Accepted Manuscript

Topical Refrigerant Spray for Pediatric Venipuncture for Outpatient Surgery

Thomas Schlieve, DDS, MD, Michael Miloro, DMD, MD

PII: S2214-5419(15)00009-7

DOI: 10.1016/j.omsc.2015.05.004

Reference: OMSC 8

To appear in: Oral and Maxillofacial Cases

Received Date: 5 February 2015

Revised Date: 28 April 2015

Accepted Date: 21 May 2015

Please cite this article as: Schlieve T, Miloro M, Topical Refrigerant Spray for Pediatric Venipuncture forOutpatient Surgery, Oral and Maxillofacial Cases (2015), doi: 10.1016/j.omsc.2015.05.004.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service toour customers we are providing this early version of the manuscript. The manuscript will undergocopyediting, typesetting, and review of the resulting proof before it is published in its final form. Pleasenote that during the production process errors may be discovered which could affect the content, and alllegal disclaimers that apply to the journal pertain.

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

Topical Refrigerant Spray for Pediatric Venipuncture

for Outpatient Surgery

Thomas Schlieve, DDS, MD, Michael Miloro, DMD, MD

Thomas Schlieve, DDS, MD

Clinical Assistant Professor

Department of Oral and Maxillofacial Surgery

University of Illinois at Chicago

801 S. Paulina Street

Chicago, Illinois, 60612

tschlieve@gmail.com

Corresponding Author:

Michael Miloro, DMD, MD, FACS

Professor and Head

Department of Oral and Maxillofacial Surgery

University of Illinois at Chicago

801 S. Paulina Street

Chicago, Illinois, 60612

(312)-996-1052 ph.

(312)-996-5987 fax

mmiloro@uic.edu

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

Topical Refrigerant Spray for Pediatric Venipuncture for Outpatient Surgery

Abstract

Anxiety in the pediatric patient population is a problem for outpatient anesthesia due to

poor patient compliance during the initiation of the anesthetic technique. A variety of techniques

have been used in the outpatient surgery and emergency department settings to improve

cooperation in the pediatric age group or those with developmental and cognitive delay. These

adjunctive techniques include the growing popularity of the use of eutectic mixtures of local

anesthetic (EMLA) cream, nitrous oxide, oral premedication, and intramuscular injections. A

highly effective technique to use during intravenous catheter insertion is the use of a refrigerant

spray, ethyl chloride, to cause a transient local hypoesthesia of the skin at the venipuncture site.

This technique is not associated with any significant contraindications or adverse reactions, and

it should be considered for both pediatric and adult patients in the oral and maxillofacial surgery

practice.

Introduction

Anxiety in the pediatric patient population can be a major deterrent to outpatient

anesthesia due to the inability of the patient to cooperate during the initiation of the anesthetic

technique. In fact, the child’s fear of initial contact, especially when that contact is with an

intravenous catheter, may be more significant than the apprehension regarding the procedure

itself. A variety of techniques have been used in the outpatient surgery and emergency

department settings to improve cooperation in the pediatric age group under 18 years of age, and

especially in those under 7 years of age, or those with developmental and cognitive delay since

they are less able to understand and comply with treatment. The presence of a parent in the room

during initiation of the anesthetic may be helpful, or harmful, for obvious reasons, so other

methods are generally used for patient and clinician relaxation.

These adjunctive techniques include the growing popularity of the use of eutectic

mixtures of local anesthetic (EMLA) cream.1,2 EMLA cream is composed of a mixture of 2.5%

lidocaine and 2.5% prilocaine in equal amounts by weight resulting in the melting point of the

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

mixture being lower than its individual components. The cream is applied to the planned

venipuncture site and an occlusive dressing is placed to cover the cream. Use of EMLA cream

has been shown to significantly decrease pain scores in children and adults during venipuncture

when compared to placebo.3,4 In a randomized trial, Çelik et. al. compared ethyl chloride and

EMLA cream in patients undergoing 18g IV insertion for dialysis procedures. In both treatment

groups, pain was significantly decreased from placebo. Additionally, there was no clinically

significant difference in pain scores between the treatment groups. This led the authors to

conclude that ethyl chloride is as effective as EMLA cream in achieving pain control with

decreased time required for administration.3 The time required for achieving adequate dermal

anesthesia is a major drawback to the EMLA technique. A minimum one hour application time

is required, with generic forms requiring up to two hours of application time, prior to an attempt

of intravenous catheter insertion.

Another method is to use nitrous oxide (N2O/O2) with a nasal hood, but children may not

allow this due to fear of feeling claustrophobic and not being able to breathe normally. When

comparing the effectiveness of 50% nitrous oxide via facemask and ethyl chloride spray,

Robinson et. al. noted no significant difference in patient reported pain scores.5 In a similar

study, Brislin et. al. found that 50% nitrous oxide via facemask significantly decreased pain

scores when compared to EMLA cream alone; however, the combination of EMLA with nitrous

oxide resulted in a decreased movement response to intravenous catheter insertion.6 Similar to

nitrous oxide, mask induction with an inhaled general anesthetic such as sevoflurane may be

limited by patient cooperation, and also carries the risks of cough, laryngospasm, breath holding,

bradycardia, salivation, and hypotension.7,8

The use of in-office oral premedication is a standard technique used by many oral and

maxillofacial surgeons and other specialists for outpatient pediatric anesthesia using a variety of

agents such as midazolam, clonidine, dexmedetomidine, ketamine, and triazolam, via a variety of

routes including oral (PO) and nasal delivery.9,10 Many uncooperative children will not consume

the liquid or permit transnasal delivery, and the oral route also suffers from an unpredictable

delay in onset of the medication effect from 15 to 60 minutes. Also, the first-pass effect of oral

medications may result in variable uptake and drug effect. There are no published studies

comparing PO medications to ethyl chloride, however, Cassinello, et. al. compared PO

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

midazolam to EMLA cream. This study concluded that the combination of EMLA cream and

midazolam decreased pain scores compared to either treatment alone, and the combination

resulted in an improved first venipuncture attempt success rate.11

Finally, the intramuscular route (IM) is used routinely, with medications such as

ketamine or midazolam, or a combination, with a more predictable dose-effect response than the

PO route, but based upon dose estimation by patient weight.12 The IM route may require patient

restraint, and it is certainly associated with a high level of anxiety and modest pain as a result of

the injection performed in this manner. The IM route may be used as the sole technique, but it

may also require re-dosing, so some clinicians choose to initiate an intravenous catheter when

adequate sedation has been achieved, to deliver addition intraoperative or postoperative

medications, or for emergency preparedness. In a series of 37 patients, Pruitt found that an IM

combination of ketamine, midazolam, and glycopyrolate provided adequate sedation for minor

emergency room procedures. In this study, 79% of patients achieved adequate anesthesia for

local anesthetic injection within 9 minutes and 11 patients were rated as “intermittent crying or

fighting” with several requiring repeat dosing or the use of a papoose board.13 Common side

effects of IM ketamine include nausea and vomiting, especially with repeated dosing, and

emergence delirium phenomena. Other adjunctive techniques used to enhance cooperation for

venipuncture include playing music or watching television or playing video games as a

distraction during intravenous catheter insertion.14

Technique

A simple, inexpensive, and highly effective technique to assist in cooperation during

intravenous catheter insertion is the use of a refrigerant spray, ethyl chloride, to cause a transient

hypoesthesia of the skin at the venipuncture site. A variety of preparations are available

including Gebauer’s Ethyl Chloride (Gebauer Company, Cleveland, Ohio, USA). The

manufacturer’s recommendation for skin application for injections and venipuncture states that

the mist spray produces a temperature of between 2oC and -4oC when applied continuously for 4

to 10 seconds, or until the skin turns white, at a distance of 3 to 9 inches (8 to 23 cm) from the

target site. The goal is to obtain a “white” appearance of the skin and not to overly “frost” the

skin in the area planned for intravenous access. This produces the required numbing or

hypoesthetic effect to allow placement of the intravenous catheter with a reduction in perceived

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

pain or sensation. The ethyl chloride spray cools the skin by rapid evaporation of the volatile

liquid itself; and, the faster the evaporation occurs, the colder the skin temperature that is

achieved. The duration of decreased sensation lasts between 30 and 60 seconds, however, it is

recommended to proceed with IV insertion immediately following evaporation of the liquid from

the skin surface. The cooling effect decreases nerve conduction velocity of C and A-delta fibers

thereby decreasing the transmittance of pain signals. Possible mechanisms include a

desensitization of pain receptors or activation of ion channels involved in pain transmission.15 A

single bottle of Gebauer ethyl chloride spray will allow approximately fifty 5 second sprays at a

cost of around $35.00 per bottle, without applying quantity discounts. This is about $0.70 cents

per patient. The cost of EMLA cream is approximately $1.33 per gram (requiring usually 2g per

site). Nitrous oxide/oxygen cost is around $0.10 cents per 2 minutes at 70% and 10L flow,

excluding the cost of the hood, circuit, delivery system, and disposable items.16

The specific details of the spray technique are presented here. The patient is seated

comfortably in the dental chair and the procedure is explained to the patient and parents as much

as can be understood based upon the age of the patient. Following the application of appropriate

monitors, the arm without the non-invasive blood pressure cuff is extended gently. It should be

noted that the use of an arm board or other restraint is generally not required. The antecubital

fossa is chosen most commonly for venipuncture, and a tourniquet is placed proximal to the

proposed site, and adequate time is allowed for venous distension (Figure 1). The area of the

antecubital fossa is prepped with an alcohol swab. An appropriately-sized catheter is chosen for

the venipuncture technique, usually a 22g catheter for the pediatric age group. The ethyl chloride

spray is then applied at a distance of 3-5 inches from the skin for a period of 3 to 5 seconds

(Figure 2), or until the skin overlying the chosen vein appears white (Figure 3). Prior to

spraying the intravenous site in the antecubital fossa, the spray can be applied to the skin of the

hand of the patient in order to demonstrate the cold sensation that the child will feel from the

spray, in order to avoid an unexpected reaction during venipuncture. Care should be taken not to

spray for longer than 10 seconds, or to the point of achieving a significant “frost” the skin as

permanent skin changes can occur due to local tissue hypothermia and cell death.20 Ethyl

chloride should be used in a well ventilated room since the direct inhalation of large amounts of

vapor can cause narcotic and general anesthetic-like effects. Intentional inhalation has been

reported to be associated with sedation, coma, and cardiac arrest. Immediately following the

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

evaporation of liquid from the skin, the venipuncture procedure is completed via a Seldinger

technique (Figure 4), and the tourniquet is removed, the catheter is taped into position, and

connected to intravenous tubing and crystalloid solution (Figure 5).

The oral and maxillofacial surgery and dental literature contains surprisingly few reports

on the use of vapocoolant spray prior to venipuncture. The most recent report in a dental journal

was in 1999 by Crecelius et al. In a randomized, placebo-controlled trial of adult patients they

compared venous cannulation under nitrous oxide sedation with or without ethyl chloride spray.

The authors noted no statistically significant decrease in pain scores when ethyl chloride was

used in addition to nitrous oxide sedation. Excluded from the study were patients under 18 years

of age and no comment was made on patient movement during cannulation or success rate of 1st

attempt at cannulation.17 Most available literature is derived from reports regarding the use by

pediatric anesthesiologists or pediatric emergency room physicians. One concern often

expressed regarding ethyl chloride spray is the possible pain associated with the anesthetic spray

itself. Cohen, et. al. and Hijazi, et. al. both noted that the discomfort associated with ethyl

chloride was equivalent to placebo, and children stated a preference for ethyl chloride over

EMLA cream.4,15 Page, et. al. reported an average pain score of 0mm on a VAS scale (0-

100mm) associated with administration of vapocoolant for catheter insertion.18 A second

concern with a refrigerant spray of any type is possible venoconstriction and increased difficulty

in obtaining IV access. Utilizing ultrasound Doppler analysis in volunteers, ethyl chloride spray

did not result in any vessel diameter change at 1, 5, and 15 minute time intervals.3 In addition,

multiple sources have noted increased first attempt success rates in pediatric patients when

vapocoolant spray is applied, with higher venipuncture success rates than those traditionally

quoted in the literature for experienced pediatric emergency department nurses.18,19,20 Although

the literature is replete with trials supporting the use of ethyl chloride to decrease pain associated

with venipuncture, a single report of no significant difference between ethyl chloride spray and

placebo was identified. 21 It should be noted that in this study ethyl chloride was applied with a

five second spray duration, and not until a white appearance of the skin was identified. Also,

there was no mention of the distance of application and the excess liquid was immediately wiped

from the skin. As the mechanism of ethyl chloride is the cooling produced by evaporation,

wiping away of the liquid prior to evaporation may have contributed to the decrease in success

noted in this study.

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

We have used this technique on all pediatric, and most adult, outpatient anesthetic cases

at the University of Illinois, College of Dentistry, Department of Oral and Maxillofacial Surgery

over the past five years. The use of this technique is considered exempt from the Institutional

Review Board at the University of Illinois at Chicago. The patient population includes an annual

average of over 1,000 outpatient moderate and deep sedation procedures, with 20-25% of cases

in children at or under 12 years of age. Since we have begun the use of this refrigerant spray

technique we have noted a significant decrease in the need to employ other adjunctive techniques

such as PO premedication, IM injections, the use of nitrous oxide or sevoflurane via inhalation,

or the need to perform the surgery in the inpatient setting. There have been no contraindications

to the use of this technique, and there have been no adverse outcomes. From a cos-analysis

standpoint, we have also noted a significant decrease in the cancellation rate of pediatric cases

due to anxiety related to starting and IV or performing an IM injection. Prior to the use of this

technique the cancellation rate over a 5 year period was approximately 10-15%, and with the

technique over the next 5 years, the cancellation rate for anxiety is less than 1%. This impacts

upon the clinic production, but the actual dollar amount is difficult to determine precisely but

certainly includes empty chair time and the inability to schedule another procedure at that time

with loss of significant clinical income. In addition, the avoidance of an “unpleasant dental

experience” for the child is paramount in order to avoid future dental phobia and lack of routine

visits to the dental office for periodic prophylactic oral health care. Lastly, this smooth technique

has avoided parent anxiety as well, since there have been no episodes of screaming from the

child that could be heard in the waiting room by parents, and this could also lead to increased

referrals in the future.

The spray technique described avoids many of the disadvantages of other options for

reducing pediatric patient anxiety prior to the venipuncture technique. EMLA cream requires an

application time of 60 minutes or more, and is equivalent in patient reported pain scores.3,4 In

addition, if venous access is unable to be obtained at the prepared site there are no additional

anesthetized sites to attempt additional access; also, EMLA would require and additional hour

for effect if placed on another proposed intravenous site. Since ethyl chloride spray can be

applied in a short period of time, anesthetizing additional sites requires minimal additional time.

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

IM sedation requires up to 9 minutes for onset of action, and is associated with side effects that

may be undesirable, as well as the pain of the IM injection.13 Nitrous oxide inhalation is

equivalent to ethyl chloride spray in reducing the pain of venipuncture, and although pain scores

are decreased, a movement response to IV insertion is typically noted with nitrous oxide.5,6

Therefore, a combination of ethyl chloride, or EMLA plus nitrous oxide, is necessary to achieve

a similar effect to ethyl chloride alone.5 In summary, the cold spray method with ethyl chloride is

associated with many advantages such as decreased pain of IV insertion, low cost, ready

availability, and no significant disadvantages. All oral and maxillofacial surgeons should

consider employing this spray technique in their clinical practice for both pediatric and adult

patients for venipuncture procedures.

References

1. Karlis V, Appelblatt R, Bourell L. Pediatric outpatient anesthesia and sedation. Selected

Readings in Oral and Maxillofacial Surgery 18 (2): 1-4.

2. Fein JA, Gorelick MH. The decision to use topical anesthetic for intravenous insertion in

the pediatric emergency department. Acad Emerg Med 13 (3): 264-8, 2006.

3. Çelik G, Özbek O, Yılmaz M, Duman I, Özbek S, Apiliogullari S. Vapocoolant spray vs

lidocaine/prilocaine cream for reducing the pain of venipuncture in hemodialysis patients:

a randomized, placebo-controlled, crossover study. Int J Med Sci 8:623, 2011

4. Hijazi R, Taylor D, Richardson J. Effect of topical alkane vapocoolant spray on pain with

intravenous cannulation in patients in emergency departments: randomised double blind

placebo controlled trial. BMJ 338:b215, 2009

5. Robinson PA, Carr S, Pearson S, Frampton C. Lignocaine is a better analgesic than either

ethyl chloride or nitrous oxide for peripheral intravenous cannulation. Emerg Med

Australas 19:427, 2007

6. Brislin RP, Stayer SA, Schwartz RE, et al. Analgesia for venipuncture in a paediatric

surgery center. J Paediatr Child Health. 1995;6:542-544.

7. Montes RG, Bohn RA. Deep sedation with inhaled sevoflurane for pediatric outpatient

gastrointestinal endoscopy. J Pediatr Gastroenterol Nutr 31(1):41-6, 2000.

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

8. Boonmak P, Boonmak S, Pattanittum P. High initial concentration versus low initial

concentration sevoflurane for inhalational induction of anaesthesia. Cochrane Database of

Systematic Reviews 2012, Issue 9. Art. No.: CD006837

9. Norambuena C, Yañez J, Flores V, Puentes P, Carrasco P, Villena R. Oral ketamine and

midazolam for pediatric burn patients: a prospective, randomized, double-blind study. J

Pediatr Surg 48(3):629-34, 2013.

10. Chiaretti A, Barone G, Rigante D, Ruggiero A, Pierri F, Barbi E, Barone G, Riccardi R.

Intranasal lidocaine and midazolam for procedural sedation in children. Arch Dis Child

96(2):160-3, 2011.

11. Cassinello F, Martín-Celemín R, Herrero E, Palencia J, de Stefano J, Pérez-Gallardo A.

Efficacy of the EMLA cream in the reduction of pain caused by venipuncture in children

premedicated with oral midazolam. Rev Esp Anestesiol Reanim. 1995 Nov;42(9):360-3.

12. Deasy C, Babl FE. Intravenous vs intramuscular ketamine for pediatric procedural

sedation by emergency medicine specialists: a review. Paediatr Anaesth 20(9):787-96,

2010.

13. Pruitt JW, Goldwasser MS, Sabol SR, Prstojevich SJ: Intramuscular ketamine,

midazolam, and glycopyrrolate for pediatric sedation in the emergency department. J

Oral Maxillofac Surg 53:13, 1995

14. Minute M, Badina L, Cont G, Montino M. Videogame playing as a distraction technique

in course of venipuncture. Pediartr Med Chir 34 (2): 77-83, 2012.

15. Cohen Reis E, Holubkov R. Vapocoolant spray is equally effective as EMLA cream in

reducing immunization pain in school-aged children. Pediatrics 100:E5, 1997

16. Vetter TR. A comparison of EMLA cream versus nitrous oxide for pediatric venous

cannulation. J Clin Anesth 7:486, 1995

17. Crecelius C, Rouhfar L, Beirne R, Venous cannulation and topical ethyl chloride in patients

receiving nitrous oxide. Anesth Prog 46:100-103, 1999

18. Page DE, Taylor DM. Vapocoolant spray vs subcutaneous lidocaine injection for

reducing the pain of intravenous cannulation: a randomized, controlled, clinical trial. Br J

Anaesth 105:519, 2010

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

19. Waterhouse MR, Liu DR, Wang VJ. Cryotherapeutic topical analgesics for pediatric

intravenous catheter placement: ice versus vapocoolant spray. Pediatr Emerg Care 29:8,

2013

20. Farion KJ, Splinter KL, Newhook K, Gaboury I, Splinter WM. The effect of vapocoolant

spray on pain due to intravenous cannulation in children: a randomized controlled trial.

CMAJ 179:31, 2008

21. Costello M, Ramundo M, Christopher NC, Powell KR. Ethyl vinyl chloride vapocoolant

spray fails to decrease pain associated with intravenous cannulation in children. Clin

Pediatr (Phila) 45:628, 2006

Figure Legends

1. Pediatric patient with tourniquet allowing venous dilation.

2. Ethyl chloride spray application technique.

3. “White” appearance of skin following spray.

4. Intravenous cannulation technique without any reaction from the patient.

5. Catheter taped in position and connected to IV tubing and crystalloid solution.

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

MA

NU

SC

RIP

T

AC

CE

PTE

D

ACCEPTED MANUSCRIPT

Topical Refrigerant Spray for Pediatric Venipuncture for Outpatient Surgery

Thomas Schlieve, DDS, MD, Michael Miloro, DMD, MD

Highlights

1. Pediatric anesthesia is a challenge due to poor cooperation from anxious children

2. The pain of injections in the child may prevent the ability to obtain intravenous access in the outpatient

setting and prevent the ability to perform the planned surgical procedure(s).

3. A simple technique using topical refrigerant spray can remove the pain associated with obtaining

intravenous access.

4. This simple procedure is well tolerated, and no failures have been observed in the pediatric population

undergoing outpatient surgery.

5. This technique should be used by all Oral and Maxillofacial Surgeons.