EMLA and sucrose solution as pain relief during circumcision of boys

During circumcision of boys, the foreskin is completely or partially removed around the penis. Circumcision can be performed on a medical indication or for religious reasons, and can be performed close after the birth of a child. Several different types of pain relief strategies are available. Sugar solution or ointment containing local anaesthetics are among the less invasive methods.

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Question

What scientific studies and systematic reviews are there on combination treatment with EMLA and sucrose solution as pain relief during circumcision of boys?

Identified literature

Table 1. Systematic reviews with low/medium risk of bias
BPM = Beats per minute; CI = Confidence Interval; DPNB = Dorsal Penile Nerve Block; EMLA = Eutectic Mixture of Local Anesthetics; MBPS = The Modified Behavioral Pain Scale; NIPS = The Neonatal-Infant Pain Scale; N-PASS = Neonatal Pain, Agitation and Sedation Scale; RB = Ring block; RCT = Randomized controlled trial; s = seconds
Included studies Population/Intervention Outcome and Results
Brady-Fryer et al, 2004, Pain relief for neonatal circumcision. [1]
Study designs:
Included only randomized controlled trials (RCT).

Number of studies:
The review included 35 RCTs

EMLA: 6 RCTs
Sucrose: 8 RCTs
Population:
Male term or preterm neonates undergoing circumcision during the neonatal period (with postnatal age maximum of 28 days after reaching 40 weeks corrected gestational age)

Intervention:
Any intervention intended to relieve pain during the circumcision (penile blocks, topical anaesthetics, sucrose solution and more)
DPNB vs EMLA
(3 studies, n=139)
NIPS, Mean difference:
–2.5 (95% CI, –3.3 to –1.7)

Cry time as a proportion of procedure time, Mean difference:
–10% (95% CI, –30 to 10)

Heart rate, Weighted mean difference:
–17 bpm (95% CI, –23 to –11)

DPNB vs Sucrose
(1 study, n=127)
MBPS, Mean difference:
–3.2 (95% CI, –4.7 to –1.8)

Cry time, Mean difference:
–66 s (95% CI, –211 to –121)

Heart rate, Weighted mean difference:
–27 bpm (95% CI, –33 to –20)

Oxygen saturation:
Not significant

Ring block vs EMLA

(1 study, n=28)
Results for cry time and heart rate were not significantly different between the groups

EMLA vs Sucrose
(2 studies, n=67)
Cry time, heart rate, oxygen saturation:
Not significant

Blood pressure:
Mean differences could not be calculated, but both means were larger in the sucrose group, indicating higher mean blood pressure

EMLA vs placebo
(6 studies, n=200)
Facial score, Weighted mean difference:
–46.5 (95% CI, –80.4 to –12.6)

Crying time, Weighted mean difference:
–15.2% (95% CI, –21 to –9.3)

Heart rate, Weighted mean difference:
–15 bpm (95% CI, –19 to –10)

Sucrose vs placebo
(2 studies, n=360)

Oxygen saturation, Weighted mean difference, (n=126):
1.8% (95% CI, 0.5 to 3.1)

The effect on cry time, heart rate and serum cortisol levels were not significant
Authors' conclusion:
“...the results of this review show that DPNB, RB and the topical anaesthetics EMLA and lidocaine cream can be recommended over no treatment for attenuation of circumcision pain. “

“Results for oral sucrose, oral analgesics and environmental modification interventions were either inconsistent or did not produce significantly different outcome results. These therapies cannot be recommended as treatments for circumcision pain.”
Stevens et al, 2016, Sucrose for analgesia in newborn infants undergoing painful procedures. [2]
Study designs:
Included only randomized controlled trials (RCT).

Number of studies:
The review included 74 RCTs
Circumcision: 4 RCTs
Population:
Term, preterm, or both term and preterm neonates, with maximum postnatal age of 28 days after reaching 40 weeks' postmenstrual age (PMA)

Intervention:
All studies that used sucrose as an intervention for any acute painful procedure, including: heel lance, venipuncture, subcutaneous injection, intramuscular injection, arterial puncture, circumcision, bladder catheterization, insertion of orogastric or nasogastric tube, and eye examination for retinopathy of prematurity (ROP).
Sucrose vs placebo
(1 study, n=56)
Mean difference in heart rate was not significant

Sucrose vs EMLA
(1 study, n=60)
N-PASS score during circumcision, Mean difference: 2.40 (95% CI, 1.85 to 2.95)

N-PASS score after 5 minutes, Mean difference:
1.40 (95% CI, 0.74 to 2.06)

Heart rate, Mean difference:
6.00 bpm (95% CI, 0.19 to 11.81)

Oxygen saturation, Mean difference:
–2.70 % (95% CI, –3.70 to –1.70)

Mean difference in respiratory rate:
Not significant

Sucrose vs EMLA + sucrose
(1 study, n=60)

N-PASS score during circumcision, Mean difference:
3.00 (95% CI, 2.42 to 3.58)

N-PASS score after 5 minutes, Mean difference
1.20 (95% CI, 0.49 to 1.91)

Heart rate, Mean difference:
12.00 bpm (95% CI, 6.62 to 17.38)

Respiratory rate, Mean difference:
0.60 cycles/minute (95% CI, –1.77 to 2.97)

Oxygen saturation, Mean difference:
–3.40 (95% CI, –4.39 to –2.41)

Sucrose vs DPNB
(1 study, n=79)

Heart rate, Mean difference
17.40 bpm (95% CI, 11.16 to 23.64)

Sucrose vs DPNB + sucrose
(1 study, n=40)
Behavioural Distress Scale score, mean difference:
–0.67 (95% CI, –1.08 to –0.26)

Mean plasma cortisol levels:
No significant difference
Authors' conclusion:
“There was high‐quality evidence that sucrose reduces different measures of newborn pain during heel lance, venipuncture and intramuscular injection. However, sucrose does not provide effective pain relief during circumcision. There is conflicting evidence for whether sucrose reduces pain for other minor painful procedures and further research is needed to investigate these more thoroughly.”

 

Table 2. Sucrose and EMLA as combination treatment
EMLA = Eutectic Mixture of Local Anesthetics; RCT = Randomised controlled trial
Author
Year
Reference
Design Neonatal age Intervention and control
Sharara-Chami et al
2017
[3]
RCT
(n=70)
36 to 41 week gestation C1: Sucrose + EMLA
C2: Sucrose + EMLA + DPNB
C3: Sucrose + EMLA + RB
C4: EMLA only
Al Qahtani et al
2014
[4]
RCT
(n=90)
24 to 25 days C1: Sucrose + EMLA
C2: EMLA
C3: Sucrose
Kaufman et al
2002
[5]
RCT
(n=57)
22 to 63 hours C1: Sucrose + EMLA
C2: EMLA + placebo (water)
Mohan et al
1998
[6]
RCT
(n=79)
1.6 to 2.3 days C1: Sucrose + EMLA
C2: EMLA + placebo (water)
C3: Sucrose
C4: Placebo (water)
Zahorodny et al
1998
[7]
RCT
(n=53)
Newborns (unknown) C1: Sucrose + EMLA
C2: EMLA + placebo (water)
C4: Placebo + placebo

 

Table 3. Sucrose and other pain relief as combination treatment
CT = Controlled trial; EMLA = Eutectic Mixture of Local Anesthetics; RB = Ring block; RCT = Randomised controlled trial; DPNB = Dorsal Penile Nerve Block
Author
Year
Reference
Design Neonatal age Intervention and control
Roman-Rodriguez et al
2014
[8]
CT
(n=791)
1.7 to 2 days C1: Sucrose + Ring block
C2: Sucrose
Razmus et al
2004
[9]
CT
(n=132)
Gestational age:
38.34 weeks
C1: Sucrose
C2: EMLA
C3: DPNB + EMLA + Sucrose
C4: Ring block + Sucrose
C5: DPNB
C6: and more
Taddio et al
2000
[10]
CT
(n=60)
2 to 17 days C1: EMLA
C2: Paracetamol + EMLA + Sucrose + DPNB
Stang et al
1997
[11]
RCT
(n=80)
Older than 20 hours C1: Sucrose + DPNB
C2: DPNB + placebo (water)
C3: DPNB + buffered lidocaine
C4: Placebo

 

Table 4. Sucrose and EMLA as single treatment
DPNB = Dorsal Penile Nerve Block; EMLA = Eutectic Mixture of Local Anesthetics; RCT = Randomized controlled trial
Author
Year
Reference
Design Neonatal age Intervention and control
Sucrose as single treatment compared to placebo
Zahorodny et al
1999
[12]
RCT
(n=61)
Gestational age: 276 to 278 days C1: Sucrose
C2: Placebo (water)
Blass et al
1991
[13]
RCT
(n=54)
28 to 54 hours C1: Sucrose
C2: Placebo (water)
C3: No treatment
EMLA as single treatment compared to DPNB
Modekwe et al
2019
[14]
RCT
(n=110)
14.9 to 16.9 days C1: EMLA
C2: DPNB
Mujeeb et al
2013
[15]
RCT
(n=100
Less than 6 months
(mean = 2.3 months)
C1: EMLA
C2: DPNB
Garry et al
2006
[16]
RCT
(n=18)
Less than 36 hours old C1: EMLA
C2: DPNB
C3: Placebo (touch)
Lehr et al
2005
[17]
RCT
(n=62)
Less than 1 week old C1: EMLA
C2: 4% lidocaine
C3: DPNB
Holliday et al
1999
[18]
RCT
(n=50)
25 to 27 days C1: DPNB + placebo (cream)
C2: EMLA
C3: placebo (cream)
Howard et al
1999
[19]
RCT
(n=60)
Older than 24 hours C1: DPNB + placebo (cream)
C2: EMLA
Butler-O’Hara et al
1998
[20]
RCT
(n=50) + 20 non-randomized
24 to 60 hours C1: EMLA
C2: DPNB
C3: No treatment
Olson et al
1998
[21]
CT
(n=20)
Newborns (unknown) C1: EMLA
C2: DPNB
Lander et al
1997
[22]
RCT
(n=52)
1 to 3 days old C1: EMLA
C2: DPNB
C3: Ring block
C4: No treatment
Sucrose as single treatment compared to DPNB
Herschel et al
1998
[23]
RCT
(n=119)
12 hours old or older C1: Sucrose
C2: DPNB
C3: No treatment
Kass et al
2001
[24]
RCT
(n=71)
1.3 to 1.4 days C1: Sucrose
C2: DPNB
C3: Placebo
EMLA as single treatment, other
Woodman et al
1999
[25]
RCT
(n=61)
Average age:
27 to 28 hours
C1: EMLA
C2: 30% lidocaine
C3: Placebo
Taddio et al
1997
[26]
RCT
(n=68)
>37 weeks gestation C1: EMLA
C2: Placebo
Benini et al
1993
[27]
RCT
(n=27)
1 to 3 days old C1: EMLA
C2: Placebo

 

Table 5. Lidocaine cream as single treatment
RCT = Randomised controlled trial
Author
Year
Reference
Design Neonatal age Intervention and control
Weatherstone et al
1993
[28]
RCT
(n=30)
Newborns (unknown) C1: 30% lidocaine cream
C2: Cream base
Mudge et al
1989
[29]
RCT
(n=44)
12 to 72 hours C1: 4% lidocaine + acid mantle
C2: Placebo (acid mantle)

 

References

  1. Brady-Fryer B, Wiebe N, Lander JA. Pain relief for neonatal circumcision. Cochrane Database Syst Rev 2004:CD004217.
  2. Stevens B, Yamada J, Ohlsson A, Haliburton S, Shorkey A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2016;7:CD001069.
  3. Sharara-Chami R, Lakissian Z, Charafeddine L, Milad N, El-Hout Y. Combination Analgesia for Neonatal Circumcision: A Randomized Controlled Trial. Pediatrics 2017;140.
  4. Al Qahtani R, Abu-Salem LY, Pal K. Effect of lidocaine-prilocaine eutectic mixture of local anaesthetic cream compared with oral sucrose or both in alleviating pain in neonatal circumcision procedure. African journal of paediatric surgery : AJPS 2014;11:56-61.
  5. Kaufman GE, Cimo S, Miller LW, Blass EM. An evaluation of the effects of sucrose on neonatal pain with 2 commonly used circumcision methods. American Journal of Obstetrics & Gynecology;186:564-8.
  6. Mohan CG, Risucci DA, Casimir M, Gulrajani-LaCorte M. Comparison of analgesics in ameliorating the pain of circumcision. Journal of perinatology : official journal of the California Perinatal Association 1998;18:13-9.
  7. Zahorodny W, Suarez Y, Marshall R, Regan M, Holland B, Brendel D. Efficacy of EMLA and Sucrose for Crying Associated with Circumcision 1190. Pediatric Research 1998;43:204-204.
  8. Roman-Rodriguez CF, Toussaint T, Sherlock DJ, Fogel J, Hsu CD. Pre-emptive penile ring block with sucrose analgesia reduces pain response to neonatal circumcision. Urology 2014;83:893-8.
  9. Razmus IS, Dalton ME, Wilson D. Pain management for newborn circumcision. Pediatric nursing 2004;30:414-427.
  10. Taddio A, Pollock N, Gilbert-MacLeod C, Ohlsson K, Koren G. Combined analgesia and local anesthesia to minimize pain during circumcision. Archives of pediatrics & adolescent medicine 2000;154:620-3.
  11. Stang HJ, Snellman LW, Condon LM, Conroy MM, Liebo R, Brodersen L, et al. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics 1997;100:E3.
  12. Zahorodny W, David ES, Estrada P, Jacqueline, Marshall R. Efficacy of a Sucrose Pacifier for Newborn Pain. Pediatric Research 1999;45:7-7.
  13. Blass EM, Hoffmeyer LB. Sucrose as an analgesic for newborn infants. Pediatrics;87:215-8.
  14. Modekwe VI, Ugwu JO, Ekwunife OH, Osuigwe AN, Obiechina SO, Okpalike IV, et al. Comparison of the efficacy of eutectic mixture of local anesthetics (EMLA) and dorsal penile nerve block (DPNB) in neonatal circumcision. Nigerian journal of clinical practice 2019;22:1737-1741.
  15. Mujeeb S, Akhtar J, Ahmed S. Comparison of eutectic mixture of local anesthetics cream with dorsal penile nerve block using lignocaine for circumcision in infants. Pakistan Journal of Medical Sciences 2013;29:27-30.
  16. Garry DJ, Swoboda E, Elimian A, Figueroa R. A video study of pain relief during newborn male circumcision. Journal of Perinatology 2006;26:106-110.
  17. Lehr VT, Cepeda E, Frattarelli DAC, Thomas R, LaMothe J, Aranda JV. Lidocaine 4% cream compared with lidocaine 2.5% and prilocaine 2.5% or dorsal penile block for circumcision. American Journal of Perinatology 2005;22:231-237.
  18. Holliday MA, Pinckert TL, Kiernan SC, Kunos I, Angelus P, Keszler M. Dorsal penile nerve block vs topical placebo for circumcision in low- birth-weight neonates. Archives of Pediatrics and Adolescent Medicine 1999;153:476-480.
  19. Howard CR, Howard FM, Fortune K, Generelli P, Zolnoun D, tenHoopen C, et al. A randomized, controlled trial of a eutectic mixture of local anesthetic cream (lidocaine and prilocaine) versus penile nerve block for pain relief during circumcision. American journal of obstetrics and gynecology 1999;181:1506-11.
  20. Butler-O'Hara M, LeMoine C, Guillet R. Analgesia for neonatal circumcision: a randomized controlled trial of EMLA cream versus dorsal penile nerve block. Pediatrics 1998;101:E5.
  21. Olson TL, Downey VW. Infant physiological responses to noxious stimuli of circumcision with anesthesia and analgesia. Pediatric nursing 1998;24:385-389.
  22. Lander J, Brady-Fryer B, Metcalfe JB, Nazarali S, Muttitt S. Comparison of ring block, dorsal penile nerve block, and topical anesthesia for neonatal circumcision: A randomized controlled trial. Journal of the American Medical Association 1997;278:2157-2162.
  23. Herschel M, Khoshnood B, Ellman C, Maydew N, Mittendorf R. Neonatal circumcision. Randomized trial of a sucrose pacifier for pain control. Arch Pediatr Adolesc Med 1998;152:279-84.
  24. Kass FC, Holman JR. Oral glucose solution for analgesia in infant circumcision. J Fam Pract 2001;50:785-8.
  25. Woodman PJ. Topical lidocaine-prilocaine versus lidocaine for neonatal circumcision: A randomized controlled trial. Obstetrics and Gynecology 1999;93:775-779.
  26. Taddio A, Stevens B, Craig K, Rastogi P, Ben-David S, Shennan A, et al. Efficacy and safety of lidocaine-prilocaine cream for pain during circumcision. New England Journal of Medicine 1997;336:1197-1201.
  27. Benini F, Johnston CC, Faucher D, Aranda JV. Topical anesthesia during circumcision in newborn infants. JAMA 1993;270:850-3.
  28. Weatherstone KB, Rasmussen LB, Erenberg A, Jackson EM, Claflin KS, Leff RD. Safety and efficacy of a topical anesthetic for neonatal circumcision. Pediatrics 1993;92:710-714.
  29. Mudge D, Younger JB. The effects of topical lidocaine on infant response to circumcision. Journal of nurse-midwifery 1989;34:335-340.
Published: Report no: ut202129 Registration no: SBU 2021/613

Literature search

Embase via Elsevier 4 November 2021

Title: EMLA and sugar solution as anesthesia during circumcision
Search terms Items found
Population: Pain management during circumcision
1. ('circumcision'/exp OR circumcis*:ti,ab,kw) AND ('anesthesia'/exp or 'anesthesiological procedure'/exp or 'analgesia'/exp OR (Anesthe* OR anaesthe* OR analges* OR (pain NEAR/3 (relie* OR management OR control))):ti,ab,kw) 1 306
Intervention: Sugar solution
2. 'sucrose'/exp OR 'glucose'/exp OR 'sugar'/exp OR 'sweetening agent'/exp OR (Sucrose OR glucose OR sugar* OR sweet):ti,ab,kw 1 052 095
3. 'lidocaine'/exp OR 'lidocaine plus prilocaine'/exp OR (Lidocaine OR EMLA OR ‘eutectic mixture of local anaesthetics’ OR ‘eutectic mixture of local anesthetics’):ti,ab,kw 85 948
Study types: Systematic review
4. ‘Systematic review’/exp OR ‘meta-analysis’/exp OR ((Systematic* NEAR/3 review*) OR ‘Meta-analysis’):ti,ab,kw 540 118
Combined sets
5. 1 AND 2 70
6. 1 AND 3 301
7. 1 AND 4 45
Final result
  5 OR 6 OR 7 416
The final search result, usually found at the end of the documentation, forms the list of abstracts.

/de
= Term from the EMTREE controlled vocabulary;/exp= Includes terms found below this term in the EMTREE hierarchy /mj= Major Topic;:ab= Abstract;:au= Author;:ti= Article Title;:ti,ab= Title or abstract;*= Truncation;' '= Citation Marks; searches for an exact phrase;NEAR/n= Requests terms that are within 'n' words of each other in either direction;NEXT/n= Requests terms that are within 'n' words of each other in the order specified

Medline via OvidSP 4 November 2021

Title: EMLA and sugar solution as anesthesia during circumcision
The final search result, usually found at the end of the documentation, forms the list of abstracts.

.ab. = Abstract; .ab,ti. = Abstract or title; .af. = All fields; Exp = Term from the Medline controlled vocabulary, including terms found below this term in the MeSH hierarchy; .sh. = Term from the Medline controlled vocabulary; .ti. = Title; / = Term from the Medline controlled vocabulary, but does not include terms found below this term in the MeSH hierarchy; * = Focus (if found in front of a MeSH-term); * or $ = Truncation (if found at the end of a free text term); .mp = Text, heading word, subject area node, title; “ “ = Citation Marks; searches for an exact phrase; ADJn = Positional operator that lets you retrieve records that contain your terms (in any order) within a specified number (n) of words of each other.
Search terms Items found
Population: Pain management during circumcision
1. (exp Circumcision, Male/ or circumcis*.ti,ab,kw.) and ((exp Anesthesia/ and Analgesia/) or exp pain/pc or exp Pain Management/ or (Anesthe* or anaesthe* or analges* or (pain adj3 (relie* or management or control))).ti,ab,kw.) 715
Intervention: Sugar solution
2. exp Sucrose/ or exp Glucose/ or exp Sugars/ or (Sucrose or glucose or sugar* or sweet).ti,ab,kw. 839  306
3. exp Lidocaine/ or exp Lidocaine, Prilocaine Drug Combination/ or (Lidocaine or EMLA or "eutectic mixture of local anaesthetics" or "eutectic mixture of local anesthetics").ti,ab,kw. 33 847
Study types: Systematic review
4. exp Systematic review/ or exp meta-analysis/ or ((Systematic* adj3 review*) or "Meta-analysis").ti,ab,kw. 364  755
Combined sets
5. 1 AND 2 32
6. 1 AND 3 161
7. 1 AND 4 22
Final result
  5 OR 6 OR 7 215
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