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Postgraduate Medicine Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ipgm20
Comparison of Midazolam and Propofol for Sedation in Pediatric Diagnostic Imaging Studies a
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Ahmet Sebe MD , Hayri Levent Yilmaz MD , Zikret Koseoglu MD , Mehmet Oguzhan Ay MD & d
Muge Gulen MD a
Department of Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey b
Department of Pediatric Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey c
Department of Emergency Medicine, Adana Numune Training and Research Hospital, Yuregir, Adana, Turkey
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d
Department of Emergency Medicine, Eskisehir Yunus Emre State Hospital, Eskisehir, Turkey Published online: 13 Mar 2015.
To cite this article: Ahmet Sebe MD, Hayri Levent Yilmaz MD, Zikret Koseoglu MD, Mehmet Oguzhan Ay MD & Muge Gulen MD (2014) Comparison of Midazolam and Propofol for Sedation in Pediatric Diagnostic Imaging Studies, Postgraduate Medicine, 126:3, 225-230 To link to this article: http://dx.doi.org/10.3810/pgm.2014.05.2770
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C L I N I C A L F E AT U R E S
Comparison of Midazolam and Propofol for Sedation in Pediatric Diagnostic Imaging Studies
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DOI: 10.3810/pgm.2014.05.2770
Ahmet Sebe, MD 1 Hayri Levent Yilmaz, MD 2 Zikret Koseoglu, MD 3 Mehmet Oguzhan Ay, MD 3 Muge Gulen, MD 4 1 Department of Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey; 2 Department of Pediatric Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey; 3Department of Emergency Medicine, Adana Numune Training and Research Hospital, Yuregir, Adana, Turkey; 4Department of Emergency Medicine, Eskisehir Yunus Emre State Hospital, Eskisehir, Turkey
Abstract
Objective: This study aims to compare the efficacy of propofol and midazolam in terms of adverse effect potentials and to determine the appropriate strategy for pediatric procedural sedation. Methods: A total of 200 pediatric patients (aged , 14 years) undergoing diagnostic procedures were recruited for this nonrandomized prospective controlled cohort study. The patients were assigned to 2 treatment arms: either propofol (Group 1: IV bolus dose of 2 mg/kg during a 2-minute period, IV maintenance dose of 100 mcg/kg/min) or midazolam (Group 2: IV bolus dose of 0.15 mg/kg during a period of 2 to 3 minutes) to achieve sedation. Demographic data, body weight, and clinical status of the patients were evaluated and recorded. The vital signs and sedation levels (ie, Ramsay sedation scale scores) were evaluated and recorded, as well as the complications detected and medications administered in 10-minute intervals throughout the sedation procedure. Findings between the study arms were compared. Results: Arterial blood pressures decreased significantly in both groups (P = 0.001). The patients in Group 1 experienced a greater difference in diastolic blood pressure (P = 0.001) than those in Group 2. Sedation scores in Group 1 were more favorable (P = 0.014) and reached the appropriate sedation level in a shorter time than those in Group 2 (P = 0.010). Likewise, recovery time of patients was shorter in Group 1 than in Group 2 (P = 0.010). Hypoxia was found to be more common in the propofol group, but the difference was not significant (P = 0.333). Conclusion: Propofol seems to be more effective, achieve the appropriate sedation level more quickly, and provide a faster onset of sedation than midazolam in pediatric procedural sedation and analgesia. Propofol is preferred for imaging studies (computed tomography and magnetic resonance imaging) to reduce the occurrence of undesired motion artefacts. Although both drugs are safe to use for sedation before pediatric imaging procedures, propofol is preferred with appropriate preparation. Keywords: midazolam; propofol; pediatrics; procedural sedation and analgesia; diagnostic imaging
Introduction
Correspondence: Ahmet Sebe, MD, Assoc. Prof, Department of Emergency Medicine, Cukurova University, Medical School, 01330, Adana, Turkey. E-mail: [email protected]
Physicians generally require sedation and analgesia for patients undergoing magnetic resonance imaging (MRI), computed tomography (CT) scans, angiography, and radiotherapy in the emergency setting.1–5 Procedural sedation and analgesia (PSA) in pediatric patients is performed in surgical theaters, clinics, wards, and emergency departments by anesthesiologists, dentists, obstetricians, orthopedists, emergency physicians, and other clinicians.6 The American Pediatric Academy (APA) published the “Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients” in response to the increasing use of sedatives, opiates, analgesics, and general anesthetic
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Sebe et al
agents in invasive diagnostic, radiologic, and minor surgical procedures outside the operation room.3,7 Every discipline, maybe even every physician, uses different PSA methods and algorithms based on their own experiences and preferences, which gives rise to the heterogeneity of the procedure.8 An ideal sedative agent should not reduce blood pressure (BP) or cause episodes of hypoxia, and should provide a shorter time to reach the desired level of sedation and more rapid discharge from the emergency room. Propofol and midazolam are among the drugs commonly used in the context of PSA. Both drugs are outstanding members of their groups, with high potency, rapid onset of effect, short recovery time, and low potential of side effects. The objective of this study is to compare the efficacy and adverse effect potentials of propofol and midazolam in the context of pediatric PSA during diagnostic imaging.
Materials and Methods
This study was conducted in the university-based emergency department and involved 200 pediatric patients (aged , 14 years) with an American Society of Anesthesiologists (ASA) Physical Status of 1 and 2 who were scheduled to undergo diagnostic procedures in the departments of radiodiagnostics and nuclear medicine after Institutional Review Board approval. The study was started after approval was received from the ethics committee of Cukurova University. Parental informed consent was obtained for all 200 patients. For this nonrandomized prospective controlled cohort study, the patients were divided into 2 treatment arms. Patients in Group l (n = 100) received IV propofol, whereas those in Group 2 received IV midazolam (n = 100). All patients were observed for adverse effects of drugs, such as hypotension, hypoxia, bradycardia-tachycardia, and prolonged sedation. The patients received an IV infusion of 0.9% normal saline and their BP, heart rate (HR), respiratory rate (RR), oxygen saturation as measured by pulse oximetry (Spo2), and body temperature were measured and recorded before the commencement of PSA. Vital signs were monitored until the patients were deemed ready for discharge. The Ramsay sedation scale (RSS) was used to score the sedation level every 10 minutes.9 The elicited data regarding vital signs were also recorded every 10 minutes. A hypotensive event was predefined as an arterial systolic BP reading 30% below basal levels, an apneic event as cessation of spontaneous breathing . 20 seconds, and hypoxia was described as an Spo2 reading , 90%.10,11 Vital signs were measured using the GE/Marquette Solar 8000M 226
Patient Monitor (TRAM-RAC, electrocardiogram module, Spo2 module, noninvasive BPs module, temperature module). Patients in Group l received an IV bolus infusion of propofol at 2 mg/kg during a 2-minute period for induction, followed by 100 mcg/kg/min for maintenance, and stopped 2 minutes before the end of the painful procedure. Patients in Group 2 received an IV bolus infusion of midazolam at 0.15 mg/kg during a period of 2 to 3 minutes. Additional doses of 0.08 mg/kg during 1- to 2-minute periods were also administered to sedated patients every 5 minutes, if necessary. An additional midazolam dose was given to 14 patients. All patients were followed up and monitored in the emergency department until they were ready for discharge based on criteria from the Connecticut Children’s Medical Center Scoring System.6 Variables of this sedation scoring system were vital signs (stable: 1, unstable: 0); respiration (normal: 2; shallow breathing, tachypnea: 1; apnea: 0); level of consciousness (alert, oriented, presedation level: 2; arousable, confused, agitated: 1; unresponsive: 0); oxygen saturation (95%–100% or presedation level: 2; 90%–94%: 1; , 90%: 0); color (pink or presedation color: 2; pale or dark: 1; cyanotic: 0); and activity (obeys commands or presedation level: 2; moves extremities: 1; no spontaneous movement: 0). Children with a score $ 8 were considered ready for discharge. Airway patency and respiratory functions were followed and maintained from commencement of PSA until discharge, and all patients received 4 to 10 L/min of oxygen via nasal cannula. If a decrease in Spo2 , 96% occurred, the head was repositioned first, and then the rate of supplemental oxygen was increased. If patients did not experience a response to these measures, verbal and tactile stimuli were performed to trigger breathing. All patients were monitored until their Spo2 levels were completely normal and they did not require supplemental oxygen. The Student t test was used to compare mean values of the groups, whereas the Mann-Whitney U test was performed to compare nonparametric measurements. The Χ2 and Kolmogorov-Smirnov tests were used to evaluate categorical variables. Repeated measures in a given group or between groups were compared using ANOVA. P values , 0.05 were accepted as statistically significant.
Results
A total of 200 pediatric patients (aged 1 month to 14 years) were enrolled in this study. Male patients constituted 62.5% (n = 125). The mean age was 42.05 ± 35.20 months, and the mean weight was 14.95 ± 7.51 kg. Half of the patients
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Comparison of Midazolam and Propofol
(n = 100) received propofol (Group 1), and the other half received midazolam (Group 2). Patients in Group l had a mean age of 42.60 ± 31.76 months (range, 1–156 months), whereas the mean age in Group 2 was 41.50 ± 38.48 months (range, 1–168 months; P = 0.82). Male patients constituted 58% of the sample in Group l and 67% in Group 2 (P = 0.06). The difference in mean weights between the groups was not found to be statistically significant (P = 0.53). Table 1 shows the classification of patients in both groups regarding presumptive diagnoses and the procedures they were scheduled to undergo. A total of 62 patients (62%) in Group 1 were interpreted as ASA I and 38 (38%) were ASA II, whereas in Group 2, 65 (65%) were ASA I and 35 (35%) were ASA II (P = 0.560). Patients in both groups experienced a significant decrease in arterial systolic BP readings during PSA (P = 0.001 for both groups), although the difference between groups was not significant (P = 0.105). Patients in both groups experienced a significant decrease in arterial diastolic BP readings during PSA (Group 1, P = 0.001; and Group 2, P = 0.014), although the difference between groups was also found to be significant, indicating a greater decrease in Group 1 (P = 0.001). Mean HR values were also found to be similar between the groups (P = 0.060), with changes in the range of 103 and 114 beats per minute. Patients in both groups experienced a significant decrease in HR during the procedure (P = 0.010 for both groups). Mean RR values measured and recorded in 10-minute intervals were also found to be similar between groups (P = 0.333). Patients in both groups experienced a significant decrease in RR during the procedure (P = 0.001 for both groups). Mean Spo2 values measured and recorded in 10-minute intervals were also found to be similar between groups (P = 0.120), in the range of 97% and 98%. Patients in both groups experienced a significant decrease in Spo2 during the procedure (Group 2, P = 0.346; Group 2, P = 0.217). Ramsay sedation scale scores were measured and recorded in 10-minute intervals throughout the procedure Table 1. Classification of Patients Based on Procedure Procedure MRI CT DTPA renal scintigraphy Total
Group l
Group 2
N
(%)
N
(%)
60 32 8 100
60 32 8 100
30 60 10 100
30 60 10 100
Abbreviations: CT, computed tomography; DTPA, diethylene triamine pentaacetic acid; MRI, magnetic resonance imaging.
and at discharge; they are shown in Table 2. Mean sedation scores of patients in Group 1 receiving propofol were significantly higher than those of patients in Group 2 receiving midazolam (P = 0.001). The most serious complications of both drugs are hypoxia and apnea, which manifest with low Spo2 levels (ie, , 90%). Hypoxia was noted in 4 (4%) and 2 patients (2%) in Groups 1 and 2, respectively (P = 0.333). Positive pressure ventilation was necessary in only 1 patient in Group 1. Supplemental oxygen was given and airway opening maneuvers performed in 5 patients with hypoxia. Positive pressure ventilation was necessary in only 1 patient in Group 1. All patients were discharged from the emergency department with healing or presedation conditions. Oxygen saturation as measured by pulse oximetry decreased to , 95% but still . 90% in 11 patients (11%) in Group 1 and 7 patients (7%) in Group 2 (P = 0.120). In this case, the patient’s head was repositioned first, and then the rate of supplemental oxygen given via nasal cannula was increased. Verbal and tactile stimuli were used to trigger breathing. Nausea was the only drug-related adverse effect noted in the sample (2 patients in Group 2). None of the patients in Group 1 needed an additional dose of propofol beyond what was indicated in the defined protocol. However, 10 patients (10%) in Group 2 needed an additional dose of midazolam (P = 0.010). The sedation period lasted 44.4 ± 9.4 minutes (range, 15–60 minutes) in Group 1, compared with 52.5 ± 14.3 minutes (range, 30–35 minutes) in Group 2 (P = 0.010). Procedures performed on the patients lasted 24.35 ± 7.54 minutes (range, 5–40 minutes) in Group 1 and 10.73 ± 9.52 minutes (range, 5–40 minutes) in Group 2 (P = 0.010). Length of stay in the emergency department (time from the end of the anesthetic administration to the point Table 2. Mean Ramsay Sedation Scale Scores Ramsay Sedation Scale Score On initiation of PSA At 10th minute At 20th minute At 30th minute At 40th minute At the end of PSA At discharge P
Mean Score ± SD Group 1
Group 2
4.66 ± 0.68 3.85 ± 0.57a 3.19 ± 0.39a 3.05 ± 0.21a 3.46 ± 0.52a 4.00 ± 0.37a 4.49 ± 0.68a
5.13 ± 0.56 4.06 ± 0.44a 3.88 ± 0.47a 3.93 ± 0.53a 4.06 ± 0.58a 4.05 ± 0.32a 4.75 ± 0.59a 0.001
P , 0.05. Abbreviations: PSA, procedural sedation and analgesia; SD, standard deviation. a
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deemed appropriate for discharge) was calculated as 20.70 ± 5.94 minutes (range, 10–30 minutes) in Group 1 and 41.77 ± 11.60 minutes (range, 20–105 minutes) in Group 2 (P = 0.010). The mean periods to reach appropriate sedation level before the commencement of the procedure were 2.00 ± 0.87 minutes (range, 1–3 minutes) in Group 1 and 7.00 ± 6.28 minutes (range, 5–15 minutes) in Group 2. Patients in Group 1 reached the appropriate sedation level in a shorter period than those in Group 2 (P = 0.01).
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Discussion
Procedural sedation and analgesia is often used to effectively perform imaging and therapeutic modalities, such as MRI, CT, angiography, and radiotherapy. Many studies have addressed this issue in recent decades.1–5 The APA published and revised the “Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients”3,7 in response to the increasing use of sedatives, opiates, analgesics, and general anesthetic agents in invasive diagnostic, radiologic, and minor surgical procedures outside the operation room. Procedural sedation and analgesia is an intermediary state between general anesthesia and consciousness that is created and maintained when anesthetic agents are administered in lower doses than are necessary in general anesthesia. This level of consciousness is preferred over anesthesia in many procedures, especially when short recovery periods are desired.9 This study compared the efficacy and adverse effect potentials of propofol and midazolam in providing pediatric PSA during imaging studies. Both drugs have been preferred over others because of their high potency, short half-lives, and low potential of adverse effects. This study was designed to delineate the appropriate strategy and help guide preference regarding which drug to use in pediatric PSA. Both systolic and diastolic BP readings decreased after the tenth minute and started to normalize to initial levels after the 30th minute. This finding can be considered expected effects of the drugs.9–11 Group 1 showed a greater reduction in systolic BP than Group 2, although the difference is not statistically significant (P = 0.105). However, diastolic BPs decreased significantly more in patients administered propofol (P = 0.001). Havel et al12 showed significant reductions in systolic BPs in pediatric patients receiving propofol and midazolam before undergoing closed reduction of isolated extremity injuries (42.9% and 45.2%, respectively). Martin et al,13 however, 228
did not note any significant hemodynamic impairment in 9 children treated with propofol in the intensive care setting. Although hypotension is a well-known untoward effect of propofol, the reduction in BP readings in the present study is not in the context of hypotension. Both patient groups experienced a slight decrease in HRs after the tenth minute from drug administration, but this reduction did not have clinical or statistical significance (P = 0.060). Nonetheless, the readings approached normal levels after the 40th minute. This finding was also attributed to predictable effects of the drugs.9–11 Tomatir et al14 compared propofol with a propofolketamine combination in pediatric patients undergoing MRI and reported that HRs decreased significantly in patients receiving propofol, compared with a slight reduction seen in those treated with propofol-ketamine. Reed et al15 administered propofol in 28 children treated with mechanic ventilation and reported only 1 episode of bradycardia associated with hypotension in 1 patient. In the present study, however, the reduction in HRs was not in the context of bradycardia.13,15–17 Both drugs have been found to cause significant reductions in RRs and oxygen saturations compared with control values. The difference in RR reductions between the groups were not statistically significant (P = 0.333). Peripheral arterial oxygen saturations fluctuated between 97% and 98% from admission to discharge. Intragroup differences in the mean values obtained at different periods were not significant (Group 2, P = 0.346; Group 2, P = 0.217). Likewise, intergroup differences were also not significant (P = 0.120). These findings regarding the RRs and oxygen saturations were also attributed to predictable effects of the drugs.9–11,18 In their study of pediatric PSA using propofol and midazolam, Havel et al12 reported hypoxemia in 11.6% in patients receiving propofol and 10.9% in those receiving midazolam. In another study comparing midazolam and ketamine in pediatric PSA, Parker et al16 found that 12% of the patients experienced a temporary but significant decrease in oxygen saturations. In the present study, the dose regimen used in Group l (2 mg/kg as the loading dose and 100 mcg/kg/min for maintenance) was found to produce adequate PSA, in accord with the previous studies. The present study showed that propofol produces a higher quality of PSA than midazolam and has a quicker onset of effect, which is consistent with the known high potency of the drug.11 Patients in Group 2 were treated with an IV bolus infusion of midazolam of 0.15 mg/kg over a 2- to 3-minute period,
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Comparison of Midazolam and Propofol
which is the minimum dose accepted for sedation. The initial loading dose of midazolam, however, failed to induce effective sedation in a substantial number of patients, necessitating additional doses (ie, 0.08 mg/kg in 3 of every 5 minutes titrated to effect).9,10,19 Jevdjić et al18 investigated 24 children prospectively. Sedation was introduced with a single bolus of IV midazolam at 0.1 mg/kg, followed by repeated small IV boluses (0.5–4.0 mg/kg) of propofol until sufficient sedation was obtained. The outcome of sedation was measured by induction time, sedation time, need for additional sedation, respiratory events, cardiovascular events, and sedation failure. The investigators argued that this sedation regimen provides short induction time, fast recovery, stable cardiorespiratory conditions, and rarely requires additional sedation, and therefore is safe and adequate for children undergoing ambulatory MRI of the brain.18 The mean effective dose for 50% of subjects for the induction of general anesthesia is 0.2 mg/kg, although significant patient variation exists. Clinically adequate moderate IV sedation with midazolam should always be achieved through slow titration.19–21 In a study comparing propofol (2.5 mg/kg IV bolus loading dose, followed by 100 mcg/kg/min for maintenance) and propofol-ketamine (ketamine, 0.5 mg/kg and propofol, 1.5 mg/kg IV bolus loading dose, followed by 75 mcg/kg/min for maintenance) in 40 infants (aged 9 days to 12 months) undergoing MRI, Tomatir et al14 concluded that the propofolketamine combination provided more effective and safer sedation than propofol alone. In a study of sedation periods in the emergency department using propofol and midazolam, Havel et al12 found the mean recovery times to be 14.9 ± 11.1 minutes and 76.4 ± 47.5 minutes, respectively.12 Karl et al22 reported mean sedation periods of 21 ± 6 minutes in patients treated with midazolam compared with 35 ± 20 minutes in those administered combined midazolam and opiates. In the present study, the mean sedation period in Group 1 (44.4 ± 9.4 minutes) was found to be significantly shorter than Group 2 (52.5 ± 14.3 minutes; P = 0.01 for both groups). In the present study, the mean time to discharge was recorded as 20.70 ± 5.94 minutes in Group 1 versus 41.77 ± 11.6 minutes in Group 2. Havel et al12 reported corresponding times of 13.6 ± 11.3 minutes and 48.2 ± 45.3 minutes, respectively (P = 0.010). Reyle-Hahn et al23 reported a recovery time of 5 ± 1 minutes after termination of propofol infusion. In the present study, patients receiving propofol had a significantly shorter periods to discharge than those treated with midazolam (P = 0.010).
Mean time to reach adequate sedation in the present study was calculated to be 2.00 ± 0.87 minutes (range, 1–3 minutes) in Group 1 and 7.00 ± 6.28 minutes (range, 5–15 minutes) in Group 2 (P = 0.010). This significant superiority of propofol is expected because of its high potency and other pharmacologic effects. Reyle-Hahn et al23 and Havel et al12 reported similar findings. However, in the present study, mean sedation scores obtained to estimate clinical levels of sedation were significantly lower in Group 1 than in Group 2 (P = 0.001). Havel et al12 reported more favorable mean sedation scores among patients treated with propofol than in those treated with midazolam, although the study was too limited in size to extrapolate the results. Tomatir et al14 reported a mean time of 28.90 ± 2.50 minutes for performance of MRI after propofol administration in a study of 40 infants, whereas in the present study, this time was 24.35 ± 7.54 minutes. In the present study, 4 patients (4%) in Group 1 and 2 patients (2%) in Group 2 were found to have hypoxia. The corresponding figures reported by Havel et al12 were 11.6% and 10.9%, respectively, although the hypoxemic episodes were temporary and easily relieved with simple, noninvasive maneuvers (P = 1.00). Merola et al24 reported no significant adverse effects (ie, protracted sedation, agitation, airway compromise) attributed to propofol administration. Absence of any serious untoward consequences in the present study can be explained by supplemental oxygen delivered to all patients via nasal cannulae throughout the PSA period. Hypoxia was the most common adverse effect attributed to the drug regimens, and the rates of these events were similar between the treatment arms, and to the data reported in the literature.12,22,25 Positive pressure ventilation was needed in only 1 patient in Group 1 and in no patients in Group 2. Havel et al12 reported that no patients receiving propofol and/or midazolam required ventilatory support in their study. This finding is also consistent with the findings reported in other literature.22,26–30 Procedural sedation is an important component of the daily practice of emergency medicine and has particular relevance in the pediatric population. In the study reported by Molina-Infante et al,26 drug synergy in the midazolam plus propofol sedation regimen promotes a deeper and longer moderate sedation, improving patient satisfaction rates but prolonging early recovery time. The study by Gemma et al28 supports the hypothesis that propofol is preferable to midazolam in maintaining sedation in children aged 3 to 7 years
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Sebe et al
during auditory functional MRI, because it facilitates the elicitation of a more focused auditory cortical activation pattern, with less temporal and spatial dispersion.
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Conclusion
Propofol seems to be more effective, achieve the appropriate sedation level more quickly, and provide a faster onset of sedation than dazolam in pediatric PSA. Furthermore, diastolic BPs and Spo2 tended to be lower and the quality of sedation more favorable in the propofol group. On the contrary, hemodynamic variables were better in the midazolam group. Hypoxia was a concern in both groups, and warranted the preparation of necessary measures and presence of skilled personnel to manage untoward consequences. Mean sedation scores of patients receiving propofol were significantly higher than those of patients receiving midazolam. Therefore, propofol would be preferred for imaging studies (CT and MRI) to reduce the occurrence of undesired motion artefacts. Although both drugs are safe to use for sedation before pediatric imaging procedures, propofol is preferred with appropriate preparation.
Conflict of Interest Statement
Ahmet Sebe, MD, Hayri Levent Yilmaz, MD, Zikret Koseoglu, MD, Mehmet Oguzhan Ay, MD, and Muge Gulen, MD, have no conflicts of interest to disclose.
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9. Hoffman F. Data on File. Basel-Switzerland: LA Roche Ltd, 2000; 1–25. 10. Kayaalp SO. Benzodiazepinler. Tıbbi Farmakoloji. 2001;9:902–903. 11. Kayaalp SO. Genel Anestezinin Farmakolojik Yönü ve Genel Anestezikler. Tıbbi Farmakoloji. 2001;9:765–788. 12. Havel CJ Jr, Strait RT, Hennes H. A clinical trial of propofol vs midazolam for procedural sedation in a pediatric emergency department. Acad Emerg Med. 1999;6(10):989–996. 13. Martin PH, Murthy BV, Petros AJ. Metabolic, biochemical and haemodynamic effects of infusion of propofol for long-term sedation of children undergoing intensive care. Br J Anaesth. 1997;79(3):276–279. 14. Tomatir E, Atalay H, Gürses E. Pediyatrik manyetik rezonans görüntülemede propofol ve propofol-ketamin konbinasyonunun karşılaştırılması. Anestezi Dergisi. 2000;8:25–29. 15. Reed MD, Yamashita TS, Marx CM, Myers CM, Blumer JL. A pharmacokinetically based propofol dosing strategy for sedation of critically ill, mechanically ventilated pediatric patient. Crit Care Med. 1996;24(9):1473–1481. 16. Parker RI, Mahan RA, Giugliano D, Parker MM. Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children. Pediatrics. 1997;99(3):427–431. 17. Ueno D, Sato J, Nejima J, et al. Effects of implant surgery on blood pressure and heart rate during sedation with propofol and midazolam. Int J Oral Maxillofac Implants. 2012;27(6):1520–1526. 18. Jevdjić J, Surbatović M, Drakulić-Miletić S, Zuníc F. Deep sedation with midazolam and propofol in children undergoing ambulatory magnetic resonance imaging of the brain [article in Serbian]. Vojnosanit Pregl. 2011;68(10):842–845. 19. Malamed SF. Sedation: A Clinical Guide to Patient Management. 5th ed. St. Louis, MO: Mosby, Inc.; 2010. 20. Pershad J, Wan J, Anghelescu DL. Comparison of propofol with pentobarbital/midazolam/fentanyl sedation for magnetic resonance imaging of the brain in children. Pediatrics. 2007;120(3):e629–e636. 21. Bagchi D, Mandal, MC, Das S, Basu SR, Sarkar S, Das J. Bispectral index score and observer’s assessment of awareness/sedation score may manifest divergence during onset of sedation: study with midazolam and propofol. Indian J Anaesth. 2013;57(4):351–357. 22. Karl HW, Coté CJ, McCubbin MM, et al. Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors. Pediatr Emerg Care. 1999;15(3):1667–1672. 23. Reyle-Hahn M, Niggemann B, Max M, Streich R, Rossaint R. Remifentanil and propofol for sedation in children and young adolescents undergoing diagnostic flexible bronchoscopy. Paediatr Anaesth. 2000;10(1):59–63. 24. Merola C, Albarracin C, Lebowitz P, Bienkowski RS, Barst SM. An audit of adverse events in children sedated with chloral hydrate or propofol during imaging studies. Paediatr Anaesth. 1995;5(6):375–378. 25. Oh JE, Lee HJ, Lee YH. Propofol versus midazolam for sedation during esophagogastroduodenoscopy in children. Clin Endosc. 2013;46(4):368–372. 26. Molina-Infante J, Dueñas-Sadornil C, Mateos-Rodriguez JM, et al. Nonanesthesiologist-administered propofol versus midazolam and propofol, titrated to moderate sedation, for colonoscopy: a randomized controlled trial. Dig Dis Sci. 2012;57(9):2385–2393. 27. Borland M, Esson A, Babl F, Krieser D. Procedural sedation in children in the emergency department: a PREDICT study. Emerg Med Australas. 2009;21(1):71–79. 28. Gemma M, de Vitis A, Baldoli C, et al. Functional magnetic resonance imaging (fMRI) in children sedated with propofol or midazolam. J Neurosurg Anesthesiol. 2009;21(3):253–258. 29. Demir G, Cukurova Z, Eren G, Tekdos Y, Hergunsel O. The effect of “multiphase sedation” in the course of computed tomography and magnetic resonance imaging on children, parents and anesthesiologists. Rev Bras Anestesiol. 2012;62(4):511–519. 30. Shorrab AA, Demian AD, Atallah MM. Multidrug intravenous anesthesia for children undergoing MRI: a comparison with general anesthesia. Paediatr Anaesth. 2007;17(12):1187–1193.
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Postgraduate Medicine Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ipgm20
Comparison of Midazolam and Propofol for Sedation in Pediatric Diagnostic Imaging Studies a
b
c
c
Ahmet Sebe MD , Hayri Levent Yilmaz MD , Zikret Koseoglu MD , Mehmet Oguzhan Ay MD & d
Muge Gulen MD a
Department of Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey b
Department of Pediatric Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey c
Department of Emergency Medicine, Adana Numune Training and Research Hospital, Yuregir, Adana, Turkey
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d
Department of Emergency Medicine, Eskisehir Yunus Emre State Hospital, Eskisehir, Turkey Published online: 13 Mar 2015.
To cite this article: Ahmet Sebe MD, Hayri Levent Yilmaz MD, Zikret Koseoglu MD, Mehmet Oguzhan Ay MD & Muge Gulen MD (2014) Comparison of Midazolam and Propofol for Sedation in Pediatric Diagnostic Imaging Studies, Postgraduate Medicine, 126:3, 225-230 To link to this article: http://dx.doi.org/10.3810/pgm.2014.05.2770
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C L I N I C A L F E AT U R E S
Comparison of Midazolam and Propofol for Sedation in Pediatric Diagnostic Imaging Studies
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DOI: 10.3810/pgm.2014.05.2770
Ahmet Sebe, MD 1 Hayri Levent Yilmaz, MD 2 Zikret Koseoglu, MD 3 Mehmet Oguzhan Ay, MD 3 Muge Gulen, MD 4 1 Department of Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey; 2 Department of Pediatric Emergency Medicine, School of Medicine, Cukurova University, Balcali, Adana, Turkey; 3Department of Emergency Medicine, Adana Numune Training and Research Hospital, Yuregir, Adana, Turkey; 4Department of Emergency Medicine, Eskisehir Yunus Emre State Hospital, Eskisehir, Turkey
Abstract
Objective: This study aims to compare the efficacy of propofol and midazolam in terms of adverse effect potentials and to determine the appropriate strategy for pediatric procedural sedation. Methods: A total of 200 pediatric patients (aged , 14 years) undergoing diagnostic procedures were recruited for this nonrandomized prospective controlled cohort study. The patients were assigned to 2 treatment arms: either propofol (Group 1: IV bolus dose of 2 mg/kg during a 2-minute period, IV maintenance dose of 100 mcg/kg/min) or midazolam (Group 2: IV bolus dose of 0.15 mg/kg during a period of 2 to 3 minutes) to achieve sedation. Demographic data, body weight, and clinical status of the patients were evaluated and recorded. The vital signs and sedation levels (ie, Ramsay sedation scale scores) were evaluated and recorded, as well as the complications detected and medications administered in 10-minute intervals throughout the sedation procedure. Findings between the study arms were compared. Results: Arterial blood pressures decreased significantly in both groups (P = 0.001). The patients in Group 1 experienced a greater difference in diastolic blood pressure (P = 0.001) than those in Group 2. Sedation scores in Group 1 were more favorable (P = 0.014) and reached the appropriate sedation level in a shorter time than those in Group 2 (P = 0.010). Likewise, recovery time of patients was shorter in Group 1 than in Group 2 (P = 0.010). Hypoxia was found to be more common in the propofol group, but the difference was not significant (P = 0.333). Conclusion: Propofol seems to be more effective, achieve the appropriate sedation level more quickly, and provide a faster onset of sedation than midazolam in pediatric procedural sedation and analgesia. Propofol is preferred for imaging studies (computed tomography and magnetic resonance imaging) to reduce the occurrence of undesired motion artefacts. Although both drugs are safe to use for sedation before pediatric imaging procedures, propofol is preferred with appropriate preparation. Keywords: midazolam; propofol; pediatrics; procedural sedation and analgesia; diagnostic imaging
Introduction
Correspondence: Ahmet Sebe, MD, Assoc. Prof, Department of Emergency Medicine, Cukurova University, Medical School, 01330, Adana, Turkey. E-mail: [email protected]
Physicians generally require sedation and analgesia for patients undergoing magnetic resonance imaging (MRI), computed tomography (CT) scans, angiography, and radiotherapy in the emergency setting.1–5 Procedural sedation and analgesia (PSA) in pediatric patients is performed in surgical theaters, clinics, wards, and emergency departments by anesthesiologists, dentists, obstetricians, orthopedists, emergency physicians, and other clinicians.6 The American Pediatric Academy (APA) published the “Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients” in response to the increasing use of sedatives, opiates, analgesics, and general anesthetic
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Sebe et al
agents in invasive diagnostic, radiologic, and minor surgical procedures outside the operation room.3,7 Every discipline, maybe even every physician, uses different PSA methods and algorithms based on their own experiences and preferences, which gives rise to the heterogeneity of the procedure.8 An ideal sedative agent should not reduce blood pressure (BP) or cause episodes of hypoxia, and should provide a shorter time to reach the desired level of sedation and more rapid discharge from the emergency room. Propofol and midazolam are among the drugs commonly used in the context of PSA. Both drugs are outstanding members of their groups, with high potency, rapid onset of effect, short recovery time, and low potential of side effects. The objective of this study is to compare the efficacy and adverse effect potentials of propofol and midazolam in the context of pediatric PSA during diagnostic imaging.
Materials and Methods
This study was conducted in the university-based emergency department and involved 200 pediatric patients (aged , 14 years) with an American Society of Anesthesiologists (ASA) Physical Status of 1 and 2 who were scheduled to undergo diagnostic procedures in the departments of radiodiagnostics and nuclear medicine after Institutional Review Board approval. The study was started after approval was received from the ethics committee of Cukurova University. Parental informed consent was obtained for all 200 patients. For this nonrandomized prospective controlled cohort study, the patients were divided into 2 treatment arms. Patients in Group l (n = 100) received IV propofol, whereas those in Group 2 received IV midazolam (n = 100). All patients were observed for adverse effects of drugs, such as hypotension, hypoxia, bradycardia-tachycardia, and prolonged sedation. The patients received an IV infusion of 0.9% normal saline and their BP, heart rate (HR), respiratory rate (RR), oxygen saturation as measured by pulse oximetry (Spo2), and body temperature were measured and recorded before the commencement of PSA. Vital signs were monitored until the patients were deemed ready for discharge. The Ramsay sedation scale (RSS) was used to score the sedation level every 10 minutes.9 The elicited data regarding vital signs were also recorded every 10 minutes. A hypotensive event was predefined as an arterial systolic BP reading 30% below basal levels, an apneic event as cessation of spontaneous breathing . 20 seconds, and hypoxia was described as an Spo2 reading , 90%.10,11 Vital signs were measured using the GE/Marquette Solar 8000M 226
Patient Monitor (TRAM-RAC, electrocardiogram module, Spo2 module, noninvasive BPs module, temperature module). Patients in Group l received an IV bolus infusion of propofol at 2 mg/kg during a 2-minute period for induction, followed by 100 mcg/kg/min for maintenance, and stopped 2 minutes before the end of the painful procedure. Patients in Group 2 received an IV bolus infusion of midazolam at 0.15 mg/kg during a period of 2 to 3 minutes. Additional doses of 0.08 mg/kg during 1- to 2-minute periods were also administered to sedated patients every 5 minutes, if necessary. An additional midazolam dose was given to 14 patients. All patients were followed up and monitored in the emergency department until they were ready for discharge based on criteria from the Connecticut Children’s Medical Center Scoring System.6 Variables of this sedation scoring system were vital signs (stable: 1, unstable: 0); respiration (normal: 2; shallow breathing, tachypnea: 1; apnea: 0); level of consciousness (alert, oriented, presedation level: 2; arousable, confused, agitated: 1; unresponsive: 0); oxygen saturation (95%–100% or presedation level: 2; 90%–94%: 1; , 90%: 0); color (pink or presedation color: 2; pale or dark: 1; cyanotic: 0); and activity (obeys commands or presedation level: 2; moves extremities: 1; no spontaneous movement: 0). Children with a score $ 8 were considered ready for discharge. Airway patency and respiratory functions were followed and maintained from commencement of PSA until discharge, and all patients received 4 to 10 L/min of oxygen via nasal cannula. If a decrease in Spo2 , 96% occurred, the head was repositioned first, and then the rate of supplemental oxygen was increased. If patients did not experience a response to these measures, verbal and tactile stimuli were performed to trigger breathing. All patients were monitored until their Spo2 levels were completely normal and they did not require supplemental oxygen. The Student t test was used to compare mean values of the groups, whereas the Mann-Whitney U test was performed to compare nonparametric measurements. The Χ2 and Kolmogorov-Smirnov tests were used to evaluate categorical variables. Repeated measures in a given group or between groups were compared using ANOVA. P values , 0.05 were accepted as statistically significant.
Results
A total of 200 pediatric patients (aged 1 month to 14 years) were enrolled in this study. Male patients constituted 62.5% (n = 125). The mean age was 42.05 ± 35.20 months, and the mean weight was 14.95 ± 7.51 kg. Half of the patients
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Comparison of Midazolam and Propofol
(n = 100) received propofol (Group 1), and the other half received midazolam (Group 2). Patients in Group l had a mean age of 42.60 ± 31.76 months (range, 1–156 months), whereas the mean age in Group 2 was 41.50 ± 38.48 months (range, 1–168 months; P = 0.82). Male patients constituted 58% of the sample in Group l and 67% in Group 2 (P = 0.06). The difference in mean weights between the groups was not found to be statistically significant (P = 0.53). Table 1 shows the classification of patients in both groups regarding presumptive diagnoses and the procedures they were scheduled to undergo. A total of 62 patients (62%) in Group 1 were interpreted as ASA I and 38 (38%) were ASA II, whereas in Group 2, 65 (65%) were ASA I and 35 (35%) were ASA II (P = 0.560). Patients in both groups experienced a significant decrease in arterial systolic BP readings during PSA (P = 0.001 for both groups), although the difference between groups was not significant (P = 0.105). Patients in both groups experienced a significant decrease in arterial diastolic BP readings during PSA (Group 1, P = 0.001; and Group 2, P = 0.014), although the difference between groups was also found to be significant, indicating a greater decrease in Group 1 (P = 0.001). Mean HR values were also found to be similar between the groups (P = 0.060), with changes in the range of 103 and 114 beats per minute. Patients in both groups experienced a significant decrease in HR during the procedure (P = 0.010 for both groups). Mean RR values measured and recorded in 10-minute intervals were also found to be similar between groups (P = 0.333). Patients in both groups experienced a significant decrease in RR during the procedure (P = 0.001 for both groups). Mean Spo2 values measured and recorded in 10-minute intervals were also found to be similar between groups (P = 0.120), in the range of 97% and 98%. Patients in both groups experienced a significant decrease in Spo2 during the procedure (Group 2, P = 0.346; Group 2, P = 0.217). Ramsay sedation scale scores were measured and recorded in 10-minute intervals throughout the procedure Table 1. Classification of Patients Based on Procedure Procedure MRI CT DTPA renal scintigraphy Total
Group l
Group 2
N
(%)
N
(%)
60 32 8 100
60 32 8 100
30 60 10 100
30 60 10 100
Abbreviations: CT, computed tomography; DTPA, diethylene triamine pentaacetic acid; MRI, magnetic resonance imaging.
and at discharge; they are shown in Table 2. Mean sedation scores of patients in Group 1 receiving propofol were significantly higher than those of patients in Group 2 receiving midazolam (P = 0.001). The most serious complications of both drugs are hypoxia and apnea, which manifest with low Spo2 levels (ie, , 90%). Hypoxia was noted in 4 (4%) and 2 patients (2%) in Groups 1 and 2, respectively (P = 0.333). Positive pressure ventilation was necessary in only 1 patient in Group 1. Supplemental oxygen was given and airway opening maneuvers performed in 5 patients with hypoxia. Positive pressure ventilation was necessary in only 1 patient in Group 1. All patients were discharged from the emergency department with healing or presedation conditions. Oxygen saturation as measured by pulse oximetry decreased to , 95% but still . 90% in 11 patients (11%) in Group 1 and 7 patients (7%) in Group 2 (P = 0.120). In this case, the patient’s head was repositioned first, and then the rate of supplemental oxygen given via nasal cannula was increased. Verbal and tactile stimuli were used to trigger breathing. Nausea was the only drug-related adverse effect noted in the sample (2 patients in Group 2). None of the patients in Group 1 needed an additional dose of propofol beyond what was indicated in the defined protocol. However, 10 patients (10%) in Group 2 needed an additional dose of midazolam (P = 0.010). The sedation period lasted 44.4 ± 9.4 minutes (range, 15–60 minutes) in Group 1, compared with 52.5 ± 14.3 minutes (range, 30–35 minutes) in Group 2 (P = 0.010). Procedures performed on the patients lasted 24.35 ± 7.54 minutes (range, 5–40 minutes) in Group 1 and 10.73 ± 9.52 minutes (range, 5–40 minutes) in Group 2 (P = 0.010). Length of stay in the emergency department (time from the end of the anesthetic administration to the point Table 2. Mean Ramsay Sedation Scale Scores Ramsay Sedation Scale Score On initiation of PSA At 10th minute At 20th minute At 30th minute At 40th minute At the end of PSA At discharge P
Mean Score ± SD Group 1
Group 2
4.66 ± 0.68 3.85 ± 0.57a 3.19 ± 0.39a 3.05 ± 0.21a 3.46 ± 0.52a 4.00 ± 0.37a 4.49 ± 0.68a
5.13 ± 0.56 4.06 ± 0.44a 3.88 ± 0.47a 3.93 ± 0.53a 4.06 ± 0.58a 4.05 ± 0.32a 4.75 ± 0.59a 0.001
P , 0.05. Abbreviations: PSA, procedural sedation and analgesia; SD, standard deviation. a
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Sebe et al
deemed appropriate for discharge) was calculated as 20.70 ± 5.94 minutes (range, 10–30 minutes) in Group 1 and 41.77 ± 11.60 minutes (range, 20–105 minutes) in Group 2 (P = 0.010). The mean periods to reach appropriate sedation level before the commencement of the procedure were 2.00 ± 0.87 minutes (range, 1–3 minutes) in Group 1 and 7.00 ± 6.28 minutes (range, 5–15 minutes) in Group 2. Patients in Group 1 reached the appropriate sedation level in a shorter period than those in Group 2 (P = 0.01).
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Discussion
Procedural sedation and analgesia is often used to effectively perform imaging and therapeutic modalities, such as MRI, CT, angiography, and radiotherapy. Many studies have addressed this issue in recent decades.1–5 The APA published and revised the “Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients”3,7 in response to the increasing use of sedatives, opiates, analgesics, and general anesthetic agents in invasive diagnostic, radiologic, and minor surgical procedures outside the operation room. Procedural sedation and analgesia is an intermediary state between general anesthesia and consciousness that is created and maintained when anesthetic agents are administered in lower doses than are necessary in general anesthesia. This level of consciousness is preferred over anesthesia in many procedures, especially when short recovery periods are desired.9 This study compared the efficacy and adverse effect potentials of propofol and midazolam in providing pediatric PSA during imaging studies. Both drugs have been preferred over others because of their high potency, short half-lives, and low potential of adverse effects. This study was designed to delineate the appropriate strategy and help guide preference regarding which drug to use in pediatric PSA. Both systolic and diastolic BP readings decreased after the tenth minute and started to normalize to initial levels after the 30th minute. This finding can be considered expected effects of the drugs.9–11 Group 1 showed a greater reduction in systolic BP than Group 2, although the difference is not statistically significant (P = 0.105). However, diastolic BPs decreased significantly more in patients administered propofol (P = 0.001). Havel et al12 showed significant reductions in systolic BPs in pediatric patients receiving propofol and midazolam before undergoing closed reduction of isolated extremity injuries (42.9% and 45.2%, respectively). Martin et al,13 however, 228
did not note any significant hemodynamic impairment in 9 children treated with propofol in the intensive care setting. Although hypotension is a well-known untoward effect of propofol, the reduction in BP readings in the present study is not in the context of hypotension. Both patient groups experienced a slight decrease in HRs after the tenth minute from drug administration, but this reduction did not have clinical or statistical significance (P = 0.060). Nonetheless, the readings approached normal levels after the 40th minute. This finding was also attributed to predictable effects of the drugs.9–11 Tomatir et al14 compared propofol with a propofolketamine combination in pediatric patients undergoing MRI and reported that HRs decreased significantly in patients receiving propofol, compared with a slight reduction seen in those treated with propofol-ketamine. Reed et al15 administered propofol in 28 children treated with mechanic ventilation and reported only 1 episode of bradycardia associated with hypotension in 1 patient. In the present study, however, the reduction in HRs was not in the context of bradycardia.13,15–17 Both drugs have been found to cause significant reductions in RRs and oxygen saturations compared with control values. The difference in RR reductions between the groups were not statistically significant (P = 0.333). Peripheral arterial oxygen saturations fluctuated between 97% and 98% from admission to discharge. Intragroup differences in the mean values obtained at different periods were not significant (Group 2, P = 0.346; Group 2, P = 0.217). Likewise, intergroup differences were also not significant (P = 0.120). These findings regarding the RRs and oxygen saturations were also attributed to predictable effects of the drugs.9–11,18 In their study of pediatric PSA using propofol and midazolam, Havel et al12 reported hypoxemia in 11.6% in patients receiving propofol and 10.9% in those receiving midazolam. In another study comparing midazolam and ketamine in pediatric PSA, Parker et al16 found that 12% of the patients experienced a temporary but significant decrease in oxygen saturations. In the present study, the dose regimen used in Group l (2 mg/kg as the loading dose and 100 mcg/kg/min for maintenance) was found to produce adequate PSA, in accord with the previous studies. The present study showed that propofol produces a higher quality of PSA than midazolam and has a quicker onset of effect, which is consistent with the known high potency of the drug.11 Patients in Group 2 were treated with an IV bolus infusion of midazolam of 0.15 mg/kg over a 2- to 3-minute period,
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Comparison of Midazolam and Propofol
which is the minimum dose accepted for sedation. The initial loading dose of midazolam, however, failed to induce effective sedation in a substantial number of patients, necessitating additional doses (ie, 0.08 mg/kg in 3 of every 5 minutes titrated to effect).9,10,19 Jevdjić et al18 investigated 24 children prospectively. Sedation was introduced with a single bolus of IV midazolam at 0.1 mg/kg, followed by repeated small IV boluses (0.5–4.0 mg/kg) of propofol until sufficient sedation was obtained. The outcome of sedation was measured by induction time, sedation time, need for additional sedation, respiratory events, cardiovascular events, and sedation failure. The investigators argued that this sedation regimen provides short induction time, fast recovery, stable cardiorespiratory conditions, and rarely requires additional sedation, and therefore is safe and adequate for children undergoing ambulatory MRI of the brain.18 The mean effective dose for 50% of subjects for the induction of general anesthesia is 0.2 mg/kg, although significant patient variation exists. Clinically adequate moderate IV sedation with midazolam should always be achieved through slow titration.19–21 In a study comparing propofol (2.5 mg/kg IV bolus loading dose, followed by 100 mcg/kg/min for maintenance) and propofol-ketamine (ketamine, 0.5 mg/kg and propofol, 1.5 mg/kg IV bolus loading dose, followed by 75 mcg/kg/min for maintenance) in 40 infants (aged 9 days to 12 months) undergoing MRI, Tomatir et al14 concluded that the propofolketamine combination provided more effective and safer sedation than propofol alone. In a study of sedation periods in the emergency department using propofol and midazolam, Havel et al12 found the mean recovery times to be 14.9 ± 11.1 minutes and 76.4 ± 47.5 minutes, respectively.12 Karl et al22 reported mean sedation periods of 21 ± 6 minutes in patients treated with midazolam compared with 35 ± 20 minutes in those administered combined midazolam and opiates. In the present study, the mean sedation period in Group 1 (44.4 ± 9.4 minutes) was found to be significantly shorter than Group 2 (52.5 ± 14.3 minutes; P = 0.01 for both groups). In the present study, the mean time to discharge was recorded as 20.70 ± 5.94 minutes in Group 1 versus 41.77 ± 11.6 minutes in Group 2. Havel et al12 reported corresponding times of 13.6 ± 11.3 minutes and 48.2 ± 45.3 minutes, respectively (P = 0.010). Reyle-Hahn et al23 reported a recovery time of 5 ± 1 minutes after termination of propofol infusion. In the present study, patients receiving propofol had a significantly shorter periods to discharge than those treated with midazolam (P = 0.010).
Mean time to reach adequate sedation in the present study was calculated to be 2.00 ± 0.87 minutes (range, 1–3 minutes) in Group 1 and 7.00 ± 6.28 minutes (range, 5–15 minutes) in Group 2 (P = 0.010). This significant superiority of propofol is expected because of its high potency and other pharmacologic effects. Reyle-Hahn et al23 and Havel et al12 reported similar findings. However, in the present study, mean sedation scores obtained to estimate clinical levels of sedation were significantly lower in Group 1 than in Group 2 (P = 0.001). Havel et al12 reported more favorable mean sedation scores among patients treated with propofol than in those treated with midazolam, although the study was too limited in size to extrapolate the results. Tomatir et al14 reported a mean time of 28.90 ± 2.50 minutes for performance of MRI after propofol administration in a study of 40 infants, whereas in the present study, this time was 24.35 ± 7.54 minutes. In the present study, 4 patients (4%) in Group 1 and 2 patients (2%) in Group 2 were found to have hypoxia. The corresponding figures reported by Havel et al12 were 11.6% and 10.9%, respectively, although the hypoxemic episodes were temporary and easily relieved with simple, noninvasive maneuvers (P = 1.00). Merola et al24 reported no significant adverse effects (ie, protracted sedation, agitation, airway compromise) attributed to propofol administration. Absence of any serious untoward consequences in the present study can be explained by supplemental oxygen delivered to all patients via nasal cannulae throughout the PSA period. Hypoxia was the most common adverse effect attributed to the drug regimens, and the rates of these events were similar between the treatment arms, and to the data reported in the literature.12,22,25 Positive pressure ventilation was needed in only 1 patient in Group 1 and in no patients in Group 2. Havel et al12 reported that no patients receiving propofol and/or midazolam required ventilatory support in their study. This finding is also consistent with the findings reported in other literature.22,26–30 Procedural sedation is an important component of the daily practice of emergency medicine and has particular relevance in the pediatric population. In the study reported by Molina-Infante et al,26 drug synergy in the midazolam plus propofol sedation regimen promotes a deeper and longer moderate sedation, improving patient satisfaction rates but prolonging early recovery time. The study by Gemma et al28 supports the hypothesis that propofol is preferable to midazolam in maintaining sedation in children aged 3 to 7 years
© Postgraduate Medicine, Volume 126, Issue 3, May 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 229 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.
Sebe et al
during auditory functional MRI, because it facilitates the elicitation of a more focused auditory cortical activation pattern, with less temporal and spatial dispersion.
Downloaded by [University of California, San Diego] at 11:55 02 September 2015
Conclusion
Propofol seems to be more effective, achieve the appropriate sedation level more quickly, and provide a faster onset of sedation than dazolam in pediatric PSA. Furthermore, diastolic BPs and Spo2 tended to be lower and the quality of sedation more favorable in the propofol group. On the contrary, hemodynamic variables were better in the midazolam group. Hypoxia was a concern in both groups, and warranted the preparation of necessary measures and presence of skilled personnel to manage untoward consequences. Mean sedation scores of patients receiving propofol were significantly higher than those of patients receiving midazolam. Therefore, propofol would be preferred for imaging studies (CT and MRI) to reduce the occurrence of undesired motion artefacts. Although both drugs are safe to use for sedation before pediatric imaging procedures, propofol is preferred with appropriate preparation.
Conflict of Interest Statement
Ahmet Sebe, MD, Hayri Levent Yilmaz, MD, Zikret Koseoglu, MD, Mehmet Oguzhan Ay, MD, and Muge Gulen, MD, have no conflicts of interest to disclose.
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