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Sedatives Used in Pediatric Imaging

Comparison of IV Pentobarbital with IV Pentobarbital with Midazolam Added

¹ Department of Anesthesia, Children's Hospital, 300 Longwood Ave., Boston, MA 02115.
² Department of Radiology, Children's Hospital, Boston, MA 02115.
³ Department of Biostatistics, Children's Hospital, Boston, MA 02115.

Received December 20, 2000; accepted after revision February 13, 2001.

 
Address correspondence to K. P. Mason.

Abstract

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OBJECTIVE. This study was designed to evaluate safety, efficacy, and success of adding IV midazolam to an established IV pentobarbital protocol for pediatric sedation for radiologic imaging. Outcomes included sedation and discharge times as well as adverse events

SUBJECTS AND METHODS. This prospective study compared two different sedation protocols developed by the radiology sedation committee and approved by the hospital sedation committee at our institution. Patients in the pentobarbital group received IV pentobarbital alone, and patients in the pentobarbital—midazolam group received a combination of IV pentobarbital and midazolam. A total of 1070 infants and children were enrolled, and sedation data were entered into a computer database and reviewed at bimonthly radiology sedation committee meetings for safety, efficacy, efficiency, failed sedations, and adverse outcomes.

RESULTS. Mean age distribution, sex, American Society of Anesthesiologists physical status classification, fasting status, weight, and types of examinations were similarly distributed between the two study groups. Analysis of variance indicated longer times were required to sedate and to discharge patients who had received pentobarbital—midazolam (p < 0.001 for both times), even after adjusting for differences in the patients' ages and weights. The pentobarbital—midazolam group required more time to be successfully sedated and more time to discharge from the recovery room. The rates of adverse events and failed sedations were similar for both groups.

CONCLUSION. Midazolam does not have a beneficial effect on pentobarbital sedation and has no effect on the rate of adverse events. The prolonged time needed both to sedate and to discharge (timed from the initial dose of sedation) pediatric patients who have received midazolam should discourage physicians from combining it with pentobarbital for pediatric sedation.

Introduction

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Infants and children undergoing radiologic imaging studies often require sedation to remain motionless. For MR imaging and CT studies in particular, motion artifacts should be at a minimum. Sedatives in our protocol include chloral hydrate, pentobarbital (Nembutal; Abbott, North Chicago, IL), fentanyl citrate (Sublimaze; Janssen, Titusville, NJ), and midazolam hydrochloride (Versed; Hoffman—La Roche, Nutley, NJ). Rates of successful sedation with these agents range from 94% to 98% [1,2,3]. IV pentobarbital is a safe and established method of sedation for pediatric imaging [4,5,6]. Unfortunately, not all children can be successfully sedated with pentobarbital, and some can suffer adverse events either during or after the sedation [7]. Overall, we have a 1.0% rate of failed sedation, a 1.2% incidence of paradoxical reactions to pentobarbital, and a 6.0% rate of adverse events [8].

IV pentobarbital, administered alone, is currently our primary sedation agent. Adjuvant medications, particularly fentanyl citrate and midazolam hydrochloride, are generally added only if the child displays resistance to the singledrug sedation. The use of multiple medications is generally reserved for those children in whom sedation cannot be achieved even after administration of the maximum dose of pentobarbital.

In an effort to decrease our rate of adverse events, failed sedations, and times to discharge, the radiology sedation committee piloted a sedation protocol that replaced the standard IV pentobarbital regimen with a combination of IV pentobarbital and midazolam. To our knowledge, a comparison of sedation outcomes between pentobarbital alone and a synergistic combination of midazolam and pentobarbital has never been performed. The purpose of this study was to evaluate the safety and efficacy of adding IV midazolam to an established IV pentobarbital protocol for pediatric sedation for radiologic imaging.

Subjects and Methods

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Database
The Children's Hospital radiology sedation committee has been responsible for setting sedation guidelines at our institution since December 1993. The committee has established a computerized database (FileMaker Pro, version 2.1; Claris, Cupertino, CA) of all sedations performed in the department of radiology. All information related to the sedation is collected and recorded by the radiology nursing staff and later transferred to the computerized database by a single designated staff member familiar with the database. This database contains information on patient demographics, the type of examination and the date on which it was performed, the medications administered and dosage per kilogram of patient weight, the patient's American Society of Anesthesiologists (ASA) physical status classification [9], adverse events, paradoxical reactions, the time required to sedate, the time required to discharge, and failed sedations.

Since November 1997, we have also recorded the medical diagnosis, the time of day of the examination, and duration of fasting status in our database. A radiology nurse contacts all patients by telephone the day after their examinations to monitor patient and parental satisfaction and to record any delayed adverse events. Reports of these delayed adverse events are also entered into our database, which is reviewed at bimonthly radiology sedation committee meetings and is used to identify adverse events, maintain quality assurance, and compare different sedation regimens.

Definition of Terms
We define a failed sedation as a case in which a patient is inadequately sedated after receiving the maximum allowable dosages (according to the sedation protocol) that results in an inability to complete the planned procedure successfully because of unacceptable motion artifacts as interpreted by a radiologist.

A paradoxical reaction (or Nembutal rage) is defined as a patient experiencing sustained, inconsolable, and severe irritability and combativeness for more than 30 min after the administration of pentobarbital or after awakening from the sedation.

Adverse events may include the following: prolonged sedation, defined as a case in which the patient either cannot be discharged 3 hr after the administration of the last sedating medication or is not back to baseline status after 24 hr; abnormal oxygen saturation, defined as a condition in which the patient experiences a sustained drop in oxygen saturation of greater than 5% from baseline for more than 1 min and is unresponsive to facemask oxygen delivered at 6 L/min, head repositioning, suctioning, or stimulation; need for resuscitation, defined as a drop in the patient's respiratory rate and oxygen saturation that requires resuscitation accompanied by assisted positive pressure ventilation, cardiopulmonary resuscitation, or the use of reversal medications; cardiovascular complications, defined as a sustained (>5 min) drop (>20%) in the patient's mean arterial pressure with or without a drop in heart rate below the lower limit of the normal range for the patient's age; unplanned admission, defined as a patient's unplanned admission to the hospital as a result of an adverse event directly related to the sedation; IV problems, defined as more than three attempts to cannulate, infiltration, or dislodgement of the patient's IV line; gastrointestinal problems, such as vomiting, aspiration, or diarrhea within 24 hr of the administration of sedation; and allergic reactions, defined as an unexplained rash or other allergic symptoms that developed after the patient received sedation.

Time to sedation is defined as the time in minutes from initial administration of sedative to achievement of adequate sedation of the patient.

Time to discharge is defined as the time in minutes from initial administration of sedative to discharge of the patient from the recovery room.

Sedation Protocol
All sedation medications are administered according to the radiology sedation committee protocol by qualified individuals with applicable credentials. According to the protocol, the radiology nurse administers and monitors the sedation with oversight by a radiologist. Any radiologist who orders sedation must have credentials in basic and pediatric life support (Basic Life Support and Pediatric Advanced Life Support). All radiology nurses are also certified in both adult and pediatric life support (Basic Life Support and Pediatric Advanced Life Support) and have extensive experience in either the pediatric emergency department or pediatric or neonatal intensive care unit.

Before administering the sedation, the radiology nurse evaluates the patient's past medical, surgical, and sedation history; collects information on the patient's review of systems, current medications, allergies, and fasting status; performs a physical examination; acquires the relevant laboratory data; and then reviews the findings of the evaluation with the responsible radiologist (staff, resident, or fellow). The radiologist may then contact the referring physician, consultant physicians, or a member of the anesthesiology department if questions arise or additional consultation is required. After the radiologist orders the sedatives, either the nurse or radiologist obtains informed consent from the parent or guardian.

Pulse oximetry, respiratory rate, and respiratory effort are monitored and recorded at 5-min intervals throughout the sedation and every 15 min during recovery. Because noninvasive blood pressure monitoring may stimulate the child, this parameter is not required for noninvasive procedures. Throughout the sedation of the patient, the nurse completes a sedation monitoring record on which the sedation plan determined by the ordering radiologist, medication orders, and a sedation flow sheet (sedation scores, medications administered, time, and mandatory vital signs) are written. On this flow sheet, the patient's vital signs are recorded throughout the recovery period, and all adverse events are noted.

After receiving institutional review board approval and parental consent, we performed this prospective study to compare outcome variables for infants and children receiving IV pentobarbital alone with those receiving a combination of IV pentobarbital and midazolam.

The pentobarbital group were patients who presented between January 1—June 30, 2000, and the pentobarbital—midazolam group were patients who presented between July 1—October 31, 2000, after the establishment of the pilot pentobarbital—midazolam protocol. A total of 1070 patients were enrolled. The pentobarbital group received 2-6 mg/kg of IV pentobarbital and the pentobarbital—midazolam group received an initial 0.1 mg/kg of IV midazolam followed after 1 min by 2-6 mg/kg IV pentobarbital. In both groups, all pentobarbital was titrated to effect in standardized 1-2 mg/kg doses. Outcome data included time to sedation, time to discharge, amount of medication required (milligrams per kilogram), rate of failed sedations, and adverse events.

Statistical Analysis
Database records were exported into a software package for statistical analysis (SPSS, version 10.0; Statistical Package for Social Sciences, Chicago, IL). A power analysis indicated that a total sample size of 1070 patients in the two groups—IV pentobarbital alone (n = 640) and combination of pentobarbital and midazolam (n = 430)—would provide 85% power to detect a 1% difference in the adverse and delayed reaction rates as well as failed sedation rates based on Fisher's exact test using commercially available software (nQuery Advisor, version 4.0; Statistical Solutions, Boston, MA). These sample sizes provided 95% power for detecting differences of 0.5 standard deviations (effect size = 0.5) in the time to sedation and time to discharge between the groups using an unpaired Student's t test.

All continuous variables including age, weight, pentobarbital dose, hours fasting before sedation, time to sedation, and time to discharge were tested for normality by the Kolmogorov—Smirnov test statistic and found to be normally distributed [10]. Therefore, means and standard deviations are reported, and differences between the two groups were assessed by unpaired Student's t tests. Analysis of variance was used to compare time to sedation and time to discharge to adjust for differences in age and weight between the two groups of patients. The Pearson's chi-square test was used to compare the groups with respect to percentages of patients of each sex; ASA physical status classification; modality of examinations they underwent (MR imaging, CT, or nuclear medicine); and use of oral or IV contrast medium. Adverse and delayed effects as well as failed sedation rates were compared by Fisher's exact test for binomial proportions. For all statistical tests, a two-tailed p value of less than 0.05 was considered significant.

Results

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Table 1 compares the two groups with respect to demographics, imaging, sedation, and outcome variables. Mean age distribution was similar for both groups: pentobarbital group, 3.3 ± 2.5 years and pentobarbital—midazolam group, 4.3 ± 2.7 years. Weight (measured in kilograms) and sex were also similarly distributed between the two groups (59% of the patients in both groups were male). ASA physical status classification was similar between the two groups—62-64% of the patients were classified as ASA 1, 35-37% were ASA 2, and 1% were ASA 3. Mean fasting time was 7 hr in each group (p = 0.42). Both groups required similar mean dosages of 4.0 mg/kg pentobarbital.

Table 1 shows the significant age and weight differences (p < 0.001 for each variable) between the two groups, with children in the pentobarbital—midazolam group being, on average, 1 year older and 3 kg heavier than those in the pentobarbital group. As shown in the table, time to sedation and time to discharge were significantly longer (p < 0.001 for each of the times) in the pentobarbital—midazolam group. Therefore, we wanted to assess whether the groups differed in time to sedation and time to discharge after adjustment for the imbalances in age and weight. We used analysis of covariance to evaluate differences in time to sedation and time to discharge, with age and weight as covariates in the model. The results indicated that, even after controlling for age and weight, significant group effects indicated that both time to sedation and time to discharge were longer in the pentobarbital—midazolam group (p < 0.001 in both cases).

The distribution of examination types—MR imaging, CT, or nuclear medicine—and the part of the body studied—head or neck, spine, abdomen, thorax, or extremity—were not significantly different between the groups (p = 0.13 and p = 0.18, respectively).

Analysis of variance indicated longer time to sedation and longer time to discharge for the pentobarbital—midazolam group (p < 0.001 for both times) even after adjusting for differences in the patients' ages and weights. The patients in the pentobarbital—midazolam group required more time to be successfully sedated (pentobarbital group, 6.5 ± 4.4 min; pentobarbital—midazolam group, 8.0 ± 4.4 min; p < 0.001). Discharge time was also longer in the pentobarbital—midazolam group by an average of 14 min (pentobarbital group, 106 ± 34 min; pentobarbital—midazolam group, 120 ± 32 min).

The rate of adverse events was similar between both groups (pentobarbital group, 2.3%; pentobarbital—midazolam group, 3.3%; p = 0.44). Specifically, the adverse events in the pentobarbital group included allergic or paradoxical reactions (n = 10), vomiting (n = 4), and a drop in oxygen saturation of greater than 5% from the baseline measurement (n = 1). Adverse events in the pentobarbital—midazolam group included allergic or paradoxical reactions (n = 7), vomiting (n = 3), a drop in oxygen saturation of greater than 5% from the baseline measurement (n = 2), and prolonged sedation (>3 hr from time of initial administration of the sedative, n = 2). No significant difference was found in the rates of failed sedations (pentobarbital group, 0.5%; pentobarbital—midazolam, 0.2%; p = 0.65).

Discussion

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In 1993, the department of radiology at our institution established sedation guidelines and set up a computerized sedation database to facilitate quality assurance, review utilization, and evaluate clinical practice and outcomes. The department of anesthesia works with the department of radiology to establish sedation protocols. A radiologist, anesthesiologist, nurse practitioner, clinical coordinator, and clinical director are integral members of the radiology sedation committee. This committee is responsible for educating and verifying the credentials of all practitioners responsible for sedation. It also monitors and institutes sedation practice in the department of radiology. All sedation protocols are approved by the radiology sedation committee and then presented to the hospital sedation committee for final approval. Sedation is administered according to guidelines established by the American Academy of Pediatrics [9] and the Joint Commission on the Accreditation of Health Care Organizations [11]. The bimonthly sedation committee meetings are an important forum for monitoring quality assurance and instituting modifications in protocol.

Using a computerized sedation database, we conducted a review of 1665 pediatric sedations at our institution and found that a predictor of sedation failure was the need for multiple medications to be added to pentobarbital [8]. This outcome was predictable, given that the administration of multiple medications is generally reserved for those children in whom sedation cannot be achieved even after administration of the maximum dose of pentobarbital.

In an effort to decrease our rates of adverse events, failed sedations, and times to discharge, we piloted a sedation protocol that replaced IV pentobarbital with a combination of IV pentobarbital and midazolam. This combination of a barbiturate (pentobarbital) and a benzodiazepine (midazolam) was chosen on the basis of the known synergistic actions between pentobarbital and midazolam [12]. Barbiturates enhance the binding of benzodiazepines to the benzodiazepine receptor [13,14,15]. By introducing midazolam before administering the initial dose of pentobarbital, we hoped that the synergistic effects of midazolam would reduce the dosage of pentobarbital required, decrease recovery times, and reduce the adverse event rate.

Our results were unexpected. The administration of midazolam before pentobarbital did not decrease the dosage (milligrams per kilogram) of pentobarbital required; the dosages of pentobarbital administered were the same for both the pentobarbital and pentobarbital—mid- azolam group. Furthermore, midazolam did not facilitate induction times with pentobarbital. The time to sedation was in fact longer in those children who received midazolam. The synergistic effect of midazolam seems to have had the most significant effect on the recovery times: longer times to recovery were seen in the pentobarbital—midazolam group. The polypharmaceutic approach to sedation, however, did not affect the rate of adverse events. This outcome was contrary to our belief that combining a barbiturate with a benzodiazepine would increase our rate of adverse respiratory events, such as an increase in airway obstructions or a drop in oxygen saturation or respiratory rates in patients. Although the nurses' anecdotally based belief was that midazolam decreased the rate of paradoxical reactions, this outcome was not proven. Our rate of adverse events was quite low—2-3%. No child in either group had a significant cardiovascular or respiratory event. The 0.2-0.5% rate of failed sedations confirms that pentobarbital is an appropriate choice for pediatric sedation for radiologic imaging.

In summary, midazolam was not found to have a beneficial effect on pentobarbital sedation and had no effect on the rate of adverse events. Despite the synergism between pentobarbital and midazolam [12], the dosages of pentobarbital administered in the presence of midazolam were approximately the same for both study groups. The prolonged times to sedation and the prolonged times to discharge with the administration of midazolam should discourage physicians from combining it with pentobarbital for pediatric sedation.

References

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1. Frush D, Bissett G, Hall S. Pediatric sedation in radiology: the practice of safe sleep. AJR 1996;167:1381 -1387[Abstract/Free Full Text]
2. Slovis TL, Parks C, Reneau D, et al. Pediatric sedation: short-term effects. Pediatr Radiol 1993;23:345 -348[Medline]
3. Vade A, Sukhani R, Dolenga M, Habisohn-Schuck C. Chloral hydrate sedation of children undergoing CT and MR imaging: safety as judged by American Academy of Pediatrics guidelines. AJR 1995;165:905 -909[Abstract/Free Full Text]
4. Hubbard AM, Markowitz RI, Kimmel B, Kroger M, Bartko MB. Sedation for pediatric patients undergoing CT and MRI. J Comput Assist Tomogr 1992;16:3 -6[Medline]
5. Strain JD, Campbell JB, Harvey LA, Foley LC. IV Nembutal: safe sedation for children undergoing CT. AJR 1988;151:975 -979[Abstract/Free Full Text]
6. Bloomfield EL, Masaryk TJ, Caplin A, et al. Intravenous sedation for MR imaging of the brain and spine in children: pentobarbital versus propofol. Radiology 1993;186:93 -97[Abstract/Free Full Text]
7. Egelhoff JC, Ball WS, Koch BL, Parks TD. Safety and efficacy of sedation in children using a structured sedation program. AJR 1997;168:1259 -1262[Abstract/Free Full Text]
8. Karian VE, Burrows PE, Zurakowski D, Connor L, Mason KP. Sedation for pediatric radiological procedures: analysis of potential causes of sedation failure and paradoxical reactions. Pediatr Radiol 1999;29:869 -873[Medline]
9. American Academy of Pediatrics Committee on Drugs. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics 1992;89:1110 -1115[Abstract/Free Full Text]
10. Armitage P, Berry G. Statistical methods in medical research, 3rd ed. Cambridge, MA: Blackwell Science, 1994: 394-400
11. Joint Commission on the Accreditation of Health Care Organizations. Accreditation manual for hospitals. Chicago: Joint Commission on Accreditation of Health Care Organizations, 1991
12. Kissin I, Mason JO, Bradley EL. Pentobarbital and thiopental anesthetic interactions with midazolam. Anesthesiology 1987;67:26 -31[Medline]
13. Leeb-Lundberg F, Snowman A, Olsen RW. Barbiturate receptors are coupled to benzodiazepine receptors. Proc Natl Acad Sci U S A 1980;77:7468 -7472[Abstract/Free Full Text]
14. Asano T, Ogasawara N. Chloride-dependent stimulation of GABA and benzodiazepine receptor binding by pentobarbital. Brain Res 1981;225:212 -216[Medline]
15. Skolnick P, Moncada V, Barker J, Paul S. Pentobarbital: dual action to increase brain benzodiazepine receptor affinity. Science 1981;211:1448 -1450[Abstract/Free Full Text]

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