Dexmedetomidine compared with propofol for pediatric sedation during cerebral angiography.

BACKGROUND: Sedation of pediatric patients undergoing cerebral angiography is challenging. Although dexmedetomidine is used for sedation in various procedures, it has not been reported for pediatric patients undergoing cerebral angiography. This study compared the safety and efficacy of dexmedetomidine with that of propofol for cerebral angiography in pediatric patients.
MATERIALS AND METHODS: Sixty-two patients (6-15 years) scheduled for elective cerebral angiography were apportioned randomly and equally to receive either propofol or dexmedetomidine sedation. Patients in the propofol group received an initial bolus of intravenous propofol (1 mg/kg) and a maintenance infusion of 100 μg/kg/min. Patients in the dexmedetomidine group received an initial bolus of intravenous dexmedetomidine (1 μg/kg over 10 min) and a maintenance infusion of 1 μg/kg/h. An additional bolus of propofol 0.5 mg/kg or dexmedetomidine 0.25 μg/kg was repeated if needed. Procedure time, time to recovery and adverse events associated with sedation were recorded.
RESULTS: All cerebral angiographies were completed successfully under sedation with dexmedetomidine or propofol. Mean cerebral angiography time was 36 ± 10 min in the propofol group and 31 ± 7 min in the dexmedetomidine group (P = 0.047). The percentage of airway events and total adverse events were significantly higher in the propofol group (P < 0.05). Heart rate decreased in the dexmedetomidine group and mean arterial pressure decreased in the propofol group (P < 0.05, each).
CONCLUSION: Although cerebral angiography can be performed successfully under sedation with either propofol or dexmedetomidine, dexmedetomidine may be a better alternative because of fewer respiratory adverse events.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Pediatric cerebrovascular diseases include arteriovenous malformation, cavernous hemangioma, moyamoya disease, venous aneurysm, and capillary telangiectasia. Central to the diagnosis, planning of treatment and management of cerebrovascular diseases is the cerebral angiography,[1] a procedure to image blood vessels in the brain. Children are rarely able to complete the exam under local anesthesia because of anxiety, agitation, pain and discomfort from the femoral artery puncture and injection of contrast agent, and brain dysfunction caused by hemorrhage or ischemia. Deep sedation or general anesthesia is therefore warranted, but general endotracheal anesthesia may prolong postoperative recovery. Provision of motionless sedation with rapid recovery and acceptably low risk of adverse events may be challenging.

Propofol is widely used for anesthesia and sedation in pediatric patients, but adverse side effects include hypotension, respiratory depression and hypertriglyceridemia.[2] An alternative option is dexmedetomidine, a highly selective α-2 adrenoceptor agonist that provides sedation, analgesia, and anxiolytic effects. It has been used in pediatric patients for premedication,[3] intraoperative administration,[4567] computed tomography (CT) scanning,[89] magnetic resonance imaging (MRI),[1011] mechanical ventilation,[1213] and other procedures.[141516] Unlike other sedatives, dexmedetomidine has been shown to induce sedation similar to natural sleep, without significant respiratory depression.[1718] However, dexmedetomidine has not been reported for pediatric patients undergoing cerebral angiography.

Therefore, the present study compared the safety and efficacy of dexmedetomidine relative to that of propofol for sedation during cerebral angiography in pediatric patients. In particular, we evaluated the number of respiratory events and hemodynamic complications during the procedure.

PATIENTS AND METHODS

Patients

The study was entered into the Chinese Clinical Trial Registry (www.chictr.org, ChiCTR-TRC-12002713) and approved by our institutional review board for human subjects. A parent or legal guardian of each patient provided written informed consent to participate in the study. Children between the ages of 6 and 15 years with American Society of Anesthesiologists (ASA) classification of I or II were eligible for inclusion in the study [Figure 1]. Exclusion criteria were: Known allergy to the medications used, obesity (body weight >20% of the ideal), ASA classification III or more (severe systemic disease or worse), cardiac abnormalities, craniofacial anomaly, respiratory problems (pneumonia, asthma, bronchitis, or severe obstructive sleep apnea), Glasgow coma scale <15, intracranial hypertension and uncontrolled epilepsy.

Figure 1

CONSORT flow diagram

Protocol

A random number table was used to equally allocate patients to either a propofol or dexmedetomidine treatment group (n = 31, each). The anesthesiologists and data collectors in the radiology procedure room were not blinded to the treatment. The subjects, their parents or legal guardians, and observers in the recovery room and follow-up were blinded to the study group.

The preoperative fasting period was 2 h for clear fluids and 6 h for solid food. No premedication was given. All patients received an intravenous infusion of 5 mL/kg/h lactated Ringer's solution. Monitoring by pulse oximetry (blood oxygen saturation [SpO2]) and electrocardiography was conducted throughout the procedure. Arterial blood pressure was monitored noninvasively at 3-min intervals.

Patients in the propofol group received an initial bolus of intravenous propofol, 1 mg/kg (Diprivan; Astra Zeneca Pharma, Cheshire, UK) over 30 s and then a maintenance infusion of 100 μg/kg/min. Patients in the dexmedetomidine group received an initial bolus of intravenous dexmedetomidine 1 μg/kg (Dexmedetomidine Hydrochloride Injection; Jiangsu HengRui Medicine, Lianyungang, Jiangsu, China) over 10 min, and then a maintenance infusion of 1 μg/kg/h (dexmedetomidine was diluted in normal saline to a dose of 4 μg/mL). Local anesthesia was performed with 1% lidocaine before the femoral artery puncture. Additional boluses of propofol (0.5 mg/kg) or dexmedetomidine (0.25 μg/kg) were administered if needed to maintain sedation.

Oxygen was administered at 3 L/min via nasal cannula throughout the procedure. Ephedrine boluses of 3–5 mg administered intravenously were allowed in addition to fluid infusion to treat hypotension (systolic arterial pressure <90 mmHg or mean arterial pressure <65 mmHg). Atropine boluses of 0.3-0.5 mg were administered intravenously to treat bradycardia (heart rate <60 bpm).

Clinical signs of airway obstruction or desaturation (SpO2 <90%) were managed with airway manipulations (jaw thrust, chin lift, or shoulder roll) to relieve obstruction. If this was not effective, an artificial airway (oral or nasal airway, or face mask) was used. Endotracheal intubation was used as the last resort. All the above respiratory events were recorded.

All the angiography procedures were performed by the same radiologist. Once the imaging was complete, the propofol or dexmedetomidine infusion was discontinued. All patients were transferred to a recovery room and observed continuously by observers blinded to the study group. Oxygen administration was continued until discharge from the recovery room. A total modified Aldrete score of ≥18 indicated the patient's readiness for discharge [Table 1].[19] Adverse events in the recovery room and the time required to meet the discharge criterion were recorded. Patients were followed for complications related to sedation (desaturation, agitation, nausea, and vomiting) by observers blinded to the study group for 24 h after the procedure.

Table 1

Modified aldrete classification

Statistical analysis

The number of subjects required in each group was determined before the study by a power calculation based on data from a previous study[20] and the results of our institution database. Twenty-eight patients in each group were required to detect a 20% difference in the incidence of airway events with an α level of error of 0.05 (two-sided) and power of 0.8 (PASS 11.0.7 Statistical Software, NCSS, Kaysville, Utah). Thirty-one cases were allocated to each group to compensate for possible dropped cases.

Data were analyzed using SPSS software (IBM SPSS Statistics, version 19, Chicago, Illinois). Data are presented as mean ± standard deviation, number of samples (n), and percentage (%) as appropriate. Age, weight, procedure time, and time to meet discharge criteria were compared using Student's t-test. Heart rate and mean arterial pressure over time were compared using the two-way repeated-measures analysis of variance. Gender and ASA classification were compared with Pearson's Chi-squared test. The percentages of patients in each group with a radiologic diagnosis or adverse events were compared using Fisher's exact test. A two-tailed P < 0.05 was considered to be statistically significant.

RESULTS

Demographics and radiologic diagnosis

This analysis consists of 62 patients, ages 6-15 years, who completed the study during the period March 2011 and May 2012 [Figure 1]. There were no statistically significant differences between the groups with regard to age, and gender, weight, ASA physical status, or radiologic diagnoses [Table 2].

Table 2

Demographics and clinicopathology of the propofol and dexmedetomidine treatment groupsa

Procedure duration and time to recovery

The procedure time for the propofol group (35.8 ± 10.7 min) was significantly longer than that of the dexmedetomidine group (31.2 ± 7.0 min, P = 0.047). There was no difference in time to meet discharge criteria between the two groups.

Adverse events

The differences in the adverse events between propofol and dexmedetomidine sedation groups are shown in Table 3.

Table 3

Adverse events associated with sedation in the propofol and dexmedetomidine groupsa

Ephedrine was administered to one patient (3.2%) in the propofol group to treat hypotension and atropine was administered to one patient (3.2%) in the dexmedetomidine group for bradycardia. Vomiting, agitation, and allergic reactions did not occur in either group.

Seven patients (22.6%) in the propofol group had airway events, whereas none of the patients in the dexmedetomidine group had an airway event (P = 0.011). Airway manipulations (jaw thrust, chin lift, shoulder roll) were required for the seven patients in the propofol group to relieve airway obstruction; for two, artificial airways (oral or nasal airway, mask ventilation) were needed. None of the patients in either group required intubation.

The percentage of total adverse events during sedation was also significantly higher in the propofol group (25.8%) than in the dexmedetomidine group (3.2%; P = 0.026). There were no differences in the percentages of other adverse events between the two groups.

Hemodynamic effects

At baseline, the mean heart rate and mean arterial pressure were similar between the groups. After induction, the mean heart rate of the dexmedetomidine group was significantly lower than in the propofol group. The baseline heart rate did not change significantly after induction with propofol. However, patients receiving dexmedetomidine experienced a significant reduction in heart rate, especially 5 min after induction [Figure 2].

Figure 2

Heart rates at baseline, at the end of induction, and 5, 10, and 15 min afterward in the propofol and dexmedetomidine groups. Data are mean ± 95% confidence interval. *P < 0.05 between the two groups; #P < 0.05 in comparison to baseline values

After induction, the mean arterial pressure of the propofol group was significantly lower than that the dexmedetomidine group. In the dexmedetomidine group, the mean arterial pressure did not change significantly relative to the baseline. However, patients receiving propofol experienced a significant reduction in mean arterial pressure, especially at the end of induction [Figure 3].

Figure 3

Mean arterial pressures at baseline, at the end of induction, and 5, 10, and 15 min afterward in the propofol and dexmedetomidine groups. Data are mean ± 95% confidence interval. *P < 0.05 between the two groups; #P < 0.05 in comparison to baseline values

DISCUSSION

The main finding of this study was that dexmedetomidine sedation for cerebral angiography in pediatric patients was associated with fewer respiratory events than propofol sedation.

Since 2011, our institution began to use dexmedetomidine as the sedative for CT, MRI, digital subtraction angiography, and other procedures in adult and pediatric patients. Many pediatric patients with cerebrovascular diseases suffer from brain dysfunction caused by hemorrhage or ischemia. Intracranial hypertension and epilepsy are the most common symptoms. Provision of anesthesia or sedation for these patients can often be challenging. For critically ill patients, general anesthesia by endotracheal intubation is the only choice. Nevertheless, most cases are relatively mild, and it is possible to complete the procedure under sedation.

An ideal sedative should cause rapid onset, adequate maintenance of the sedative state to allow completion of the procedure, and rapid recovery. It should also be safe with few adverse events. Respiratory depression is the most important risk and predictor of sedation-related morbidity and mortality.[21]

Propofol is one of the most widely used anesthetics in anesthesia and sedation for adult and pediatric patients. It has been used to induce deep sedation for CT and MRI in pediatric patients,[2022] mainly because it has a rapid onset and recovery time, an absence of nausea or vomiting, and less respiratory depression. However, in the present study, we demonstrated that the incidence of airway events and the subsequent need for airway intervention to relieve airway obstruction were significantly greater in the propofol group than in the dexmedetomidine group. Similar to our findings, Zgleszewski et al.[20] showed that propofol is associated with a significantly greater incidence of adverse respiratory events compared with pentobarbital.

The changes in the configuration that cause obstruction in the upper airway during anesthesia with propofol in pediatrics have been studied. Litman et al.[23] showed that the dimensions of the upper airways of children change significantly on awakening from propofol anesthesia, and in most children the narrowest point in the pharynx was at the level of the soft palate. In their study Evans et al.[24] they found that increasing the depth of propofol anesthesia in children was associated with upper airway narrowing throughout the upper airway, and was most pronounced in the hypopharynx at the level of the epiglottis. Our results are consistent with the imaging findings of these studies.

Pharmacologically, propofol induces anesthesia through the inhibitory neurotransmitter γ-aminobutyric acid, while dexmedetomidine acts by stimulation of α-2 adrenergic receptors in the locus coeruleus. Propofol may cause more intense rapid-eye-movement sleep, which is associated with central inhibition of ventilation,[2526] whereas dexmedetomidine has been shown to induce sedation similar to natural sleep.[1718]

Another important finding of the present study was that the cerebral angiography took significantly longer for the propofol group than for patients who received dexmedetomidine. This can be explained by the significantly greater number of airway events in the propofol group, which required the radiologist to hold the procedure to allow for correction of the problem.

In this study, other adverse events were infrequent and incidence did not differ between the groups. Both propofol and dexmedetomidine sedation allowed completion of the cerebral angiography for all subjects. Dexmedetomidine caused significant reductions in heart rate, and propofol caused significant reductions in mean arterial blood pressure. These hemodynamic reductions were statistically, but not clinically, significant. Although there was one patient who required pharmacologic intervention in each group, the changes in hemodynamics were relatively mild and transient.

It is known that the most significant adverse reactions associated with dexmedetomidine are hypotension and bradycardia, resulting from its sympatholytic activity; both have been reported in several pediatric studies,[81027] although rarely do either require clinical intervention. We found that dexmedetomidine caused significant reductions in heart rate, but did not change the mean arterial pressure significantly in this pediatric population. However, despite the high affinity of dexmedetomidine for the α-2 rather than the α-1 adrenergic receptor (1620:1),[28] it should be used cautiously in patients at risk of bradycardia or hemodynamic instability.

Our study has some limitations. First is the absence of blinding for the anesthesiologist administering sedation. However, this was not possible in view of the nature of drugs and the need to manage complications efficiently if they arose. Second, although our results showed a significant difference in the incidence of airway events it did not show differences in other adverse events. However, our study was not statistically designed to analyze differences in other adverse events. A larger sample size may be required to find the true incidence of adverse events in this population.

CONCLUSION

Dexmedetomidine was associated with fewer respiratory adverse events, and therefore may be better alternative as a sedative for cerebral angiography in pediatric patients.

AUTHOR'S CONTRIBUTIONS

Peng K and Li J helped performing the research and data analysis and writing the manuscript. Ji FH contributed to the recruitment of patients. Li Z helped performing the study. Corresponding author (Peng K) conceived and designed the study. All authors have approved the final manuscript.