Published online September 11, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. e1078-e1086 (doi:10.1542/peds.2005-1694)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luhmann, J. D.
Right arrow Articles by Kennedy, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luhmann, J. D.
Right arrow Articles by Kennedy, R. M.
Related Collections
Right arrow Therapeutics & Toxicology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

A Randomized Comparison of Nitrous Oxide Plus Hematoma Block Versus Ketamine Plus Midazolam for Emergency Department Forearm Fracture Reduction in Children

Jan D. Luhmann, MDa, Mario Schootman, PhDb, Scott J. Luhmann, MDc and Robert M. Kennedy, MDa

a Division of Emergency Medicine, Department of Pediatrics
b Division of Health Behavior Research, Departments of Pediatrics and Medicine
c Department of Orthopaedic Surgery, St Louis Children's Hospital, Washington University School of Medicine, St Louis, Missouri


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVES. Ketamine provides effective and relatively safe sedation analgesia for reduction of fractures in children in the emergency department. However, prolonged recovery and adverse effects suggest the opportunity to develop alternative strategies. We compared the efficacy and adverse effects of ketamine/midazolam to those of nitrous oxide/hematoma block for analgesia and anxiolysis during forearm fracture reduction in children.

METHODS. Children 5 to 17 years of age were randomly assigned to receive intravenous ketamine (1 mg/kg)/midazolam (0.1 mg/kg; max: 2.5 mg) or 50% nitrous oxide/50% oxygen and a hematoma block (2.5 mg/kg of 1% buffered lidocaine). All of the children received oral oxycodone 0.2 mg/kg (max: 15 mg) at triage ≥45 minutes before reduction. Videotapes were obtained before (baseline), during (procedure), and after (recovery) reduction and scored using the Procedure Behavioral Checklist by an observer blinded to study purpose. The primary outcome measure was the mean change in Procedure Behavioral Checklist score from baseline to procedure, with greater change indicating greater procedure distress. Other outcome measures of efficacy included recovery times and visual analog scale scores to assess patient distress, parent report of child distress, and orthopedic surgeon satisfaction with sedation. Adverse effects were assessed during the emergency visit and by telephone 1 day after reduction. Data were analyzed using repeated measures, that is, analysis of variance, {chi}2, and t tests.

RESULTS. There were 102 children (mean age: 9.0 ± 3.0 years) who were randomly assigned. There was no difference in age, race, gender, and baseline Procedure Behavioral Checklist scores between ketamine/midazolam (55 subjects) and nitrous oxide/hematoma block (47 subjects). Mean changes in Procedure Behavioral Checklist scores were very small for both groups. The mean change in Procedure Behavioral Checklist was less for nitrous oxide/hematoma block, and patients and parents reported less pain during fracture reduction with nitrous oxide/hematoma block. Recovery times were markedly shorter for nitrous oxide/hematoma block compared with ketamine/midazolam. Orthopedic surgeons were similarly satisfied with the 2 regimens. Of the ketamine/midazolam subjects, 11% had O2 saturations <94%. Other adverse effects occurred in both groups, but more often in ketamine/midazolam both during the emergency visit and at 1-day follow-up.

CONCLUSIONS. In children who had received oral oxycodone, both nitrous oxide/hematoma block and ketamine/midazolam resulted in minimal increases in distress during forearm fracture reduction at the doses studied. The nitrous oxide/hematoma block regimen had fewer adverse effects and significantly less recovery time.

Key Words: analgesia • fractures • emergency department use • sedation

Abbreviations: ED—emergency department • K/M—ketamine used with midazolam • N2O—nitrous oxide • HB—hematoma block • PBCL—Procedure Behavior Checklist • VAS—visual analog scale • CI—confidence interval • ASA—American Society of Anesthesiologists

Deep sedation of children for intensely painful fracture reduction is increasingly common in the emergency department (ED). Dedicated patient monitoring to assure effective cardiopulmonary and other vital functions is critical until the patient has recovered sufficiently to maintain these functions independently.1–3 Procedural sedation techniques for fracture reduction that result in prolonged recovery place a significant burden on health care resources in a busy ED.

Intravenous ketamine is increasingly used alone or with midazolam (K/M) for pediatric fracture reduction and has few serious adverse effects.4–10 However, recovery sufficient for discharge may take 1 to 2 hours. In addition, adverse effects, such as vomiting, and the need for intravenous access if a titration technique is used suggest the opportunity to investigate alternative methods for pediatric fracture reduction sedation/analgesia.1–6

Inhaled nitrous oxide (N2O) also has been reported to reduce pain and distress associated with fracture reduction in children.11–13 N2O is more effective when augmented by injection of lidocaine into the hematoma (hematoma block [HB]) of fractures of the middle to distal forearm,12 the site of ~75% of children's fractures requiring reduction.4, 5 N2O has a short recovery time, does not require intravenous access, and has few adverse effects.11–13 N2O plus fracture HB (N2O/HB) has not been directly compared with K/M for sedation analgesia during forearm fracture reduction in children.

The purpose of this study was to compare the efficacy and adverse effects of intravenous K/M versus N2O/HB for analgesia and anxiolysis during forearm fracture reduction in children, including differences in recovery times. We hypothesized that both regimens would effectively reduce procedural distress, but children who received K/M would have less increase in distress during fracture reduction compared with those who received N2O/HB. In addition, we hypothesized that children who received N2O/HB would have significantly shorter recovery time and fewer adverse effects.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
We conducted a prospective, randomized trial in American Society of Anesthesiologists (ASA) physical status class I or II children 5 to 17 years old presenting to the ED of St Louis Children's Hospital for reduction of middle to distal forearm fractures. Children were excluded if there was an open fracture; a history of previous fracture reduction or adverse effect associated with previous ketamine, midazolam, N2O, or lidocaine administration; a diagnosis of acute otitis media or psychiatric disease; or if they had food or liquid intake within 2 hours of the planned reduction. In accordance with our standard care for children with suspected fractures in the ED, all of the children received oral oxycodone 0.2 mg/kg (maximum: 15 mg) at triage before obtaining radiographs or study enrollment. The time between oxycodone administration and fracture reduction was not controlled and varied considerably, typically 1 to 3 hours, because of availability of personnel for fracture reduction.

After informed consent and, when appropriate, assent had been obtained, children were randomly assigned to receive intravenous K/M or inhaled N2O/HB before fracture reduction. One of the authors (M.S.), who did not have any contact with patients or investigators during the study, generated the allocation procedure. The randomization code was developed using a computer random number generator to select random permuted blocks of varying length and maintained in sealed opaque envelopes until consent to participate was obtained. To minimize baseline distress associated with intravenous placement, patients randomly assigned to receive K/M had an intravenous catheter inserted using subcutaneously injected buffered lidocaine for skin and venous wall anesthesia. Midazolam 0.1 mg/kg with a maximum of 2 mg for anxiolysis and the antisialagogue glycopyrrolate 5 µg/kg with a maximum of 200 µg were administered ~2 minutes before fracture reduction. Ketamine 1 mg/kg was administered ~1 minute before fracture reduction.

Patients randomly assigned to the N2O/HB group received a mixture of 50% N2O/50% O2 through a scented face mask for ~3 minutes before placement of the HB. N2O was administered using a customized continuous circuit apparatus that allowed gradual increases in N2O by a Washington University School of Medicine attending or fellow level pediatric emergency medicine physician.14 Before performing the fracture reduction, the resident physician in orthopedic surgery administered the HB. We sterilely injected 2.5 mg/kg of 1% buffered lidocaine (0.25 mL/kg) with a maximum dose of 150 mg (15 mL) into the fracture hematoma using an 18-gauge needle. In subjects with fractures of both the radius and ulna, the buffered lidocaine dose was divided between fractures sites. Localization of the fracture site hematoma was achieved by manual palpation with secondary confirmation of needle position by fluoroscopy as needed. Proper location of the HB was confirmed by aspiration of the fracture hematoma immediately before injection of the lidocaine. Failure of either K/M or N2O/HB was defined as patient distress either sufficient to interfere with fracture reduction or unacceptable in the opinion of the sedating physician. If failure occurred, supplemental ketamine was titrated to enable effective fraction reduction.

The primary outcome measure for efficacy was the change in subject distress from baseline to procedure as measured by the Procedure Behavior Checklist (PBCL), an observational measure that has been validated for children as young as 4 years old.15 The PBCL evaluates both the intensity and frequency of 10 defined behaviors that indicate distress (Table 1). Videotapes of subjects from baseline through recovery were scored using the PBCL by a single trained observer who was blinded to the study purpose. The observer rated each of the 10 PBCL behaviors from 1 to 5 during each of 3 intervals: baseline, procedure, and recovery. The baseline interval began immediately after study enrollment, included intravenous placement for K/M subjects, and ended after sedation medications were administered (K/M given or N2O begun). The procedure interval included the HB (for N2O/HB group), fracture reduction, and the painful cast molding. The recovery interval began after completion of cast molding, included the rest of the casting, and ended when a recovery Aldrete score of 10 was achieved.16 The 10 behavior ratings for each interval were assigned at the conclusion of the interval and reflected the behaviors throughout the entire interval. These were summed for each interval to give the PBCL score of the interval. PBCL scores range from 10 to 50, with higher scores indicating greater distress. Interobserver reliability between the observer and a psychologist experienced in PBCL scoring showed a mean weighted {kappa} of 0.82 for 5 tapes. Recovery time was the duration in minutes of the recovery interval. Physicians, nurses, parents, and subjects were not blinded because of the obvious differences in sedation administration techniques.


View this table:
[in this window]
[in a new window]
  		TABLE 1 PBCL Score

 
We measured patient and parent rating of pain using a 10-point visual analog scale (VAS). These VAS ratings compared the secondary outcome measures of efficacy. The orthopedic surgeon performing the reduction scored his/her satisfaction with the sedation technique at the conclusion of the procedure. Higher VAS scores indicated greater pain, anxiety, recall, and satisfaction. We also asked subjects and parents if they would choose the same sedation regimen for a future reduction as a global measure of satisfaction.

Primary outcome measures for adverse effects were abnormalities in cardiopulmonary function as measured by vital signs and pulse oximetry. An emergency nurse dedicated to patient monitoring and documentation during sedation and recovery recorded data on a standardized data collection form. Data were recorded every 5 minutes during the procedure and then during recovery until a level of moderate sedation1 occurred; thereafter, data were recorded every 15 minutes until full recovery. Hypoxia was defined as an oxygen saturation <93% while breathing room air or N2O mixed with oxygen. Level of consciousness, vomiting, and any other adverse effects were also recorded.

We assessed other adverse effects that occurred during the ED visit or after discharge but within 1 day of the reduction procedure using questionnaires completed by the subjects. Subjects completed the questionnaire about adverse effects that occurred in the ED just before discharge, and the 1-day follow-up questionnaire was completed over the telephone. Adverse effects, including vomiting, headache, ataxia, difficulty breathing, nightmares, excessive crying, hallucinations, earache, and lethargy, were assessed.

Data Analysis
Data were analyzed using SAS 8.02 (SAS Institute, Cary, NC) and EpiCalc 2000, version 1.02 (available at: www.brixtonhealth.com). We used repeated-measures analysis of variance to test mean changes in PBCL score from baseline to procedure and to recovery between children who received K/M compared with those who received N2O/HB for forearm reduction. We used t tests to statistically test differences in mean recovery time between the 2 groups. We used {chi}2 to statistically test differences in the proportions of adverse effects and regimen acceptability by the children and their parents between both groups. We calculated 95% confidence intervals (CIs) to describe the variability in observed estimates.17 A P < .05 was considered to be statistically significant. We calculated sample size regarding efficacy using the PBCL as the critical measure. At the recommendation of a psychologist (E. Chen, PhD, written communication, 2003) experienced in using the PBCL, a change of 1 in the PBCL from baseline to reduction intervals was used as the effect size. Patients were analyzed according to the intention-to-treat method. To achieve statistical power of 0.80 and a significance level of 0.05, a sample size of 50 per group or a total of 100 patients was needed. No subgroup analyses were performed.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Efficacy
We enrolled 102 children: 55 were randomly assigned to receive K/M and 47 to receive N2O/HB. The 2 groups were similar with regard to age, gender, race, ASA class, fracture location (Table 2), and baseline PBCL score (Table 3).


View this table:
[in this window]
[in a new window]
  		TABLE 2 Subject Characteristics

 

View this table:
[in this window]
[in a new window]
  		TABLE 3 Efficacy Outcome Measures

 
Both groups had very little increase in distress during the fracture reductions. The mean change in PBCL scores from baseline to procedure, the primary outcome measure, was statistically greater for K/M (P = .02), indicating greater distress during reduction (Fig 1). The effect size for this change between groups was 1.6 (95% CI: 0.25 to 3.0). Consistent with this finding, although there were no significant differences in mean PBCL scores between sedation groups during baseline, procedure, and recovery intervals (Table 3), repeated-measures analysis of variance showed an interaction between the type of sedation and the time of PBCL measurement (P = .04). The change from baseline to recovery was not statistically different between sedation groups (P = .57). Subjects who received N2O/HB were rated by nurses to be more responsive than subjects who received K/M during the procedure (fracture reduction and molding; Fig 2). Mean recovery time was significantly shorter for children who received N2O/HB (16 minutes; median: 14 minutes) compared with K/M (83 minutes; median: 85 minutes; Fig 3).


Figure 1
View larger version (11K):
[in this window]
[in a new window]
  		FIGURE 1 Level of subject responsiveness during fracture reduction.

 

Figure 2
View larger version (10K):
[in this window]
[in a new window]
  		FIGURE 2 Mean PBCL scores before, during, and after fracture reduction. PBCL scale ranges: 10 = no distress to 50 = maximal distress.

 

Figure 3
View larger version (10K):
[in this window]
[in a new window]
  		FIGURE 3 Mean recovery time after fracture reduction.

 
There were protocol failures in both groups. One subject randomly assigned to receive N2O/HB was determined to be inadequately sedated for reduction and subsequently received intravenous ketamine. Five subjects randomly assigned to receive K/M required more ketamine than the study dose of 1 mg/kg. The range of ketamine doses in these 5 subjects was 2 to 4 mg/kg. These subjects were analyzed according to the intent-to-treat method. All of the fracture reductions were successfully completed.

Subjects randomly assigned to receive N2O/HB reported less memory of pain during reduction than those randomly assigned K/M, and their parents reported less observed pain during reduction (Table 3). There were no differences between groups in self-reported subject or parent anxiety or subject recall of the procedure. When asked if they would choose the same regimen if their child required a future fracture reduction, a greater proportion of parents whose children received N2O/HB replied affirmatively (Table 3). There were no significant differences between groups when children answered the same question. Orthopedic surgeon satisfaction between groups was similar (Table 3).

Adverse Effects
Subjects randomly assigned to receive K/M were more likely to have an adverse effect while in the ED, and both groups reported adverse effects within the first day postreduction (Table 4). During the procedure, vomiting occurred in 4% of subjects who received K/M and 6% of subjects who received N2O/HB; an additional 20% in each group vomited before discharge from the ED. Transient hypoxia occurred in 11% of subjects in the K/M group with 1 experiencing both vomiting and hypoxia; these incidents were managed with airway repositioning and oxygen administration by simple mask.


View this table:
[in this window]
[in a new window]
  		TABLE 4 Adverse Effects (Self-Report by Questionnaire)

 
Limitations
This study was conducted by physicians and nurses experienced in deep sedation, the care of critically ill and injured children, and use of a "child-friendly" N2O delivery system custom built at our institution, but similar to commercially available dental/oral surgical devices. Because fracture HB use has been reported primarily for middle to distal forearm fractures, only fractures in these sites were studied. For these reasons and because only 5- to 17-year-old subjects were studied, caution in generalization of these results to other clinical settings, ages, fracture sites, and procedures is warranted.

Respiratory depression as an adverse event was indirectly approximated by detecting oxygen saturation of <93%. Subjects receiving 50% N2O were actually receiving the N2O blended with 50% oxygen; thus, oxygen desaturation was unlikely to occur unless severe respiratory depression occurred. It is possible that some subjects receiving N2O experienced mild respiratory depression, similar to that experienced by some who received K/M, yet no desaturation occurred because of the concurrent administration of oxygen. Further studies using end-tidal CO2 monitoring may help clarify this issue.

Because of the obvious differences in sedation techniques between groups, full blinding was not possible. However, when the PBCL scorer of the videotapes (our primary outcome measure) was asked after scoring all of the tapes what she thought was the study purpose, she responded, "to evaluate different orthopedic techniques (maneuvers) for reducing fractures." For all of the other outcome measures, blinding did not occur. Finally, plasma lidocaine levels were not measured to assure that rapid absorption of lidocaine from the HB did not contribute to depth of sedation and adverse effects.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Efficacy
Contrary to our hypothesis, at the doses studied, subjects who received N2O/O2 plus lidocaine HB had statistically less increase in distress and less memory of pain during orthopedic reduction of acute middle to distal forearm fractures compared with subjects who received K/M. Although the increase in distress from baseline was statistically less for the N2O/HB group (P = .02), it should be noted that both groups had very low PBCL scores both at baseline and during fracture reduction indicating low levels of distress; mean increases in PBCL scores were 0.3 for N2O/HB and 2.1 for K/M of a possible 40. Whether the difference in PBCL scores of 1.8 is clinically significant is unclear. To our knowledge, careful validation of how much change in PBCL is considered clinically significant has not been performed (L. Zeltzer, written communication, 2005). Both groups had high success rates of fracture reduction.

Ketamine-based sedation/analgesia has been shown to be very effective in reducing pain and distress associated with extremely painful orthopedic forearm fracture reductions.4, 5 Although less extensively studied, N2O-based sedation/analgesia11–13 and lidocaine HB analgesia18–20 have also been shown to provide effective reduction of pain and distress during forearm fracture reductions, especially in combination.12 However, the 2 had not been compared previously.

The dose of ketamine chosen for the current study was based on our previous work in which a mean dose of 1.05 ± 0.52 mg/kg of ketamine (along with 0.11 mg/kg of midazolam) was determined by titration to be effective for fracture reduction.4 This ketamine dose is consistent with that used by some authors7, 8, 10, 21 but less than that recommended by others.5, 9 In the current study, each patient also received an oral oxycodone dose of 0.2 mg/kg administered in triage. The analgesic effectiveness of this regimen was supported by the very small increase in PBCL scores from baseline during the fracture reduction. Larger doses of ketamine would likely induce deeper sedation, even less distress, and less recall but would also likely result in even longer recovery.

Midazolam was administered intravenously in a fixed dose of 2 mg to reduce patient anxiety before ketamine sedation and may have deepened sedation. Whether midazolam reduces ketamine-induced dysphoria during recovery has been questioned.21–23 The similar PBCL scores during recovery in both groups suggest that this dose of midazolam did not noticeably impact subject recovery.

Other researchers have shown that 50% N2O facilitates forearm fracture reductions in children.11, 13, 24, 25 The apparatus used in these studies and most commonly available for delivery of N2O in the emergency setting (Nitronox) requires patient generation of a sufficient negative pressure to open a demand valve to deliver a fixed 50% N2O/50%O2. The N2O/O2 delivery device in the current study was a locally constructed valveless, continuous circuit apparatus that allowed variable delivery of N2O from 0% to 50% as the patient breathed normally.14 Our compact design is less intrusive in the room space but is functionally similar to commercially available devices used by oral surgeons and dentists. This device allows the N2O percentage to be gradually increased (usually over 2–5 minutes) to 50% to avoid the sometimes frightening sudden onset of the floating, tingling effects of the gas that may occur if the patient initially receives 50% N2O.26 To further enhance acceptance of the N2O, children were also encouraged to choose a lip balm flavor such as bubble-gum or watermelon to scent the mask and to hold the mask, if desired, during delivery.

However, many children exhibit significant distress during fracture reduction when 50% N2O is the sole analgesic administered.11, 13, 24, 25 Hennrikus et al12 found that addition of a lidocaine fracture HB significantly augmented the effectiveness of the N2O sedation. HBs have been shown to be a safe and effective method to anesthetize a forearm fracture site before manipulation18–20, 27 and not to affect fracture healing28 or increase the rate of infection when placed with sterile technique.29 We believe placement of an HB and subsequent fracture reduction without anxiolysis would frighten many children and would incompletely block procedural pain. Consistent with the work of Hennrikus et al,12 the current study found that the combination of 50% N2O with the HB, augmented by oral oxycodone, provided effective analgesia, including those with completely displaced and overriding fractures. This may be because displaced fractures likely have large hematomas, which may enable a more effective HB in comparison with greenstick fractures with little or no hematoma. Most of the patients in this study had distal forearm fractures with epiphyseal, physeal, or metaphyseal involvement. Because of the small number of subjects, we did not compare effectiveness of the HB between these sites or diaphyseal sites or between displaced and nondisplaced fractures.

A maximum dose of 2.5 mg/kg of lidocaine for the HB, chosen for the current study, has been shown to be safe in adults undergoing HB for forearm fracture reduction.30 Meining et al31 found that this dose resulted in maximum plasma lidocaine levels of 1100 ng/mL, well below the thresholds of ~5 to 10000 ng/mL for neurologic and cardiac toxicity. Although no overt signs of lidocaine toxicity, such as seizures or dysrhythmias, occurred in any subject in the current study, significant systemic absorption of lidocaine through an intraosseous mechanism may have resulted in central nervous system depression and enhanced N2O sedation; this issue warrants further study.

Recovery Time
Recovery was remarkably shorter with N2O/HB compared with K/M with means of 16 vs 83 minutes, respectively. Indeed, many subjects were near full recovery by completion of casting, because the N2O was turned off after the painful molding of the cast around the fracture site had been performed. This allowed the subjects to recover while the nonpainful proximal portion of the cast was completed. Recovery from the ketamine sedation may have been slightly longer because of the addition of midazolam, but recovery from this combination has been shown not to be significantly longer than with ketamine alone.21, 22

The poor solubility of N2O in plasma results in rapid onset of effect and rapid recovery.26 It is this rapid recovery that makes this agent of special interest in the busy ED. Patients should be observed by parents for 5 to 10 minutes after discontinuation of N2O, because they may be ataxic or have emesis during this period, but bedside monitoring by a health care provider usually is not required.

Safety
The frequency of adverse events while in the ED, especially ataxia, nightmares, and hallucinations, was greater in subjects who received K/M. However, these symptoms occurred in some within the N2O/HB group as well, and some within both groups had vomiting, headache, and crying postsedation before discharge. Both groups also reported numerous but similar adverse effects within 1 day postsedation with nightmares, more frequently reported in the K/M group. The higher frequency of nightmares found in this study compared with previous work by ourselves and others4, 21, 22 may partly be because of difficulty in defining adverse psychotomimetic effects. For this study, nightmares were defined as frightening dreams, and subjects drew their own conclusions. The long-term clinical significance of psychotomimetic effects on children needs further investigation.

Oxygen saturations <93% transiently occurred in 11% of subjects in the K/M group and in none of the N2O/HB group; all were resolved with airway opening maneuvers and/or supplemental oxygen administration without use of positive pressure. The addition of K/M may have been responsible for some of the transient hypoxemia. Wathen et al21 noted desaturation <90% in 7% of patients with K/M and in 2% with ketamine alone. Ad hoc analysis in our previous study found, despite using larger doses of midazolam, no clear relationship between the dose of midazolam and desaturation <90% with K/M.4 Another contributor to respiratory depression may have been the oxycodone administered in triage. As noted in the "Limitations" section above, the N2O/HB group was receiving 50% O2 blended with the N2O, and, thus, respiratory depression as indirectly suggested by oxygen desaturation may have been obscured; however, these subjects were also less deeply sedated. Diffusional hypoxia after cessation of N2O has been described26 but was not noted in any subject in this study.

It should be noted that some children who received the combination of oxycodone and N2O/HB experienced deep sedation, thus patients receiving this regimen should be monitored as for deep sedation.1–3 In the current study, the physician administering the N2O was also responsible for monitoring the subject's cardiopulmonary status and was empowered to intervene immediately, if necessary, for subject safety, for example, to help clear the airway during vomiting. Administration of the N2O and monitoring of the patient could be performed by other health care workers trained in its use, as permitted by local regulation. Because of the use of lidocaine for the HB, providers responsible for the sedation should be prepared for management of seizures or cardiac dysrhythmias because of unlikely but potential lidocaine toxicity.30

Vomiting is an adverse effect of both ketamine4, 9 and N2O.14, 26, 32–34 Furthermore, a greater frequency of postoperative nausea and vomiting has been reported in pediatric patients than in adults.35 The incidence rates have been estimated at 34% in children 6 to10 years old and 32% in children >11 years.36 N2O may cause nausea and vomiting through stimulation of the sympathetic nervous system with catecholamine release, changes in middle ear pressure with stimulation of the vestibular system, and increased distension of the gastrointestinal tract.37 Protective laryngeal reflexes are believed to remain intact with 50% N2O alone38 but may be blunted in patients more deeply sedated with the combination of N2O and oxycodone. Laryngeal reflexes are also believed to remain largely intact with ketamine,9, 39–41 but it is unclear whether the addition of relatively low doses of midazolam impacts these reflexes. Vomiting occurred during the deepest sedation in 4% of subjects who received K/M and 6% of subjects who received N2O/HB, yet no clinical signs of pulmonary aspiration were noted in any subject. The lack of symptoms of aspiration after emesis suggests that protective airway reflexes remained at least partially intact in both groups. However, the sample size of this study is not large enough to accurately access aspiration risk.

The frequency of vomiting with both regimens is approximately double that of our previous studies4, 42 but consistent with that of recovery from general anesthesia.43 Because the addition of an opioid to anesthetic regimens has been shown to increase postoperative vomiting, it is likely that the increase in emesis in the current study is attributable in part to the coadministration of oxycodone, which was not part of the earlier studies. However, the advantages of increased patient comfort during manipulations for radiographs and while awaiting reduction seem clinically significant. Whether the frequency of emesis can be reduced by coadministration of antiemetic agents, such as ondansetron, remains to be determined.

Significance
This first direct comparison of a commonly used regimen (K/M) to a regimen based on N2O and local anesthesia (lidocaine HB), with both regimens augmented by systemic analgesia (oxycodone), has demonstrated that the N2O-based regimen is an effective alternative to deep sedation induced by ketamine for forearm fracture reduction. The primary advantages of the N2O/HB regimen are its remarkably short recovery time and lack of need for venous access; as noted above, many subjects were fully responsive and interactive by the time casting was completed. Ketamine administered intramuscularly also avoids the need for venous access but results in a median recovery time of ~2 hours.44 Rapid recovery may make this N2O/HB regimen especially attractive in a busy ED with limited resources.

Another advantage of the combination of local anesthesia with N2O sedation is that effective analgesia is provided with less sedation. Anecdotally, several children who received the N2O/HB regimen indicated that they preferred not being "put to sleep." The linking of local anesthesia with N2O anxiolysis, moderate analgesia, and amnesia also has been used to reduce distress during the suturing of facial lacerations in young children,42 oncological bone marrow aspiration and lumbar puncture,45, 46 and decades of dental procedures. This strategy may enable health care workers to tailor sedation strategies to patients' preferences for procedures in which local anesthesia can be achieved, for example, abscess drainage.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
In children who had received oral oxycodone, both the combination of inhaled N2O with lidocaine fracture HB and the combination of intravenous ketamine and midazolam resulted in minimal increases in distress during forearm fracture reduction. However, the N2O/HB regimen had significantly less recovery time than the K/M regimen. Orthopedic surgeons were similarly satisfied with both regimens. Although adverse effects occurred in both groups, they were fewer for children who received N2O plus fracture HB.


   ACKNOWLEDGMENTS
 
We gratefully acknowledge D.M. Jaffe, MD, Edith Chen, PhD, and Luke Voytas for their participation in this study.


   FOOTNOTES
 
Accepted Apr 19, 2006.

Address correspondence to Jan D. Luhmann, MD, Division of Emergency Medicine, Washington University School of Medicine, One Children's Place, Suite 4S50, Campus Box 8116, St Louis, MO 63110. E-mail: luhmann_j{at}kids.wustl.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. American Academy of Pediatrics, Committee on Drugs. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: addendum. Pediatrics. 2002;110 :836 –838[Abstract/Free Full Text]
  2. American Society of Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002;96 :1004 –1017[CrossRef][Web of Science][Medline]
  3. Joint Commission on Accreditation of Healthcare Organizations. Standards and intents for sedation and anesthesia care. In: Revisions to Anesthesia Care Standards, Comprehensive Accreditation Manual for Hospitals. Oakbrook Terrace, IL: Joint Commission on Accreditation of Healthcare Organizations 2001. Available at: www.jcaho.org/standard/aneshap.html. Accessed May 16, 2005
  4. Kennedy RM, Porter FL, Miller JP, Jaffe DM. Comparison of Fentanyl/Midazolam with Ketamine/Midazolam for pediatric orthopedic emergencies. Pediatrics. 1998;102 :956 –963[Abstract/Free Full Text]
  5. McCarty EC, Mencio GA, Walker AL, Green NE. Ketamine sedation for the reduction of children's fractures in the emergency department. J Bone Joint Surg Am. 2000;82-A :912 –918[Abstract/Free Full Text]
  6. Green SM, Rothrock SG, Harris T, Hopkins GA, Garrett W, Sherwin T. Intravenous ketamine for pediatric sedation in the emergency department: Safety profile with 156 cases. Acad Emerg Med. 1998;5 :971 –976[Web of Science][Medline]
  7. Dachs RJ, Innes GM. Intravenous ketamine sedation of pediatric patients in the emergency department. Ann Emerg Med. 1997;29 :146 –150[CrossRef][Web of Science][Medline]
  8. 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 :427 –431[Abstract/Free Full Text]
  9. Green S, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation in children. Ann Emerg Med. 2004;44; 460 –471[Web of Science][Medline]
  10. Royal Australasian College of Physicians. Guideline Statement: Management of Procedure-Related Pain in Children and Adolescents. 2005. Available at: www.racp.edu.au. Accessed May 4, 2005
  11. Wattenmaker I, Kasser JR, McGravey A. Self-administered nitrous oxide for fracture reduction in children in an emergency room setting. J Orthop Trauma. 1990;4 :35 –38[Medline]
  12. Hennrikus WL, Shin AY, Klingelberger CE. Self-administered nitrous oxide and a hematoma block for analgesia in the outpatient reduction of fractures in children. J Bone Joint Surg Am. 1995;77-A :335 –339[Abstract/Free Full Text]
  13. Hennrikus WL, Simpson RB, Klingelberger CE, Reis MT. Self–administration nitrous oxide analgesia for pediatric fracture reductions. J Pediatr Orthop. 1994;14 :538 –542[Web of Science][Medline]
  14. Luhmann JD, Kennedy RM, Jaffe DM, McAllister JD. Continuous-flow delivery of nitrous oxide and oxygen: a safe and cost-effective technique for inhalation analgesia and sedation of pediatric patients. Pediatr Emerg Care. 1999;15 :388 –392[Web of Science][Medline]
  15. LeBaron S, Zeltzer L. Assessment of acute pain and anxiety in children and adolescents by self-reports, observer reports, and a behavior checklist. J Consult Clin Psychol. 1984;2 :729 –738
  16. Aldrete JA, Kroulik D. A post anesthetic recovery score. Anesth Analg. 1970;49 :924 –934[Free Full Text]
  17. Young KD, Lewis RJ. What is confidence? Part 1: the use and interpretation of confidence intervals. Ann Emerg Med. 1997;30 :307 –310[CrossRef][Web of Science][Medline]
  18. Furia JP, Alioto RJ, Marquardt JD. The efficacy and safety of the hematoma block for fracture reduction in closed, isolated fractures. Orthopedics. 1997;20 :423 –426[Web of Science][Medline]
  19. Kendall JM, Allen P, Younge P, Meek SM, McCabe SE. Haematoma block or Bier's block for Colles' fracture reduction in the accident and emergency department: which is best? J Accid Emerg Med. 1997;14 :352 –356[Abstract/Free Full Text]
  20. Johnson PQ, Noffsinger MA. Hematoma block of distal forearm fractures: is it safe? Orthop Rev. 1991;11 :977 –979
  21. Wathen JE, Roback MG, Mackenzie T, Bothner JP. Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled emergency department trial. Ann Emerg Med. 2000;36 :579 –588[CrossRef][Web of Science][Medline]
  22. Sherwin TS, Green SM, Khan A, Chapman DS, Dannenberg B. Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures? A randomized, double-blind, placebo-controlled trial. Ann Emerg Med. 2000;35 :239 –244[CrossRef][Web of Science][Medline]
  23. Kennedy RM, McAllister JD. Midazolam with ketamine: Who benefits? Ann Emerg Med. 2000;35 :297 –299[CrossRef][Web of Science][Medline]
  24. Evans JK, Buckley SL, Alexander AH, Gilpin AT. Analgesia for the reduction of fractures in children: a comparison of nitrous oxide with intramuscular sedation. J Pediatr Orthop. 1995;15 :73 –77[Web of Science][Medline]
  25. Gregory PR, Sullivan JA. Nitrous oxide compared with intravenous regional anesthesia in pediatric forearm fracture manipulation. J Pediatr Orthop. 1996;16 :187 –191[Web of Science][Medline]
  26. Clark M, Brunick A. Handbook of Nitrous Oxide and Oxygen Sedation. St Louis, MO: Mosby; 1999
  27. Case RD. Haematoma block: a safe method of reducing Colles' fractures. Injury. 1985;16 :469 –470[CrossRef][Web of Science][Medline]
  28. Henry B, Kenison M, McVay C, et al. The effect of local hematoma blocks on early fracture healing. Orthopedics. 2002;25; 469 –470[Medline]
  29. Furman JR. Pain relief and related concerns in children's fractures. In: Beaty JH, Kasser JR, eds. Rockwood and Wilkens' Fractures in Children. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:50–73
  30. Meining RP, Quick A, Lobmeyer L. Plasma lidocaine levels following hematoma block for distal radius fractures. J Orthop Trauma. 1989;3 :187 –191[Medline]
  31. Ritchie JM, Greene NM. Local anesthetics. In: Goodman A, Gilman LS, eds. Pharmacologic Basis of Therapeutics. New York, NY: MacMillian; 1980:309–310
  32. Evers A, Koblin D. Inhalational anesthetics. In: Evers A, Maze M, eds. Anesthetic Pharmacology Physiologic Principles and Clinical Practice. Philadelphia, PA: Elsevier; 2004:369–393
  33. Gamis AS, Knapp JF, Glenski JA. Nitrous oxide analgesia in a pediatric emergency department. Ann Emerg Med. 1989;18 :177 –181[CrossRef][Web of Science][Medline]
  34. Eger EI. Nitrous Oxide/N2O. New York, NY: Elsevier; 1985
  35. Watcha MF, White PF. Postoperative nausea and vomiting. Anesthesiology. 1992;77 :162 –184[Web of Science][Medline]
  36. Cohen M, Cameron C, Duncan P. Pediatric anesthesia morbidity and mortality in the perioperative period. Anesth Analg. 1990;70 :160 –168[Abstract/Free Full Text]
  37. Scholz J, Steinfath M. Prophylaxis and therapy of postoperative nausea and vomiting. In: Herbert MK, Holzer P, Roewer N, eds. Problems of the Gastrointestinal Tract in Anesthesia, the Perioperative Period, and Intensive Care. Berlin, Germany: Springer; 1999:313–326
  38. Roberts GJ, Wignall BK. Efficacy of the laryngeal reflex during oxygen-nitrous oxide-sedation. Br J Anaesth. 1982;54 :1277 –1281[Abstract/Free Full Text]
  39. Taylor PA, Towey RM. Depression of laryngeal reflexes during ketamine anaesthesia. Br Med J. 1971;2 :688 –689[Abstract/Free Full Text]
  40. Carson I, Moore J, Balmer J, Dundee J, McNabb T. Laryngeal competence with ketamine and other drugs. Anesthesiology. 1973;38 :128 –133[Web of Science][Medline]
  41. Green SM, Krauss B. Pulmonary aspiration risk during emergency department: procedural sedation-an examination of the role of fasting and sedation depth. Acad Emerg Med. 2002;9 :35 –42[CrossRef][Web of Science][Medline]
  42. Luhmann J, Kennedy RM, Lang Porter F, Miller JP, Jaffe DM. A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. Ann Emerg Med. 2001;37 :20 –27[CrossRef][Web of Science][Medline]
  43. Spahr-Schopfer I, Habre W. Emergence and postoperative care. In: Bissonnette B, Dalen S, eds. Pediatric Anesthesia Principles and Practices. New York, NY: McGraw Hill; 2002:661–675
  44. Green SM, Rothrock SG, Lynch EL, et al. Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. Ann Emerg Med. 1998;31 :688 –697[CrossRef][Web of Science][Medline]
  45. Annequin D, Carbajal R, Chauvin P, Gall O, Tourniaire B, Murat I. Fixed 50% nitrous oxide mixture for painful procedures: a French survey. Pediatrics. 2000;105(4) . Available at: www.pediatrics.org/cgi/content/full/105/4/e47
  46. Kanagasundaram SA, Lane LJ, Cavalletto BP, Keneally JP, Cooper MG. Efficacy and safety of nitrous oxide in alleviating pain and anxiety during painful procedures. Arch Dis Child. 2001;84 :492 –495[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Emerg. Med. J.Home page
F E Babl, E Oakley, A Puspitadewi, and L N Sharwood
Limited analgesic efficacy of nitrous oxide for painful procedures in children
Emerg. Med. J., November 1, 2008; 25(11): 717 - 721.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
D. J. Sucato and Y.-J. Kim
What's New in Pediatric Orthopaedics
J. Bone Joint Surg. Am., June 1, 2008; 90(6): 1401 - 1411.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luhmann, J. D.
Right arrow Articles by Kennedy, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luhmann, J. D.
Right arrow Articles by Kennedy, R. M.
Related Collections
Right arrow Therapeutics & Toxicology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?