Effects of Lignocaine Administered Intravenously or Intratracheally on Airway and Hemodynamic Responses during Emergence and Extubation in Patients Undergoing Elective Craniotomies in Supine Position.

INTRODUCTION: Sympathoadrenergic responses during emergence and extubation can lead to an increase in heart rate (HR) and blood pressure whereas increased airway responses may lead to coughing and laryngospasm. The aim of our study was to compare the effects of lignocaine administered intravenously (IV) or intratracheally on airway and hemodynamic responses during emergence and extubation in patients undergoing elective craniotomies.
METHODOLOGY: Sixty patients with physical status American Society of Anaesthesiologists Classes I and II aged 18-70 years, scheduled to undergo elective craniotomies were included. The patients were randomly divided into three groups of twenty patients; Group 1 receiving IV lignocaine and intratracheal placebo (IV group), Group 2 receiving intratracheal lignocaine and IV placebo (I/T group), and Group 3 receiving IV and intratracheal placebo (placebo group). The tolerance to the endotracheal tube was monitored, and number of episodes of cough was recorded during emergence and at the time of extubation. Hemodynamic parameters such as HR and blood pressure (systolic, diastolic, mean arterial pressure) were also recorded.
RESULTS: There was a decrease of HR in both IV and intratracheal groups in comparison with placebo group (P < 0.005). Rise in blood pressure (systolic blood pressure, diastolic blood pressure and mean arterial pressure) was comparable in both Groups 1 and 2 but was lower in comparison with placebo group (P < 0.005). Cough suppression was comparable in all the three groups. Grade III cough (15%) was documented only in placebo group.
CONCLUSION: Both IV and intratracheal lignocaine are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation. There was comparable cough suppression through intratracheal route and IV routes than the placebo group.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Manipulation of airway during laryngoscopy and endotracheal intubation is associated with sympathetic responses which result in a rise in heart rate (HR) and blood pressure. These sympathoadrenergic responses reported by King et al.[1] are also seen during extubation, recovery, and emergence from anesthesia. The exact mechanism responsible for these hemodynamic responses is unknown. It may be associated with the release of catecholamines occurring during this stressful period. Acute hemodynamic changes during extubation can lead to life-threatening arrhythmias, myocardial ischemia, acute cardiac failure, pulmonary edema, or cerebrovascular hemorrhage in susceptible individuals.[2] These responses, in turn, can be catastrophic in several situations such as ocular surgeries, intracranial surgeries, cardiac surgeries, and aneurysmal surgeries.[34]

Respiratory complications after tracheal extubation are three times more common than during intubation and induction of anesthesia.[5] Bucking and coughing frequently occur during extubation and may lead to negative pressure pulmonary edema with an abrupt increase in intraocular pressure, intrathoracic pressure, intraabdominal pressure, and intracranial pressure. This can increase the mortality and morbidity of the patient.[46]

Early recovery and extubation in neurosurgical patients is the preferred method when the preoperative state of consciousness is relatively normal, and surgery does not involve critical brain areas or extensive manipulation.[4] Several techniques have been applied to alleviate the hemodynamic responses and coughing during emergence and extubation. They include deep extubation, administration of intravenous (IV) narcotics, dexmedetomidine, calcium channel blockers, and administration of lidocaine.[78] Lignocaine is one of the commonly used drugs by IV,[9] endotracheal tube (ETT) cuff,[10] or laryngotracheal route[11] to blunt the circulatory and airway reflexes during emergence from general anesthesia. IV lignocaine may lead to prolonged emergence from general anesthesia.[11] The mechanism of action of lignocaine may be due to either the local anesthetizing action of the airway mucosa or systemic absorption of the drug. Lignocaine may be rapidly absorbed into the circulation from the tracheobronchial tree with its blood concentrations being the same as after an IV injection.[12]

Jee and Park[13] compared the effects of administration of intratracheal 2% lidocaine with IV lidocaine and placebo to study airway and circulatory reflexes in patients undergoing surgery using general anesthesia for elective minor orthopedic surgery, plastic superficial surgery, or lower abdominal surgery. Based on this study, the aim of this study was to investigate whether intratracheal lignocaine in a dose of 1.5 mg/kg given before skull pin removal attenuates cough and hemodynamic response in neurosurgical patients during emergency and compared this with IV and placebo groups.

Methodology

This prospective, randomized, double-blind, placebo-controlled study was conducted in a tertiary care hospital in Northern India from August 2014 to August 2016.

After obtaining approval from the Institutional Review Board for conducting the study and informed consent, sixty patients of either sex with physical status American Society of Anaesthesiologists (ASA) Classes I and II aged 18–70 years, scheduled to undergo elective craniotomies in supine position were included in the study. Patients with a history of sore throat, upper respiratory tract infection, laryngeal or tracheal pathology, asthma or chronic obstructive pulmonary disease, allergy to local anesthetics, and patients on beta-blocker therapy were excluded from the study.

The patients were randomly divided into three groups (by a computer-generated randomized table) of twenty patients with Group 1 receiving IV lignocaine and intratracheal placebo (IV group), Group 2 receiving intratracheal lignocaine and IV placebo (I/T group), and Group 3 receiving IV and intratracheal placebo (placebo group). 1.5 mg/kg of 2% preservative-free lignocaine (Xylocard) was administered to each group either IV or intratracheally, and the placebo group received the same volume of normal saline. The same volume of drug and placebo (0.9% NaCl) was prepared and coded in two 10 ml syringes by the attending anesthesiologist, keeping the observer blind to the type of drug administered. The decoding of the drugs was done at the end of completion of the study. During the preoperative visit, all the patients were clinically evaluated, assessed, and investigated, and the study protocol was explained to all the patients and written informed consent taken from them. No patient received any premedication. The anesthesia protocol was standardized for all the patients. Anesthesia was induced with fentanyl 2 µg/kg and propofol 2 mg/kg. Vecuronium 0.15 mg/kg body weight was administered to facilitate endotracheal intubation. After endotracheal intubation, anesthesia was maintained with a mixture of oxygen and nitrous oxide with isoflurane. Vecuronium was administered to maintain two twitches on the neuromuscular monitor. Isoflurane was administered at 1 minimum alveolar concentration (MAC) till dural closure. At dural closure, sevoflurane was introduced to maintain 1 MAC and discontinued at the removal of pins or last surgical skin suture applied. Intraoperative monitoring included electrocardiogram, HR, pulse oximetry, capnography, invasive arterial blood pressure, central venous pressure, nasopharyngeal temperature, inhalational agent concentration, and neuromuscular monitoring using BeneView T5 monitor on Mindray Wato Ex-65 workstation. At skull pin insertion, 50 µg of injection fentanyl was administered to blunt the hemodynamic responses to skull pin insertion. Repeated doses of injection fentanyl 1 µg/kg were administered every hourly till dural closure. IV paracetamol (1 g) was given to all the patients at the end of the surgery.

The study drug was prepared and administered at the time of wound dressing by the attending anesthesiologist. After administration of the study drug, its effect on airway and circulatory reflexes was noted in terms of episodes of cough and hemodynamic parameters in each group till 5 min after extubation.

The residual neuromuscular block was reversed using neostigmine 0.05 mg/kg and glycopyrrolate 0.02 mg/kg. Patients were extubated when they were breathing spontaneously and were obeying commands. The tolerance to ETT was monitored, and number of episodes of cough was recorded during emergence and at the time of extubation. Smoothness of extubation was graded as follows:

Grade I: No cough or mild cough only during removal of ETT

Grade II: Coughing while breathing regularly

Grade III: Coughing before regular breathing is established.

Hemodynamic parameters such as HR and blood pressure (systolic, diastolic, mean arterial pressure) were recorded at baseline, after administration of study drug, before extubation, and every minute after extubation for 5 min. The total time taken for extubation was taken as the time from the discontinuation of sevoflurane till the time of endotracheal extubation.

The data collected intraoperatively were summarized and compiled. It was entered into a spreadsheet (Microsoft Excel) and then exported to data editor of SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA). The sample size was based on a similar previous study by Daelim et al[13] in which three groups of patients were studied who received intratracheal lignocaine, IV lignocaine, and placebo. With an alpha error of 5%, beta error of 20%, and power of 80%, the sample size for each group was calculated to twenty. The sample size was determined assuming that the anticipated analysis of continuous variables will be done using analysis of variance and associations between categorical variables will be assessed using Chi-square tests with Yates’ continuity correction. P < 0.05 was considered statistically significant.

RESULTS

There were no statistical differences among the three groups with respect to age, gender, weight, duration of anesthesia, and ASA class [Table 1] with all the three groups being comparable. Similarly, the mean time from the last dose of fentanyl to extubation, mean time from discontinuation of sevoflurane to extubation, and mean time interval (minutes) from the administration of study drug to extubation in the three groups were comparable and statistically insignificant [Table 2].

Table 1

Demographic data of patients in the three groups

Table 2

Mean emergence times of the patients in the three groups

Heart rate was comparable preoperatively, at the time of administration of test drugs and pre-extubation in all the three groups. However, there was a significant decrease (P < 0.001) in HR in both Group 1 (IV group) and Group 2 (intratracheal group) when compared with Group 3 (placebo group) in the postextubation period. There was no statistically significant difference in HR (P values) between Groups 1 and 2. However, there was a statistically significant difference between Group 1 versus Group 3 (P < 0.001) and Group 2 versus Group 3 starting from 1 min postextubation to 5 min postextubation [Table 3].

Table 3

Heart rate of patients in the three groups at different intervals and their intergroup comparison

The mean systolic blood pressure was comparable preoperatively, at the time of administration of the study drugs and preextubation in all the three groups. The mean systolic blood pressure in Group 1 (patients receiving IV lignocaine and intratracheal 0.9% saline) and Group 2 (patients receiving intratracheal lignocaine and IV 0.9% saline) showed an attenuation of blood pressure when compared to patients in Group 3 (patients receiving both IV and intratracheal placebo). This attenuation in blood pressure was statistically significant (P < 0.005). Hence, lignocaine 1.5 mg/kg was found to be effective in suppressing the rise in blood pressure at the time of extubation.

However, the intergroup comparison between IV group and intratracheal group was comparable and statistically insignificant suggesting the multimodal mechanism of action of lignocaine [Table 4]. There was a similar decrease in mean diastolic blood pressure in Group 1 and Group 2 starting from 1 min postextubation to 5 min postextubation (P <0.05) [Table 5].

Table 4

Systolic blood pressure of the patients at different intervals in three groups and their intergroup comparison

Table 5

Diastolic blood pressure of the patients in the three groups at different intervals and their intergroup comparison

Cough suppression was seen in Group 1 (patients receiving IV lignocaine and intratracheal 0.9% saline) and Group 2 (patients receiving intratracheal lignocaine and IV 0.9% saline). We observed that patients in Group 1 had 11 events (55%) of Grade I cough with no event of Grade III cough. The patients in Group 2 had 13 events (65%) of Grade I cough with no event of Grade III cough. The patients in Group 3 have 9 events (45%) of Grade I cough and three events of Grade III cough occurred (15%) [Table 6]. There was a cough suppression in Groups 1 and 2 as compared to placebo Group 3; however, it was not statistically significant. There were no episodes of laryngospasm or bronchospasm in our patients.

Table 6

Cough grades of the patients in the three groups

DISCUSSION

Avoidance of tachycardia, hypertension, and coughing during skull pin removal and during extubation is a desired prerequisite of every neurosurgical procedure. Lignocaine has long been used to modulate unwanted airway and circulatory responses through IV injection, endotracheal cuff inflation, intratracheal instillation, tube lubrication, and aerosolized form.[1415]

Lowrie et al.[16] evaluated the impact of tracheal extubation on changes in plasma concentrations of epinephrine and norepinephrine in 12 patients undergoing major elective surgeries. They found a significant increase in epinephrine levels from 0.9 to 1.4 pmol/ml 5 min after extubation. However, we could not measure serum lignocaine levels due to lack of facilities in our hospital.

There was no statistically significant difference in HR (P values) between Group 1 (receiving IV lignocaine) and Group 2 (receiving intratracheal lignocaine). However, there was a statistically significant difference between Group 1 (receiving IV lignocaine) versus Group 3 receiving placebo (P < 0.001) and Group 2 (receiving intratracheal lignocaine) versus Group 3 receiving placebo starting from 1 min postextubation to 5 min postextubation. A similar study was conducted by Savitha et al.[17] Ninety patients were randomly divided into three groups to receive placebo (saline), 0.5 mg/kg injection lignocaine or 1 mg/kg lignocaine. The authors found that lignocaine 1 mg/kg was superior to 0.5 mg/kg in attenuating the hemodynamic responses to tracheal extubation. Their study results were comparable to our results in terms of attenuation of circulatory and airway responses. Khezri et al.[18] did a similar study dividing the patients into two groups to receive either 2% injection lignocaine 1.5 mg/kg IV or intratracheally. Heart rate, systolic blood pressure, bucking, and number of coughs were continuously monitored for 30 min postextubation. The results in their study were comparable to our study results in terms of both circulatory and airway responses in the postextubation period. Similarly, Bidwai et al.[19] observed the HR and blood pressure response to endotracheal extubation with IV lignocaine 1 mg/kg and control group (saline). They found out that patients who received lignocaine did not have an elevation in HR or systolic blood pressure at or after extubation when compared with the saline group.

As shown in Table 2, the mean systolic blood pressure in Group 1 (patients receiving IV lignocaine and intratracheal 0.9% saline) and Group 2 (patients receiving intratracheal lignocaine and IV 0.9% saline) showed an attenuation of blood pressure when compared to patients in Group 3 (patients receiving both IV and intratracheal placebo). This attenuation in blood pressure was statistically significant (P < 0.005). Hence, lignocaine 1.5 mg/kg was found to be effective in suppressing the rise in blood pressure at the time of extubation.

However, intergroup comparison of the blood pressure between IV group and intratracheal group was comparable and statistically insignificant suggesting the multimodal mechanism of action of lignocaine. There was a similar decrease in mean diastolic blood pressure in Group 1 and Group 2 starting from 1 min postextubation to 5 min postextubation (P < 0.05). The attenuation of hemodynamic responses could have been a result of local mucosal anesthetic effect and systemic absorption of lignocaine.

Coughing during emergence from general anesthesia is a physiological response to tracheal extubation which can result in potentially dangerous patient movements, hypertension, tachycardia or other arrhythmias, myocardial ischemia, surgical bleeding, bronchospasm, increasing intraocular and intracranial pressures, especially in neurosurgical patients, which is very detrimental.

Smoothness of extubation was graded in terms of grading of cough as follows:

Grade I: No cough or mild cough only during removal of ETT

Grade II: Coughing while breathing regularly

Grade III: Coughing before regular breathing is established.

In our study, cough suppression was there in Group 1 (patients receiving IV lignocaine and intratracheal 0.9% saline) and Group 2 (patients receiving intratracheal lignocaine and IV 0.9% saline).

We observed that patients in Group 1 had 11 events (55%) of Grade I cough with no event of Grade III cough. The patients in Group 2 had 13 events (65%) of Grade I cough with no event of Grade III cough. The patients in Group 3 have 9 events (45%) of Grade I cough and three events of Grade III cough occurred (15%).

A similar study was done by George et al.;[20] a total of 114 patients undergoing elective craniotomies were included in the study. They divided the patients into three groups and were given 1 mg/kg of IV 2% lignocaine (Group 1), placebo (Group 2), 1 mg/kg of 2% lignocaine instilled down the ETT (Group 3) before skull pin removal. They found that 2% lignocaine instilled through endotracheal route was not superior to IV route or placebo in attenuating cough and extubation response when given 20–30 min before extubation. The results were contrary to our study results in terms of hemodynamic response attenuation probably because the dose of drug used in our study was higher (1.5 mg/kg) and mean time interval between the study drug and extubation was lesser (21 min).

Jee and Park[13] did a study and found that lignocaine instilled through the ETT suppresses cough if given approximately 5 min before extubation and found it to be superior to IV injection. They suggested a local mucosal effect when using this route. Nagrale et al.[21] prospectively studied ninety patients and evaluated hemodynamic effects and cough suppression of IV propofol, lignocaine, and esmolol administered 2 min before extubation. There was a significant decrease in hemodynamic response and about 90% cough suppression in the group receiving IV lignocaine 2 min before extubation. This was attributed to the fact that IV lignocaine deepens the plane of anesthesia and thus suppresses the hemodynamic and airway reflexes at extubation.

Plasma concentrations of lignocaine required to suppress the cough reflex under general anesthesia are reported to be between 2.3 and 3 µg/ml during the emergence.[19] The plasma concentration of lignocaine from endotracheal administration may be same or less than that from IV lignocaine.[22] The lignocaine administered through the ETT may spread distally due to the action of gravity in the supine position. However, the presence of wet mucous blanket might facilitate the diffusion of lignocaine proximally in the tracheobronchial tree. This may anesthetize the mucosa and block the receptors involved in the airway reflexes. Therefore, reflex suppression of endotracheal lignocaine may probably be attributable to its mucosa anesthetizing effect.

CONCLUSION

We concluded from our study that both IV and intratracheal lignocaine 1.5 mg/kg are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation when compared with the placebo. The attenuation of hemodynamic responses at the time of extubation was comparable between the patients receiving IV lignocaine and intratracheal placebo and patients receiving intratracheal lignocaine and IV placebo. Cough suppression through intratracheal route was comparable with IV route. However, cough suppression with intratracheal or IV lignocaine was superior over the placebo group.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.