Comparison between transtracheal and intravenous 2% lignocaine in attenuating hemodynamic stress response following direct laryngoscopy and endotracheal intubation: a randomized controlled trial

Abstract

Background and aims

Lignocaine is used through various routes to mitigate the hemodynamic surge associated with laryngoscopy and endotracheal intubation during general anesthesia. This study hypothesized that post-induction administration of transtracheal 2% lignocaine at 1.5 mg/kg would have a similar effect to intravenous 2% lignocaine at the same dosage, providing an alternative for attenuating the hemodynamic stress response.

Methods

A total of 138 consenting patients were randomized into two groups. Following induction, Group IV patients received 2% lignocaine at 1.5 mg/kg intravenously, while Group TT patients received 2% lignocaine at 1.5 mg/kg transtracheally. The primary outcome was the comparison of hemodynamic responses at different time points around intubation. The secondary outcome was the incidence of sore throat. Data analyses were done using the Statistical Software Jupyter Notebook, running in a Python 3.11 environment.

Results

Post-induction hypotension was significantly less pronounced in the TT group [Mean blood pressure (median with IQR) IV group 68(60-78) mm of Hg vs. TT group 71(66-82.25) mm of Hg, P = 0.018]. TT group patients experienced a significantly smaller post-intubation surge at 3 minutes in blood pressure and heart rate compared to the IV group [Mean blood pressure (median with IQR) IV group 79(71-87) mm of Hg vs. TT group 73(65-81) mm of Hg, P = 0.009 and Heart rate (median with IQR) IV group 80(70-94) per minute vs. 71.5(64-82.75) per minute P = 0.015].

Conclusion

Transtracheal lignocaine is more likely to maintain stable hemodynamics during intubation compared to intravenous lignocaine.

Trial registration

CTRI/2023/06/054125 [Registered on: 19/06/2023]. This trial is registered with the Clinical Trial Registry of India https://ctri.nic.in/Clinicaltrials/login.php.

Introduction

Intubation is a preferred method for patients undergoing general anesthesia to secure a patent airway and facilitate mechanical ventilation. Direct laryngoscopy and endotracheal intubation typically trigger increased sympathetic and adrenomedullary catecholamine activity, leading to surges in heart rate and blood pressure [1]. In vulnerable patients such as uncontrolled hypertensives, patients with ischemic heart disease and elevated intracranial pressure even a brief rise in these parameters can precipitate adverse events such as arrhythmias, myocardial infarction, cardiac failure, intracerebral hemorrhage [2].

Various methods have been employed to attenuate the hemodynamic stress response associated with laryngoscopy and intubation. Lignocaine has proven effective in mitigating these responses when administered via different routes: as an oral topical viscous solution [3, 4], aerosolized/nebulized solution [5], laryngotracheal spray [6], and intravenous (IV) injection [7, 8]. While transtracheal lignocaine is commonly used during awake fiberoptic intubation, its use for preventing hemodynamic surges during intubation following general anesthesia is not common. We found only one similar study with limited sample size during the literature search [9]. The scarcity of literature highlights the gaps in current knowledge on this topic.

This study aims to evaluate the efficacy of transtracheal 2% lignocaine in preventing post-intubation hemodynamic surge at a dosage of 1.5 mg/kg, administered after induction of general anesthesia. We hypothesized that the control of hemodynamic response with this method would be comparable to intravenous 2% lignocaine at the same dosage. If the transtracheal approach proved to be more effective than the intravenous approach, then it could be useful in high risk patients. We also hypothesized that as transtracheal lignocaine will act locally on the tracheal mucosa, it will offer the added benefit of preventing postoperative sore throat.

Methods

This prospective, interventional, single-blinded, randomized controlled trial was conducted after obtaining approval from the institutional ethics committee (IEC MPMMCC DCGI Reg. Number: ECR/150/Inst/up/2021 Study reference number OIEC/11000607/2023/00005) and was registered with the Clinical Trial Registry of India (https://ctri.nic.in/Clinicaltrials/login.php CTRI/2023/06/054125 Registered on: 19/06/2023). The study involved 138 patients classified as American Society of Anesthesiologists (ASA) physical status I-II, aged 18–60 years, with a Mallampati score of I or II. Patients scheduled for elective surgical procedures under general anesthesia, requiring single-attempt oral intubation via direct laryngoscopy, were included. Exclusion criteria encompassed patient refusal, inability to provide valid consent, pregnancy, known hypersensitivity to lignocaine and anticipated difficult airway. Written informed consent was obtained from all participants. The patients were recruited between the periods from 21st June 2023 to 20fth April 2024. The study adhered to the principles of the Helsinki Declaration 2013 and followed good clinical practices. The study complied with the CONSORT guidelines.

Patients were randomized into two groups using a computer-generated simple randomization chart by an independent researcher. The investigator opened the sequentially numbered opaque envelop for each participant to determine the group allotment: the intravenous group (Group IV) and the transtracheal group (Group TT). Group allotment was conveyed to the concerned anesthesiologist while the participants remain unaware about the group allocation. Baseline vitals were recorded in the preoperative holding area.

A standardized anesthesia protocol was followed for all patients. In the operating room, intravenous access was secured, and standard ASA monitors were attached. Ringer lactate was initiated intravenously at a rate of 2 ml/kg/hr. Patients were pre-oxygenated with 100% oxygen at 10 L/min for 3 minutes. General anesthesia was induced using fentanyl 2 µg/kg, propofol 2–2.5 mg/kg, and atracurium 0.5 mg/kg. Hypotensive episodes were treated with a 3 mg intravenous bolus of mephentermine. Mechanical ventilation was used to maintain normocapnia, with a tidal volume of 6–8 ml/kg ideal body weight and positive end-expiratory pressure (PEEP) of 5 cm H2O.

In Group IV, patients received preservative-free 2% lignocaine (Loxicard® 2%, Neon Laboratories Ltd, India) at 1.5 mg/kg intravenously immediately after induction. Three minutes post-administration, tracheal intubation was performed orally with an appropriate-sized endotracheal tube using a Macintosh laryngoscope in a single attempt.

In Group TT, patients received preservative-free 2% lignocaine (Loxicard® 2%, Neon Laboratories Ltd, India) at 1.5 mg/kg transtracheally immediately after induction. With the patient in a head-extended position, the cricothyroid membrane was identified and punctured perpendicularly using a 22 G needle attached to a 5 ml syringe loaded with the drug. Aspiration of air confirmed needle placement and the drug was instilled into the trachea. After 3 minutes of transtracheal injection of lignocaine, the trachea was intubated orally with an appropriate-sized endotracheal tube using a Macintosh laryngoscope in a single attempt.

Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) were measured prior to intubation, immediately post-intubation, and at 1, 3, and 5 minutes post-intubation. The duration of laryngoscopy and intubation was recorded for both groups. General anesthesia was maintained with 50% nitrous oxide in oxygen each at 3 L/min and sevoflurane at a 2% dial concentration. After five minutes, routine anesthesia protocols were resumed, and surgical preparation commenced. The incidence of sore throat was noted in both groups once the patients were shifted to the recovery room.

The sample size was calculated using the UCSF-CTSI (University of California San Francisco Clinical and Translational Science Institute) online calculator [10], assuming a 5 mm Hg difference in mean of blood pressures between the two groups, with a standard deviation of 10 mm Hg, a 95% confidence interval, and 80% power. This resulted in a requirement of 63 patients per group. With an anticipated 10% attrition rate, the total sample size was adjusted to 138 patients.

Statistical analyses were performed using Jupyter Notebook [11] running in a Python 3.11 environment. The Shapiro–Wilk test was used to assess the normal distribution of continuous data. Non-normally distributed continuous and ordinal data were analyzed using the Wilcoxon rank-sum test, while normally distributed continuous data were analyzed using the two-tailed Student’s t-test. The Chi-square test was used for categorical data. A p-value of <0.05 was considered statistically significant. A post hoc power and sample size analysis was conducted to validate the findings.

Results

A total of 144 patients were assessed for eligibility, with six patients not meeting the inclusion criteria. Consequently, 138 patients were recruited for the study, and data from 127 patients were included in the final analysis (Fig. 1). Demographic parameters were comparable between the two groups (Fig. 2, Table 1). The duration of laryngoscopy and intubation was similar in both groups [mean ± SD: 22.15 ± 9.24 seconds in Group IV versus 20.74 ± 8.41 seconds in Group TT, P = 0.371]. There were no complications related to transtracheal or intravenous administration of lignocaine in any patient.

Fig. 1.

Consolidated Standard of Reporting Trials (CONSORT) flow diagram

Fig. 2.

Demographic parameters

Table 1.

Demographic parameters

Variables	Group IV (n = 61)	Group TT (n = 66)	P value
Age	43(37–51)	40.5(33–48)	0.274
BMI	23.6(20.4–26.5)	21.65(20.23–25.25)	0.136
Sex	F: 0.64/M: 0.36	F: 0.80/M: 0.20	0.062
ASA PS	II: 0.64/I: 0.36	II: 0.62/I: 0.38	0.978

Values are in median with IQR and ratio

BMI Body Mass index, ASA PS American Society of Anesthesiologists physical status

The analysis of trends in vitals over time during intubation revealed distinct patterns between Group IV and Group TT. Post-induction, there was a noticeable fall in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) in both groups, with the decrease being less pronounced in the TT group. After intubation, patients in the TT group exhibited a lower surge in blood pressure and heart rate (HR) compared to the IV group. Overall, the TT group demonstrated a more stable hemodynamic profile throughout the observed time points (Fig. 3).

Fig. 3.

Trend chart of the vitals over time. SBP - Systolic blood pressure, DBP - Diastolic blood pressure, MBP - Mean blood pressure, HR - Heart rate, b – Baseline, pi - prior to intubation, ai - immediately after intubation, 1 - 1 minute post-intubation, 3 - 3 minutes post-intubation, 5 - 5 minutes post-intubation

Significant differences were observed in several key measurements (Tables 2, 3, 4 and 5). Post-induction, the fall in SBP and MBP was significantly less in the TT group (SBP: p=0.009, MBP: p=0.019). At 3 minutes post-intubation, surge in SBP, DBP, MBP, and HR were all significantly lower in the TT group compared to the IV group (SBP: p=0.008, DBP: p=0.002, MBP: p=0.009, HR: p=0.015). Additionally, at 5 minutes post-intubation, SBP remained significantly lower in the TT group (p=0.030).

Table 2.

Systolic blood pressure during intubation

Variables	Group IV (n = 61)	Group TT (n = 66)	P value
SBPb	129.49±14.41	125.73±12.45	0.116
SBPpi	90(82–102)	96.5(86.25–106.75)	0.009
SBPai	121.13±22.95	122.42±20.06	0.735
SBP1	113(103–133)	112(97.25–126.25)	0.320
SBP3	104(93–118)	97(88–107.75)	0.008
SBP5	96(91–107)	93(87–99)	0.030

Values are in mean±SD, and median with IQR

SBP Systolic blood pressure mm of Hg, b Baseline, pi prior to intubation, ai immediately after intubation, 1 1 minute post-intubation, 3 3 minutes post-intubation, 5 5 minutes post-intubation

Table 3.

Diastolic blood pressure during intubation

Variables	Group IV (n = 61)	Group TT (n = 66)	P value
DBPb	80(73–85)	82(74.5–87)	0.412
DBPpi	58.64±14.11	63.11±12.32	0.059
DBPai	79.44±15.68	78.85±14.22	0.823
DBP1	75.90±16.17	72.06±12.63	0.137
DBP3	68.92±12.22	62.33±10.75	0.002
DBP5	63.72±10.75	60.30±11.18	0.082

Values are in mean±SD, and median with IQR

DBP Diastolic blood pressure mm of Hg, b Baseline, pi prior to intubation, ai immediately after intubation, 1 1 minute post-intubation, 3 3 minutes post-intubation, 5 5 minutes post-intubation

Table 4.

Mean blood pressure during intubation

Variables	Group IV (n = 61)	Group TT (n = 66)	P value
MBPb	95.43±9.66	95±8.93	0.796
MBPpi	68(60–78)	71(66–82.25)	0.018
MBPai	91.54±17.83	92.15±15.57	0.837
MBP1	87(78–101)	84(73.25–95.25)	0.349
MBP3	79(71–87)	73(65–81)	0.009
MBP5	74.31±11.62	71±10.09	0.088

Values are in mean±SD, and median with IQR

MBP Mean blood pressure mm of Hg, b Baseline, pi prior to intubation, ai immediately after intubation, 1 1 minute post-intubation, 3 3 minutes post-intubation, 5 5 minutes post-intubation

Table 5.

Heart rate during intubation

Variables	Group IV (n = 61)	Group TT (n = 66)	P value
HRb	83.03±12.71	83.06±12.93	0.990
HRpi	81(73–86)	76.5(68–88.75)	0.227
HRai	95.80±18.47	89.45±19.20	0.060
HR1	89.21±19.47	83.65±17.67	0.094
HR3	80(70–94)	71.5(64–82.75)	0.015
HR5	73(65–85)	69(63.25–77.75)	0.136

Values are in mean±SD, and median with IQR

HR Heart rate/minute, b Baseline, pi prior to intubation, ai immediately after intubation, 1 1 minute post-intubation, 3 3 minutes post-intubation, 5 5 minutes post-intubation

The analysis of the trend in Rate-Pressure Product (RPP) over time during intubation indicated that the TT group consistently exhibited lower PRP values compared to the IV group after intubation (Fig. 4). The Rate-Pressure Product, calculated by multiplying the heart rate (HR) by the systolic blood pressure (SBP), serves as a physiological measure to assess the workload of the heart. At 3 minutes post-intubation, the RPP was significantly lower in the TT group (p=0.002).

Fig. 4.

Trend chart of rate pressure product over time. RPP - Rate Pressure Product, b – Baseline, pi - prior to intubation, ai - immediately after intubation, 1 - 1 minute post-intubation, 3 - 3 minutes post-intubation, 5 - 5 minutes post-intubation

Incidences of sore throat were similar in both groups (IV 6.5% vs. TT 9%, p-value: 0.842).

A post hoc power analysis revealed a power of 0.804 for mean blood pressure at 3 minutes post-intubation (MBP3), with a suggested sample size of 60, indicating that the study was adequately powered to detect differences in MBP3 between the groups.

Discussion

Lignocaine has been employed through various routes to attenuate hemodynamic stress response associated with laryngoscopy and intubation. Intravenous administration of 2% lignocaine at a dose of 1.5 mg/kg, given 3 minutes before endotracheal intubation, is a common practice aimed at mitigating the hemodynamic response induced by laryngoscopy and intubation [2]. Within the recommended dosage intravenous lignocaine is less likely to cause central nervous and cardiovascular system toxicity. The risk of allergic reaction may be very low [12]. Transtracheal application of lignocaine is a routine and safe procedure utilized to facilitate intubation during awake fiberoptic intubation by anesthetizing the infraglottic larynx and upper trachea [13], thereby aiding in the prevention of hemodynamic surge during awake intubation. We used transtracheal lignocaine after induction of general anesthesia to prevent hemodynamic surge during endotracheal intubation. It was performed after induction of general anesthesia hence patients didn’t feel any discomfort. The potential complications of transtracheal injection (subcutaneous and intratracheal bleeding, infection, subcutaneous emphysema, pneumomediastinum, pneumothorax, vocal cord damage, and esophageal perforation) are extremely rare (0.01%) [14].

The study revealed that transtracheal lignocaine was more likely to achieve a stable hemodynamics during induction of general anesthesia by mitigating both the post-induction hypotension as well as post-intubation hemodynamic surges compared to intravenous lignocaine following general anesthesia. It indicates possible usefulness of the transtracheal approach in vulnerable group of patients (uncontrolled hypertensives, patients with ischemic heart disease) where a stable hemodynamics is necessary. Previous study also demonstrated that transtracheal lignocaine effectively prevents hemodynamic surges in hypertensive patients during laryngoscopy and intubation [9].

Post-induction hypotension was less in the TT group. Despite the general anesthesia, a mild cough reflex was observed in most patients following transtracheal lignocaine administration. The mild cough along with sympathetic stimulation during transtracheal lignocaine administration may have been the cause of less post-induction hypotension in the TT group.

Post-induction transtracheal lignocaine might not be as effective in anesthetizing the upper tracheal mucosa as during awake intubation where the cough reflex aids in drug dispersion. The stress response to intubation is primarily elicited by laryngoscopy and endotracheal tube placement, with the maximum response occurring during tracheal placement of the endotracheal tube [15, 16]. In the TT group, the stress response during laryngoscopy was blunted by general anesthesia aided with some degree of drug spread to upper tracheal mucosa related to mild cough.

The attenuating effect of intravenous lignocaine has been attributed to the arteriolar vasodilatation [17], blunting of the autonomic response [18], cough suppression [19, 20], and enhancement of the depth of general anesthesia [21]. The systemic arteriolar vasodilatory effect of IV lignocaine might have enhanced the hypotensive effects of propofol causing greater post-induction hypotension in IV group.

The post-intubation hemodynamic surge was less in the TT group with significance achieved at 3 minutes. Vitals almost reached the pre-induction level at 3 minutes in the TT group (Fig. 3) indicating a subdued hemodynamic stress response post-intubation compared to those who received IV medication. The topical effect of 2% lignocaine comes in 1–3 minutes with a peak effect in 5–10 minutes [22]. Patients in the transtracheal group were intubated three minutes after lignocaine administration, with clinically significant stable vitals recorded three minutes post-intubation. The significant effect observed at 6 minutes post-transtracheal lignocaine administration aligns with the peak effect timing of topical lignocaine.

The lower Rate-Pressure Product in the TT group highlights the effectiveness of the transtracheal lignocaine in minimizing cardiac workload during the post-intubation period. The trend favored the TT group, indicating a potential benefit in ensuring hemodynamic stability and reducing cardiac stress during intubation.

To determine whether our study is adequately powered, a post hoc power analysis was done. A power of 0.804 was achieved for mean blood pressure at 3 minutes post-intubation (MBP3) with a suggested sample size of 60. Our study included 138 patients, indicating an adequate sample size to determine the superiority of transtracheal lignocaine over intravenous lignocaine in maintaining hemodynamic stability at 3 minutes post-intubation.

As the study was single blinded, the study team was aware about the intervention received by the patient which might cause biases in data collection and interpretation. Although statistically significant differences in hemodynamics were also noted between the intravenous and transtracheal groups prior to intubation and at 5 minutes post-intubation, the sample size of the study was not sufficient to achieve the power of 80%. Hence the study is not adequately powered to compare the differences at those time points. The study was conducted only on ASA I and II patients hence the results cannot necessarily be extrapolated to the vulnerable population. These are the limitations of our study. Future studies can be done using a double blinded study design on hypertensive patients. Larger multicentric trials and different dosages of transtracheal lignocaine may also be explored.

Conclusion

The study revealed that transtracheal lignocaine was effective in reducing post-induction hypotension and controlling post-intubation blood pressure and heart rate surges compared to intravenous lignocaine following general anesthesia. It clearly demonstrates the usefulness of transtracheal approach over intravenous approach in maintaining stable hemodynamics during induction of general anaesthesia.

Abbreviations

IV

Intravenous

TT

Transtracheal

ASA

American Society of Anesthesiologists

PEEP

Positive end-expiratory pressure

SBP

Systolic blood pressure

DBP

Diastolic blood pressure

MBP

Mean blood pressure

HR

Heart rate

RPP

Rate-Pressure Product

Authors’ contributions

Concepts, Design, Definition of intellectual content: MP, UC, SC, SSH, NKS, SB, SR and JK. Literature search: MP and UC. Experimental studies and data acquisition: MP, UC, SC, SSH, NKS, SB, SR and JK. Data analysis and Statistical analysis: MP, UC and JK. All authors did the manuscript preparation, manuscript editing, manuscript review and guarantor. All authors read and approved the final manuscript.

Funding

Open access funding provided by Department of Atomic Energy. Nil.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

A copy of the approval and consent form is available for review by the Editor of this journal.

The study was approved by Institutional Ethics Committee (IEC) (DCGI Reg. Number: ECR/150/Inst/up/2021). Mahamana Pandit Madan Mohan Malaviya Cancer Centre & Homi Bhabha Cancer Hospital (Units of Tata Memorial Centre/Dept. of Atomic Energy, Govt. of India/Varanasi, Uttar Pradesh – 221005). Study reference number OIEC/11000607/2023/00005.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.