Effects of intravenous lignocaine on haemodynamic responses to laryngoscopy and tracheal intubation in adults under general anaesthesia: A systematic review and meta-analysis

Abstract

Background and Aims:

Haemodynamic fluctuations during laryngoscopy and tracheal intubation remain a key concern in anaesthetic practice, with cardiovascular stress responses posing risks of serious complications. This meta-analysis aims to assess the benefits and risks of pre-intubation intravenous (IV) lignocaine, focusing on enhancing haemodynamic stability and developing evidence-based dosing guidelines.

Methods:

Searches were performed in PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov, and key references up to 16 February 2025 to identify randomised controlled trials (RCTs) comparing adult patients who received or did not receive IV lignocaine prior to tracheal intubation. Data from eligible studies were pooled to calculate the combined risk ratio (RR) or mean difference (MD).

Results:

Eighteen studies (1056 participants) were included. A single IV injection of lignocaine at 40 mg fixed-dose and 0.5–2 mg/kg was studied for preventing haemodynamic fluctuations induced by laryngoscopy and tracheal intubation. Relative to non-lignocaine, IV lignocaine suppressed the increases in mean arterial pressure (MAP) [MD: −3.85; 95% confidence interval (CI): −6.61, −1.09; P = 0.006; I² = 84%] and heart rate (HR) (MD: −4.72; 95% CI: −7.55, −1.90; P = 0.001; I² = 86%) caused by laryngoscopy and tracheal intubation. The lignocaine group had fewer complications compared with the non-lignocaine group.

Conclusions:

IV lignocaine 1–2 mg/kg can effectively suppress the increase in MAP caused by laryngoscopy and tracheal intubation. However, the effectiveness of lignocaine regarding HR seems to require optimisation based on both dosage and ethnicity.

INTRODUCTION

Laryngoscopy is a fundamental technique for tracheal intubation and is crucial for maintaining the airway during surgery. However, the process of laryngoscopy and tracheal intubation can trigger significant haemodynamic fluctuations, which may lead to severe cardiovascular complications, especially in high-risk patients.[1] Consequently, it is essential to optimise perioperative strategies to mitigate these effects.

To maintain haemodynamic stability during tracheal intubation, pharmacological interventions such as β-blockers,[2,3] opioids,[4] lignocaine,[5] and clonidine[6] have been studied. Intravenous (IV) lignocaine reduces propofol/rocuronium-induced pain[7,8] and suppresses opioid- or tracheal intubation-related cough reflexes.[9] However, its modulation of haemodynamic fluctuations during laryngoscopy and tracheal intubation remains contentious. Zou et al.[10] reported that both 1.0 mg/kg and 1.5 mg/kg attenuated mean arterial pressure (MAP) elevation (with superior efficacy at 1.0 mg/kg); however, neither dose suppressed post-intubation heart rate (HR) increase. In contrast, Manne et al.[11] demonstrated that 1.5 mg/kg significantly reduced MAP and stabilised HR. These conflicting outcomes underscore the need for systematic evaluation of dose-response relationships.

A 2013 systematic review first demonstrated the suppressive effect of IV lignocaine in terms of haemodynamic responses to laryngoscopy and tracheal intubation.[12] Recent controversies, however, have necessitated a methodologically rigorous reappraisal of this evidence. This study aims to systematically analyse existing randomised controlled trials (RCTs) to compare the effects of IV lignocaine versus other interventions on attenuating haemodynamic fluctuations induced by laryngoscopy and tracheal intubation in adult patients under general anaesthesia. It also seeks to evaluate the safety and dose–response relationship of IV lignocaine to establish evidence-based dose recommendations for perioperative cardiovascular instability management.

METHODS

The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID: CRD42024582240). The study is reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.[13]

Search strategy and study selection

Before starting their literature search, a strategy was set [Supplementary Table 1]. Following this strategy, two independent authors searched PubMed, Embase, the Cochrane Library, and Web of Science databases. A strategy utilising both subject headings and free terms was implemented. The following English search terms were employed: “Anesthesias, General,” “General Anesthesias,” “Anesthesia, General,” “General Anesthesia,” “Lignocaine,” “Lignocaine,” “Lignocaine Monoacetate,” “Lignocaine Hydrocarbonate,” “Lignocaine Hydrochloride,” “Lignocaine Monohydrochloride,” “Lignocaine Carbonate,” “2-2EtN-2MePhAcN,” “2-(Diethylamino)-N-(2,6-Dimethylphenyl) Acetamide,” “Xyloneural,” “Dalcaine,” “Xylocaine,” “Lignocaine Sulfate (1:1),” “Lignocaine Carbonate (2:1),” “Lignocaine Monohydrochloride, Monohydrate,” “Xylocitin,” “Xylesthesin,” “Octocaine,” “randomised controlled trial,” “randomised,” “placebo,” and “RCT.” An advanced search was conducted, with retrieval time spanning from the inception of various databases to 16 February 2025. In addition to the primary database searches, we conducted a hand search of the ClinicalTrials.gov registry. We carried out a manual scrutiny of the reference lists pertaining to key articles and reviews on PubMed. The results indicated that all relevant studies had already been identified through the database searches, and no results from relevant clinical trials were found. The retrieved documents underwent a comprehensive screening process where their titles and abstracts were carefully evaluated. Two authors independently conducted the screening procedure, and EndNote 21 software (version 21; Clarivate Analytics, Philadelphia, PA, USA) was employed to eliminate duplicate manuscripts. The remaining manuscripts were then manually checked to ensure that no duplicates remained. Subsequently, the authors referenced earlier conducted a comprehensive review of all the papers. When disagreements arose during the article selection process, a third author was consulted to address the discrepancy. This study included only English-language literature to ensure that the research team could accurately understand and analyse the relevant content.

Supplementary Table 1.

PubMed search strategy

Search number	Query
#10	Search: (((“Anesthesia, General”[Mesh]) OR (((Anesthesias, General[Title/Abstract]) OR (General Anesthesia[Title/ Abstract])) OR (General Anesthesias[Title/Abstract]))) AND ((“Lignocaine “[Mesh]) OR ((((((((((((((Lignocaine[Title/Abstract]) OR (2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide[Title/Abstract])) OR (Lignocaine Hydrocarbonate[Title/Abstract])) OR (Xyloneural[Title/Abstract])) OR (Lignocaine Hydrochloride[Title/Abstract])) OR (Lignocaine Monohydrochloride[Title/Abstract])) OR (Xylocaine[Title/Abstract])) OR (Lignocaine Sulfate (1:1[Title/Abstract]))) OR (Lignocaine Monoacetate[Title/Abstract])) OR (Lignocaine Carbonate (2:1[Title/Abstract]))) OR (Lignocaine Carbonate[Title/Abstract])) OR (Lignocaine Monohydrochloride, Monohydrate[Title/Abstract])) OR (Xylocitin[Title/Abstract])) OR (Octocaine[Title/Abstract])))) AND ((“Randomized Controlled Trial” [Publication Type]) OR (((randomized[Title/Abstract]) OR (placebo[Title/Abstract])) OR (RCT[Title/Abstract])))
#9	Search: (“Randomized Controlled Trial” [Publication Type]) OR (((randomized[Title/Abstract]) OR (placebo[Title/Abstract])) OR (RCT[Title/Abstract]))
#8	Search: ((randomized[Title/Abstract]) OR (placebo[Title/Abstract])) OR (RCT[Title/Abstract])
#7	Search: “Randomized Controlled Trial” [Publication Type] Sort by: Most Recent
#6	Search: (“Lignocaine “[Mesh]) OR ((((((((((((((Lignocaine[Title/Abstract]) OR (2-(Diethylamino)-N-(2,6-Dimethylphenyl) Acetamide[Title/Abstract])) OR (Lignocaine Hydrocarbonate[Title/Abstract])) OR (Xyloneural[Title/Abstract])) OR (Lignocaine Hydrochloride[Title/Abstract])) OR (Lignocaine Monohydrochloride[Title/Abstract])) OR (Xylocaine[Title/Abstract])) OR (Lignocaine Sulfate (1:1[Title/Abstract]))) OR (Lignocaine Monoacetate[Title/Abstract])) OR (Lignocaine Carbonate (2:1[Title/Abstract]))) OR (Lignocaine Carbonate[Title/Abstract])) OR (Lignocaine Monohydrochloride, Monohydrate[Title/Abstract])) OR (Xylocitin[Title/ Abstract])) OR (Octocaine[Title/Abstract]))
#5	Search: (((((((((((((Lignocaine[Title/Abstract]) OR (2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide[Title/Abstract])) OR (Lignocaine Hydrocarbonate[Title/Abstract])) OR (Xyloneural[Title/Abstract])) OR (Lignocaine Hydrochloride[Title/Abstract])) OR (Lignocaine Monohydrochloride[Title/Abstract])) OR (Xylocaine[Title/Abstract])) OR (Lignocaine Sulfate (1:1[Title/Abstract]))) OR (Lignocaine Monoacetate[Title/Abstract])) OR (Lignocaine Carbonate (2:1[Title/Abstract]))) OR (Lignocaine Carbonate[Title/ Abstract])) OR (Lignocaine Monohydrochloride, Monohydrate[Title/Abstract])) OR (Xylocitin[Title/Abstract])) OR (Octocaine[Title/ Abstract])
#4	Search: “Lignocaine “[Mesh] Sort by: Most Recent
#3	Search: (“Anesthesia, General”[Mesh]) OR (((Anesthesias, General[Title/Abstract]) OR (General Anesthesia[Title/Abstract])) OR (General Anesthesias[Title/Abstract]))
#2	Search: ((Anesthesias, General[Title/Abstract]) OR (General Anesthesia[Title/Abstract])) OR (General Anesthesias[Title/Abstract])
#1	Search: “Anesthesia, General”[Mesh] Sort by: Most Recent

Eligibility criteria

For the meta-analysis, studies meeting the PICOS criteria were included: Population: Adult patients (age ≥18 years) undergoing general anaesthesia requiring tracheal intubation with laryngoscopy and classified as American Society of Anesthesiologists (ASA) I–II and Mallampati airway grade I–II; Intervention: IV lignocaine administered before laryngoscopy and tracheal intubation; Comparison: Placebo, no intervention, or other medications; Outcome: The primary outcomes were the haemodynamic changes following tracheal intubation. Haemodynamic parameters were recorded at baseline and post-intubation; peak values were selected for studies reporting multiple data points post-intubation. Changes in haemodynamic parameters from baseline to post-intubation were calculated based on these data. Secondary outcomes were possible adverse events of IV lignocaine; and Study design: RCTs

The exclusion criteria included (1) cardiothoracic surgery, (2) lignocaine mixed with other drugs, (3) pretreatment involving venous occlusion, (4) studies where the control group received additional interventions beyond standard care unless these measures were applied equally in both groups, (5) incomplete or missing data, (6) conference proceedings and abstracts were only considered if their data were published in the form of full articles, and (7) non-English literature.

Data extraction

Two authors gathered pertinent information from each selected study using a pre-designed review form. Any disagreements were addressed via discussion among all authors. The following information was collected: authors, publication year, trial design, patients’ demographics (age, gender, country, and ASA physical status), the dosage and timing of lignocaine, and any outcome that met the inclusion criteria. Engauge Digitiser Version 12.1 was used to estimate values in the figures.

Risk of bias assessment

The Cochrane Risk of Bias tool (RoB 2)[14] was used to assess the methodological quality of the included studies. Two researchers independently evaluated five domains: randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. Any discrepancies were resolved through discussion with a third author. The bias risk was categorised into three categories: low risk, some concern, and high risk. Additionally, inter-rater reliability analysis using Cohen’s kappa coefficient (κ = 0.76) demonstrated substantial reviewer agreement [Supplementary Figure 1 ^{(1.4MB, tif)} ].

Statistical analysis

Data synthesis was performed using Review Manager 5.4 (The Cochrane Collaboration, Copenhagen, Denmark) and Stata 17.0 (StataCorp LLC, College Station, TX, USA). Continuous outcomes were analysed using the inverse variance method, presented as mean differences (MD) with 95% confidence intervals (CI). Dichotomous outcomes were pooled using the Mantel-Haenszel method, expressed as risk ratios (RR) with 95% CI. The I-squared (I²) statistic was employed to evaluate heterogeneity. A fixed-effects model was initially applied; a random-effects model was used where substantial heterogeneity existed (I² >50%).[15] Subgroup analyses, categorised by lignocaine dosage regimens and ethnic groups, assessed the post-intubation alterations in MAP and HR compared to baseline measurements. Sensitivity analyses using leave-one-out methodology were performed to evaluate robustness through iterative exclusion of individual studies. Publication bias was assessed with funnel plots when >10 studies were included. Methodological quality was rigorously appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

RESULTS

Study search and characteristics

We found 4091 records by searching the databases, and no records via ClinicalTrials.gov or by hand-searching the reference lists of included studies and relevant reviews were found. After deduplication and sequential screening, 18 studies involving 1056 participants were included [Figure 1]. The designs comprised 10 double-blind,[16,17,18,19,20,21,22,23,24,25] single-blind trials,[26] with the remaining seven labelled as RCTs without explicit blinding details.[10,11,27,28,29,30,31] Geographical distribution comprised studies from India (5 studies[11,23,29,30,31]), the United States (3 studies[17,19,28]), China (2 studies[10,26]), Korea (2 studies[20,21]), Africa (2 studies[24,25]), Iran (1 study[22]), and Turkey (1 study[18]). Participants’ mean age ranged from 21.0 to 65.3 years, with all studies except Liu et al.[26] explicitly involving elective surgical procedures. Two studies[10,16] contained two intervention arms each, while Stevens et al.[19] included three. Lignocaine dosing regimens consisted of fixed 40 mg or weight-adjusted 0.5–2 mg/kg administrations. Detailed patient characteristics are provided in Table 1. To illustrate the consistency in dosing across groups, we have included a detailed comparison table of specific anaesthesia protocols in Supplementary Table 2.

Figure 1.

Flow diagram of retrieved, excluded, and eventually analysed studies

Table 1.

Characteristics of RCTs included in the meta-analysis

Study ID	Sample size (lignocaine/non-lignocaine)	Country	ASA Class	Age (L/N)	Gender (M/F)	Time (min)	Dosage (mg/kg)	Adverse events
Zou et al.[10] 2021	90 (60/30)	China	I–II	46.0 (11.8)/45.0 (14.0)	44/46	−2	1, 1.5	20/12
Manne et al.[11] 2017	40 (20/20)	India	I–II	37.9 (11.4)/37.9 (14.9)	9/31	−5	1.5	NA
Yörükoglu et al.[16] 2003	100 (50/50)	Turkey	I–II	36.5 (2.7)/40.0 (3.5)	45/55	−1.5, −2	1.5	0
Singh et al.[17] 1995	20 (10/10)	USA	I–II	48.0 (15.0)/53.0 (11.0)	20/0	−2.5	1.5	0
Kocamanoglu et al.[18] 2015	56 (29/27)	Turkey	I–II	49.1 (9.0)/50.2 (8.8)	NA	−5	1.5	0
Stevens et al.[19] 1997	120 (60/60)	USA	I–II	34.0 (9.0)/37.0 (10.0)	6/34	−1.5	1	NA
Kim et al.[20] 2007	32 (16/16)	Korea	I–II	21.0 (2.0)/22.0 (2.0)	32/0	−1	1.5	NA
Joo et al.[21] 2014	56 (28/28)	Korea	I–II	37.6 (13.3)/38.7 (12.5)	28/28	−2	40mg	NA
Derakhshan et al.[22] 2019	52 (26/26)	Iran	II	64.9 (10.1)/65.3 (10.2)	33/19	−1.5	1.5	NA
Thippeswamy et al.[23] 2018	60 (30/30)	India	I–II	43.2 (11.7)/42.6 (9.3)	34/26	−3	1.5	NA
Singh et al.[24] 2013	80 (40/40)	African	I–II	42.0 (13.8)/41.8 (12.7)	29/51	−2	1.5	0/5
Ibiribigbe et al.[25] 2023	60 (30/30)	Nigeria	II	50.1 (13.8)/50.9 (4.8)	46/14	−5	1.5	NA
Liu et al.[26] 2022	40 (20/20)	China	I–II	53.0 (9.0)/52.6 (6.7)	16/24	NA	1	2/8
Youn et al.[27] 2017	60 (30/30)	Korea	I–II	42.7 (2.5)/45.2 (2.2)	37/23	NA	0.5	NA
Swanton et al.[28] 2001	20 (9/11)	USA	I–II	33.0 (10.6)/39.7 (11.0)	4/16	−1	1.5	NA
Gurulingappa et al.[29] 2012	50 (25/25)	India	I	20-60	NA	NA	1.5	NA
Kashyap et al.[30] 2021	60 (30/30)	India	I–II	31.7 (8.8)/33.0 (7.3)	11/49	NA	2	NA
Cheeran et al.[31] 2023	60 (30/30)	India	I–II	50.6 (7.2)/50.3 (6.1)	47/13	−15	1.5	NA

Data are presented as mean (standard deviation) or range [minimum - maximum]. *L/N=Values are presented as lignocaine group/non-lignocaine group. ASA=American Society of Anesthesiologists, NA=Data not available, the exact time of tracheal intubation was defined as 0, before was defined as “-”

Supplementary Table 2.

Detailed information on preoperative medications and anaesthetic induction drugs

Study ID	Sample size (lignocaine/ non-lignocaine)	Country	Preoperative and anaesthetic induction medication explanation
Zou et al.[10] 2021	90(60/30)	China	Lignocaine Group 1: Induction with sufentanil 0.4 pg/kg, midazolam 0.04 mg/kg, cisatracurium 0.2 mg/kg, propofol 0.5 mg/kg, then 10-30 mg until unconsciousness. Immediately give 1 mg/ kg lignocaine in 5 s, then perform video-laryngoscope-assisted ETI after 2 min, completing intubation within 30 s. Lignocaine Group 2: Induction with sufentanil 0.4 μg/kg, midazolam 0.04 mg/kg, cisatracurium 0.2 mg/kg, propofol 0.5 mg/kg, then 10-30 mg until unconsciousness. Immediately give 1.5 mg/kg lignocaine in 5 s, then perform video-laryngoscope-assisted ETI after 2 min, completing intubation within 30 s. Non-lignocaine: Induction with sufentanil 0.4 μg/kg, midazolam 0.04 mg/kg, cisatracurium 0.2 mg/kg, propofol 0.5 mg/kg, then 10-30 mg until unconsciousness. An equal volume of NS was administered over 5 s, then a video-laryngoscope-assisted ETI was performed after 2 min, completing intubation within 30 s.
Manne et al.[11] 2017	40(20/20)	India	Lignocaine: Preop: midazolam 0.1 mg/kg IM, rocuronium 0.2 mg IV, tramadol 2 mg/kg IV. Preoxygenated with 100% oxygen for 3 min. At 90 s pre-induction, lignocaine 1.5 mg/kg IV, thiopental 5 mg/kg, succinylcholine 1.5 mg/kg. Direct laryngoscopy and intubation at 90 s. Non-lignocaine: Preop: midazolam 0.1 mg/kg IM, rocuronium 0.2 mg IV, tramadol 2 mg/kg IV. Preoxygenated with 100% oxygen for 3 min. One minute pre-induction, 5 mL saline IV, then thiopental 5 mg/kg, lignocaine 1.5 mg/kg IV, succinylcholine 1.5 mg/kg. Direct laryngoscopy and intubation at 90 s.
Yörükoglu et al.[16] 2003	100 (50/50)	Turkey	Lignocaine Group 1: Preop: 0.5 mg atropine IM, 50 mg ranitidine. After 3-min pre-oxygenation, give alfentanil 10 μg/kg, lignocaine 1.5 mg/kg (over 5 s), then 2 mg/kg propofol in over 20 s. 20 s later, give rocuronium IV in 5 s, then intubate at 60 s. Non-lignocaine Group 1: Preop: 0.5 mg atropine IM, 50mg ranitidine. After 3-min pre­oxygenation, give alfentanil 10 μg/kg, then 2 mg/kg propofol in over 20 s. 20 s later, give rocuronium IV in 5 s, then intubate at 60 s. Lignocaine Group 2: Preop: 0.5 mg atropine IM, 50mg ranitidine. After 3 min pre-oxygenation, give alfentanil 10 μg/kg, lignocaine 1.5 mg/kg (over 5 s), then 2 mg/kg propofol in over 20 s. 20 s later, give rocuronium IV in 5 s, then intubate at 90 s. Non-lignocaine Group 2: Pre-op: 0.5 mg atropine IM, 50 mg ranitidine. After 3-min pre­oxygenation, give alfentanil 10 μg/kg, then 2 mg/kg propofol in over 20 s. 20 s later, give rocuronium IV in 5 s, then intubate at 90 s.
Singh et al.[17] 1995	20 (10/10)	USA	Lignocaine: Anaesthesia was induced with thiopental 5 mg/kg + vecuronium 0.15 mg/kg (at time 0 min). Lignocaine 1.5 mg/kg IV at time 1 min. Non-lignocaine: Anaesthesia was induced with thiopental 5 mg/kg + vecuronium 0.15 mg/kg (at time 0 min). Saline 5 mL IV at time 0 min.
Kocamanoglu et al.[18] 2015	56(29/27)	Turkey	Lignocaine: 1 min pre-induction, a blinded doctor gave patients a 5 mL solution (lignocaine 1.5 mg/kg). Induction used fentanyl 1μg/kg, propofol 2.5 mg/kg, then succinylcholine 1.5 mg/kg. Intubation was done with a 5.0 or 6.0 mm Portex® micro-laryngeal tube. Non-lignocaine: 1 min pre-induction, a blinded doctor gave patients a 5 mL solution (5 mL saline). Induction used fentanyl 1 μg/kg, propofol 2.5 mg/kg, then succinylcholine 1.5 mg/kg. Intubation was done with a 5.0 or 6.0 mm Portex® micro-laryngeal tube.
Stevens et al.[19] 1997	120(60/60)	USA	Lignocaine Group 1: Alf 40 μg/kg + 5 mL NS + etomidate 0.3 mg/kg + 5 mL NS Non-lignocaine Group 1: Alf 40 μg/kg + 5 mL NS + etomidate 0.3 mg/kg + 5 mL NS Lignocaine Group 2: Alf 40 μg/kg + Lignocaine 1 mg/kg + propofol 2 mg/kg + 5 mL NS Non-lignocaine Group 2: Alf 40 μg/kg + 5 mL NS + propofol 2 mg/kg + 5 mL NS Lignocaine Group 3: Alf 40 μg/kg + Lignocaine 1 mg/kg + thiopental 4mg/kg + 5 mL NS Non-lignocaine Group 3: Alf 40 μg/kg + 5 mL NS + thiopental 4 mg/kg + 5 mL NS
Kim et al.[201 2007	32(16/16)	Korea	Lignocaine: Administer 0.2 mg of rocuronium bromide (IV) and induce anaesthesia with 2 mg/kg of propofol, followed by 1.5 mg/kg of lignocaine within 30 s, then give 1 mg/kg of succinylcholine. Non-lignocaine: Administer 0.2 mg of rocuronium bromide (IV) and induce anaesthesia with 2 mg/kg of propofol, followed by 0.1 mL/kg saline within 30 s, then give 1 mg/kg of succinylcholine.
Joo et al.[21] 2014	56(28/28)	Korea	Lignocaine: The pre-assigned study drug (40 mg lignocaine) was administered slowly over 2 min. After 60 s, propofol 2 mg/kg was injected, followed by rocuronium 0.9 mg/kg within 5 s. Tracheal intubation was performed after 1 min of manual mask ventilation with 100% oxygen. Non-lignocaine: The pre-assigned study drug (saline) was administered slowly over 2 min. After 60 s, propofol 2 mg/kg was injected, followed by rocuronium 0.9 mg/kg within 5 s. Tracheal intubation was performed after 1 min of manual mask ventilation with 100% oxygen.
Derakhshan et al.[22] 2019	52(26/26)	Iran	Lignocaine: Included: hypertensive patients. Excluded: systolic BP >170 mmHg, diastolic BP >100 mmHg, or on beta-blockers. Given fentanyl 2 μg/kg IV, lignocaine 1.5 mg/kg IV, thiopental 4 mg/kg IV, cisatracurium 0.2 mg/kg IV. Intubated 4 min later with an appropriate ET tube, after giving the study drug (IV lignocaine 1.5 mg/kg) 90 s before. Non-lignocaine: Included: hypertensive patients. Excluded: systolic BP >170 mmHg, diastolic BP >100 mmHg, or on beta-blockers. Given fentanyl 2 μg/kg IV, lignocaine 1.5 mg/kg IV, thiopental 4 mg/kg IV cisatracurium 0.2 mg/kg IV. Intubated 4 min later with an appropriate ET tube, after giving the study drug (placebo) 90 s before.
Thippeswamy et al.[23] 2018	60(30/30)	India	Lignocaine: Preoperative night: 0.5 mg alprazolam orally. Three minutes pre-intubation: lignocaine 1.5 mg/kg IV, thiopental 5 mg/kg IV, succinylcholine 2 mg/kg IV. Intubate via oral laryngoscopy with a disposable, appropriately sized ET tube within 15-20 s. No extra drugs or stimuli for 10 min post-intubation. Patients needing a second attempt excluded. Non-lignocaine: Preoperative night: 0.5 mg alprazolam orally. Three minutes pre-intubation: equal-volume saline IV, thiopental 5 mg/kg IV, succinylcholine 2 mg/kg IV. Intubate via oral laryngoscopy with a disposable, appropriately sized ET tube within 15-20 s. No extra drugs or stimuli for 10 min post-intubation. Patients needing a second attempt excluded.
Singh et al. [24] 2013	80(40/40)	African	Lignocaine: Mallampati grade I. Record the total duration of laryngoscopy, excluding patients if it exceeds 15 s. Preop: 0.008 mg/kg rocuronium IM + midazolam 0.04 mg/kg IV (over 30 s). Administer thiopental 6 mg/kg IV in incremental doses until loss of eyelash reflex, then vecuronium 0.12 mg/kg IV (over 20 s). Ventilate with 1% halothane, then give lignocaine 1.5 mg/ kg IV 2 min before laryngoscopy and intubation. Non-lignocaine: Mallampati grade I. Record the total duration of laryngoscopy, excluding patients if it exceeds 15 s. Preop: 0.008 mg/kg rocuronium IM + midazolam 0.04 mg/kg IV (over 30 s). Administer thiopental 6 mg/kg IV in incremental doses until loss of eyelash reflex, then vecuronium 0.12 mg/kg IV (over 20 s). Ventilate with 1% halothane, then give placebo 2 min before laryngoscopy and intubation.
Ibiribigbe et al.[25] 2023	60(30/30)	Nigeria	Lignocaine: Included: hypertensive patients aged 30-55, BP <160/90 mmHg. Preop: 10 mg diazepam and antihypertensives orally. Infused 30 mg/kg magnesium sulfate in 100 mL saline over 10 min. At the end of the infusion, 1.5 mg/kg lignocaine was diluted to 10 mL with sterile water and injected over 30 s. Induction: 4 mg/kg thiopental sodium IV, 1.5 mg/kg succinylcholine IV. Laryngoscopy and intubation at 5 min post-lignocaine. Excluded: intubation >30 s or >2 attempts. Non-lignocaine: Included: hypertensive patients aged 30-55, BP <160/90 mmHg. Preop: 10 mg diazepam and antihypertensives orally. Infused 30 mg/kg magnesium sulfate in 100 mL saline over 10 min. Induction: 4 mg/kg thiopental sodium IV, 1.5 mg/kg succinylcholine IV. Laryngoscopy and intubation at 5 min post-lignocaine. Excluded: intubation >30s or >2 attempts.
Liu et al.[26] 2022	40(20/20)	China	Lignocaine: Induction with midazolam 0.05 mg/kg, propofol 1.5 mg/kg, sufentanil citrate 0.3 μg/ kg, and cisatracurium besylate 0.1 mg/kg. Administered lignocaine hydrochloride 1 mg/kg during induction, then infused lignocaine at 1 mg/kg/h. Non-lignocaine: Induction with midazolam 0.05 mg/kg, propofol 1.5 mg/kg, sufentanil citrate 0.3 μg/kg, and cisatracurium besylate 0.1 mg/kg. This group received equal-volume saline during induction.
Youn et al. [27] 2017	60(30/30)	Korea	Lignocaine: Pre-induction: 0.2 mg rocuronium. One minute before propofol, 0.5 mg/kg lignocaine + 200 mL warmed carrier fluid over 20 min. Then 2 mg/kg propofol, followed by 0.6 mg/kg rocuronium after loss of eyelash reflex. Anaesthesia maintained with 1 MAC desflurane, 50% O2/air. Monitored vital signs, then infused remifentanil and gave propofol for intubation. Non-lignocaine: Pre-induction: 0.2 mg rocuronium. Twenty minutes before propofol injection, received 200 mL warmed carrier fluid. Then 2 mg/kg propofol, followed by 0.6 mg/kg rocuronium after loss of eyelash reflex. Anaesthesia maintained with 1 MAC desflurane, 50% O2/air. Monitored vital signs, then infused remifentanil and gave propofol for intubation.
Swanton et al [28] 2001	20(9/11)	USA	Lignocaine: No premedication. After preoxygenation, administer fentanyl 2 μg/kg. One minute later, give thiopental sodium 4-6 mg/kg and vecuronium 0.1 mg/kg. Two minutes after induction, give lignocaine 1.5 mg/kg (over 5 s). Perform laryngoscopy and intubation 1 min later. Non-lignocaine: No premedication. After preoxygenation, administer fentanyl 2 μg/kg. One minute later, give thiopental sodium 4-6 mg/kg and vecuronium 0.1 mg/kg. Two minutes after induction, give NS (over 5 s). Perform laryngoscopy and intubation 1 min later.
Gurulingappa et al.[29] 2012	50(25/25)	India	Lignocaine: All patients received premedication with pentazocine 0.05 mg/kg IV, atropine 0.01 mg/kg IM, and midazolam 0.01 mg/kg IV 30 min before induction. Anaesthesia was induced with thiopentone 5 mg/kg IV, succinylcholine 2 mg/kg IV, and IV lignocaine 1.5 mg/kg. Non-lignocaine: All patients received premedication with pentazocine 0.05 mg/kg IV, atropine 0.01 mg/kg IM, and midazolam 0.01 mg/kg IV 30 min before induction. Anaesthesia was induced with thiopentone 5 mg/kg IV, succinylcholine 2 mg/kg IV, and a placebo (normal saline).
Kashyap et al. [30] 2021	60(30/30)	India	Lignocaine: No induction drugs specified and nebulised 0.075 mL/kg saline and 2% lignocaine 2 mg/kg IV. Non-lignocaine: No induction drugs specified. Nebulised 0.075 mL/kg saline and 10 mL NS IV given
Cheeran et al. [31] 2023	60(30/30)	India	Lignocaine: Preop: midazolam 0.025 mg/kg, fentanyl 2 μg/kg, ondansetron 0.1 mg/kg IV. Ten minutes pre-induction, received lignocaine 1.5 mg/kg IV over 10 min (diluted to 6 mL with saline) and maintained infusion. Preoxygenated for 3 min. Induction: propofol 2 mg/kg IV, vecuronium 0.1 mg/kg IV, then intubated. Non-lignocaine: Preop: midazolam 0.025 mg/kg, fentanyl 2 μg/kg, ondansetron 0.1 mg/kg IV. Ten minutes pre-induction, 6 mL saline given over 10 min and maintained as infusion. Preoxygenated for 3 min. Induction: propofol 2 mg/kg IV, vecuronium 0.1 mg/kg IV, then intubated.

*ETI=Endotracheal Intubation, NS=Normal Saline, IM=Intramuscular Injection, IV=Intravenous Injection, preop=preoperative, Alf=Alfentanil, BP=blood pressure, ET tube=Endotracheal tube, MAC=Minimum Alveolar Concentration

Quality assessment (risk of bias assessment)

Based on the RoB 2 assessment, five of the 18 included RCTs were deemed to have “some concerns” in their overall risk of bias. These concerns stemmed from bias arising from the randomisation process, where insufficient reporting of allocation sequence generation and concealment methods was identified. However, baseline characteristics between groups in these trials exhibited no statistically significant imbalances. The remaining 13 trials were assessed as “low risk” across all five RoB 2 domains, as detailed in Figure 2.

Figure 2.

Risk-of-bias assessment by the Cochrane Risk of Bias tool (RoB 2) for each randomised controlled trial included in the analysis

Effects on haemodynamics

All outcomes were presented as changes from baseline after tracheal intubation, expressed as mean (SD). The findings of this meta-analysis revealed that IV lignocaine significantly attenuated the rise in MAP induced by laryngoscopy and tracheal intubation. However, the effects of IV lignocaine on HR seem to be influenced by both dosage and ethnic group.

MAP changes

Fourteen trials involving 814 patients compared lignocaine with non-lignocaine in reducing the fluctuations in MAP following laryngoscopy and tracheal intubation.[10,11,16,17,18,19,20,21,23,24,26,27,30,31] Heterogeneity analysis revealed I² =84%, which signals significant heterogeneity. The study suggested this heterogeneity might be due to the different doses of lignocaine. Therefore, subgroup analysis was performed according to the lignocaine doses, which reduced the heterogeneity, but I² remained above 50%. As a result, the random-effects model was used to aggregate the effect sizes. The findings revealed that IV lignocaine at 1–2 mg/kg doses was more effective than the non-lignocaine group, whereas IV lignocaine at doses of 0.5 mg/kg and 40 mg was ineffective [Figure 3].

Figure 3.

Forest plot shows the effect of intravenous lignocaine on MAP after laryngoscopy and tracheal intubation. CI = confidence interval, SD = standard deviation, IV = inverse variance, MAP = mean arterial pressure

HR changes

Eighteen trials[10,11,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31] involving 1056 patients compared tested whether additional lignocaine was useful in reducing the HR reaction to tracheal intubation The heterogeneity test revealed significant heterogeneity (I² =91%), which was likely due to differences in the doses of lignocaine used, as shown by the dose-stratified analysis [Figure 4]. Specifically, the subgroup receiving 1.5 mg/kg still exhibited significant heterogeneity (I² >75%). Further subgroup analysis suggested that ethnic differences might be the underlying source of this heterogeneity. Yörükoglu et al.’s study,[16] which involved pre-induction intramuscular administration of atropine, and Ibiribigbe et al.’s study,[25] which used magnesium sulphate (MgSO₄) in combination, were identified by the sensitivity analysis as potential sources of confounding factors. After excluding these studies, the heterogeneity within the subgroup was significantly reduced (I² <75%), and a random-effects model was adopted for the pooled analysis.

Figure 4.

Forest plot that shows the effect of intravenous lignocaine on HR after laryngoscopy and tracheal intubation. CI = confidence interval, SD = standard deviation, IV = inverse variance, HR = heart rate in beats per min

The results showed that the groups receiving 0.5 mg/kg and a fixed dose of 40 mg of lignocaine had significantly better HR control than the non-lignocaine group (P < 0.05). The groups receiving 1 mg/kg and 2 mg/kg doses showed no significant effects. The subgroup analysis of the 1.5 mg/kg lignocaine, stratified by ethnicity, showed a significant effect in South Asian populations (MD: −13.19; 95% CI: −16.39, −9.99), marginal in African populations (MD: −4.40; 95% CI: −8.05, −0.75), and not statistically significant in East Asian, Middle Eastern, and Western populations [Figure 5]. This dose-effect relationship suggests that the regulatory effect of lignocaine on HR is highly dose-dependent and varies significantly across different regions.

Figure 5.

Forest plot demonstrating the effect of 1.5 mg/kg lignocaine on HR after laryngoscopy and tracheal intubation. CI = confidence interval, SD = standard deviation, IV = inverse variance, HR = heart rate in beats per min

Adverse events

Six of the 18 RCTs[16,17,18,24,26,30] reported adverse reactions. Among them, three studies (176 participants) indicated an absence of adverse effects with lignocaine. Other studies did not report adverse events in a systematic manner. The heterogeneity test results indicated P > 0.1 and I² < 50%. Thus, a fixed-effects model was employed to aggregate the effect sizes. Outcome analysis revealed a significant discrepancy across the two groups from a statistical standpoint (RR: 0.60; 95% CI: 0.39, 0.93; P = 0.02; I² = 42%). This indicates that the lignocaine group exhibited a lower rate of adverse reactions compared with the non-lignocaine group, being 0.6 times that of the non-lignocaine group [Figure 6]. Our meta-analysis suggests that IV lignocaine at dosages of up to 2 mg/kg is generally well-tolerated.

Figure 6.

Forest plot comparing the overall number of complications in the lignocaine group versus the non-lignocaine group. CI = confidence interval, M-H = Mantel-Haenszel

Sensitivity analysis

For outcomes with substantial heterogeneity (I² >50%), leave-one-out sensitivity analyses were conducted. In the analysis of MAP (I² =84%), excluding Youn et al.[27] markedly reduced heterogeneity to 57%, while the pooled estimate remained consistent. Other exclusions had minimal impact on heterogeneity (I² range: 82%–85%). For HR (I² =91%), all iterations showed stable effect sizes and limited heterogeneity fluctuations (I² range: 87%–91%). These results confirm that Youn et al.[27] was the key driver of MAP heterogeneity, whereas HR estimates were robust across analyses.

Publication bias

We constructed funnel plots for MAP and HR variations [Figure 7], complemented by Begg’s and Egger’s statistical tests. Neither Begg’s test (MAP: P = 0.73; HR: P = 0.79) nor Egger’s test (MAP: P = 0.15; HR: P = 0.59) reached significance thresholds, demonstrating methodological consistency in bias assessment.

Figure 7.

Funnel plots of MAP (a) and HR (b) changes caused by laryngoscopy and tracheal intubation in lignocaine and non-lignocaine groups. CI = confidence interval, MD = mean difference, SE (MD) = standard error of mean difference, MAP = mean arterial pressure, HR = heart rate in beats per min

Quality of evidence

The quality of evidence for all outcomes was assessed using the GRADE guidelines [Supplementary Table 3]. The primary reasons for a lower quality rating stem from inconsistency.

Supplementary Table 3.

Summary of findings (SOF)

Lignocaine compared to non-lignocaine for adults under general anaesthesia
Patient or population: adults under general anaesthesia
Intervention: lignocaine
Comparison: non-lignocaine
Outcomes	Anticipated absolute effects (95% CI)		Relative effect (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)
	Risk with non-lignocaine	Risk with lignocaine
The effect of intravenous lignocaine on MAP	-	MD 3.38 lower (6.1 lower to 0.66 lower)	-	844 (17 RCTs)	⨁⨁⨁◯ Moderate
The effect of intravenous lignocaine on HR	-	MD 3.88 lower (6.42 lower to 1.34 lower)	-	1026 (21 RCTs)	⨁⨁◯◯ low
Adverse events	308 per 1000	185 per 1000 (120 to 287)	RR 0.60 (0.39 to 0.93)	240 (4 RCTs)	⨁⨁⨁◯ Moderate

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI=confidence interval, MD=mean difference, RR=risk ratio, GRADE=grading of recommendations assessment, development, and evaluation, RCTs=randomised controlled trials, MAP=mean arterial pressure, HR=heart rate. GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

DISCUSSION

Our systematic review analysed 18 RCTs evaluating five IV lignocaine regimens (0.5, 1.0, 1.5, 2.0 mg/kg, and 40 mg fixed dose) for haemodynamic modulation during laryngoscopy and tracheal intubation under general anaesthesia. Substantial sample size disparities existed between dose groups, with the 1.5 mg/kg regimen (employed in 13 of the 18 included trials[10,11,16,17,18,20,22,23,24,25,28,29,31]) demonstrating numerical dominance. Subgroup analysis revealed the 1.5 mg/kg dose achieved optimal efficacy in attenuating procedure-induced MAP elevation, consistent with pharmacological evidence confirming its superior sympathetic blockade within safe thresholds.[32,33] Notably, this regimen exhibited ethnic variations in HR modulation, demonstrating significant efficacy in South Asian populations, marginal effects in African populations, and non-significant outcomes in East Asian, Middle Eastern, and Western populations, suggesting pharmacodynamic population-specific characteristics.

This study represents the first meta-analysis evaluating ethnicity-associated variations in lignocaine’s efficacy for attenuating intubation responses. By incorporating 11 additional RCTs (2014–2023, n = 634), we substantially expand and reinforce the findings of Qi et al.’s[12] 2013 work while providing novel insights. Through our results, when considered alongside previous research, pre-intravenous lignocaine administration emerges as an innovative dual-effect strategy: it effectively suppresses the haemodynamic surge induced by laryngoscopy and tracheal intubation while concurrently mitigating multiple induction-related adverse effects, including propofol- or rocuronium-induced injection pain[7,8]and opioid-associated coughing,[9] thereby enhancing procedural comfort. This intervention demonstrates exceptional safety with minimal adverse effects and a broad therapeutic window. We propose that this intervention warrants consideration as a valuable addition to intubation protocols, particularly in environments requiring pragmatic, economically sustainable solutions.

While the lignocaine group demonstrated a lower adverse reaction rate than the non-lignocaine group in this study, the safety profile of IV lignocaine remains incompletely characterised. Among reviewed trials, six reported drug-related adverse events, three documented none, and others provided inconsistent safety data. Notably, hypotension and tachycardia events reported by Zou et al.[10] may necessitate a careful assessment of their causal relationship with lignocaine. Similarly, clinical manifestations such as cough, hypertension, and bradycardia were observed in the study by Liu et al.[26] They are also questionable in terms of their direct association with lignocaine. These uncertainties highlight the need for more rigorous causality assessments in clinical research. Although our findings align with existing literature supporting the acceptable safety of IV lignocaine within recommended doses, significant heterogeneity in adverse event monitoring and reporting standards across studies complicates accurate safety evaluations. Future efforts should prioritise establishing a unified safety evaluation system, particularly standardising monitoring protocols for cardiovascular and neurological systems, to clarify lignocaine’s dose-toxicity relationship while addressing current inconsistencies in safety data interpretation.

The optimal timing for lignocaine administration remains a topic of debate. Conventional clinical practice and the majority of studies generally advocate administering lignocaine intravenously 1–2 minutes before airway manipulation.[34,35] However, some researchers have suggested that administration at least 3 minutes in advance is necessary to achieve the best effect in suppressing airway reflexes.[36,37] In our meta-analysis, only five studies administered IV lignocaine more than 3 minutes before intubation, while the timing was unclear in four studies. The remaining nine studies all administered the drug within 3 minutes of the start of the experiment. Although we conducted a subgroup analysis based on the timing of administration, we did not identify any significant sources of heterogeneity. This may be related to the differences in lignocaine doses used across studies and the limited number of studies included.

Limitations

This meta-analysis has several methodological limitations. Firstly, the included trials were all single-centre designs with predominantly small sample sizes (n < 100 in most studies), resulting in limited statistical power. This was particularly evident in small-sample subgroups (n ≤ 30), where CI spanned the null value, indicating heightened susceptibility to extreme values and inadequate control of confounders. Secondly, despite implementing strict inclusion criteria (e.g., restricting to ASA class I–II patients) to mitigate heterogeneity, critical technical parameters (laryngoscope type, intubation duration, first-attempt success rates) and variations in local anaesthetic administration protocols remained inconsistently reported. Furthermore, the 29-year study span (1995–2023) encompassed significant advancements in airway management technologies (e.g., evolution from traditional Macintosh blades to modern video laryngoscopes such as GlideScope and C-MAC D-blade) and material innovations (e.g., antimicrobial-coated endotracheal tubes), which were not systematically controlled for, potentially introducing temporal bias. Thirdly, current evidence remains exclusively applicable to low-risk adult populations, lacking validation in high-risk groups such as those with arrhythmias or coronary artery disease. While the GRADE assessment downgraded evidence quality for certain outcomes due to heterogeneity, trial sequential analysis was not performed to evaluate cumulative evidence stability. Future research should prioritise large-scale multicentre trials to develop dynamic models integrating technological variables and dose parameters (e.g., fixed-dose vs weight-based regimens), establishing universal clinical decision thresholds.

CONCLUSION

Our meta-analysis reveals that intravenous lignocaine at doses ranging from 1 to 2 mg/kg effectively mitigates the mean arterial pressure spikes caused by laryngoscopy and tracheal intubation. However, the modulation of heart rate responses by intravenous lignocaine appears to require optimisation based on both dosage and ethnicity. Future research should explore the underlying mechanisms and develop more precise dosing strategies.

Data availability

The data for this systematic review and meta-analysis may be requested with reasonable justification from the authors (email to the corresponding author) and shall be shared upon request.

Supplementary material

This article has supplementary material and can be assessed at this link. Supplementary Material at http://links.lww.com/IJOA/A24.

Conflicts of interest

There are no conflicts of interest.

Supplementary Figure 1

Inter-rater reliability measured with Cohen’s Kappa

Funding Statement

Nil.