Table 1. Summary of eligible studies.

Reference	Recruitment years, Country, Study Type	BUFFERED Local anesthetic with buffer and concentration	NON-BUFFERE D group Local anesthetic	Co-Interventions	Inclusion / Exclusion criteria	Gender Average Age [Range]	Summary of Risk of Bias
Chopra et al. [9] 2016	N/A	1.8 ml 2% lidocaine with 1:200,000 epi and 8.4% Sodium bicarbonate (10:1 ratio)	1.8 ml 2% lidocaine with 1:200,000 epi	N/A	Frankl's behavior rating grade three or four	18F/12M	Unclear
	India,				Not require any sedation	[6–8 years](n = 17)
	Split mouth				No analgesics for 24 hrs before the appointment	[9–12 years](n = 13)
	N = 30
Comerci et al. [10] 2015	N/A	1.7 ml 2% lidocaine with 1:100,000 epi and 8.4% sodium bicarbonate (9:1 ratio)	1.7 ml 2% lidocaine with 1:100,000 epi	Long buccal nerve block	Aged 18 years or older	5F/15M	Unclear
	USA,				Treatment requiring bilateral IA and LB nerve blocks	46 years
	Split mouth				Good general health ASA I or ASA II	[27–81 years]
	N = 20				Baseline pain level of all patients was 0
Donaldson [11] 2006 (not included in meta-analysis)	N/A	1.8ml of 2% lidocaine HCl with 1:100,000 epi and 8.4% sodium bicarbonate(17:1 ratio)	1.8ml of 2% lidocaine HCl with 1:100,000 epi	N/A	ASA I	20F/24M	High
	USA,				> 80 pounds	Age: N/A
	splint mouth				Presence of bilateral non-carious, vital permanent canines
	(n = 44)				No large restorations, periodontal disease or previous trauma in the lower arch/No soft tissue pathology at the injection site/No medication that could interact with the lidocaine or could alter pain perception
Kashyap et al. [12] 2011	N/A	2.5 ml 2% lidocaine with 1:80,000 epi and 8.4% sodium bicarbonate (10:1 ratio)	2.5 ml 2% lidocaine with 1:80,000 epi	Lingual nerve block	100 healthy patients who needed procedures under local anesthesia in the mandibular region	Not stated	Unclear
	India			Long buccal block
	Parallel RCT
	(n = 100)
	(n = 50 in each group)
Malamed et al. [5] 2013	N/A	1.8 ml 2% lidocaine with 1:100,000 epi and 8.4% sodium bicarbonate (9:1 ratio)	1.8 ml 2% lidocaine with 1:100,000 epi	N/A	Healthy volunteers	Gender: N/A	Unclear
	USA					41.6 years
	Split mouth					[23–76 years]
	n = 18
Phero et al. [13] 2017	N/A	4 ml 2% lidocaine with 1:100,000 epi and 8.4% sodium bicarbonate (9:1 ratio)	4 ml 2% lidocaine with 1:100,000 epi	No co-intervention	Two sessions at the UNC Oral and Maxillofacial Surgery Clinic, ASA I	11F/12M	Unclear
	USA,				Exclusion: Allergy to lidocaine class of anesthetic drugs, local anesthetic drug use in past week, current symptoms teeth or oral mucosa	Median = 21 years
	split mouth					[18–30 years]
	(n = 23)
Saatchi et al. [14] 2015	N/A	3.6 ml of 2% lidocaine with 1:80,000 epi and 8.4% sodium bicarbonate (9:1 ratio)	3.6 ml 2% lidocaine with 1:80,000 epi in which 0.36ml lidocaine was replaced by distilled water	N/A	Vital mandibular posterior tooth with active pain and a long response to cold testing with Endo-Frost cold spray	46F/34M	Unclear
	Iran,					35 years in buffered group
	Parallel RCT					36 years in nonbuffered group
	(n = 80)					[20–55 years]
	(40 in each group)
Schellenberg et al. [15] 2015	N/A	2.8ml 4% lidocaine with 1:100,000 epi and 8.4% sodium bicarbonate (9:1 ratio) (n = 50)	2.8ml 4% lidocaine with 1:100,000 epinephrine (n = 50)	0.9 ml non-buffered 2% lidocaine with 1:100,000 epi buccal soft tissue anesthesia	Emergency patients	61F/39M	Unclear
	USA,				Good health	35 years in buffered group
	RCT				Have a vital mandibular posterior tooth with actively experiencing moderate to severe pain Had a prolonged response to cold testing with Endo-Ice	36 years in non-buffered group
	(n = 100)					[18–64 years]
	(50 in each group)
Tavaka [16] 2013	N/A	1.7 ml 2% lidocaine, with 1:100,000 epi and 8.4% sodium bicarbonate (ratio not stated, the onset system)	1.7 ml 2% lidocaine, with 1:100,000 epi	Long buccal nerve block with separated VAS units for this injection	Informed consent provided 9-12 years of age	10F/10M	Unclear
	USA,				Comprehend the visual analog scale, numeric rating scale, and verbal rating scale	[9–12 years]
	Split mouth				Present moderate mandibular dental disease bilaterally Have 4 to 7 natural teeth present in each mandibular quadrant with moderate dental disease on at least one tooth
	(n = 20)				Be willing to attend the clinic for 3 or more appointments
					Exclusion: Received an anesthetic, analgesic or sedative within 24 hours prior to the therapy appointments
Warren et al. [17] 2017	N/A	4.4 ml of 1% lidocaine with 1:100,000 epi and 8.4% sodium bicarbonate (9:1 ratio)	4 ml 2% lidocaine with 1:100,000 epi	Lingual and Long buccal nerve block	Treated at the oral and maxillofacial surgery clinic 2 weeks apart, ASA I	12F/11M	Unclear
	USA,				Exclusion: Allergy to lidocaine class of anesthetic drugs, local anesthetic drug use in past week, current symptoms teeth or oral mucosa	Median = 25 years
	Splint mouth					[18–30 years]
	(n = 23)
Whitcomb et al. [18] 2010	N/A	3.6 ml 2% lidocaine with 1 : 100,000 epi and 8.4% sodium bicarbonate (5:1 ratio)	3.6 ml 2% lidocaine with 1:100,000 epi	N/A	Good health	12 F/ 28 M	Unclear
	USA,				Not taking any medications that would alter their perception of pain	26 years
	Split mouth					[18–38 years]
	(n = 40)