	NR	2.3 ± 0.6	2.1 ± 0.8	NR	NR	2.6 ± 0.5	2.7 ± 0.6	NR

Data presented as mean ± SD.

Time-points: 1, before sedation; 2, full sedation, before endoscopy; 3, 5 min after beginning of endoscopy; and 4, after completion of endoscopy and discontinuance of drugs.

P < 0.05 versus time-point 1 in same group, ^bP < 0.05 versus midazolam group; paired t-test and Wilcoxon test.

RSS, Ramsay sedation scale; NR, not recorded; NRS, numeric rating scale.

According to data obtained from questionnaires, patients in the dexmedetomidine group rated their overall satisfaction with the procedure higher than those in the midazolam group (96.6% vs 83.3%, P < 0.05). A total of six patients (dexmedetomidine group n = 1; midazolam group n = 5) thought that they required either more or less sedation than they received. No patient reported experiencing any severe pain during the procedure. The amnesic effect was equivalent in both groups, with no patient reporting any recollection of intra-procedure events.

A total of eight patients required additional sedation and analgesia (dexmedetomidine group n = 3; midazolam group n = 5). No patient experienced rebound hypertension, tachycardia or acute reversal of sedative and analgesic effects in either group. No patient required prolonged post-procedure monitoring, unplanned admission or subsequent medical attention.

Discussion

Upper gastrointestinal endoscopy is a routine procedure, but patients may experience discomfort and pain. Topical anaesthesia alone has been advocated for endoscopy in order to avoid the cost and risk of conscious sedation,^13,14 but this approach is likely to be less acceptable to patients and reduce their willingness to undergo repeat procedures. Sedation is routinely used in upper gastrointestinal endoscopy,^15–17 with care taken to balance patient comfort and post-procedure side effects. The most suitable agents for conscious sedation during upper gastrointestinal endoscopic procedures are still being investigated. In common with other reports,^10,18,19 the present study compared the sedatives dexmedetomidine and midazolam. Our data showed that patients in the dexmedetomidine group experienced better peripheral oxygen saturation and RSS scores than those in the midazolam group.

Dexmedetomidine has been approved for sedation in critically ill patients in the intensive care unit, and during surgery, cardiac catheterization and radiology.^4–7 Dexmedetomidine also has been reported to reduce the stress response to surgery and intensive care,^20,21,22 and has been shown to be a useful sedative agent for colonoscopy.¹⁰

Midazolam was selected as the medication for comparison in our study owing to its frequent use as a sedative in gastroscopy and endoscopy.^10,18,19 Midazolam is usually used alone for gastroscopy and is combined with opioids (meperidine or fentanyl) for colonoscopy and endoscopic retrograde cholangiopancreatography (ERCP).^10,23 Some studies have recommended propofol as a sedative in upper gastrointestinal endoscopy, but difficulties in estimating the correct dosage and the lack of a direct antagonist limit its use, particularly in high-risk patients.²⁴ Dexmedetomidine and midazolam were used in the present study because these drugs have distinctive pharmacological profiles and their respective adverse effects require different management strategies.^10,18,19

Dexmedetomidine is commonly administered as a bolus of 0.5–1.0 µg/kg, followed by an infusion of 0.2–2.0 µg/kg per h. The initial loading dose may cause adverse cardiovascular reactions such as hypertension, hypotension, bradycardia or sinus arrest, especially in patients taking medication capable of producing negative chronotropic effects (e.g. β-adrenergic antagonists and digoxin) or those with hypovolaemia.^25–27 An infusion of 0.5 µg/kg per h has been shown to be highly effective in promoting sedation and analgesia for mechanical ventilation even without prior bolus.^28,29 In the present study, the bolus dose was reduced to 0.3 µg/kg to avoid rapid haemodynamic changes,^26,27 and a continuous infusion of 0.2–0.3 µg/kg per h was used. This relatively low total dose may explain the absence of respiratory and cardiovascular complications in our study, and the low initial loading dose followed by continuous infusion of dexmedetomidine provided adequate, well controlled sedation. High doses of sedative drugs are likely to cause complications, especially in high-risk patients.³⁰

Airway protection and the maintenance of cardiovascular stability are important responsibilities of the endoscopist during upper gastrointestinal endoscopy. Oxygen desaturation is a common complication during sedation, possibly due to the overuse of sedative agents and subsequent lack of ventilation.³⁰ Patients in the dexmedetomidine group had higher SpO₂ than those in the midazolam group in the present study, indicating that dexmedetomidine had no significant respiratory depressive effects. Since dexmedetomidine binds to α2 receptors rather than gamma-aminobutyric acid (GABA) receptors, patients can be easily aroused from sedation and experience less significant respiratory depression than those sedated using midazolam.^31,32 Endotracheal intubation should be considered in patients with poor respiratory status (SpO₂ < 85%) or those who are deeply unconscious (RSS score ≥6).

Hypotension resulting from cardiac instability is a concern during upper gastrointestinal endoscopy. The invasive nature of the procedure can lead to patient anxiety, hyperventilation and arrhythmia. Dexmedetomidine has been associated with bradycardia, which can be reversed with drug treatment and will resolve spontaneously after weaning.^28,29 No patient experienced clinically significant bradycardia in the present study, and there were no cases of rebound hypertension or tachycardia following discontinuation of either drug.

This study has several limitations. First, the retrospective nature of the study introduces potential bias in data collection and incomplete data for some patients. Secondly, the small cohort precluded reaching statistical significance for all study endpoints, and much larger numbers of patients must therefore be evaluated to confirm the safety profile of dexmedetomidine. Thirdly, the study included only low-risk patients (ASA I or II), since high-risk patients (ASA III–IV) are generally sedated by anaesthetists in our institution. Finally, this was a single-centre study and others may have different findings.

In conclusion, our results suggest that dexmedetomidine has a good safety profile and is an effective sedative for use in upper gastrointestinal endoscopy.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflict of interests.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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Dexmedetomidine versus midazolam for sedation in upper gastrointestinal endoscopy

Abstract

Objectives

Methods

Results

Conclusion

Keywords

Introduction

Patients and methods

Study population

Anaesthesia

Data collection

Statistical analyses

Results

Discussion

Footnotes

Declaration of conflicting interest

Funding

References