PEDIATRICS Vol. 99 No. 5 May 1997,
p. e8
Copyright ©1997 by the American Academy of Pediatrics
ELECTRONIC ARTICLE:
Intravenous Methohexital for Brief Sedation of Pediatric Oncology
Outpatients: Physiologic and Behavioral Responses
,
From the Divisions of *
Hematology/Oncology and § Critical
Care Medicine, DeVos Children's Hospital, Grand Rapids, Michigan; and
Department of Pediatrics, Michigan State University College of
Human Medicine, East Lansing, Michigan.
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGMENTS
ABBREVIATIONS
REFERENCES
Objective. In this successor to a preliminary retrospective study, we sought to confirm the apparent safety and efficacy of intravenous methohexital (MHX) for brief, unconscious sedation of pediatric hematology/oncology outpatients undergoing painful, invasive procedures.
Methods. This prospective study was conducted in a children's hospital-based hematology/oncology clinic. Following published monitoring guidelines for deep pediatric sedation, MHX (1.0 mg/kg) was administered immediately before each procedure, 1% xylocaine was given locally, and additional MHX was titrated to maintain minimal response to pain during the procedure. For each patient, the procedural and physiologic response data reported below were recorded from the onset of sedation through recovery. Behavioral distress responses were measured using a standardized pediatric observational tool (Procedure Behavioral Checklist).
Results. Two hundred and thirty-three procedures were
carried out in 76 patients ranging .1 to 19.6 years of age. The mean cumulative MHX dose/procedure was 4.6 ± 2.9 mg/kg. The mean
lengths of time from initiation of sedation until completion of the
invasive procedure, attainment of patient arousability, discontinuation of monitoring, and attainment of patient alertness were 8 ± 5, 19 ± 8, 19 ± 9, and 22 ± 9 minutes, respectively.
Relative to presedation values, mean arterial pressure (MAP), heart
rate, and respiratory rate showed maximum mean percent changes of
16.6, +17.8, and +13.4, respectively (all clinically insignificant). Complications among procedures were transient and included hiccoughs and myoclonus (each 10%); oropharyngeal secretions (6%); and pain at
the injection site, emergence phenomena, and mild stridor (each
3%).
Of two procedures (.9%) affected by transient upper airway obstruction
associated with emesis or secretions, only one briefly needed mask
ventilation. No procedures required intubation or early termination. In
49 additional procedures assessed for patient distress, observed pain
responses were absent to mild in 45 (92%) and moderate in 4.
Conclusion. MHX appropriately administered provides sedation which is effective, safe, well tolerated, and of short duration, making MHX attractive for use in pediatric oncology outpatients and other populations with similar sedation needs. methohexital, pain, procedures, quality of life, sedation.
Invasive diagnostic or therapeutic procedures, such as lumbar punctures and bone marrow aspirations and biopsies, are required for the management of most children with cancer and serious hematologic disorders. The physical and emotional distress caused by these procedures are notable and have been well documented in behavioral studies of children with cancer.1 Because procedure-related discomfort has been identified by children as the most negative aspect of their cancer treatment, efforts to improve their quality of life have included minimizing the acute distress associated with the procedures.4 One such approach has been the use of brief sedation or anesthesia to reduce the anticipation and actual experience of pain during the invasive procedures.
The selection of a sedation agent appropriate for that purpose is dependent upon several factors. These include the procedures, which vary in type, combination, duration, invasiveness, and frequency; the patients, who have variable coping capabilities; and the treatment setting, which is typically a busy outpatient clinic. Accordingly, desirable characteristics in a sedation agent for this patient population include rapid onset, predictable efficacy, controllable duration, and short recovery time, as well as convenient administration, manageable side effects, and feasibility relative to institutional resources.
With the above in mind, since 1991 we have operated a joint sedation program staffed by our Divisions of Hematology/Oncology and Critical Care Medicine, in which children are routinely offered brief, unconscious sedation while undergoing their invasive outpatient procedures. In our institution, the agent used almost exclusively for this purpose has been methohexital sodium for intravenous use (MHX; Brevital, Lilly). MHX is an ultrashort-acting barbiturate which results in rapid induction of sleep with fewer cumulative effects and more rapid recovery than with other barbiturates.5 MHX was selected for use in our program because its properties appeared consistent with those of a desirable sedation agent described above, as suggested by the prior experience of our pediatric intensivists using MHX for invasive procedures in critically ill children. Our preliminary experience using MHX for the sedation of pediatric oncology outpatients was recently reported in a retrospective study.6
Because of limitations related to its retrospective design, however, we undertook this larger, prospective study in which we sought to confirm the apparent safety and efficacy of MHX for pediatric oncology outpatients undergoing invasive procedures. The specific aims of this study were: 1) to characterize in greater detail the physiologic responses of children receiving MHX sedation while undergoing invasive procedures; 2) to determine more accurately the types and incidences of adverse reactions in children receiving MHX sedation; and 3) to measure the levels of behavioral distress exhibited by children undergoing invasive procedures while receiving MHX sedation.
During the time period encompassed by this study, all children with cancer or hematologic disorders requiring invasive procedures were offered MHX sedation unless there were medical contraindications to its use, including demonstrated hypersensitivity or intolerance of MHX or other barbiturates; significant congenital or acquired upper airway obstruction; and oral intake within 6 hours before the procedure. Patients electing to receive MHX sedation as standardly administered at our institution constituted the subjects of this study. Informed consent was obtained from the responsible adult before each sedation procedure. Sedation procedures were conducted by a board-certified pediatric intensive care specialist (responsible solely for MHX administration, patient monitoring, and management of associated complications); a pediatric hematology/oncology physician or nurse practitioner (responsible solely for performing the invasive procedure); and a pediatric hematology/oncology procedure nurse. Sedation was provided in accordance with current American Academy of Pediatrics guidelines for elective use of deep sedation in children.7 All procedures were performed within the pediatric hematology/oncology clinic in a dedicated sedation procedure room equipped with wall suction, wall oxygen with appropriate administration devices, and monitoring equipment described below. Complete pediatric resuscitation equipment was immediately available at all times. The study was approved by our Institutional Review Board before collection of physiologic and behavioral response data reported here.
Sedation Procedure
Sedation procedures were performed as we have described previously.6 In brief, venous access was secured before sedation using tunneled central venous catheters when present, or peripheral angiocatheters if not. Upon entry of each child into the sedation procedure room, vital signs and transcutaneous capillary oxygen saturation (SaO2) were measured as monitors were applied. Before drug administration, the sedation procedure was reviewed with the child and parents. MHX (1.0 mg/kg) was then given by slow intravenous push as supplemental oxygen by nasal cannula was started at the discretion of the intensivist. Parents remained at bedside until their child was unconscious, at which time the child was positioned, 1% xylocaine (buffered with NaHCO3) was administered locally, and the invasive procedure(s) was performed. Additional MHX was titrated as needed to achieve and maintain a level of sedation where patient movement required only minimal restraint. Monitoring of vital signs and SaO2 were carried out as described below. Upon completion of the invasive procedure(s), parents returned to bedside as their child awakened.Physiologic Response Assessments
To measure the physiologic responses of children undergoing MHX sedation, the following medical instrumentation was used: Hewlett Packard Cardiorespiratory Monitor/Terminal, Model 78534B (heart and respiratory rates); Dinamap Vital Signs Monitor, Model 1846 SX (blood pressure); and Nellcor Pulse Oximeter, Model N-100 (SaO2). Physiologic response measurements were begun with initiation of sedation and recorded at 3 minute intervals until patients became arousable following recovery from sedation, as defined below. Data capture forms were completed prospectively by the procedure nurse to record the following information for each procedure: 1) date; underlying diagnosis; current weight; relevant interval history; type of invasive procedure(s); and route of venous access; 2) heart and respiratory rates, blood pressure, and SaO2 at 3-minute intervals; 3) cumulative MHX dose administered; 4) rate of oxygen flow, if utilized; 5) lengths of time from initiation of sedation to completion of the invasive procedure(s), attainment of arousability (defined as the recovery of appropriate and purposeful responses to verbal and tactile stimuli), discontinuation of monitoring, and attainment of alertness (defined as the recovery of presedation levels of cognitive interaction with the environment); 6) the occurrence and severity of several defined adverse reactions, including pain at the injection site, hiccoughs, myoclonus, oropharyngeal secretions, stridor, laryngospasm, clinically significant vital sign changes, and emergence phenomena; and 7) any other clinical information deemed relevant by either attending physician.Behavioral Distress Assessments
Separate informed consent was obtained for participation in this portion of the study. Behavioral responses of children undergoing MHX sedation for painful procedures were measured utilizing the Procedure Behavioral Checklist, a standardized observational distress scale developed by LeBaron and Zeltzer.8 For each sedation event, one of two dedicated observers involved with the study (M.T.N. or a trained registered nurse) evaluated eight defined distress behaviors exhibited by the child, categorized as verbal (crying, screaming, and verbalized stalling, anxiety, and pain) or muscular (muscle tension, physical movement, and need for restraint). For each behavior, the maximal response was recorded as absent, very mild, mild, moderate, intense, or extremely intense. Distress responses were recorded prospectively at four time points: preprocedure (child entering treatment room); intraprocedure (during the painful procedure itself); postprocedure (during recovery from sedation); and at end of monitoring (child leaving treatment room).Patients and Procedures: Characteristics
The gender, ages, and diagnoses of the 76 study patients are displayed in Table 1. As indicated in Table 2, 233 consecutive outpatient procedures performed with patients receiving MHX sedation comprised the physiologic response component of this study (an additional 49 procedures were performed for behavioral distress assessments). Of the 233 procedures, 159 (68.2%) were isolated diagnostic or therapeutic lumbar punctures (for intrathecal administration of cancer chemotherapeutic agents). Bone marrow aspirations with or without biopsies constituted 70 (30.0%) of the procedures, 31 of which were followed by lumbar puncture. Four miscellaneous procedures were brainstem audio-evoked response measurements (two), echocardiography (one), and removal of a tunneled central venous catheter (one), all in combination with lumbar puncture or in children refractory to standard forms of sedation. For the 233 procedures, venous access for MHX administration was by existing tunneled central venous catheters in 173 (74.2%) and temporary peripheral angiocatheter in 60 (25.8%).|
Table 1. Patient Characteristics |
|
Table 2. Outpatient Procedures Performed |
Procedural Data
As indicated in Table 3, patients in this study underwent an average of 3 ± 2 procedures (range, 1 to 11). The mean cumulative MHX dose per procedure, representing the initial loading dose plus quantities given subsequently to maintain the desired level of sedation, was 4.6 ± 2.9 mg/kg (range, 1.1 to 9.5). The average duration of the invasive procedure itself was 8 ± 5 minutes (range, 2 to 29). As defined in Materials and Methods, the average time from onset of sedation to the achievement of arousability was 19 ± 8 minutes; to the discontinuation of all monitoring was 19 ± 9 minutes; and to the achievement of alertness was 22 ± 9 minutes; as determined from the 94 procedures in which all three values were recorded. Most procedures were performed with low-flow supplemental oxygen being administered at the discretion of the attending pediatric intensivist.|
Table 3. Summary of Procedural Data From 233 Outpatient Procedures |
Physiologic Responses
Figure 1 displays the mean percent changes in vital signs during MHX sedation, compared with baseline values, shown at 3-minute intervals from initiation of sedation through 30 minutes (only 10 of the 233 procedures extended beyond this time). Transient increases of all vital signs were noted within the first 9 minutes of monitoring, coinciding with the painful procedure. For both the heart and respiratory rates, maximal percent increases of 17.8 and 13.4, respectively, were noted at 6 minutes, before gradually returning toward baseline with further time. While the MAP also increased initially, it decreased with further time to below baseline values, with the maximal percent decrease of 16.6 being observed in the relatively small number of patients still being monitored at 30 minutes. Substantial variation between patients in the magnitude of their vital sign changes was noted at every time point. None of the measured vital sign changes was noted to be clinically significant.
Fig. 1. Mean percent changes in heart rate (top), respiratory rate (middle), and mean arterial pressure (bottom) during methohexital sedation, as compared with baseline values. For each procedure, heart rate, respiratory rate, and blood pressure were recorded at 3-minute intervals from onset of sedation through recovery of arousability. Systolic and diastolic blood pressure measurements were later converted to mean arterial pressue values. The percent change in each vital sign, compared with the baseline (presedation) value, was calculated for each time point of each procedure. Mean values for these percent changes at each time point were then determined by combining data from all procedures. The standard error is shown when the value exceeds 1. Data are derived from those procedures in progress at each time point through 30 minutes from onset of sedation.
[View Larger Version of this Image (15K GIF file)]
Adverse Reactions
Based on our previous experience, patients were monitored for several potential adverse reactions during MHX sedation (see Materials and Methods). If noted, these, their severity, and any other reactions were recorded on the data capture forms. All adverse reactions encountered in the 233 procedures are summarized in Table 4. As indicated, the vast majority of reactions were mild, transient, and required minimal or no intervention for management. The most common reactions were transient hiccoughs or peripheral myoclonus, affecting 24 and 23 procedures, respectively. Fifteen (6.4%) procedures were associated with mild-moderate oropharyngeal secretions which were easily managed by simple suctioning at the discretion of the attending pediatric intensivist. In eight (3.4%) procedures with peripheral venous access, patients briefly complained of a burning sensation proximal to the infusion of the initial MHX loading dose. During patient recovery from sedation, seven (3.0%) procedures were associated with transient behavioral phenomena such as tearfulness or restlessness, which completely resolved with reassurance and a low-stimulation environment. Mild to moderate stridor was noted in six (2.6%) procedures, all managed with simple airway positioning (and increased supplemental oxygen in one). Interestingly, only five of the patients with oropharyngeal secretions, and none of those with stridor, had an interval history of upper respiratory symptoms before sedation.|
Table 4. Number of Adverse Reactions Among 233 Outpatient Procedures |
Behavioral Distress Responses
To confirm the efficacy of MHX sedation, formal behavioral distress assessments were performed during 49 additional, consecutive, evaluable, invasive procedures. The clinical characteristics of patients, types of invasive procedures, and sedation methods used were comparable to those in the 233 procedures described above. Using the Procedure Behavioral Checklist, the severity of eight defined verbal and muscular distress responses was rated at the preprocedure, intraprocedure, postprocedure, and end of monitoring phases of sedation. As indicated in Table 5, verbal distress responses were "absent" or "very mild" in virtually all phases of sedation in all 49 procedures. Muscular distress responses consisted chiefly of transient, unconscious withdrawing movement upon initiation of the procedure itself (intraprocedure phase of sedation), where a rating of "moderate" was noted in four procedures (ratings of "absent," "very mild," or "mild" were noted in the remainder). As indicated in Table 5, minimal to no muscular or verbal distress was noted following cessation of the painful stimuli (during the postprocedure and end of monitoring phases).|
Table 5. Number of Invasive Procedures Associated With Behavioral Distress During MHX Sedation (n = 49)* |
The purpose of this study was to confirm and extend our encouraging initial experience using intravenous MHX for brief, unconscious sedation of pediatric oncology outpatients undergoing invasive procedures.6 In this present study, we have prospectively evaluated a larger number of patients for more detailed physiologic response data, as well as for behavioral response data using a standardized observational tool. The results reported here indicate that MHX does indeed induce brief sedation which is effective, safe, well tolerated, and possesses favorable characteristics for use in the pediatric oncology outpatient clinic setting. Our study population was both large (relative to other published pediatric oncology sedation studies) and typical for patient characteristics and invasiveness of procedures performed in such patients.
Received for publication Feb 27, 1996; accepted Jun 19, 1996.
Presented in part at the annual meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 20-23, 1995.
Reprint requests to (D.R.F.) Division of Pediatric Hematology/Oncology, DeVos Children's Hospital, 100 Michigan NE, Grand Rapids, MI 49503.
This project was supported in part by American Cancer Society grant ACSIRG-188 in conjunction with the Comprehensive Cancer Center of Michigan State University College of Human Medicine (AES; DRF and DJS, sponsors).
The authors acknowledge the contributions of Michael J. Bouthillier, PharmD, Alan Davis, PhD, and Sandra Hardy, RN, BSN. Expert secretarial assistance was provided by Ms Arlene Sprengelmeyer.
MHX, methohexital. MAP, mean arterial pressure.
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Pediatrics (ISSN 0031 4005). Copyright ©1997 by the American Academy of Pediatrics
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