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Original Article

Propofol sedation with fentanyl or midazolam during oesophagogastroduodenoscopy in children

Disma, N.1; Astuto, M.1; Rizzo, G.1; Rosano, G.1; Naso, P.2; Aprile, G.2; Bonanno, G.2; Russo, A.2

Author Information
European Journal of Anaesthesiology: November 2005 - Volume 22 - Issue 11 - p 848-852
doi: 10.1017/S0265021505001432

Abstract

Introduction

Oesophagogastroduodenoscopy is a widely used diagnostic or therapeutic procedure for diseases of the upper gastrointestinal tract. Children or uncooperative patients may not tolerate insertion of the endoscope and may not remain immobile for the duration of the procedure and thus require sedation. Conscious sedation does not always permit a safe procedure and deep sedation or general anaesthesia may be required. Deep sedation is defined by the American Society of Anesthesiologists (ASA) as ‘patient not responsive to either verbal or light tactile stimuli’ [1].

There is no standard and ideal protocol for sedation and a variety of anaesthetic techniques have been described, including intravenous (i.v.) or inhalational anaesthesia with or without tracheal intubation [2,3].

Intravenous sedation, during which the child breathes spontaneously without an artificial airway, is an alternative to inhalational anaesthesia with an artificial airway. Propofol has been successfully used in various minor outpatient procedures in children [4]. The pharmacokinetics and pharmacodynamics of propofol result in an early return of alertness with decreased nausea and vomiting [5,6].

The first aim of this study was to assess propofol sedation in children undergoing oesophagogastroduodenoscopy and to investigate safety and tolerance when propofol is used alone or combined with fentanyl or midazolam. The second aim was to evaluate recovery time and time to discharge from the hospital as well as to document any adverse reaction or side-effects related to the anaesthetic technique. The endoscopist was also asked for a general evaluation of the total procedure.

Methods

The study protocol was approved by the Hospital Ethics Committee and informed consent both for the study and anaesthesia, was obtained from the patients' parents. We studied 240 paediatric outpatients, ASA I-II, aged 1-12-yr old, scheduled for diagnostic endoscopic procedures of the upper gastrointestinal tract. A randomized, prospective, three-study-group design was used. All the patients were enrolled during the period between January 2001 and May 2004 at the University Policlinic of Catania (Italy).

Patients were randomly allocated to receive either propofol alone (Group P), propofol and midazolam (Group PM) or propofol and fentanyl (Group PF).

The procedures were performed with a video-endoscope (Olympus GIF-100, Hamburg, Germany) in the endoscopy unit by the same paediatric gastroenterologist, who had more than 20 yr experience in the procedure. The patients were instructed to take nothing by mouth as follows: children aged 12-36 months for at least 6 h before the procedure, children older than 36 months for at least 8 h before the procedure.

When the patients arrived in the endoscopy unit about 1 h before the procedure, the paediatric anaesthetist obtained a medical history and carried out a physical examination and clinical assessment [7]. Vital signs (heart rate (HR), blood pressure (BP), etc.) were recorded and defined as baseline values.

All patients received a standard premedication with oral midazolam (0.5 mg kg−1; max 7.5 mg) 20 min before the procedure. EMLA cream (AstraZeneca, Italy) was applied to possible venipuncture sites. Before sedation was started, the pharynx was sprayed with lidocaine for topical anaesthesia. A venous line was established and the study drugs were administered by the anaesthetist.

The patients in all three groups were given propofol 3 mg kg−1 (Diprivan emulsion 1%, AstraZeneca, Italy) divided into three doses of 1 mg kg−1 each given over 1 min. Patients in Group P were only given propofol. Patients in Group PM received 0.1 mg kg−1 of i.v. midazolam 2 min before starting the propofol injections. The patients in Group PF were given a bolus of 1 μg kg−1 fentanyl 2 min before starting propofol. Insertion of the endoscope was permitted 2 min after giving the third dose of propofol.

Supplemental propofol (1 mg kg−1) was administered if the depth of sedation was insufficient.

HR, mean arterial pressure (MAP), respiratory rate and oxygen saturation (pulse oximeter) were recorded using an automatic device (Siemens SC9000, Danvers, USA) at 1 min intervals during the procedure and every 5 min during recovery. All patients were given supplemental oxygen via a nasal cannula (3 L min−1) and allowed to breathe spontaneously without tracheal intubation. The endoscopy was performed in the left lateral position, and the anaesthetist was prepared to interrupt the procedure and check the airway at any time if necessary.

Respiratory and cardiovascular complications were recorded by the anaesthetist. Movement and coughing during instrument insertion were considered to be a sign of insufficient sedation. Hypoxia was defined as oxygen saturation below 90%; bradycardia and tachycardia were defined as a HR 30% below or above baseline. Hypotension was defined as a MAP 30% under baseline. Adverse events were defined as minor (self-limiting, duration less than 30 s) or major, if pharmacological intervention, bag-valve-mask ventilation, or endotracheal intubation were necessary. Duration of the procedure and necessity to reinsert the endoscope were noted. At the end of the procedure, the gastroenterologist, who was blinded as to the sedation regimen, was asked to rate the ease of the procedure on a three-point scale (easy, adequate, impossible). After the procedure, the patients were transferred to the recovery room for further monitoring of vital signs.

Patient recovery was assessed at 5 min intervals using a modified Aldrete score according to which patients receive 0-2 points for each of five physiological variables (motor activity, respiration, circulation, consciousness and temperature) [8]. Patients were considered ready to be discharged from the recovery room when they scored eight points or more and communicated normally. Time to discharge was defined as the time from the end of the procedure until the child fulfilled the discharge criteria.

The children's parents were instructed to contact the hospital in case of adverse events that could be related to the procedure (nausea, vomiting, abdominal pain, difficulty in breathing), during the 24 h after discharge from the hospital.

Statistical analysis was performed using Systat 7.0 (SPSS Inc, Chicago, IL). Data are presented as mean values (SD). Patient characteristics data were compared using t-test. Duration of the endoscopic procedure and recovery times were compared using the U-test. The numbers of patients requiring supplemental propofol were compared by the χ2-test. Time to first rescue administration and the incidence of adverse events during the procedure were compared by analysis of variance (ANOVA), with post hoc correction for multiple comparisons. Probability values below 0.05 were considered statistically significant.

Results

Two hundred and forty children undergoing diagnostic endoscopic procedures of the upper gastrointestinal tract were studied. Eighty patients were assigned to the propofol group (P), 78 patients in the propofol-midazolam group (PM), and 82 to the propofol-fentanyl group (PF).

The patients in the three groups were well matched (Table 1). There were no differences in duration of endoscopy, recovery time or the endoscopist's rating (Table 2).

Table 1
Table 1:
Patient characteristics data.
Table 2
Table 2:
Duration of procedures and time to discharge (in minutes), and endoscopist's ratings.

Supplemental propofol for insufficient sedation was required by 31 patients in Group P (39%), eight of whom required two supplemental doses. Fourteen patients in Group PM (18%) and 11 patients in Group PF (13%) also required additional propofol. The groups differed significantly and statistical analysis showed a significant difference between Groups P and PM and Groups P and PF but there was no evidence of a statistical significance between Groups PM and PF (Table 3). The time between introduction of the endoscope and the administration of the first supplemental propofol dose is shown in Figure 1. The three groups did not differ in this respect.

Table 3
Table 3:
Number of patients requiring supplemental propofol.
Figure 1.
Figure 1.:
Time from the introduction of the endoscope to the first supplemental dose of propofol. Time is shown on the ordinate in seconds. No difference was found between the three groups ( P = 0.345).

The procedures were carried out successfully and propofol was tolerated well. All adverse events were managed without the need of pharmacologic treatment. Adverse events were seen in 15 patients in Group P, five patients in Group PM and four patients in Group PF. Five patients in Group P were treated with bag-and-mask ventilation for less than 1 min (Table 4). Adverse events were significantly less frequent in Groups PM and PF than in Group P. None of the patients suffered post-anaesthetic morbidity, and none of the parents contacted the hospital for adverse events occurring after discharge.

Table 4
Table 4:
Incidence of adverse events during gastroscopy.

Discussion

Oesophagogastroduodenoscopy is a procedure that is not well tolerated by children or uncooperative patients due to the discomfort of the passage of the endoscope through the mouth, pharynx and upper gastrointestinal tract. In this study we tested the quality and safety of deep sedation using propofol alone or in combination with fentanyl or midazolam, for children undergoing this procedure.

There is no ideal protocol for sedation in children undergoing endoscopic procedures. Different approaches have been adopted in various hospitals, according to experience and technology. Bishop and colleagues described gastroscopy in non-sedated children and showed that when it is performed without sedation there is a decrease in total procedure time [9]. We think that gastroscopy in non-sedated children could be a viable option only for very motivated children. Sedation is preferred in many hospitals and has some advantages: monitoring of vital signs is delegated to the anaesthetist, the patient does not move and sedation allows the endoscopist to prolong the endoscopic study if necessary. The common disadvantages of deep sedation or general anaesthesia are the cost and the necessity of involving an anaesthetist [10].

We used an induction dose of 3 mg kg−1 of propofol without a continuous infusion, because gastroscopy is usually a very short procedure. Martlew and colleagues showed that the propofol induction dose in infants is higher than in adults [11]. In agreement with a pharmacokinetic study that showed a synergistic effect between propofol and fentanyl [12] and propofol and midazolam [13], our results confirmed that a lower dose of propofol can be used when it is combined with fentanyl or midazolam, and the clinical results also support a pharmacological synergism between propofol and midazolam. The higher dose of propofol required in children would explain in part the high demand for additional propofol when administered alone.

A combination of propofol, meperidine/fentanyl and midazolam was used in 100 adult patients by Cohen and colleagues. Their study showed that endoscopy can be performed at a moderate level of sedation by combining a low dose of propofol with a narcotic agent and/or benzodiazepine and that the use of a small dose of a narcotic agent and midazolam in combination with propofol does not prolong patient recovery. These results support our data in which the combination of propofol and midazolam or fentanyl does not prolong recovery time for children [14].

The presence of an anaesthetist during endoscopy procedures is not universally accepted. Although usually safe, the sedation of paediatric patients has serious associated risks, such as airway obstruction, hypoxia, hypoventilation, and apnoea. In some hospitals in the USA, in which the demand for sedation of paediatric patients is increasing, sedation can be performed by accredited non-anaesthesia clinicians [15]. Hassall suggested that the best outcome of endoscopic procedures, with regard to safety of paediatric patients and their satisfaction is achieved when sedation is controlled by the anaesthetist rather than the endoscopist [16]. In agreement with Hassall, we think that i.v. propofol administration or inhalational anaesthesia must be conducted by anaesthetists, who are the only physicians with experience in airway management and the cardiorespiratory pathophysiology of infants and children.

Propofol is a potent and predictable i.v. anaesthetic that can be used in low doses to sedate children. However, the sedative dose can easily be exceeded, leading to unintended anaesthesia. For this reason, propofol should be recommended for use by anaesthetists only. Sury and colleagues published a study that describes a nurse-led sedation service for magnetic resonance imaging of children [17]. The authors evaluated the nurses at Great Ormond Street Hospital, but this approach is only feasible at high-level hospitals and for oral administration of sedatives. We consider the anaesthetist's presence particularly recommended during sedation for invasive or painful procedures, like endoscopy.

Inhalational anaesthesia with an artificial airway has been shown to eliminate the potential for failed sedation [10] but it requires anaesthetic equipment and devices in the diagnostic unit or that the procedure be performed in the operating room. Squires and colleagues reported that inhalational anaesthesia increased the total cost of upper gastrointestinal endoscopy in children more than i.v. anaesthesia and that the use of inhalational anaesthesia was associated with a greater risk of complications [18]. In our study, we performed all paediatric endoscopies in the endoscopy unit; while we use the operating room when the patient was in a critical condition or when there is a risk of respiratory problems.

Swartz and colleagues investigated gastric contents in children with gastrointestinal symptoms scheduled for upper gastrointestinal endoscopy. They demonstrated that these children did not have a greater volume or acidity of gastric contents than children without gastrointestinal symptoms [19]. Following this investigation, we carried out propofol sedation with spontaneously breathing patients and no patients had complications related to aspiration of gastric contents.

Several recent articles describe the use of propofol for sedation and general anaesthesia in patients undergoing gastrointestinal endoscopy and document its favourable properties [20-23].

Propofol has the important advantage of a rapid onset of action, a titratable level of effect, and a short half-life that leads to timely recovery from anaesthesia. However, there are important side-effects of propofol anaesthesia, including respiratory depression, myoclonus and hypotension. A generous dose of propofol for induction of anaesthesia can induce transient oxygen desaturation, a fall in systolic BP and obstructive apnoea requiring airway positioning or bag-and-mask ventilation. A low dose of propofol is associated with inadequate sedation and with several complications especially during painful procedures. The combination of propofol with other sedative agents is a reasonable option to avoid high doses of propofol and a prolonged recovery time. Our study shows that the combination of midazolam or fentanyl with propofol produces better conditions, with a significantly reduced incidence of side-effects during the endoscopic procedure, compared to propofol alone.

In conclusion, this study highlight several important findings. First, i.v. sedation with propofol for endoscopic procedures appears safe in paediatric patients, no major adverse events occurred in the three study groups. Second, inclusion of fentanyl or midazolam to propofol sedation significantly reduces the total dosage of propofol required to obtain an adequate depth of sedation and permits easy performance of an upper gastrointestinal endoscopic procedure. Third, fewer minor adverse events were observed when fentanyl or midazolam was administered 2 min before propofol probably because of the better tolerance of endoscope insertion. Fourth, recovery time and discharge from the hospital were similar in the three groups. Fifth, the endoscopist did not note any difference between the different anaesthetic techniques. None of the parents of children contacted the hospital for adverse events related to the procedure in the 24 h after gastroscopy. These data are extremely promising but need to be confirmed by a larger study.

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Keywords:

CONSCIOUS SEDATION; CHILD; PROPOFOL; MIDAZOLAM; FENTANYL; GASTROSCOPY

© 2005 European Society of Anaesthesiology