Published online May 1, 2008
PEDIATRICS Vol. 121 No. 5 May 2008, pp. 979-987 (doi:10.1542/peds.2007-0814)
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ARTICLE

Needle-Free Powder Lidocaine Delivery System Provides Rapid Effective Analgesia for Venipuncture or Cannulation Pain in Children: Randomized, Double-Blind Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment Trial

William T. Zempsky, MDa, Jolene Bean-Lijewski, MD, PhDb, Ralph E. Kauffman, MDc, Jeffrey L. Koh, MD, MBAd, Shobha V. Malviya, MDe, John B. Rose, MDf, Patricia T. Richards, MD, PhDg and Daniel J. Gennevois, MDg

a Department of Pediatrics, University of Connecticut School of Medicine and Connecticut Children's Medical Center, Hartford, Connecticut
b Department of Anesthesiolgy, Scott and White Memorial Hospital, Temple, Texas
c Department of Medical Research, Children's Mercy Hospitals and Clinics, Kansas City, Missouri
d Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon
e Department of Anesthesiology, University of Michigan Health System, Ann Arbor, Michigan
f Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
g Anesiva, South San Francisco, California


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. The Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment trial was a randomized, single-dose, double-blind, phase 3 study investigating whether a needle-free powder lidocaine delivery system (a sterile, prefilled, disposable system that delivers lidocaine powder into the epidermis) produces effective local analgesia within 1 to 3 minutes for venipuncture and peripheral venous cannulation procedures in children.

METHODS. Pediatric patients (3–18 years of age) were randomly assigned to treatment with the needle-free powder lidocaine delivery system (0.5 mg of lidocaine and 21 ± 1 bar of pressure; n = 292) or a sham placebo system (n = 287) at the antecubital fossa or the back of the hand 1 to 3 minutes before venipuncture or cannulation. All patients rated the administration comfort of the needle-free systems and the pain of the subsequent venous access procedures with the Wong-Baker Faces Pain Rating Scale (from 0 to 5). Patients 8 to 18 years of age also provided self-reports with a visual analog scale, and parents provided observational visual analog scale scores for their child's venous access pain. Safety also was assessed.

RESULTS. Immediately after administration, mean Wong-Baker Faces scale scores were 0.54 and 0.24 in the active system and sham placebo system groups, respectively. After venipuncture or cannulation, mean Wong-Baker Faces scale scores were 1.77 ± 0.09 and 2.10 ± 0.09 and mean visual analog scale scores were 22.62 ± 1.80 mm and 31.97 ± 1.82 mm in the active system and sham placebo system groups, respectively. Parents' assessments of their child's procedural pain were also lower in the active system group (21.35 ± 1.43 vs 28.67 ± 1.66). Treatment-related adverse events were generally mild and resolved without sequelae. Erythema and petechiae were more frequent in the active system group.

CONCLUSIONS. The needle-free powder lidocaine delivery system was well tolerated and produced significant analgesia within 1 to 3 minutes.

Key Words: lidocaine • transdermal administration • local anesthetics • venipuncture • peripheral cannulation • pain assessment • visual analog scale • medical device

Abbreviations: AE—adverse event • ANOVA—analysis of variance • COMFORT—Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment • VAS—visual analog scale

Inadequate pain control has significant negative implications for children, including long-term consequences regarding their reactions to later painful events and acceptance of subsequent health care interventions.1,2 Although many studies in the pain management field have focused on postoperative and chronic pain, simple insertion of a needle has been shown to be one of the most frightening and distressing medical procedures for hospitalized children.3–5 Accordingly, the American Academy of Pediatrics, the American Pain Society, and the Infusion Nurses Society have issued guidelines recommending pain management strategies, including the use of local anesthetics, for peripheral intravenous cannulation and venipuncture in children.6–8 A variety of options for local anesthesia exist in this setting, including 2.5% lidocaine/2.5% prilocaine cream,9–13 liposomal lidocaine cream,14–17 the lidocaine/tetracaine patch,18 and lidocaine iontophoresis,19–23 but their use may be limited by relatively slow onset times, inconvenient and messy application methods, vasoconstriction side effects, or the requirement for complex specialized equipment and training. It is expected that compliance with the guidelines would improve if analgesic options that were not limited by these drawbacks were available.

The needle-free powder lidocaine delivery system (Fig 1) is a sterile, single-use, prefilled, disposable system designed to produce convenient and rapid analgesia for peripheral venous cannulation and venipuncture procedures in children. One to 3 minutes before venipuncture or cannulation, the system is placed directly against the skin at the site of the anticipated needle insertion. Then the start button is depressed, releasing pressurized, medical-grade, helium gas from an enclosed microcylinder, which ruptures a cassette containing 0.5 mg of lidocaine powder and accelerates the released particles to velocities sufficient to penetrate the epidermis. Previous clinical investigations in adults and children demonstrated that local analgesia occurs within 1 to 3 minutes after administration, resulting in a significant reduction in procedural pain.24–28 The current report describes a phase 3 study, designated Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-free Powder Lidocaine or Placebo Treatment (COMFORT-003), that assessed the efficacy and safety of the needle-free powder lidocaine delivery system in pediatric patients undergoing venipuncture or peripheral venous cannulation at the antecubital fossa or the back of the hand.


Figure 1
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  		FIGURE 1 Needle-free powder lidocaine delivery system.

 

   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients
COMFORT-003 was a randomized, double-blind, sham placebo-controlled, single-dose, phase 3 study conducted between December 20, 2004, and May 6, 2005, at 6 hospitals in the United States (Scott and White Memorial Hospital, Temple, TX; Children's Mercy Hospital, Kansas City, MO; Doembecher Children's Hospital, Portland, OR; C. S. Mott Children's Hospital, Ann Arbor, MI; Children's Hospital of Philadelphia, Philadelphia, PA; and Connecticut Children's Medical Center, Hartford, CT). The trial received institutional review board approval at each hospital and was conducted in accordance with good clinical practice29 and the Declaration of Helsinki.30 Written informed consent was to be provided by each parent or guardian, and verbal or written assent was to be obtained from each child or adolescent.

Eligible patients were male or female youths 3 to 18 years of age who were undergoing venipuncture or peripheral venous cannulation at the antecubital fossa or the back of the hand as part of their standard medical care. Patients were excluded if they had undergone similar venous access procedures at the proposed site within the previous 2 weeks; exhibited local infections, tattoos, surgical scars, implantable devices, or skin pathological conditions that could interfere with the study; had insufficient cognitive skills to complete the study assessments; or presented with a history of allergic reactions to any local anesthetic, tape, or adhesive dressing.

Study Design
Eligible patients were randomly assigned 1:1 to receive a single treatment with the needle-free powder lidocaine delivery system or a sham placebo system at the proposed venipuncture or cannulation site at the back of the hand or the antecubital fossa. The active system (Zingo [lidocaine hydrochloride monohydrate] powder intradermal injection system; Anesiva, South San Francisco, CA) contained 0.5 mg of lidocaine hydrochloride monohydrate powder (nominal particle size, 40 µm) and medical-grade helium at a pressure of 21 ± 1 bar. The sham placebo system contained no lidocaine but otherwise was identical in configuration, external appearance, and sound production. For administration of study treatments, the skin was cleansed with an alcohol wipe, the active or sham placebo system was pressed firmly over the proposed venous access site, and the start button was depressed (time = 0 minutes). Venipuncture or cannulation procedures were conducted 1 to 3 minutes later. Venipuncture was performed with a needle and syringe or a "butterfly" needle set, and venous cannulation was performed with a peripheral venous catheter. Selection of the insertion site and the gauge of the needle or catheter was at the investigator's discretion. Transparent dressings were used for venous cannulation procedures to permit dermal assessments at the administration site.

Study Assessments
Each patient evaluated venipuncture or cannulation pain immediately after the procedure by using a modification of the modified Wong-Baker Faces Pain Rating Scale31 (from 0 to 5), anchored at 0 for "no hurt" and 5 for "hurts worst." Patient instructions were based on those for the Faces Pain Scale-Revised32 and were different from the instructions for the Faces scale in asking patients to assess their level of pain ("Point to the face that shows how much you hurt right now") rather than their emotional response to the pain ("Each face is for a person who feels happy because he has no pain [hurt] or sad because he has some or a lot of pain; choose the face that best describes how you are feeling"). Patients 8 to 18 years of age also assessed their pain immediately after the procedure by using a 100-mm visual analog scale (VAS) anchored at 0 for "no pain" and 100 for "worst possible pain."

In addition, all patients assessed the comfort of treatment administration with the modified Wong-Baker Faces Pain Rating Scale immediately after treatment (before the subsequent venous access procedure). At the time of study enrollment, parents were asked to estimate their child's previous venipuncture or cannulation pain by using a 100-mm VAS anchored at 0 for "no pain" and 100 for "worst possible pain." Immediately after the study venous access procedure, parents estimated their child's pain during the procedure. Finally, investigators recorded the success or failure of each procedure.

Adverse events (AEs) were monitored immediately after study treatment (0 minutes), after the venous access procedure (1–3 minutes), and at 15 and 30 minutes. All AEs were assessed for severity (mild, moderate, or severe) and causal relationship to the study treatment (definitely related, probably related, possibly related, or unrelated). Investigators monitored patients for serious AEs, defined as medical occurrences that were life-threatening, necessitated or prolonged hospitalization, or resulted in persistent or significant disability or incapacity.

Because the active system deposits lidocaine particles into the skin, the site of administration was assessed by the investigator for erythema, edema, pruritus, or petechiae immediately before and 1, 15, and 30 minutes after treatment. Dermal tolerability assessment scales are summarized in Table 1. The numerical scales for erythema and edema were based on the 5-point scale described by Draize et al.33 The numerical scales for pruritus and petechiae were created during development of the needle-free powder lidocaine delivery system. Additional skin assessments at 1 to 3 hours were performed if the patient required additional monitoring because of erythema (grade ≥3), edema (grade ≥3), or petechiae (grade ≥4).


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  		TABLE 1 Investigator Skin Assessment Criteria

 
Statistical Methods
The objective of this study was to test the hypothesis that the needle-free powder lidocaine delivery system was more effective than the sham placebo system in providing analgesia for pediatric venipuncture or peripheral cannulation pain. The primary efficacy parameter was the patient's self-report of venous access pain on the Wong-Baker Faces Pain Rating Scale. The secondary efficacy parameters included the self-reported VAS score for venous access pain among patients 8 to 18 years of age and the parental observational VAS estimates of the child's pain, during both the current and prestudy procedures.

The sample-size calculation was based on a previous clinical study in which the needle-free powder lidocaine delivery system was used on the back of the hand among patients 3 to 18 years of age. Mean Wong-Baker Faces scale scores for the 3- to 12-year-old children were 1.25 and 1.91 with the active and sham placebo systems, respectively, with a SD of 1.65. A sample size of 135 patients per treatment group was needed to detect the indicated differences in pain scores between the treatment groups with 90% power, using a 5% significance level for a 2-sided test. Therefore, 252 patients per treatment group would have >90% power to detect a desired pain score difference. To ensure balanced patient numbers in 3 age groups (3–7, 8–12, and 13–18 years of age), 168 patients per age group were to be randomly assigned to each treatment. If venipuncture or cannulation was unsuccessful on the first attempt, then patients were to be replaced.

Randomization in the trial was accomplished through block randomization (block size: 4 patients). Four sets of randomization numbers were generated at a central laboratory (HHI Clinical Research and Statistical Services, Hunt Valley, MD); the sets were intended for patients 3 to 7 years of age, patients 8 to 12 years of age, patients 13 to 18 years of age, and replacement patients. Each site participating in the study was issued 4 sets of devices, 1 for each of the 3 age groups and 1 replacement set. As each patient was enrolled, participating sites used the next sequential device from the set of devices for the appropriate age group. The blinded randomization list was maintained at the central laboratory. Assignment of replacements was performed at the central laboratory by using a mapping document that mapped each original randomization number to a replacement number with the same treatment, with maintenance of the blinded conditions. Patients, personnel who administered the study treatments, and personnel who evaluated the outcomes were blinded to group assignments.

Two-sided tests with significance levels of .05 were used for all hypothesis testing except for interaction testing, for which significance levels of .10 were used. For the Wong-Baker Faces scale score analyses, the average pain score for each treatment group was estimated by using the least-squares mean from an analysis of variance (ANOVA) model. Treatment effect was defined as the difference in the least-squares means for the 2 treatment groups. Use of a parametric ANOVA method with ordinal Faces scale data was considered appropriate because the outcome variable had ≥6 categories, a situation in which parametric and nonparametric methods generally provide similar results, particularly when the distribution of the variable is somewhat symmetric. In such cases, parametric methods provide a more-easily interpretable evaluation of the effects of the independent variables on the outcome variable. In addition, when the ordinal variable is treated as a continuous variable, it is possible to use 1 summary statistic (the mean) per group to make simple direct comparisons between groups, rather than comparing distributions of the multiple categories of the outcome variable across groups.

For the VAS analyses, the average pain score for each treatment group was estimated by using the least-squares mean from a 2-way ANOVA model, with treatment effect defined as the difference in the least-squares means for the 2 treatment groups. Success rates were compared between treatment groups by using a Cochran-Mantel-Haenszel test. A posthoc comparison of current versus historical pain was conducted by calculating the difference between the parent's VAS assessment of their child's current pain and their estimate of pain during previous venipuncture or cannulation procedures. The latter analysis was conducted by using 2-way ANOVA, with treatment and age group as effects in the model.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients
A total of 579 youths (3–18 years of age) undergoing venipuncture or cannulation procedures as part of their standard clinical care received study treatment (Fig 2). Of these, 292 were treated with the needle-free powder lidocaine delivery system and 287 with the sham placebo system. Because this was a single-dose study of very short duration, no patients were lost to follow-up monitoring. Twenty-five patients (active system, 14 patients; sham placebo system, 11 patients) did not complete the trial, in nearly all cases because of failed first venipuncture or cannulation attempts. Among those patients who left the trial before completion, 11 of 14 in the active system group and 9 of 11 in the sham placebo system group had recorded pain scores and tolerability results and therefore were included in the subsequent analyses. The remaining 5 patients who did not complete the trial (active system, 3 patients; sham placebo system, 2 patients) did not have recorded Faces scale scores after the needle-stick procedure. Worst-case scores (Faces scale scores of 5) were imputed for the latter 5 patients, who also were included in the subsequent analyses.


Figure 2
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  		FIGURE 2 The COMFORT-003 trial.

 
Demographic parameters were well balanced in the 2 treatment groups (Table 2). In the active system group, 42.8% of patients (125 of 292 patients) underwent venipuncture and 57.2% (167 of 292 patients) underwent intravenous cannulation. Similar venipuncture and cannulation rates were recorded in the sham placebo system group (41.1% [118 of 287 patients] and 58.9% [169 of 287 patients], respectively). Needle sizes were similarly distributed in the 2 treatment arms, as were the locations of the procedure; 45.9% of patients (134 of 292 patients) in the active system group and 44.6% of patients (128 of 287 patients) in the sham placebo system group underwent the venous access procedure on the back of the hand, and 54.1% (158 of 292 patients) and 55.4% (159 of 287 patients), respectively, underwent the procedure at the antecubital fossa. Patients in the study had been admitted to the hospital for a wide array of medical, diagnostic, and surgical procedures, and many were receiving medications concomitantly.


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  		TABLE 2 Patient Parameters

 
Efficacy Evaluations
All patients evaluated their venipuncture or cannulation pain with the Wong-Baker Faces Pain Rating Scale immediately after the procedures. Patients 8 to 18 years of age also rated their pain on a 100-mm VAS. In both assessments, patients treated with the needle-free powder lidocaine delivery system had significantly lower pain scores than did those treated with the sham placebo system (Fig 3). The mean Wong-Baker Faces scale scores for the active system and sham placebo system groups were 1.77 ± 0.09 and 2.10 ± 0.09, respectively (P = .011). The mean VAS scores for the 8- to 18-year-old patients were 22.62 ± 1.80 mm and 31.97 ± 1.82 mm, respectively (P < .001). No significant interaction between treatment and age group was observed in the ANOVA model (P = .25), which demonstrated similar treatment effects across age categories.


Figure 3
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  		FIGURE 3 Self-reported patient pain scores. Mean Wong-Baker FACES pain scores (A, all patients) and mean VAS scores (B, patients 8–18 years of age) after venipuncture or peripheral cannulation procedures, as evaluated by the patient. Bars represent ± SE. a Age-adjusted mean.

 
Parents' estimates of their children's venous access pain during previous procedures were similar in the active system and sham placebo system groups (42.97 ± 1.73 mm and 41.98 ± 1.72 mm, respectively) (Fig 4). The parents' mean VAS scores for the venous access procedures during the study were significantly lower in the active system group (21.35 ± 1.43 mm) than in the sham placebo system group (28.67 ± 1.66 mm; P < .001). The treatment effect of –7.24 ± 2.18 mm, based on an ANOVA model, represented a 25.0% reduction in the mean VAS pain score assessed by parents in the active system group, relative to those in the sham placebo system group. This translated into a significantly greater difference between current and historical VAS scores in the active system group (–22.06 mm) than in the sham placebo system group (–12.33 mm; P < .001 by ANOVA). Venous access procedures were performed successfully on the first attempt for 95.2% (278 of 292 patients) and 96.5% (277 of 287 patients) of patients in the active system and sham placebo system groups, respectively (P = .2886).


Figure 4
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  		FIGURE 4 Parent-assessed pain scores. Mean parental VAS score estimates for their child's previous (historical assessment) and current (study assessment) venous access pain. P values are based on an analysis of variance model, with treatment, age group, and interaction as factors. Bars represent ± SE.

 
Safety and Tolerability
In total, 39 (13.4%) of 292 patients who received active system treatment and 36 (12.5%) of 287 patients who received sham placebo system treatment reported an AE (treatment related or not related) during the study (Table 3). No patient in either treatment group withdrew because of an AE. Three patients experienced 5 serious AEs that were not related to study treatment, that is, 1 patient in the active system group with an anaphylactic reaction to contrast medium and 2 patients in the sham placebo system group with laryngospasm and migraine with dehydration and leukocytosis.


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  		TABLE 3 Adverse Events

 
Treatment-related AEs were rare in both groups, and most were localized to the site of administration. Twelve patients (4.1%) in the active system group had treatment-related AEs (contusion [3 patients], erythema [2 patients], application site bruising, nausea, application site bleeding, cellulitis, hypoesthesia, hemorrhage, and postoperative anxiety). Nine AEs were assessed as mild and 3 as moderate (application site bruising, cellulitis, and contusion). Nine patients (3.1%) in the sham placebo system group had treatment-related AEs that were assessed as mild (venipuncture site bruising [5 patients], application site bruising [2 patients], application site burning, and pyrexia). All treatment-related AEs resolved without sequelae, and no patient experienced a serious treatment-related AE.

Patients' mean self-reported Wong-Baker Faces scale scores assessed immediately after study treatment were 0.54 in the active system group and 0.24 in the sham placebo system group, approaching "no hurt" on the Wong-Baker Faces scale. Dermal assessments are shown in Table 4. Because the 15- and 30-minute assessments were made after venipuncture or cannulation, they reflected the combined effects of the study treatment and the venous access procedure. Mean erythema scores ranged from 0.2 to 0.7 in the active system group and from 0.1 to 0.4 in the sham placebo system group at all observation time points. The rate of grade 1 to 2 erythema was somewhat higher in the active system group at all time points, and there was 1 case (0.3%) of grade 3 erythema in the active system group at 15 minutes. Edema and pruritus were relatively rare in the study, with mean scores of 0 to 0.1 in both treatment groups at all time points. Mean petechiae scores ranged from 0.7 to 0.9 in the active system group and from 0.0 to 0.1 in the sham placebo system group at all assessment time points. Grade 1 to 3 petechiae were more common in the active system group immediately after treatment (39.4% vs 2.1%), at 15 minutes (45.2% vs 5.6%), and at 30 minutes (45.9% vs 4.9%). Two cases (0.7%) of grade 4 petechiae were observed immediately after treatment in the active system group. All recorded dermal reactions resolved spontaneously, without sequelae.


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  		TABLE 4 Investigator Skin Assessment Results

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
COMFORT-003 was a pivotal phase 3 study comparing the analgesic efficacy of a needle-free powder lidocaine delivery system and a sham placebo system in children 3 to 18 years of age who were undergoing peripheral venipuncture or intravenous cannulation procedures at the antecubital fossa or the back of the hand. Needle-stick pain was significantly lower in the needle-free powder lidocaine delivery system group, according to both patient self-report and parental observation. Mean Wong-Baker Faces scale scores for the entire population, mean VAS scores for patients 8 to 18 years of age, and mean parental observational VAS scores were all significantly lower in the active system group. Furthermore, a larger reduction in parental assessment of current pain, relative to previous venous access pain, was reported for the active system group. Importantly, the analgesic effects were observed in a broad patient population from 6 geographically distinct children's hospitals. This population had a range of acute and chronic medical and surgical conditions necessitating low-acuity short-term care or long-term care, and many patients in the study were receiving medications concomitantly.

These data confirm and extend previous studies that demonstrated the ability of the needle-free powder lidocaine delivery system to provide an analgesic effect for pediatric venipuncture and cannulation procedures.24–27 In particular, one important confirmatory feature of the present study was the observation that the needle-free powder lidocaine delivery system provided analgesia when used 1 to 3 minutes before the venous access procedure. Existing cream and patch alternatives require a 20- to 60-minute waiting period after application before full onset of the analgesic effect.18,34,35 Lidocaine iontophoresis has a shorter onset of action but still requires 10 to 15 minutes for full effect, as well as specialized equipment and training.23,34 Consequently, currently available options require multiple interactions with the clinician to sequence appropriately the topical anesthetic administration, the subsequent waiting period, and the skin preparation and peripheral venous access procedure. The rapid onset of effect observed with the needle-free powder lidocaine delivery system allows for the venous access procedure to occur almost immediately after anesthetic delivery. This should increase the likelihood that children can benefit from topical anesthesia during venous access procedures, as recommended by the guidelines, without sacrificing clinical workflow.

Two other features of this study are noteworthy. First, venipuncture or cannulation was conducted successfully on the first attempt for 95.2% and 96.5% of patients in the active system and sham placebo system groups, respectively. These rates are higher than those reported in similar studies35 and indicate that the needle-free system did not create adverse psychological or physiologic (eg, vasoconstriction) conditions that impeded successful venipuncture or cannulation. Second, mean Faces scale and VAS scores recorded immediately after system actuation were <1, consistent with a high degree of administration comfort.

The absolute difference in mean Wong-Baker Faces scale scores between the active system and sham placebo system groups was relatively modest in the study. This difference between treatment groups and the range of pain scores observed in the study are both consistent with other reports in literature.17,23,36,37 For instance, in one large-scale trial examining the impact of lidocaine or saline iontophoresis on venipuncture and cannulation pain in children 5 to 17 years of age, similar differences between active and placebo treatment were observed.23 Modest treatment effects of this type may be attributable, in part, to a self-selection bias, that is, children with the greatest fear of needles may decline to participate, opting instead for "guaranteed," nonexperimental, local anesthetic administration or mask induction. As a result, patients enrolling in a clinical trial on venous access pain may have lower fear of and/or sensitivity to needles than the general population. This possibility is consistent with the relatively low observed pain scores in both treatment groups in this and other studies. In addition, the modest difference between treatment groups may reflect a potentially significant placebo effect with the sham placebo device. Treatment with the needle-free system required placement over the target area, which induced a tactile stimulation, and actuation of the device produced an auditory stimulus (ie, a pop). Both of these stimuli might have biased the patient's perceptions of the subsequent painful stimulus. Finally, potential placebo effects might have been bolstered by the distraction of the delivery mechanism, which was shown in several studies to reduce pain.38 Pain scores were recorded soon after treatment with the needle-free systems (1–3 minutes), when patients might have been distracted by the recent study treatment, the subsequent skin preparation, and the presence of study staff members.

Treatment with the needle-free powder lidocaine delivery system was safe and well tolerated in this study of >500 pediatric patients. The overall rates of treatment-related AEs were similar in the active system and sham placebo system groups (4.1% and 3.1%, respectively). Most AEs were considered mild to moderate in severity, and all AEs resolved without additional treatment or sequelae. In addition, most AEs were localized to the application site, consistent with a previous pharmacokinetic study in adults.28 In that previous study, 38 healthy adults received treatment at the right or left antecubital fossa with a needle-free system configured for 0.5 mg of lidocaine and 20 bar of pressure. At all subsequently tested time points, lidocaine levels remained below the minimal detectable blood plasma concentration of 5 ng/mL, which demonstrated low systemic distribution of the anesthetic beyond the site of administration.28 Because the needle-free powder lidocaine delivery system accelerates lidocaine particles into the epidermis, a variety of prespecified assessments of dermal tolerability were conducted in the current study. As expected, the frequency and severity of application site abnormalities were greater in the active system group, particularly for erythema and petechiae. However, most skin reactions were minor, short-lived, and self-limited, and no patient was treated concomitantly with a medication or nondrug treatment for an application site abnormality.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
The needle-free powder lidocaine delivery system was more effective than the sham placebo system in limiting the pain associated with venipuncture or peripheral venous cannulation in children 3 to 18 years of age. The analgesic effect occurred within 1 to 3 minutes after administration and was not associated with significant AEs. Increases in erythema and petechiae were seen after treatment, but these dermal reactions were minor, short-lived, and self-limited. The convenience and rapid effect of the needle-free powder lidocaine delivery system may make it more likely that children will receive local anesthesia for venous access pain, as recommended by the guidelines.


   ACKNOWLEDGMENTS
 
Anesiva, provided financial support for this study.

We acknowledge the following for their essential support and services during the course of these studies: Bertha Robbins, MS, Lisa Benson, CCRP, Julie O'Rear, RN, Audra Hernandez, RN, Tammy Gutierrez, LVN, Denise Fitzsimmon-Williams, MD, Nicki Gorman, RN, Mary Matzeder, RN, Gina Stanke, RN, Constance Burke, BSN, RN, S. Devi Chiravuri, MD, Kristy Faust, CRNA, Amy Kostrzewa, MD, and Kim Minger, RN, BSN.


   FOOTNOTES
 
Accepted Sep 7, 2007.

Address correspondence to William T. Zempsky, MD, Pain Relief Program, Connecticut Children's Medical Center, 282 Washington St, Hartford, CT 06106. E-mail: wzempsk{at}ccmckids.org

Financial Disclosure: Dr Zempsky received research support from Anesiva for this study and has received payments as a consultant. Drs Bean-Lijewski, Kauffman, Koh, Malviya, and Rose received research support from Anesiva for this study. Dr Richards was an employee of Anesiva at the time of the clinical trial described in this report. Dr Gennevois is a consultant for Anesiva.

This trial has been registered at www.clinicaltrials.gov (identifier NCT00140088).


What's Known on This Subject

Needle-free powder lidocaine administration has been demonstrated to provide anesthesia before venipuncture and peripheral intravenous cannulation in small clinical trials.

 

What This Study Adds

This study demonstrates the safety and efficacy of needle-free powder lidocaine administration for topical local anesthesia before venipuncture and peripheral intravenous cannulation in a large group of children.

 


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

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