Methods

Single‐centre RCT, paediatric emergency department, United States

Participants

151 patients younger than 18 years old with lacerations on the scalp (n = 31), face (n = 79) or extremity (n = 41)

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 5 to 10 minutes (n = 56)
2. Intradermal infiltration with lidocaine 1% (n = 53)
3. Topical placebo solution, applied for 5 to 10 minutes (n = 42)

Outcomes

1. Before laceration repair, the physician probed the wound with a 25‐gauge needle to determine adequacy of initial anaesthesia.
2. The physician graded participant compliance during the suturing process on a 4‐point scale (1 ‐ complete compliance, 2 ‐ occasional resistance, 3 ‐ frequent resistance, 4 ‐ continuous resistance).
3. Supplemental lidocaine infiltration was required.

Results of topical TAC versus topical placebo include the following.
1. Adequate initial anaesthesia (topical TAC = 89% vs topical placebo = 17%; P < 0.0001)
2. Physician compliance scale (1‐4) ratings (complete compliance to continuous resistance) (mean score ± SD: topical TAC = 1.25 ± 0.57 vs topical placebo = 1.93 ± 0.96; P < 0.002)
3. Requirement of supplemental lidocaine infiltration (topical TAC = 18% vs topical placebo = 83%; P < 0.0001)

Results of topical TAC versus infiltrated local anaesthetic include the following.
1. Adequate initial anaesthesia (topical TAC = 89% vs infiltrated local anaesthetic = 79%; P = non‐significant)
2. Physician compliance scale (1‐4) ratings (complete compliance to continuous resistance) (mean score ± SD: topical TAC = 1.25 ± 0.57 vs infiltrated local anaesthetic = 1.94 ± 1.12; P < 0.002)
3. Requirement of supplemental lidocaine infiltration (topical TAC = 18% vs infiltrated local anaesthetic = 23%; P = non‐significant)

Intervention dates

August 1986 to May 1987

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "The last digit of the patient's medical record number was used to enter patients into either the intradermal or topical group".

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "The last digit of the patient's medical record number was used to enter patients into either the intradermal or topical group".

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

High risk

Quote: "Individual study vials containing 5ml of TAC or placebo were prepared in the pharmacy of University of Massachusetts Medical Center following a standard protocol and assigned numbers"; "The ED staff member evaluating and suturing the patient were blind to the solution contained in the vials".

Comment: Comparisons of topical TAC and topical placebo were probably blinded. However, comparisons between lidocaine infiltration and topical TAC were probably unblinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

153 eligible patients, 2 refused to participate. 151 randomized, no missing outcome data

selective reporting of outcomes
All outcomes

Unclear risk

All outcomes discussed in Methods section reported in Results. Subgroup analysis based on location of laceration was not prespecified.

Other bias (sample size)

High risk

56 TAC:

53 lidocaine

42 placebo

Methods

Single‐centre RCT, emergency department, community‐based teaching hospital, United States

Participants

35 adult and paediatric patients (minimum age of 2 years) with facial and scalp lacerations, ≤ 6 cm in length

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 10.4%), applied for 20 minutes (n = 18)
2. Topical TLE solution (lidocaine 5% and epinephrine 1:2000), applied for 20 minutes (n = 17)

Outcomes

1. The participant reported discomfort using a facial effective pain scale (1‐9), which consisted of 9 faces with various emotional expressions. However, in a few cases, the participant was too young to use the pain scale, so the physician estimated the participant's pain using the same Faces scale. The study combined self‐reported and surrogate Faces pain scale scores in the final results.
2. Rescue lidocaine infiltration was required.
3. The study reported any acute adverse reactions directly related to the anaesthetic.

Results included the following.
1. Faces pain scale (1‐9) scores (mean score ± SD: topical TLE = 3.29 ± 1.92 vs topical TAC = 2.66 ± 1.78; P = 0.33)
2. Requirement for supplemental lidocaine infiltration (topical TLE = 6% vs topical TAC = 6%; P = not reported)
3. No acute anaesthetic‐related adverse effects

Intervention dates

May to August 1992

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "The TAC and TLE solutions were arbitrarily assigned to a single‐dose (10ml), sequentially numbered vials by the pharmacist. The vials, with the specific contents unknown to the emergency physician, were forwarded to the ED as requested".

Comment: probably not done

Allocation concealment (selection bias)

Low risk

Quote: "The solutions were made visibly identical by adding methylene blue to the TLE solution so that it matched the intrinsic blue colour of TAC".

"The vials, with the specific contents unknown to the emergency physician, were forwarded to the ED as requested".

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "The solutions were made visibly identical by adding methylene blue to the TLE solution so that it matched the intrinsic blue colour of TAC".

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

35 participants in study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

All outcomes described in Methods were fully reported in Results section. Adverse events noted

Other bias (sample size)

High risk

Total N = 35:

17 participants in the TLE group; 18 in the TAC group

Methods

Single‐centre RCT, Department of Emergency Medicine, Children’s Hospital Wisconsin, Milwaukee, Wisconsin, United States

Participants

55 paediatric patients with facial lacerations

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 10 to 15 minutes (n = 24)
2. Topical AC solution (epinephrine 1:2000, cocaine 11.8%), applied for 10 to 15 minutes (n = 31)

Outcomes

1. The physician calculated the total number of 'sutures eliciting pain' using the following system. Each suture placed involved 2 points; an entrance and an exit piercing of the wound tissue with the needle. A painful response consisted of a verbal participant experiencing a painful sensation or a non‐verbal participant beginning to cry, or crying with greater intensity. The total number of 'sutures placed eliciting pain' was calculated by dividing the total number of painful responses by 2.
2. The study reported any acute adverse effects due to the anaesthetic.

Results included the following.
1. The physician calculated the total number of 'sutures eliciting pain' (topical AC = 7/103 (4%) vs topical TAC = 7/151 (7%); P = not‐reported).
2. No acute anaesthetic‐related adverse effects were noted.

Intervention dates

Not reported

Declaration of interest

No explicit documentation regarding conflicts of interest.

Notes

Source of funding: general academic paediatric development fellowship from The Robert Wood Johnson Foundation; and Grant 10066 from The Robert Wood Foundation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "...as in each case an assistant randomly selected one of the two solutions for physician application..."

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "an assistant randomly selected one of the two solutions for physician application..."

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "The managing physician was 'blind' to which preparation was being administered...the physician was informed of the solution composition only after the suturing procedure and pain scoring were completed".

Comment: probably done, assuming the 2 solutions were visually identical

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

55 participants in study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported in the prespecified way.

Other bias (sample size)

High risk

55 paediatric participants:

1. Topical TAC solution, n = 24

2. Topical AC solution, n = 31

Methods

RCT, single centre, emergency department, United States

Participants

139 adult and paediatric patients older than 5 years of age, with laceration of the face (n = 53), scalp (n = 33), extremity (n = 52) or trunk (n = 1), measuring < 5 cm in length

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 5 to 10 minutes (n = 69)
2. Topical cocaine solution 11.8%, applied for 5 to 10 minutes (n = 70)

Outcomes

1. The physician assessed the adequacy of initial anaesthesia by pricking the wound with a pin. If pain was elicited with pinprick, then 1% lidocaine was infiltrated, and the participant was assigned to the 'poor anaesthesia' group.
2. Among participants who did not require infiltrated lidocaine, the physician rated the effectiveness of anaesthesia during suturing on a numerical scale (0‐10).

3. Investigators reported acute adverse reactions directly related to the anaesthetic.

Results include the following.
1. Incidence of 'poor anaesthesia' (topical cocaine = 20% vs topical TAC = 12%; P = not reported)
2. Physician rating of anaesthetic effectiveness on a numerical scale (0‐10; least effective to most effective) (mean scores ± SD: topical cocaine = 6.44 ± 3.48 vs topical TAC = 7.74 ± 3.03; P = 0.005)
3. No acute anaesthetic‐related adverse effects

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Source of funding: Saint Francis Hospital and Medical Center

Study author contacted for additional information but did not reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "TAC and cocaine solutions were randomly distributed with only a number from 1‐150 appearing on each vial".

Comment: unclear; exact mechanism of randomization not described

Allocation concealment (selection bias)

Unclear risk

Quote: "TAC and cocaine solutions were randomly distributed with only a number from 1‐150 appearing on each vial".

"The investigator was blinded as to the identity of the agent. The code was kept in the pharmacy and was available to the investigators only in case of emergency".

Comment: unclear; allocation concealment possible if a pharmacy‐controlled randomization process was used. However, this is not explicitly reported, so we decided upon unclear risk.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "The investigator was blinded as to the identity of the agent. The code was kept in the pharmacy and was available to the investigators only in case of emergency".

Comment: probably done, assuming local anaesthetic solutions are identical in colour

Incomplete outcome data (attrition bias)
All outcomes

Low risk

148 participants were enrolled and 9 were excluded from the study before unblinding and analysis (4 improper application, 4 participant younger than 5 years and one with laceration too large). We concluded low risk of bias because the number of excluded participants was balanced between the 2 interventions, and reasons for exclusion are unlikely to be related to pain scores during suturing.

selective reporting of outcomes
All outcomes

Unclear risk

All outcomes described in Methods section were reported in Results. Subgroup analyses by site and age were not prespecified.

Other bias (sample size)

Unclear risk

Total N = 139:

70 in the cocaine‐treated group

69 in the TAC‐treated group

Methods

Single‐centre RCT, Department of Medicine, Section of Emergency Medicine, Louisiana State University, New Orleans, Louisiana, United States

Participants

95 patients age 5 to 17 years with lacerations on the face (n = 64) or scalp (n = 31), ≤ 7 cm in length

Interventions

1. Topical LAT gel (lidocaine 4%, epinephrine 1:2000, tetracaine 0.5%), applied for 10 to 30 minutes (n = 48)
2. Topical TAC gel (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 10 to 30 minutes (n = 47)

Outcomes

1. Participant‐rated modified multi‐dimensional pain scale (0‐10)
2. Physician‐rated modified multi‐dimensional pain scale (0‐10)
3. Percentage of sutures causing pain
4. Requirement of supplemental lidocaine infiltration
5. Acute adverse reactions directly related to the anaesthetic reported by investigators

Results include the following.
1. Participant‐reported modified multi‐dimensional pain scale (0‐10) scores (mean ranked sum: topical LAT = 49.0 vs topical TAC = 46.9; P = 0.71)
2. Physician‐assigned multi‐dimensional pain scale (0‐10) scores (mean ranked sum: topical LAT = 48.7 vs topical TAC = 47.3; P = 0.80)
3. Percentage of sutures placed causing pain (mean ranked sum: topical LET = 49.57 vs topical TAC = 46.39; P = 0.51)
4. Requirement of supplemental lidocaine infiltration (topical LET = 4%, topical TAC = 6%; P = not reported)
5. No acute anaesthetic‐related adverse effects

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Funding not reported

‐Study author contacted for additional information but did not reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Gels were randomized according to a random numbers table".

Comment: probably done

Allocation concealment (selection bias)

High risk

Quote: "randomized according to a random numbers table"

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Patients and physicians performing suturing were blinded to which gels were being used. Only the numbers 1‐100 appeared on the capped syringes".

Comment: probably done, assuming the 2 gels were visually identical

Incomplete outcome data (attrition bias)
All outcomes

Low risk

100 participants entered into the trial, but 5 were excluded before statistical analysis because topical anaesthesia was inadequate and lidocaine infiltration was required. Two participants in the LAT group and 3 in the TAC group were excluded. We judged low risk of bias because the number of excluded participants was balanced between the 2 interventions.

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported: Physicians and participants or parents rated anaesthesia effectiveness during suturing utilizing a modified multi‐dimensional pain scale.

Prespecified secondary outcomes were also reported: Participants or parents reported the number of sutures causing pain, which was analysed as percent of total sutures placed.

Quote: “Both physician and patient or parent rated the anaesthesia effectiveness during suturing utilizing a modified multidimensional pain scale…. Patients or parents reported the number of sutures causing pain, which was analysed as percent of total sutures placed”.

Table 1 lists demographics (age, sex), wound size, location, amount of anaesthetic used and number of sutures placed.

Table 2 reports percent of sutures causing pain in each topical anaesthesia group.

Table 3 reports physician vs participant rating for pain scores for each topical anaesthesia group.

Other bias (sample size)

High risk

LAT GEL = 48 participants

TAC gel = 47 participants

Methods

Single‐centre RCT, Department of Medicine, Section of Emergency Medicine, Louisiana State University, New Orleans, Louisiana, United States

Participants

95 adult patients with laceration of the face (n = 81) or scalp (n = 13) ≤ 7 cm in length

Interventions

1. Topical LAT solution (lidocaine 4%, epinephrine 1:2000, tetracaine 0.5%), applied for 10‐30 minutes (n = 48)
2. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 10‐30 minutes (n = 47)

Outcomes

1. Participant‐rated VAS (100 mm) pain score
2. Physician‐rated VAS (100 mm) pain score
3. Percentage of sutures eliciting pain

Results include the following.
1. Participant‐reported VAS (100 mm) pain scores (mean ranked sum: topical LET = 45.3 vs topical TAC = 50.8; P = 0.27)
2. Physician‐reported VAS scores (mean ranked sum: topical LAT = 41.6 vs topical TAC = 54.6; P = 0.01)
3. Percentage of sutures causing pain (mean ranked sum: topical LET = 42.8% vs topical TAC = 53.3%; P = 0.36)

Intervention dates

Declaration of interest

Not reported

Notes

Funding resource: supported by a grant from the Louisiana State University Emergency Medicine Residency Grant Fund.

Study author contacted for additional information but did not reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Solutions were randomized according to a random numbers table".

Comment: probably done

Allocation concealment (selection bias)

Low risk

Quote: "The solutions were prepared by a pharmacist and were available in coded sterile, capped 3ml syringes".

"Both TAC and LAT were clear solutions..."

"Patients and physicians performing wound closure were blinded".

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "The solutions were prepared by a pharmacist and were available in coded sterile, capped 3ml syringes with a cotton ball for application".

"Both TAC and LAT were clear solutions mixed from powders".

"Patients and physicians performing wound closure were blinded".

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

High risk

100 total participants enrolled but only 95 were included in final data analysis. Four participants were excluded because they required additional injected lidocaine (1 LAT group, 3 in TAC group), and 1 because of improper data collection. We judged 'no' (high risk of bias) because requirement of additional lidocaine is directly related to pain intensity during laceration repair.

selective reporting of outcomes
All outcomes

Low risk

All outcomes described in Methods reported fully in Results. Adverse events reported

Other bias (sample size)

Unclear risk

47 receiving TAC and 48 receiving LAT. Total N = 95

Methods

Single‐centre RCT, urban emergency department, United States

Participants

66 paediatric and adult patients, older than 5 years of age with laceration on the face (n = 30), scalp (n = 10) or extremity (n = 24), 1.5 to 10 cm in length

Interventions

1. Topical LAT gel (lidocaine 4%, epinephrine 1:2000, tetracaine 0.5%), applied for 10 to 20 minutes (n = 33)
2. Intradermal infiltration with lidocaine 1%, epinephrine, buffered with 8.4% NaHCO3 (n = 33)

Outcomes

1. Participant‐rated VAS (100 mm) pain scale scores
2. Physician‐rated VAS (100 mm) pain scale scores
3. Requirement of supplemental lidocaine infiltration
4. Percentage of sutures placed eliciting pain

Results included the following.
1. Participant self‐reported VAS (100 mm) pain scores (median values (interquartile range): topical LAT = 0 (0‐1.35) vs infiltrated local anaesthetic = 0 (0‐0.6); P = 0.48, standard deviations not reported)
2. Physician‐reported VAS (100 mm) pain scores (median values (interquartile range): topical LAT = 0 (0‐0.55) vs infiltrated local anaesthetic = 0 (0‐0.35); P = 0.83, standard deviations not reported)
3. Percentage of sutures causing pain (topical LAT = 13% vs infiltrated local anaesthetic = 6%; P = 0.28)
4. Requirement of supplemental infiltrated anaesthesia (LAT = 6% vs infiltrated anaesthetic = 0%; P = not reported)

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Funding not reported

Study author contacted for additional information but did not reply

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The doses of anaesthetic were numbered 1‐66 according to a computer generated random table of numbers prepared before the study".

Comment: probably done

Allocation concealment (selection bias)

High risk

Quote: "physicians and patients were not blinded to the form of anaesthesia".

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

High risk

Quote: "Because of the obvious differences in form and application, physicians and patients were not blinded to the form of anaesthesia".

Comment: probably not done

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

66 participants included in study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported: Participant and physician ranked pain of suturing with validated linear visual analogue scale.

Prespecified secondary outcomes were also reported: Necessity for additional lidocaine and treatment success or failure were recorded at the time of the procedure.

Quote: “The primary endpoints were patient and physician perception of application or injection pain and anaesthesia effectiveness…. Patients and physicians ranked the pain of injection or application and the pain of suturing using a previously validated linear visual analog scale so that each laceration had four associated measurements of pain”.

Quote: “The length of the laceration, location, length of time anaesthesia lasted, amount of anaesthesia used, necessity for additional lidocaine, and treatment success or failure were recorded at the time of the procedure, along with any complications”.

Table 1 lists demographics (age, sex), wound size, initial amount of anaesthesia, need for more anaesthesia and location.

Table 2 reports physician and participant ratings of pain of local and topical anaesthetic application (VAS) ‐ effectiveness.

Table 3 reports physician vs participant rating for pain scores of suturing (VAS).

Table 4 reports percent of sutures causing pain per participant.

Other bias (sample size)

High risk

Quote: “66 subjects were entered in the study. Topical LAT = 33, infiltrated lidocaine = 33”.

Methods

Single‐centre RCT, community teaching hospital emergency department, United States

Participants

100 adult patients older than 18 years of age with lacerations involving scalp (n = 15), face (n = 15), lower extremity (n = 13), upper extremity (n = 15) or hands (n = 42) Laceration length ranged from < 1 cm to > 5 cm.

Interventions

1. Topical LE solution (lidocaine 5%, epinephrine 0.025%), applied for 10 to 15 minutes for 1 to 4 sequential layered applications (n = 50)

2. Intradermal infiltration with lidocaine (n = 50)

Outcomes

1. Participant‐rated VAS (100 mm) pain scale scores

2. Amount of lidocaine required (mg)

3. Number of applications of topical anaesthetic

4. Difficulty with wound healing or infection

Results included the following.

1. Participant‐reported VAS (100 mm) pain scores (mean score ± SD: topical TLE = 0.16 ± 0.46 vs infiltrated lidocaine = 0.20 ± 0.49; P = 0.59)

2. Amount of lidocaine required (mean score: TLE = 135 mg vs infiltrated lidocaine = 124 mg; P = 0.90, SD not reported)

3. Number of anaesthetic applications of TLE (mean score = 2.7; 2 participants (4%) required 1 layer, 17 (34%) required 2 layers, 26 (52%) required 3 layers, 5 (10%) required 4 layers)

4. No participants had poor wound healing or infection.

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "We performed a prospective, randomized controlled trial.."

Comment: unclear; study reported to be randomized but method of sequence generation not described

Allocation concealment (selection bias)

High risk

Comment: probably not done. Interventions of topical anaesthesia vs infiltrated anaesthesia are visually different. No mechanism used to conceal the intervention from participants or study personnel was described.

Blinding (performance bias and detection bias)
All outcomes

High risk

Quote: "100 patient[s] were enrolled in a randomized controlled trial..."

Comment: probably not done, as study did not report blinding and compared topical vs infiltrated forms of anaesthesia

Incomplete outcome data (attrition bias)
All outcomes

Low risk

100 enrolled participants in study, no missing outcome data or exclusions

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported: patient‐reported VAS pain scores

Prespecified secondary outcomes were also reported: amount of lidocaine required, number of applications of topical anaesthetic and difficulty with wound healing.

Quote: “The effectiveness of anaesthesia was assessed by the patient immediately after the procedure using a 1‐10 visual analog pain scale administered by a third‐party. The subject was instructed to assess the pain from application or anaesthesia, and the pain from suturing the wound”.

Table 2. Application of anaesthesia

Table 3. Pain during application of anaesthetic

Table 4. Effectiveness of anaesthesia during wound repair

Table 5. Follow‐up interview after wound repair for 79 participants

Other bias (sample size)

Unclear risk

Infiltrated lidocaine = 50 participants

Topical TLE = 50 participants

Methods

Two‐centre RCT, emergency departments, Uunited States

Participants

467 patients, 18 years of age or younger, with dermal lacerations on the face, scalp, extremity and trunk

Interventions

1. TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%),
applied for 30 minutes (n = 262)

2. Intradermal infiltration with lidocaine 1% (n = 205)

Outcomes

Pain during the suturing process was not directly assessed.
1. Before laceration repair, the physician probed the wound with a 26‐gauge needle to determine adequacy of initial anaesthesia (adequate, inadequate or unable to access). The physician administered infiltrated anaesthetic to participants in the TAC group with 'inadequate' anaesthesia.
2. Investigators reported any acute adverse reactions to the anaesthetic.

Results include the following.
1. Adequate initial anaesthesia for facial and scalp lacerations (topical TAC = 81% vs infiltrated local anaesthetic = 87%; P = 0.005). Adequate initial anaesthesia for the extremity and trunk wound group (topical TAC = 43% vs infiltrated local anaesthetic = 89%; P < 0.0001)
2. No acute anaesthetic‐related adverse effects

Intervention dates

December 1986 to November 1987

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "Randomization of anaesthetic treatment was determined by the final digit of the patients medical record number, with odd numbers receiving lidocaine and even numbers receiving TAC".

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "Randomization of anaesthetic treatment was determined by the final digit of the patient's medical record number".

"unblinded study"

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

High risk

Quote: "We conducted a prospective, randomized, unblinded study..."

Comment: probably not done

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

467 participants included in the study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

All outcomes described in Methods section were fully reported in Results, including subgroup analyses by area of laceration.

Other bias (sample size)

Low risk

262 children received TAC (218 facial or scalp and 44 extremity or trunk wounds), and 205 received lidocaine (158 facial or scalp and 47 extremity or trunk wounds).

Methods

RCT, single‐centre, hospital emergency department, Northern Ireland

Participants

110 (54 topical anaesthetic putty, 56 lidocaine infiltration), median age (range): infiltration 35 (18‐84), topical anaesthetic putty 35 (20‐81)

Male: 94 (85.5%), female: 16 (14.5%). Topical anaesthetic putty group had 10 F, 44 M; lidocaine infiltration group had 6 F, 50 M.

Wounds: < 8 cm long and needing suturing or stapling

Interventions

1. Topical anaesthetic putty (containing 4.94% w/w lidocaine hydrochloride,
equivalent to 4% w/w lidocaine base)

2. Lidocaine infiltration (1% w/v)

Outcomes

Primary outcomes:

Participant‐reported 0‐10 VAS during sensory testing with a 21‐gauge needle “directly after treatment”. Mean pain score was 0.78 + 1.12 (SD) after lidocaine infiltration, 1.49 + 1.76 after topical anaesthetic putty. Overlapping 1‐sided 95% CI limits plus (because data were not normally distributed) non‐parametric contrasting of median scores; both showed non‐inferiority of topical anaesthetic putty c/w infiltrated lidocaine

Secondary outcomes:

Need for rescue anaesthesia (required by 3 in infiltration group and 4 in topical anaesthetic putty group), “wound evaluation score” obtained 7‐10 days after treatment (12 in topical anaesthetic putty group had less than perfect scores vs 5 in infiltration group), presence of wound infection (4 in infiltration group vs 2 in topical anaesthetic putty group), dehiscence (2 in topical anaesthetic putty group) and adverse effects (1 inflamed wound in topical anaesthetic putty group, 1 required resuturing in each group)

No anaesthetic toxicity reported

Intervention dates

Not reported

Declaration of interest

The wound putty used in this study was not a proprietary product and was not produced commercially. The putty was manufactured by 2 of the study authors ‐ Drs. Murphy and McCarron. After the success of this trial, Drs. Jenkins and McCarron sought to protect certain aspects of the putty formulation in both the United States and Europe. This patent application was pending at the time of publication and was related to a certain aspect of the formulation that enables lidocaine to be included.

The authors of this study received no funding from commercial sources to support the study. Funding for this study was obtained through a peer‐reviewed competitive process from the Public Health Agency in Northern Ireland.

Drs. Jenkins and McCarron were pursuing sources of capital to commercialise the putty but had not yet secured this funding.

Notes

Sourse of funding: supported by the Research and Development Office (Northern Ireland) Trauma and Rehabilitation Recognised Research Group (RRG 8.46 RRG/3273/06)

Rescue medication: no systemic anaesthesia or analgesia mentioned. However, “The decision to offer or use rescue anaesthesia rested with the treating investigator”. Rescue = wound margin infiltration with a further dose of 1% lidocaine for the 7 (4 in the topical anaesthetic putty group, 3 in the lidocaine infiltration group) who received it

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization sequence generated by Microsoft Excel version 14.3.9 through a permuted block randomization technique, with a block size of 8

Allocation concealment (selection bias)

Low risk

Randomization sequence provided in opaque, serially numbered envelopes

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label

Quote: “Because of the nature of the treatment, it was not feasible to blind either the participants or the investigators to the treatment received".

[Extractor’s note: not necessarily true, could have used placebo infiltration and placebo topical putty]

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants completed the first, acute part of the study; 19 did not complete the follow‐up wound assessment.

selective reporting of outcomes
All outcomes

Low risk

All outcome‐related data collected during the acute phase were complete.

Other bias (sample size)

Unclear risk

54 topical anaesthetic putty

56 lidocaine infiltration

Methods

Single‐centre RCT, Accident and Emergency Department of Gloucestershire Royal Hospital, United Kingdom

Participants

107 paediatric patients, 3‐16 years old, with lacerations < 4 cm in length, located anywhere on the body except mucous membranes or digits

Interventions

1. Topical AC solution (epinephrine 1:2000, cocaine 4.7%), applied for 10‐15 minutes (n = 51)
2. Intradermal infiltration with lidocaine 1% (n = 51)

Outcomes

1. Children younger than 10 years of age rated pain during both laceration repair and anaesthetic application using the Wong‐Baker Faces Scale. Patients 10 years of age or older used a VAS (10 cm) score to rate pain during suturing and anaesthetic administration.
2. Physician‐rated VAS (10 cm) pain scale scores
3. Parent‐rated VAS (10 cm) pain scale scores
4. Parent rated overall acceptability of the procedure.
5. Study reported any acute adverse effects to the anaesthetic.

Results include the following.
(standard deviations not reported)
1. Participant‐rated pain scores (pooled VAS and Wong‐Baker Faces scores) (mean score: topical AC = 4.50 vs infiltrated local anaesthetic = 4.40; P = NS)
2. Physician‐rated VAS (10 cm) pain scale scores (mean score: topical AC = 2.60 vs infiltrated local anaesthetic = 3.60; P = NS)
3. Parent‐rated VAS (10 cm) pain scale scores (mean score: topical AC = 3.10 vs infiltrated local anaesthetic = 3.80; P = NS)
4. Parent rating of overall acceptability of the procedure (topical AC = 14.5% unacceptable vs infiltrated local anaesthetic = 39% unacceptable; P < 0.01)
5. No acute anaesthetic‐related adverse effects

Intervention dates

January to November 1994

Declaration of interest

No explicit documentation regarding conflicts of interest

Notes

No sources of funding mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "Children presenting with an appropriate laceration were consecutively assigned to receive either conventional intradermal lignocaine or topical AC preparation".

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "consecutively assigned to receive either conventional intradermal lignocaine or topical AC preparation"

"Groups could not be blinded".

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

High risk

Quote: "The nature of the trial meant that the two groups could not be blinded".

Comment: probably not done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

120 participants were enrolled but 13 were excluded before data analysis (incomplete data collection for 8, 2 received Steristrips and not sutures, 3 did not attend follow‐up). We concluded low risk of bias because reasons for exclusion were unlikely to be related to pain scores during laceration repair.

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported in the prespecified way.

Other bias (sample size)

Unclear risk

1. Topical AC solution, n = 56

2. Intradermal infiltration with lidocaine, n = 51

Methods

RCT (unclear if single centre or multi‐centre)

Participants

41 adult and paediatric patients, 5 to 23 years of age, with simple lacerations < 5 cm in length

Interventions

1. Topical LET gel (lidocaine, epinephrine, tetracaine), applied for 60 minutes (n = 22)

2. EMLA cream (lidocaine 2.5%, prilocaine 2.5%), applied for 60 minutes (n = 19)

Outcomes

1. Participant‐rated VAS (100 mm) pain scale scores
2. Legal guardian‐rated VAS (100 mm) pain scale scores (when applicable)

3. Physician‐rated VAS (100 mm) pain scale scores

4. Requirement of supplemental lidocaine infiltration

Pain scores were obtained at 4 points in time: after irrigation, first suture or staple placement, last suture or staple placement and during supplemental infiltration of lidocaine (if applicable).

Results include the following.
1. Participant self‐reported VAS (100 mm) pain scores were not significantly different between the 2 anaesthetic groups (mean pain scores not provided; P > 0.05).

2. Legal guardian‐reported VAS (100 mm) pain scores were not significantly different between the 2 groups (mean pain scores not provided; P > 0.05).

3. Physician‐reported VAS (100 mm) pain scores were greater in the EMLA group during irrigation (mean VAS EMLA = 21.4 mm vs LET gel = 10.1 mm; P = 0.3) and during first suture/staple placement (mean VAS EMLA = 41.7 mm vs LET gel = 14.0 mm; P = 0.004).

4. Requirement of supplemental infiltrated anaesthesia: 13/19 participants in the EMLA group required infiltrated lidocaine (68%) compared with 5/22 in the LET group (23%) (P = 0.005%)

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Trial published as an abstract only. Source of funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "We conducted a double‐blind, randomized trial...".

Comment: unclear, as method of sequence generation not described

Allocation concealment (selection bias)

Unclear risk

Comment: unclear

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Quote: "We conducted a double‐blind, randomized trial..."

Comment: unclear, as reported to be double‐blind but no details provided

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

41 participants included in the study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported.

Other bias (sample size)

High risk

41 participants:

1. Topical LET gel, n = 22

2. EMLA cream, n = 19

Methods

Single‐centre (2 hospitals) RCT, emergency departments of 2 tertiary referral hospitals (1 paediatric), Adelaide South Australia

Participants

180 adult and paediatric patients, 6 years of age or older, with lacerations 3‐7 cm in length, located on the head (n = 114) or extremity (n = 66)

Interventions

1. Topical MAC solution (bupivacaine 0.5%, epinephrine 1:2000, cocaine 10.0%), applied for at least 10 to 15 minutes for head lacerations and for 30 minutes for extremity wounds (n = 92)
2. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 10.0%), applied for at least 10 to 15 minutes for head lacerations and for 30 minutes for extremity wounds (n = 88)

Outcomes

1. Children younger than 12 years of age rated pain during laceration repair using the Wong‐Baker Faces scale.
2. Participants 12 years of age or older used a VAS (10 cm) score to rate pain during suturing.
3. The physician assessed the effectiveness of initial anaesthesia using pinprick.
4. Participants noted their preference for topical anaesthesia in the future.
5. Investigators reported any acute adverse effects to the anaesthetic.

Results include the following.
1. Children younger than 12 years of age used the Wong‐Baker Faces Scale (1‐9) (mean score ± SD: topical MAC = 2.35 ± .50 vs topical TAC = 2.46 ± 2.34; P = 0.96).
2. Participants 12 years of age or older used the VAS (100 mm) pain scale (mean score ± SD: topical MAC = 6.9 ± 10.9 vs topical TAC = 12.0 ± 14.5; P = 0.16).

3. Adequacy of initial anaesthesia (topical MAC = 73% vs topical TAC = 74%; P = 0.87)
4. Participants' preference for topical anaesthesia in the future (topical MAC = 77% vs topical TAC = 81%; P = 0.42)
5. No acute anaesthetic‐related adverse effects

Intervention dates

Feburary 1992 to April 1994

Declaration of interest

No explicit documentation regarding conflicts of interest

Notes

Source of funding: grant from Society of Hospital Pharmacists of Australia

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The study was a double‐blinded, randomized, prospective trial.."

Comment: unclear, as study reported to be randomized but method of sequence generation was not described

Allocation concealment (selection bias)

Low risk

Quote: "Solutions of MAC and modified TAC were prepared and placed in syringes marked A or B by a pharmacist not involved in study. All study participants remained blinded throughout the trial".

Comment: probably done, assuming solutions were visually identical

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Solutions of MAC and modified TAC were prepared and placed in syringes marked A or B by a pharmacist not involved in study. All study participants remained blinded throughout the trial".

Comment: probably done, assuming solutions were visually identical

Incomplete outcome data (attrition bias)
All outcomes

Low risk

191 participants were enrolled but 10 were excluded before data analysis (5 younger than 6 years of age, 2 had wounds greater than 5 mm deep, 2 were not sutured, 1 had a digital laceration). We concluded low risk of bias because reasons for exclusion were unlikely to be related to pain scores during laceration repair.

selective reporting of outcomes
All outcomes

Unclear risk

The study protocol did not describe prespecified outcomes.

Other bias (sample size)

Unclear risk

180 participants:

1. Topical MAC solution, n = 92

2. Topical TAC solution, n = 88

Methods

Single‐centre RCT, Department of Emergency Medicine, Singapore General Hospital

Participants

n = 40, > 1 year to 70 years (only 1 patient > 10 years old was included in the study), 29 males (72.5%), 11 females (27.5%). Length of the wounds was 3.1 cm for the LG group and 3.5 cm for the LI group. Depth of the wounds was 0.5 cm and 0.57 cm, respectively.

Interventions

1. LAT gel (n = 23): mean length of wound/cm (SE) 3.1 cm (SE 0.31). Mean depth of wound/cm (SE) 0.5 (0.07). Location of wound: head 17/23 (74.0%), trunk 0/23 (0%) and limb 6/23 (26%)

2. Infiltrated lidocaine (n = 17): mean length of wound/cm (SE) 3.5 cm (SE 0.36). Mean depth of wound/cm (SE) 0.57(0.08). Location of wound: head 11/17 (64.7%), trunk 0/17 (0%) and limb 6/17 (35.3%)

Outcomes

1. LAT gel:

a. Efficacy: 10 cm VAS pain score by participant (mean ± SE) = 2.5 (0.52)

b. Pain during application (mean ± SE): 1.5 (0.40)

Pain score by parents, clinician or participants younger than 10 years old; results not provided

2. Lignocaine infiltration:

a. Efficacy: 10 cm VAS pain score by participant (mean ± SE) = 2.6 (0.58)

b. Pain during application (mean ± SE): 3.5 (0.46)

Pain score by parents, clinician or participants younger than 10 years old; results not provided

Complications:

1. No acute anaesthetic complications in either group

2. One week later, assessed for wound complications

1. LAT gel (study lists 25 but probably typographical error because only 23 participants in this treatment arm)

a. Wound Infection, 5/25 (5/23?)

b. Wound dehiscence = 1/25 (1/23?)

c. Stitches lost = 1/25 (1/23?)

2. Lignocaine infiltration

a. Wound Infection, 2/14

b. Wound dehiscence, 0/14

c. Stitches lost, 0/14

Intervention dates

Janurary to April 2003

Declaration of interest

None.

Notes

Souce of funding: none

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Suitable participants were assigned to 2 arms of treatment via sealed envelopes. However, precise method of sequence generation was not described.

Allocation concealment (selection bias)

Unclear risk

Use of assigned envelopes described but information proved insufficient to allow a decision between low risk and high risk

Blinding (performance bias and detection bias)
All outcomes

High risk

Not blinded and outcome could be affected by lack of blinding

Incomplete outcome data (attrition bias)
All outcomes

Low risk

40 patients recruited and no drop‐outs mentioned

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported.

Other bias (sample size)

High risk

LAT gel = 23 participants

Infiltrated lidocaine = 17 participants

Methods

Single‐centre RCT, Army Medical Center emergency department, United States

Participants

158 adult and paediatric patients, range 10 months to 53 years old (mean = 9 years old)

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for minimum of 10 minutes
(n = 82)
2. Intradermal infiltration with lidocaine (n = 76)

Outcomes

1. Participants 10 years of age or older rated anaesthetic efficacy (complete, partial or none) depending on whether they experienced pain during laceration repair.
2. Also, after completion of wound repair, participant or parent rated anaesthetic acceptability (excellent, good or poor).

Results include the following.
1. Verbal rating (complete, partial or none) of anaesthetic efficacy (complete: topical TAC = 84% vs infiltrated local anaesthetic = 88%; P = not reported)
2. Anaesthetic acceptability: Participants 17 years of age and younger preferred topical TAC (P < 0.005); no difference between the 2 anaesthetic groups among participants older than 17 years of age.

Intervention dates

October to December 1979

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "A prospective study of topical TAC and lidocaine infiltration was taken with the last digit of the patients military sponsor's social security number used as the selection variable, odd numbered patients were anaesthetised with topical TAC; even numbered patients were anaesthetised with lidocaine".

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "the last digit of the patient's military sponsor's social security number used as the selection variable"

Comment: probably not done. Anaesthetic agents visually different, and no mention of safeguards to prevent concealment of identity

Blinding (performance bias and detection bias)
All outcomes

High risk

Quote: none

Comment: probably not blinded, as the paper did not state whether participants or clinicians were blinded between topical and infiltrated anaesthetics

Incomplete outcome data (attrition bias)
All outcomes

Low risk

A total of 158 participants enrolled with no drop‐outs or exclusions.

selective reporting of outcomes
All outcomes

High risk

All outcomes described in Methods section were reported in Results, but method of assessing anaesthetic adequacy appears inconsistent between Methods and Results sections.

Subgroup analysis by age was described in Methods, but results were not presented for all subgroups for each outcome.

Wound complications were measured at 3 time points, but results were presented only for overall rate. No adverse events due to anaesthetic administration were reported.

Some results are presented only graphically.

Other bias (sample size)

Unclear risk

82 received topical TAC and 76 received lidocaine infiltration for anaesthesia.

Methods

Single‐centre RCT, emergency department, University of Minnesota‐affiliated Children’s Hospital, Minneapolis, Minnesota, United States

Participants

194 paediatric patients with lacerations of the face and scalp

Interventions

1. Topical LAT solution (lidocaine 4%, epinephrine 1:2000, tetracaine 0.5%), applied for 20 minutes (n = 103)
2. Topical LAT gel (lidocaine 4%, epinephrine 1:2000, tetracaine 0.5%), applied for 20 minutes (n = 91)

Outcomes

1. The physician assessed the adequacy of initial anaesthesia by probing the wound with a 27‐gauge needle. If any pain was elicited with probing, the anaesthetic was considered 'inadequate' and infiltrated lidocaine was given.
2. At the conclusion of laceration repair, the physician rated anaesthetic effectiveness (complete, partial or incomplete) based on painful responses during suturing.
3. The study reported acute adverse reactions directly related to the anaesthetic.

Results include the following.
1. Adequacy of initial anaesthesia (adequate anaesthesia: LET solution = 84% vs LET gel = 82%; P > 0.05)
2. Effectiveness of anaesthesia (complete anaesthesia: LET solution = 76% vs LET gel = 85%; P = 0.007)
3. No acute anaesthetic‐related adverse effects

Intervention dates

March 1995 to March 1996

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "A computer‐generated random number table was used by a hospital pharmacy personnel to label standard amber vials from 1 to 200".

Comment: probably done

Allocation concealment (selection bias)

Low risk

Quote: :hospital pharmacy personnel to label standard amber vials from 1 to 200"

"it was required that the study medication be applied by a nurse not involved in the suturing"

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "To ensure blinding of suture personnel, in the trial, it was required that the study medication be applied by a nurse not involved in the suturing"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

200 participants enrolled and 3 withdrawn before test of initial anaesthesia because participants were unco‐operative or complicated laceration did not meet inclusion criteria. Of the 197 available for analysis, 3 data sheets were inadvertently lost.

We concluded low risk of bias because plausible effect size among missing outcomes was not enough to have a clinically relevant impact on observed effect size.

selective reporting of outcomes
All outcomes

Unclear risk

All prespecified primary and secondary outcomes were reported: physician determination of adequacy of anaesthetic before repair and anaesthetic effectiveness during repair. Adverse effects also reported

Quote: “Pain assessment was a 2‐stage process that evaluated adequacy of anaesthesia before suturing and effectiveness of anaesthesia during suturing”.

“Effectiveness of anaesthesia during suturing was divided into 3 categories: complete, partial, and incomplete”.

“Complications assessed were redness, drainage, fever, tenderness, swelling, or contact with medical personnel for wound‐related issues other than suture removal”.

Quote: “Of the 194 patients, 162 (83.5%) obtained adequate anaesthesia as determined by the 27‐gague needle test”.

Table 3. Efficacy of LET solution versus LET gel for topical anaesthesia of face and scalp (includes information on complete, partial and Incomplete effectiveness)

Complications: “No adverse effects were noted in the 194 patients during the procedure. 13 patients who were not able to be contacted… one patient in each study arm sought medical care for a wound infection".

Other bias (sample size)

Unclear risk

Quote: “LET solution = 103 subjects, LET gel = 91 subjects”

Methods

Single‐centre RCT, Spokane Minor Emergency Centers, Spokane, Washington, United States

Participants

107 paediatric patients 10 years of age or younger, with laceration on the face (n = 84) or scalp (n = 23)

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 10 minutes (n = 56)
2. Topical TA solution (tetracaine 0.5%, epinephrine 1:2000), applied for 10 minutes (n = 51)

Outcomes

1. The physician rated anaesthetic effectiveness (complete, partial or inadequate) according to the ability of the participant to tolerate manipulation of the wound during repair. The anaesthesia was 'complete' if the participant did not cry, complain or wince during suturing. The anaesthesia was 'partial' if the participant had some discomfort but did have an avoidance reaction. 'Inadequate' anaesthesia was defined as obvious discomfort with minimal manipulation of the wound.
2. Rescue lidocaine infiltration was required.
3. The study reported any acute adverse reactions to the anaesthetic.

Results include the following.
1. Physician rating (complete, partial or inadequate) of anaesthetic effectiveness (complete anaesthesia: topical TA = 47.1% vs topical TAC = 75%; P < 0.05)
2. Requirement of rescue lidocaine infiltration (topical TA = 27.5% vs topical TAC = 8.9%; P = 0.01)
3. No acute anaesthetic‐related adverse effects. However, after returning home from the emergency department, 10.7% of children treated with TAC and 7.8% who received topical AC became drowsy or excitable. No evidence suggested that symptoms were causally related to the topical anaesthetic, and the study author concluded that these were not anaesthetic‐induced adverse effects.

Intervention dates

January to July 1983

Declaration of interest

Not reported

Notes

Funding not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "Patients who received topical anaesthesia were randomized by alternating between A and B solutions".

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "...randomized by alternating between A and B solutions"

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Neither patients nor treating physicians were informed of the composition of the anaesthetic solutions".

Comment: probably done, assuming topical TAC and TA were visually identical

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

107 participants included in study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported: Treating physician rated anaesthetic effectiveness on the basis of participant tolerance of manipulation of wound during suturing (complete, partial, inadequate).

The only prespecified secondary outcome was wound infection, which was reported.

Quote: “The relative effectiveness of anaesthesia was assessed subjectively by treating physician based on ability of patient to tolerate manipulation of would during repair”.

Table 1. Anesthesia effectiveness (treatment)

Table 2. Wound location (initial examination)

Table 3. Signs of wound infection (follow‐up visits)

Other bias (sample size)

Unclear risk

Quote: “Topical TAC = 56 patients, topical TA = 51 patients”

Methods

Single‐centre RCT, emergency department of a university‐affiliated private children's hospital, United States

Participants

151 patients, age 1 to 17 years, with facial (69.6%) and scalp (30.4%) lacerations

Interventions

1. Topical TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 15 minutes (n = 73)
2. Topical LET solution (lidocaine 4%, epinephrine 0.1%, tetracaine 0.5%), applied for 15 minutes (n = 78)

Outcomes

1. The physician assessed the adequacy of initial anaesthesia by probing the wound with a 27‐gauge needle.
2. After laceration repair, the physician rated anaesthetic effectiveness (complete, partial or incomplete). Anaesthesia was 'complete' if the participant did not have a painful response to suturing. Anaesthesia was 'partial' if the participant had a painful response to suturing, between 15 and 30 minutes after removal of topical solution. Anaesthesia was considered 'incomplete' if the participant had a painful response within 15 minutes after removal of the topical agent.
3. Investigators reported any acute adverse reactions directly related to the anaesthetic.

Results include the following.
1. Adequacy of initial anaesthesia (topical LET = 74.4% vs topical TAC = 79.5%; P = 0.46)
2. Physician‐rated anaesthetic effectiveness (complete, partial, incomplete) (complete anaesthesia: topical LAT = 82.4% vs topical TAC = 75.9%; P = 0.18)
3. No acute anaesthetic‐related adverse effects

Intervention dates

June 1992 to May 1993

Declaration of interest

Not reported

Notes

Source of funding: financial support provided by the FA Bean Education and Research Fund, Minneapolis Children's Medical Center

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "...vials of the anaesthetic solutions were assigned random numbers.."

Comment: unclear, as study was reported to be randomized, but method of sequence generation was not described

Allocation concealment (selection bias)

Low risk

Quote: "Both TAC and LET solutions are aqueous and have the same blue tint and viscosity".

"labelled to ensure appropriate blindness of suture personnel"

"A double blind topical application using 3ml of the test solutions was performed [at] study entry".

Comment: probably done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Both TAC and LET solutions are aqueous and have the same blue tint and viscosity. Unit‐dose, amber vials of the anaesthetic solutions were assigned random numbers; labelled to ensure appropriate blindness of suture personnel; and stored under refrigeration in the ED. A double blind topical application using 3ml of the test solutions was performed [at] study entry".

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

171 participants were initially enrolled, but data analysis was performed for only 151 participants. Five participants were excluded after consent was obtained (1 sedated before anaesthetic administration, 2 topical anaesthetics applied for inappropriate duration, 2 data sheets lost). 15 additional participants were withdrawn before evaluation of anaesthetic effectiveness because participants were unco‐operative or because it was discovered that the wound involved deeper tissue layers than inclusion criteria permitted. We concluded low risk of bias because reasons for exclusion were unlikely to be related to pain scores during laceration repair

selective reporting of outcomes
All outcomes

Unclear risk

All outcomes described in Methods were fully reported in Results section, but subgroup analyses (area of face, age of participant) were not prespecified. Adverse events were reported

Other bias (sample size)

Unclear risk

73 participants were treated with TAC; 78 participants received LET

Methods

Single‐centre RCT, emergency department, Children’s Hospital, Columbus, Ohio, United States

Participants

240 patients, 2 to 17 years old, with lacerations ≤ 5 cm
located on the face (n = 134), scalp (n = 57) or extremity (n = 49)

Interventions

1. Bupivanor (BN) solution (0.48% bupivacaine with 1:26,000 norepinephrine), applied for 20 minutes (n = 30)
2. Etidonor (EN) solution (0.95% etidocaine with 1:26,000 norepinephrine), applied for 20 minutes (n = 30)
3. Mepivanor (MN) solution (1.90% mepivacaine with 1:26,000 norepinephrine), applied for 20 minutes (n = 30)
4. Prilonor (PN) solution (3.81% prilocaine with 1:26,000 norepinephrine), applied for 20 minutes (n = 30)
5. TAC solution (tetracaine 1.00%, epinephrine 1:4000, cocaine 4.0%), applied for 20 minutes (n = 60)
6. Infiltrated lidocaine 1% (n = 60)

Outcomes

1. Participants 5 years of age or older, with reported discomfort on the VAS (100 mm) pain scale
2. Observer‐reported VAS (100 mm) pain scale scores (suture technicians and research assistants)
3. Observer‐reported Likert (1‐7) pain scale scores (parents and suture technicians).
4. Observer‐rated (RICDRS) Restrained Infants and Children Disress Rating Scale (0‐8) (research assistant and suture technician)
5. Suture technician‐rated anaesthetic effectiveness scale

Results (topical BN vs topical EN vs topical MN vs topical PN vs topical TAC vs infiltrated local anaesthetic) include the following.
(standard deviations not reported for any outcomes)
1. Participant‐reported VAS (100 mm) pain scores (mean scores: topical BN = 18.3 vs topical EN = 46.5 vs topical MN = 27.0 vs topical PN = 36.0 vs topical TAC = 12.0 vs infiltrated local anaesthetic = 26.3) (TAC significantly outperformed EN; P < 0.05; no significant differences between any other groups)
2a. Suture technician‐reported VAS (100 mm) pain scores (mean scores: topical BN = 2.0 vs topical EN =6.3 vs topical MN = 4.8 vs topical PN = 6.2 vs topical TAC = 2.8 vs infiltrated local anaesthetic = 2.0 (EN significantly outperformed by BN, TAC and infiltrated anaesthetic; P < 0.05; no significant differences between any other groups)
2b. Research assistant‐reported VAS (100 mm) pain scores (mean scores: topical BN =3.3 vs topical EN =7.7 vs topical MN = 4.9 vs topical PN = 8.9 vs topical TAC = 2.9 vs infiltrated local anaesthetic = 1.9) (TAC outperformed both EN and PN; P < 0.05; infiltrated anaesthetic outperformed both EN and PN; P < 0.05; no significant differences between any other groups)
3a. Suture technician‐reported Likert (1‐7) pain scores (mean scores: topical BN = 2.05 vs topical EN = 2.6 vs topical MN = 2.4 vs topical PN = 2.1 vs topical TAC = 1.55 vs infiltrated local anaesthetic = 1.6 (TAC outperformed both EN and MN; P < 0.05; infiltrated anaesthetic outperformed both EN and MN; P < 0.05; no significant differences between any other groups)
3b. Parent‐reported Likert (1‐7) pain scores (mean scores: topical BN = 2.8 vs topical EN = 3.5 vs topical MN = 3.3 vs topical PN = 3.6 vs topical TAC = 2.11 vs infiltrated local anaesthetic = 2.33 (TAC outperformed EN, MN and PN; P < 0.05; infiltrated anaesthetic outperformed EN and PN; P < 0.05; no significant differences between any other groups)
4a. Suture technician‐reported RICDRS (0‐8) (mean scores: topical BN = 2.5 vs topical EN = 3.6 vs topical MN = 2.3 vs topical PN = 2.5 vs topical TAC = 1.4 vs infiltrated local anaesthetic = 1.63 (TAC outperformed EN; P < 0.05; infiltrated anaesthetic outperformed EN; P < 0.05; no significant differences between any other groups)
4b. Research assistant‐reported RICDRS (0‐8) (mean scores: topical BN = 2.4 vs topical EN = 3.1 vs topical MN = 2.7 vs topical PN = 2.9 vs topical TAC = 1.6 vs infiltrated local anaesthetic = 1.8 (TAC outperformed both EN and PN; P < 0.05; infiltrated anaesthetic outperformed EN; P < 0.05; no significant differences between any other groups)
5. Anaesthetic effectiveness scale (scores not reported) (TAC outperformed EN and MN; P < 0.05; infiltrated anaesthetic outperformed BN, EN, MN, PN; P < 0.05; no significant differences between any other groups)

Intervention dates

July to December 1992

Declaration of interest

No explicit documentation regarding conflicts of interest

Notes

Source of funding: Ohio State University Seed Grant Program, Bremer Research Foundation, Ohio State University and Samuel J. Roessler Memorial Scholarship Fund

Study author contacted to request additional study data; study author replied but unable to provide the missing information. High risk of bias for local anaesthetic vs topical anaesthetic, as this comparison was not blinded. However,unclear risk of bias in 3 domains for comparisons of different topical anaesthetics because of appropriate blinding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Study patients were assigned to one of six anaesthetic treatment groups using block randomization".

Comment: unclear, as exact method of selecting the blocks was not reported

Allocation concealment (selection bias)

Unclear risk

Comment: unclear

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Comparisons among the five topical preparations were double blinded. Because lidocaine was given as an injection, its identity was not blinded"; "Anesthetics were prepared in advance by Children's Hospital pharmacy, sealed in envelopes labelled with a study identification number, and stored in a locked cabinet in the emergency department".

Comment: probably blinded between comparisons of different topical agents, but probably not blinded between comparisons of infiltrated lidocaine and topical anaesthetic

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

240 participants included in the study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported in the prespecified way.

Other bias (sample size)

Unclear risk

240 participants enrolled:

1. Bupivanor (BN) solution, n = 30

2. Etidonor (EN) solution, n = 30

3. Mepivanor (MN), n = 30

4. Prilonor (PN) solution, n = 30

5. TAC solution, n = 60

6. Infiltrated lidocaine, n = 60

Methods

Single‐centre RCT, emergency department or a large children’s hospital, United States

Participants

71 patients, 2‐16 years old, with lacerations ≤ 5 cm in length located on the face (n = 43) or scalp (n = 28)

Interventions

1. Mepivanor (MN) solution (mepivacaine 2%, norepinephrine 1:100,000), applied for 20 minutes (n = 24)
2. TAC solution (tetracaine 1.0%, epinephrine 1:4000, cocaine 4.0%), applied for 20 minutes (n = 24)
3. Intradermal infiltration with lidocaine 1% (n = 23)

Outcomes

1. Observer‐reported VAS (100 mm) pain scale scores (suture technicians, research assistants and videotape reviewers)
2. Observer‐reported Lickert (1‐7) pain scale scores (parents, suture technicians)
3. Requirement for supplemental lidocaine infiltration

Results (topical MN vs topical TAC vs infiltrated local anaesthetic) include the following.
1a. Suture technician‐reported VAS (100 mm) pain scores (mean score ± SD: topical MN = 7.1 ± 12.5 vs topical TAC = 2.0 ± 2.7 vs infiltrated anaesthetic = 1.8 ± 4.0) (Both topical TAC and infiltrated anaesthetic outperformed topical MN; P = 0.003.)
1b. Research assistant‐reported VAS (100 mm) pain scores (mean score ± SD: topical MN = 14.8 ± 19.5 vs topical TAC = 4.7 ± 8.5 vs infiltrated anaesthetic = 3.0 ± 4.0). (Both topical TAC and infiltrated anaesthetic outperformed topical MN; P = 0.0003.)
1c. Videotape reviewer‐reported VAS (100 mm) pain scores (mean score ± SD: topical MN = 5.0 ± 12.5 vs topical TAC = 5.25 ± 16.42 vs infiltrated anaesthetic = 2.0 ± 5.9) (no reported differences between groups; P > 0.05)
2a. Suture technician‐reported Likert (1‐7) pain scores (mean score ± SD: topical MN = 2.2 ± 1.4 vs topical TAC = 1.7 ± 0.9 vs infiltrated anaesthetic = 1.6 ± 1.0) (no reported differences between groups; P = 0.18)
2b. Parent‐reported Likert (1‐7) pain scores (mean score ± SD: topical MN = 3.7 ± 1.9 vs topical TAC = 2.4 ± 1.8 vs infiltrated anaesthetic = 2.4 ± 1.6) (Both topical TAC and infiltrated anaesthetic outperformed topical MN; P = 0.02.)
3. Requirement for supplemental lidocaine infiltration (topical MN = 37.5% vs topical TAC = 8.3%; P = 0.04)

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Source of funding: Support was provided by a grant from the Children’s Hopsital Research Foundation, Columbus, Ohio (Grant #020‐876).

Obtained additional study data by directly contacting study author

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Enrolled patients were assigned to receive one of three anaesthetic preparations by block randomization".

Comment: unclear, as exact method of selecting the blocks not described in the study

Allocation concealment (selection bias)

Unclear risk

Comment: unclear

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Comparions between topical Mepivanor and TAC were blinded to all observers. Since lidocaine was given as an injection, its identity was not blinded to those present for the procedure. However, after the anaesthetic was administered, suturing procedures were videotaped. These videotapes were later reviewed by an observer who was completely blinded to which local anaesthetic the patient had received".

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

71 participants included in the study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported: observer‐reported VAS pain score by suture technicians, research assistants ascertained at the end of the suturing procedure. Also, Lickert pain scale scores (participant, suture technician)

Prespecified secondary outcomes were also reported: pain during application of anaesthesia and requirement for supplemental lidocaine infiltration.

Quote: “Pain perceptions of suture technicians, research assistants were ascertained at the end of the suturing procedure by means of the visual analogue scale (VAS)… Pain perceptions of the parents and suture technicians were also measured using a seven‐point Likert scale…Observers were instructed to base their pain scores on the pain experienced as the needle pierced the skin in order to measure actual anaesthetic performance”.

Figure 1. Mean VAS pain score by anaesthetic treatment group for suture

technicians compared with research assistants compared with videotape reviewer.

Figure 2. Mean Likert scale to rate the amount of pain they thought the child experienced during suturing by each anaesthetic treatment group for suture technicians compared with parents for all laceration types of repair.

Additional reporting:

“Suture technicians were instructed to give additional lidocaine by infiltration.. if they felt that the child had inadequate wound anaesthesia. Two patients received lidocaine rescue in the TAC group compared to 9 patients in the Mepivanor group”.

“..Sixty six patients returned within 48 hours for a wound check. All wounds were healing without complication at that time, except for one patient…. There was one additional complication reported at the 2‐week follow up for a patient”.

Other bias (sample size)

High risk

Quote: “Seventy‐one patients were enrolled in the study. 23 received lidocaine, 24 received TAC, 24 were given Mepivanor”.

Methods

Single‐centre RCT, emergency department, Children’s Hospital, Columbus, Ohio, United States

Participants

240 patients, 1 to 18 years of age, with lacerations ≤ 5 cm in length, located on the face (51%), scalp (30%), extremity (18%) or other site (1%)

Interventions

1. Prilophen (PP) solution (prilocaine 3.56%, phenylephrine 0.99%), applied for 20 minutes (n = 60)
2. Tetraphen (TP) solution (tetracaine 1.0%, phenylephrine 5.0%), applied for 20 minutes (n = 60)
3. Tetralidophen (TLP) solution (tetracaine 1.0%, lidocaine 1.0%, phenylephrine 2.5%), applied for 20 minutes (n = 60)
4. TAC solution (tetracaine 1.0%, epinephrine 1:4000, cocaine 4.0%), applied for 20 minutes (n = 60)

Outcomes

1. Participants 5 years of age or older reported VAS (100 mm) pain scale scores.
2. Observer‐reported VAS (100 mm) pain scale scores (suture technicians, research assistants and parents)
3. Observer‐reported Likert (1‐7) pain scale scores (suture technicians, research assistants and parents)
4. Suture technicians rated anaesthetic effectiveness (complete, partial or no anaesthesia)

Results (topical PP vs topical TP vs topical TLP vs topical TAC) include the following.
1. Participant self‐reported VAS (100 mm) pain scores (mean score ± SD: topical PP = 29.0 ± 43.4 vs topical TP = 24.2 ± 37.2 vs
topical TLP = 30.6 ± 40.3 vs topical TAC = 17.6 ± 34.1) (no reported differences between groups; P = 0.5)
2a. Suture technician‐rated VAS (100 mm) pain scores (mean score ± SD: topical PP = 7.4 ± 16.0 vs topical TP = 5.1 ± 12.6 vs
topical TLP = 6.0 ± 13.5 vs topical TAC = 3.5 ± 11.8) (Topical TAC performed significantly better then topical PP; reported P = 0.04.)
2b. Research assistant‐rated VAS (100 mm) pain scores (mean score ± SD: topical PP = 1.6 ± 2.6 vs topical TP = 1.9 ± 4.2 vs
topical TLP = 1.3 ± 1.7 vs topical TAC = 0.9 ± 1.7) (no reported differences between groups; P = 0.09)
2c. Parent‐rated VAS (100 mm) pain scores (mean score ± SD: topical PP = 20.0 ± 21.7 vs topical TP = 20.2 ± 21.7 vs
topical TLP = 18.2 ± 18.6 vs topical TAC = 14.0 ± 18.6) (no reported differences between groups; P = 0.09)
3a. Suture technician‐reported Likert (1‐7) pain scores (median score: topical PP = 2.0 vs topical TP = 1.0 vs topical TLP = 2.0 vs topical TAC = 1.0) (Topical TAC performed significantly better than topical PP or topical TLP; P = 0.01.)
3b. Research assistant‐reported Likert (1‐7) pain scores (median score: topical PP = 2.0 vs topical TP = 1.0 vs topical TLP = 2.0 vs topical TAC = 1.0) (Topical TAC performed significantly better than topical PP or topical TLP; P = 0.03.)
3c. Parent‐reported Likert (1‐7) pain scores (median score: topical PP = 2.0 vs topical TP = 2.0 vs topical TLP = 2.0 vs topical TAC = 2.0) (mo reported differences between any of the groups; P = 0.06)
4. Anaesthetic effectiveness (complete anaesthesia: topical PP = 63% vs topical TP = 67% vs topical TLP = 65% vs topical TAC = 80%) (mo reported differences between any of the groups; P =.18)

Intervention dates

June to September 1994

Declaration of interest

No explicit documentation regarding conflicts of interest

Notes

Source of funding: Grant 020‐898 from Children’s Hospital Research Foundation and Samuel J. Roessler Memorial Scholarship Fund

Study author contacted to request additional study data; study author replied but unable to provide missing information

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomly assigned to one of four anaesthetic treatment groups.."

Comment: unclear, as study was reported to be randomized but method of sequence generation was not described

Allocation concealment (selection bias)

Unclear risk

Comment: unclear

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Quote: "using a prospective, randomized, double‐blind design..."

"Anesthetic agents were sealed in envelopes labelled with a study identification number and stored in a locked cabinet in the emergency department".

Comment: probably done, assuming topical solutions visually identical

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

240 participants included in the study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported in the prespecified way.

Other bias (sample size)

Unclear risk

240 children enrolled:

1. Prilophen (PP) solution, n = 60

2. Tetraphen (TP) solution, n = 60

3. Tetralidophen (TLP) solution, n = 60

4. TAC solution, n = 60

Methods

Single‐centre RCT, emergency department or a large children’s hospital, United States

Participants

180 patients, 1 to 18 years old, with lacerations ≤ 5 cm, located on the face (n = 76), scalp (n = 59), extremity (n = 43) or other (n = 2)

Interventions

1. Prilophen (PP) solution (3.56% prilocaine, 0.10% phenylephrine), applied for 20 minutes (n = 60)
2. Bupivaphen (BP) solution (0.67% bupivacaine, 0.10% phenylephrine), applied for 20 minutes (n = 60)
3. TAC solution (tetracaine 1.0%, epinephrine 1:4000, cocaine 4.0%), applied for 20 minutes (n = 60)

Outcomes

1. Participants 5 years of age and older self‐reported pain using a VAS (100 mm) scale.
2. Observer‐reported VAS (100 mm) pain scale scores (suture technicians, research assistants and parents)

Results (topical PP vs topical BP vs topical TAC) included the following.
1. Participant self‐reported VAS (100 mm) pain scores (mean score ± SD: topical PP = 21.0 ± 28.0 vs topical BP = 41.0 ± 35.0 vs topical TAC = 18.0 ± 24.0) (no differences reported between groups; P = 0.07)
2a. Suture technician‐rated VAS (100 mm) pain scores (mean score ± SD: topical PP = 3.8 ± 8.5 vs topical BP = 5.0 ± 9.0 vs topical TAC = 1.5 ± 3.0) (Topical TAC outperformed topical BP; P = 0.006; no differences between TAC and PP; no differences between BP and PP)
2b. Research assistant‐rated VAS (100 mm) pain scores (mean score ± SD: topical PP = 3.0 ± 6.0 vs topical BP = 3.8 ± 4.9 vs topical TAC = 1.4 ± 2.1) (Topical TAC outperformed topical BP; P = 0.002; no differences between TAC and PP; no differences between BP and PP)
2c. Parent‐rated VAS (100 mm) pain scores (mean score ± SD: topical PP = 24.0 ± 24.5 vs topical BP = 29.0 ± 28.0 vs topical TAC = 17.0 ± 20.5) (TAC outperformed BP; P = 0.03; no differences between TAC and PP; no differences between BP and PP)

Intervention dates

Not reported

Declaration of interest

Not reported

Notes

Funding source: supported by Grant 020‐898 from the Children’s Hospital Research Foundation, Columbus, Ohio. Stipend support for medical students was provided by the Samuel L. Roessler Memorial Medical Scholarship Fund.

Study author contacted to request additional study data; study author replied but unable to provide missing information

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "68 patients were assigned to each of the three anaesthetic treatment groups using block randomization".

Comment: unclear, as exact method of selecting the blocks not reported

Allocation concealment (selection bias)

Unclear risk

Comment: unclear

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Quote: "using a prospective, randomized, double‐blind design..."

"Anesthetics were sealed in envelopes labelled with a study identification number and stored in a locked cabinet in the ED".

Comment: probably done, assuming solutions visually identical

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

180 participants included in the study but reporting of attrition or exclusions insufficient to permit judgement

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary and secondary outcomes were reported: VAS pain scores during suturing by participants and observers (suture technicians, research assistants, parents)

Quote: “Pain perceptions of suture technicians, research assistants, parents and patients 5 years of age and older were ascertained using a visual analogue scale (VAS)… Observers based pain scores on the pain experienced as the needle pierced the skin in order to measure actual anaesthetic performance”.

Figure 1. Mean VAS pain score by anaesthetic treatment group for suture

technicians compared with research assistants for all types of laceration of repair.

Figure 2. Mean VAS pain score by anaesthetic treatment group for participants compared with parents for all types of laceration repair.

Figure 3. Mean VAS pain score by anaesthetic treatment group for suture technicians compared with research assistants for only face and scalp laceration repairs.

Figure 4. Mean VAS pain score by anaesthetic treatment group for participants compared with parents for face and scalp lacerations only.

Additional reporting:

1. Complications at follow‐up were listed as “2 wound infections, 1 case of wound drainage that resolved without antibiotics, 3 cases of lost stitches, and 3 cases of wound dehiscence”.

Other bias (sample size)

Unclear risk

Quote: “Participants were 180 children. Three groups each of 60 subjects each: TAC vs Prilophen vs Bupivaphen".

Methods

Single‐centre RCT, urban paediatric emergency department, Boston, Massachusetts, United States

Participants

156 patients, 3 to 18 years old, with lacerations on the face/scalp (n = 102), extremity (n = 47) or trunk (n = 7)

Interventions

1. TAC 1 solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 11.8%), applied for 15 to 30 minutes (n = 49)
2. TAC 2 solution (tetracaine 1.0%, epinephrine 1:2000, cocaine 4.0%), applied for 15 to 30 minutes (n = 49)
3. TAC 3 solution (tetracaine 1.0%, cocaine 4.0%), applied for 15 to 30 minutes (n = 58)

Outcomes

1. Physician rating of anaesthetic effectiveness (complete, partial or no anaesthesia). Anaesthesia was 'complete' if the participant did not move, flinch or grimace during repair. Anaesthesia was 'partial' if the participant complained of pain, moved or grimaced. If supplemental lidocaine infiltration was required, then 'no anaesthesia' was given.
2. Requirement for a second application of topical anaesthetic
3. Requirement for supplemental lidocaine infiltration
4. The study reported acute adverse effects directly due to the anaesthetic.

Results for TAC 1 (standard formulation) vs TAC 3 (tetracaine‐cocaine) include the following.
1. Incidence of complete anaesthesia (topical TAC 1 = 73% vs topical TAC 3 = 28%; P < 0.001)
2. Requirement for a second dose of topical anaesthetic (topical TAC 1 = 30% vs topical TAC 3 = 66%; P < 0.003)
3. Requirement for supplemental lidocaine infiltration (topical TAC 1 = 6% vs topical TAC 3 = 9%; P = not reported)

Results for TAC 2 (higher concentration tetracaine, lower concentration cocaine) vs TAC 3 (tetracaine‐cocaine) include the following.
1. Incidence of complete anaesthesia (topical TAC 2 = 63% vs topical TAC 3 = 28%; P < 0.001)
2. Requirement for a second dose of topical anaesthetic (topical TAC 2 = 46% vs topical TAC 3 = 66%; P < 0.003)
3. Requirement for supplemental lidocaine infiltration (topical TAC 2 = 2% vs topical TAC 3 = 9%; P = not reported)
4. A single paediatric participant developed an erythematous rash 1 day after application of standard topical TAC.

Intervention dates

Not reported

Declaration of interest

No explicit documentation regarding conflicts of interest

Notes

Source of funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The solutions were batched in lots of 10 doses to limit expiration of the study drugs. The order of batching was generated using a standard table of random numbers".

Comment: probably done

Allocation concealment (selection bias)

High risk

Quote: "The order of batching was generated using a standard table of random numbers".

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Quote: "...we conducted a randomized, prospective, double‐blind, clinical trial comparing three different formulations of cocaine‐containing topical anaesthetics".

Unclear: In the Introduction section, reported to be a double‐blind study, but no details provided in Methods or any other sections

Incomplete outcome data (attrition bias)
All outcomes

Low risk

A total of 165 participants were randomized in the study, and no missing outcome data or exclusions

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported in the prespecified way.

Other bias (sample size)

High risk

165 participants:

1. TAC 1 solution, n = 49

2. TAC 2 solution, n = 49

3. TAC 3 solution, n = 58

Methods

Single‐centre RCT, emergency department at Arizona Health Sciences Center, Arizona, United States

Participants

68 adult patients, older than 18 years of age, with lacerations < 5 cm in length, located on the face (n = 22) or non‐facial (n = 46)

Interventions

1. TAC solution (tetracaine 0.5%, epinephrine 1:2000, cocaine 10.0%), applied for 5 to 10 minutes (n = 36)
2. Tetracaine solution (tetracaine 0.5%), applied for 5 to 10 minutes (n = 32)

Outcomes

1. Participant‐rated numerical pain scale score (0‐10)
2. Requirement of supplemental lidocaine infiltration

Results include the following.
1. Participant‐rated numerical pain scale (0‐10) score (mean pain scores: topical tetracaine = 5.6 vs topical TAC = 3.53; P < 0.05; standard deviations not reported)
2. Requirement for rescue lidocaine infiltration (topical tetracaine = 59% vs topical TAC = 36%; P = not reported)

Intervention dates

Not reported

Declaration of interest

No explicit documentation regarding conflicts of interest

Notes

Source of funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Quote: "Prior to delivery to the emergency department, the TAC and tetracaine solutions were assigned odd or even numbers"; "Randomization was achieved by matching the vials to the odd or even numbers at the end of the hospital number".

Comment: probably not done

Allocation concealment (selection bias)

High risk

Quote: "Randomization was achieved by matching the vials to the odd or even numbers at the end of the hospital number".

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "Only the pharmacist preparing the solutions knew which vials contained tetracaine and which contained TAC".

Comment: probably done, assuming visually identical solutions

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

68 patients participated in the study. It is not clear whether the same number were randomized, or whether any were withdrawn.

selective reporting of outcomes
All outcomes

Low risk

The study protocol is available, and all of the study’s prespecified outcomes have been reported in the prespecified way.

Other bias (sample size)

High risk

Total N = 68:

1. TAC solution, n = 36

2. Tetracaine solution, n = 32

Methods

Single‐centre RCT, emergency department of Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States

Participants

32 patients, 5 to 18 years old, with lacerations < 5 cm long, located on the extremity (n = 32)

Interventions

1. EMLA cream (lidocaine 2.5%, prilocaine 2.5%), applied for maximum of 60 minutes (n = 16)
2. TAC solution (formulation not reported by study), applied for maximum of 30 minutes (n = 16).

Outcomes

1. Participant‐rated VAS (100 mm) pain scores
2. Observer‐rated VAS (100 mm) pain scores by suturing physician and parent
3. Requirement for supplemental lidocaine infiltration

Results included the following.
1. Participant‐rated VAS (100 mm) pain scores (mean score ± SD: EMLA = 46.0 ± 26.0 vs topical TAC = 40.0 ± 25.0; P = 0.50)
2. Parent‐rated VAS (100 mm) pain scores (mean score ± SD: EMLA = 42.0 ± 15.0 vs topical TAC = 43.0 ± 25.0; P = 1.0) and physician‐rated VAS (100 mm) pain scores (mean score ± SD: EMLA = 30.0 ± 16.0 vs topical TAC = 26.0 ± 14.0; P = 0.45)
3. Requirement for supplemental lidocaine infiltration (EMLA = 15% vs topical TAC = 55%; P = 0.03)

Intervention dates

April to December 1994

Declaration of interest

Not reported

Notes

Funding source: supported by Grant 5M01 RR00084 from the General Clinical Research Center, Children’s Hospital of Pittsburgh

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "...the patient was randomized into one of the two study groups by a table of random numbers"

Comment: probably done

Allocation concealment (selection bias)

High risk

Quote: "...the patient was randomized into one of the two study groups by a table of random numbers"

Comment: probably not done

Blinding (performance bias and detection bias)
All outcomes

Low risk

Quote: "The suturers, who were blinded to the patients' assignments, were not investigators in the study and were not allowed to see the patient until the anaesthetic had been removed and the wound irrigated"

Comment: probably done

Incomplete outcome data (attrition bias)
All outcomes

Low risk

A total of 32 participants enrolled with no drop‐outs or exclusions

selective reporting of outcomes
All outcomes

Low risk

All prespecified primary outcomes were reported: observer‐ or participant‐reported VAS pain scores during suturing

One prespecified secondary outcome was also reported: need for supplemental infiltrated lidocaine

Quote: “Assessment of pain associated with the entire procedure was conducted independently by the suturing physician, the patient, and the parent or guardian on the 10‐cm visual analogue scale (VAS)”

Table. Pain scores on a 10‐cm VAS contains participant, parent and physician VAS scores

Figure. Efficacy of EMLA and TAC demonstrates efficacy adequacy of anaesthesia after the procedure began

Additional reporting:

Complications were listed with “one case of wound dehiscence before suture removal in each group and no wound infections were seen in either group"

Other bias (sample size)

High risk

Quote: “a convenience sample of 32 patients were enrolled in our study group: EMLA cream 16 subjects and TAC solution 16 patients”