Nebulized Lidocaine and Intranasal Midazolam for NGT Insertion in Children

Phase 3

• Conditions: Procedural Anxiety; Procedural Pain
• Interventions: Other: Placebo; Drug: Nebulized Lidocaine; Drug: Intranasal Midazolam

• Registration Number: NCT04571879
• Lead Sponsor: Hamad Medical Corporation

Brief Summary

Nasogastric tube (NGT) is a commonly performed procedure in the Emergency Department. Although it is not a major procedure, it is usually associated with a bad experience and cause discomfort and pain in kids. This randomized controlled double-blinded double-dummy trial aims to investigate the efficacy of local topical anesthetic and/or anxiolysis for pain/anxiety related to NGT insertion. Eligible patients are children with gastroenteritis aged 6 months to 5 years requiring NGT rehydration. The intervention are 3 arms of nebulized lidocaine with midazolam compared to nebulized midazolam alone or placebo. The primary outcome is procedure-related pain assessment using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale during final NGT insertion attempt.

Detailed Description

Nasogastric tube (NGT) insertion is commonly performed in the emergency department (ED) which can cause some pain/anxiety \[Shih S and Rosen P, 2018\]. The pain/discomfort related to NGT insertion comes from anxiety, gagging and sensitivity of nasopharynx and oropharynx \[Tapiawala SN et al, 2008\]. Success rate depends on cooperation, which limits order for nasogastric tube insertion in most patients especially in non-pediatric hospitals.

The pain and anxiety associated with such procedures in kids is a source of noxious stimuli to the nervous system. Not only does pain have a negative impact on neurological development, but children whose pain has not been adequately treated in infancy or early childhood reported lower pain thresholds as adolescents and adults \[Ruda M.A.et al, 2000\]. If not addressed, this pain can lead to distress for children, their parents and those performing the procedures, preprocedural anxiety in the future and can result in negative long-term emotional outcomes \[Blount R.L et al,2006; Brewer S.G. et al, 2006\].

Nebulized 2% lidocaine at doses of 4 and 8 mg/kg has shown to be safe in infants and children, with all blood levels obtained were well below the toxic range \[Gjonaj S et al, 1997\]. Nebulized lidocaine in doses up to 8 mg/kg appears to be safe and gave statistically significant reduction in pain score when used before flexible bronchoscopy \[Gjonaj S et al, 1997\]. Nebulized/intranasal lidocaine did not seem to be of benefit when used alone in the two previous trials for NGT insertion in children \[Babl FE et al,2009; Craig SS et al, 2019\]. On the other hand it greatly reduced discomfort associated with NG tube in adult population \[Cullen L et al, 2004\]. This might be explained by the anxiety and lack of cooperation, especially in young kids, which might limit the validity of pain score during the whole procedure.

Midazolam has a controlled sedation with a quicker recovery time. The safety and tolerability profile of midazolam in pediatric patients is comparable/superior to that observed in adults \[Pacifici GM, 2014\]. Midazolam is a GABA receptor agonist providing anxiolysis for procedures in pediatric population. Midazolam has been shown to be safe and effective for use in children \[Wilton NC et al,1988; Theroux MC et al, 1993\]. Intranasal midazolam has shown improvements with anxiety and crying, as well as need for restraint \[Theroux MC et al, 1993\]. Midazolam anxiolysis has been tried in pediatrics and ordered as nebulization, found to have a plasma concentration bioavailability which is comparable to the intranasal midazolam by the ratio (nebulized:nasal) of 1:2.9. \[McCormick AS et al, 2008\]. Clinically effective serum concentrations of intranasal midazolam can be reached within less than 10 min after nasal application \[Knoester PD et al, 2002\].

Lidocaine / Midazolam has been commonly used in different procedures in pediatric emergency department; such as urethral catheterization, intravenous cannulation, lumbar puncture with a great safety margin.

Study Timeline

• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-30
• Study First Posted: 2020-10-01
• Study Start: 2021-08-25
• Status Verified: 2022-06
• Last Update Submitted: 2023-03-01
• Last Update Posted: 2023-03-02
• Primary Completion: 2023-12-30
• Study Completion: 2024-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1 Previously healthy children 6 months to 5 years old presenting with AGE and some dehydration who were planned to have a nasogastric tube inserted as part of their ED treatment.

Exclusion Criteria

1. Indication for an urgent insertion of a nasogastric tube.
2. Congenital anomalies of nose, nasopharynx, oropharynx, or oral cavity.
3. .Patients allergic to midazolam or lidocaine.
4. .Congenital Heart disease or arrhythmia.
5. .Known hepatic or renal impairment
6. .Developmentally abnormal children
7. .Patients with seizure disorder
8. .Pre-existing abnormal neurological conditions
9. .Child is taking medications known to interact with lidocaine and/or midazolam (antiarrhythmic drugs, suxamethonium, phenytoin, antidepressants, propranolol, citicoline).
10. .Known case of severe gastroesophageal reflux disease or aspiration pneumonia.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	Intranasal Midazolam	Nebulized 2% lidocaine hydrochloride 4 mg/kg to be delivered via nebulization (up to a maximum of 15 ml) and given over ½ hr. Intranasal midazolam 0.5 mg/kg delivered via intranasal atomization (up to a maximum of 10 mg).
Arm 2	Intranasal Midazolam	Intranasal midazolam 0.5 mg/kg to be delivered via intranasal atomization (up to a maximum of 10 mg). Nebulized placebo (Normal saline) in a volume comparable to 2% lidocaine at 4 mg/kg (up to a maximum of 15 ml) and given over ½ hr.
Arm 3	Placebo	Intranasal placebo (normal saline) in a volume comparable to midazolam 0.5 ml/kg to be delivered via intranasal atomization Nebulized placebo (Normal saline) in a volume comparable to 2% lidocaine at 4 mg/kg (up to a maximum of 15 ml) and given over ½ hr.
Arm 1	Nebulized Lidocaine	Nebulized 2% lidocaine hydrochloride 4 mg/kg to be delivered via nebulization (up to a maximum of 15 ml) and given over ½ hr. Intranasal midazolam 0.5 mg/kg delivered via intranasal atomization (up to a maximum of 10 mg).

Primary Outcome Measures

Name	Time	Method
Pain severity rating scale (FLACC) during insertion of NGT.	1 year	score from 0 to 10. Higher scores mean worse outcome

Secondary Outcome Measures

Name	Time	Method
Observer/caregiver pain severity rating:	1 year	Score from 1 to 100. Higher scores mean worse outcome
FLAC score at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and 180 minutes post insertion.	up to 180 minutes	Scores from 0 to 10. Higher scores mean worse outcome
The ease of procedure: difficulty of insertion on an ordinal scale from 1 to 5, where 5 is the most difficult insertion.	1 year	Score from 1 to 5. Higher scores mean worse outcome
Procedural complications/adverse events.	1 year	Records complications and adverse effects
Duration of NGT feed.	up to 180 minutes	The observer records data on chart
The number of attempts required to successfully insert the NGT	1 year	The number of attempts of successful NGT insertion
Length of stay in ED	up to 180 minutes	Length of stay in minutes
Tolerated volume of NGT feed.	1 year	Amount of fluid (ml)

Trial Locations

Locations (2)

Sidra Medicine; 🇶🇦 Doha, Qatar

Pediatric Emergency Center, Hamad Medical Corporation; 🇶🇦 Doha, Qatar