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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 15  |  Issue : 4  |  Page : 216-222

Attenuation of cardiovascular responses to tracheal extubation with labetalol


Department of Anesthesiology and Intensive Care, Al-Azhar University Hospital of Girls, Cairo, Egypt

Date of Submission21-Mar-2018
Date of Acceptance15-Jul-2018
Date of Web Publication19-Jul-2018

Correspondence Address:
Mokhtar M Younes
Department of Anesthesiology and Intensive Care, Al-Azhar University Hospital, Cairo, 31952 postal code 251
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_14_18

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  Abstract 


Background Stress response to tracheal extubation causes autonomic or endocrine disturbances such as hypertension, tachycardia, and arrhythmias that may be potentially dangerous in patients with cardiovascular disease. It is better to avoid the occurrence of stress response by preemptive therapy. Various pharmacological methods are used to suppress this response, but none of them is 100% effective. So, it is desirable to use a drug with rapidly recognizable and easily treatable adverse effects.
Aim The aim of this study was to compare the effects of labetalol, fentanyl, and lidocaine in suppressing hemodynamic stress response to tracheal extubation.
Patients and methods This prospective, randomized, controlled, double-blinded study was conducted in multicenter Fakhry Hospital, Al Hussain University hospital and Al Zahra University hospital on 80 patients classified as American Society of Anesthesiologists physical status I or II who were undergoing elective general surgery under general anesthesia between January 2017 and June 2017. These 80 patients were randomized through computer-generated and sealed opaque envelope method into four equal groups, each of them with 20 patients. All patients received a standardized anesthetic protocol. Fifteen minutes before extubation, patients received either labetalol 0.25 mg/kg or fentanyl 2.0 µg/kg or lidocaine 2% 1.5 mg/kg or isotonic saline. All patients were extubated by anesthesiologists who were blinded to the studied drugs, and all were continuously monitored for 20 min after extubation. The primary outcome was hemodynamic changes, heart rate (HR) and mean arterial blood pressure (MAP), which were recorded before and after extubation. The secondary outcomes were respiratory rate and oxygen saturation (SpO2), which were recorded after extubation on room air, and the degree of sedation after extubation, as assessed by Ramsay sedation score.
Results The results of our study reveal that HR and MAP were comparable in all the groups until 10 min before extubation. Later, there was an increase in HR and MAP in lidocaine and saline groups. There was statistically significant decrease in HR and MAP in labetalol and fentanyl groups at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with lidocaine and saline groups. Moreover, there was a statistically significant decrease in HR and MAP in labetalol group at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with fentanyl group.
Conclusion We conclude that both labetalol and fentanyl effectively blunt hemodynamic response to tracheal extubation in patients undergoing elective surgeries under general anesthesia and can be safely used. Labetalol at dose of 0.25 mg/kg is a better agent than fentanyl (2.0 µg/kg) and lidocaine (1.5 mg/kg) in attenuating the sympathetic response to tracheal extubation. However, patients in the fentanyl group showed greater degree of sedation without any deleterious effects.

Keywords: fentanyl, labetalol, lidocaine, Ramsay sedation score, stress response, tracheal extubation


How to cite this article:
Younes MM, Mahareak AA, Salem EA, Nooreldin T. Attenuation of cardiovascular responses to tracheal extubation with labetalol. Al-Azhar Assiut Med J 2017;15:216-22

How to cite this URL:
Younes MM, Mahareak AA, Salem EA, Nooreldin T. Attenuation of cardiovascular responses to tracheal extubation with labetalol. Al-Azhar Assiut Med J [serial online] 2017 [cited 2018 Oct 20];15:216-22. Available from: http://www.azmj.eg.net/text.asp?2017/15/4/216/237128




  Introduction Top


Endotracheal intubation is an essential part of general anesthesia techniques for major surgical procedures. Both intubation and extubation are associated with various cardiovascular and airway responses leading to tachycardia, hypertension, arrhythmias, myocardial ischemia, coughing, bronchospasm, increased bleeding, raised intracranial, and intraocular pressure [1].

Closed monitoring and control of blood pressure (BP) are very important at the end of surgery and during tracheal extubation to avoid brief periods of hypertension during emergence from anesthesia and occurrence of postoperative bleeding. It is better to avoid the occurrence of hypertension by preemptive therapy. Various strategies have been employed to control emergence hypertension such as extubation in a deep plane of anesthesia, and many drugs as diltiazem, lidocaine, labetalol, esmolol, and intravenous (i.v.) opiates such as morphine, fentanyl, and remifentanil are used. However, there is no single or commonly accepted method [2].

Labetalol is a unique oral and parenteral antihypertensive adrenergic antagonist that has an effect on both selective α1 and nonselective β1 and β2. It has a rapid onset of action, it reaches its peak effect at 5–15 min after i.v. injection, it rapidly redistributes (5.9-min redistribution half-life) [3], and it lowers BP by decreasing systemic vascular resistance (α1-blockade), whereas reflex tachycardia is attenuated by simultaneous β-blockade. Cardiac output remains unchanged [4]. Fentanyl is a lipid-soluble potent synthetic opioid agonist. It has a rapid onset of action, its peak effect is at 5–7 min, and it has short duration of action of 30–60 min. It decreases BP and heart rate (HR) through vasodilatation, depression of vasomotor, and stimulation of vagal center. Overdose is treated by pure opioid antagonist naloxone [5].

Lidocaine is an amide-type local anesthetic that exerts its pharmacological action through the block of sodium channels in neural tissues, thereby interrupting neuronal transmission. The systemic effects of lidocaine are also probably or at least partially, related to this mechanism. The exact mechanism by which i.v. lidocaine provides systemic analgesia remains largely unknown [6].

Lidocaine is one of the commonly used drugs by i.v. route, through endotracheal tube (ETT) cuff, or laryngotracheal route by topical spray or jelly to blunt the circulatory and airway reflexes during emergence from general anesthesia.

This study was conducted to compare the efficacy and preventative effects of labetalol, fentanyl, and lidocaine in controlling BP and pulse rate during emergence from anesthesia.


  Patients and methods Top


This prospective, randomized, controlled, double-blind study was conducted in multicenter Fakhry Hospital, Al Hussain University hospital and Al Zahra University hospital on 80 patients classified as American Society of Anesthesiologists physical status I or II from January 2017 to June 2017. Following the local Ethics Committee approval, a written informed consent was taken. All patients were older than 21 years, of both sex, weighing 55–85 kg, with American Society of Anesthesiologists physical status I or II, and their Mallampatti classification was equal to 1, and were scheduled for elective general surgery under general anesthesia. Patients having compromised renal, or cardiac status, an upper respiratory tract infection or asthma, history of pulmonary disease, anticipated difficult intubation, hypertension, controlled hypertension on medication, baseline pulse less than 60 beats/min, and baseline systolic blood pressure (SBP) less than 90 mmHg were excluded from the study. These 80 patients were randomized through computer-generated and sealed opaque envelope method into four equal groups, each of them with 20 patients: group L received labetalol 0.25 mg/kg, group F received fentanyl 2 μg/kg, group X received lidocaine 1.5 mg/kg, and group S received 10-ml saline.

In preanesthetic waiting area, after securing an i.v. access, patients were premedicated with injection midazolam 2 mg and ondansetron 4 mg. Hemodynamic parameters such as HR, BP, oxygen saturation, and Ramsay sedation score were recorded before and after premedication.

In the operation theater, the patient’s body weight, fasting, consent, and preanesthetic check-up were checked. On the operating room table, standard anesthesia technique was used. Patients were induced with propofol (2 mg/kg), morphine (0.1 mg/kg), and then atracurium (0.5 mg/kg). They were ventilated with 40% oxygen in nitrous oxide (N2O) with sevoflurane 2–3%, using circle system with a flow of 3 l. Patients were intubated using 7.5 mm internal diameter ETT with large-volume low-pressure cuff. Anesthesia was maintained on O2 : N2O (0.3 L : 0.3 L) and sevoflurane 2–3% dial concentration adjusted to maintain minimum alveolar concentration. Fifteen minutes before expected last surgical suture ensuring train-of-four ratio 0.3 (train-of-four watch), sevoflurane was stopped, and equal amount of tested drugs (10 ml) was given over a period of 5 min. The tested drugs were prepared by an anesthesiologist who was not involved in the study. The residual muscle paralysis was reversed using neostigmine (0.05 mg/kg) and glycopyrrolate (0.02 mg/kg). Pharyngeal secretions were gently aspirated before the sevoflurane vaporizer was turned off.

The primary outcome was hemodynamic changes before and after extubation, and was assessed before premedication (base line), after premedication, after induction, at and after intubation, 10 and 5 min before extubation, at extubation, and 5, 10, and 20 min after tracheal extubation.

The secondary outcome was respiratory rate and oxygen saturation, which were recorded 5, 10, and 20 min after tracheal extubation on room air, and the degree of sedation after extubation, which was assessed before premedication (base line), after premedication, at extubation, and 5, 10, and 20 min after tracheal extubation by Ramsay sedation score.

Ramsay sedation score [7]

  1. Patient is anxious and agitated or restless, or both.
  2. Patient is co-operative, oriented, and tranquil.
  3. Patient responds to commands only.
  4. Patient exhibits brisk response to light glabellar tap or loud auditory stimulus.
  5. Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus.
  6. Patient exhibits no response.


We defined the following terms for study:
  1. Hypotension − defined as SBP less than 25% of baseline value or 90 mmHg, whichever is lower.
  2. Hypertension − defined as SBP greater than 25% of baseline value or 150 mmHg, whichever is higher.
  3. Tachycardia − defined as HR greater than 25% of baseline value.
  4. Bradycardia − defined as HR less than 60 beats/min.
  5. Bradypnea − defined as respiratory rate less than 12 cycles per minute.
  6. An arrhythmia − any ventricular or supraventricular premature beat or any rhythm other than sinus.


Statistical analysis

Data were coded and entered using the statistical package SPSS version 22 (SPSS Inc., Chicago, Illinois, USA). Data were summarized using mean and SD for normally distributed quantitative variables, and comparisons between groups were done using analysis of variance followed by post-hoc test if there is significance. For Ramsay sedation scores, a median and range value were used for description, and Kruskal–Wallis test was used to compare among the four groups; Mann–Whitney U-test was used for pairwise comparisons when Kruskal–Wallis test is significant. Qualitative data were presented as frequencies and percentages, and χ2-test was used to compare among the four groups. The significance level was set at P less than or equal to 0.05.


  Results Top


All patients completed the study, with 20 patients in each group. Thus, the data from the 80 patients were included and analyzed.

There was no statistically significant difference among the four groups regarding patients’ demographics data. The mean age of patients was 44±2, 45±6, 44.9±4.23, and 46±5 years for labetalol, fentanyl, lidocaine, and saline groups, respectively. The mean weights of four groups were 73±8, 75±9, 74±7, and 79±8 kg, respectively ([Table 1]).
Table 1 Patient demographic data, surgical duration, anesthesia duration, and recovery time

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Regarding HR, it was comparable in all the groups until 10 min before extubation. Later, there was an increase in HR in lidocaine and saline groups. There was a statistically significant decrease in HR in labetalol and fentanyl groups at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with the lidocaine and saline groups.

Moreover, there was a statistically significant decrease in HR in labetalol group at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with fentanyl group ([Table 2]).
Table 2 Heart rate changes in different studied groups

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Regarding mean arterial pressure (MAP), it was comparable in all the groups until 10 min before extubation. Later, there was an increase in MAP in lidocaine and saline groups. There was a statistically significant decrease in MAP in labetalol and fentanyl groups at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with lidocaine and saline groups. Moreover, there was a statistically significant decrease in MAP in labetalol group at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with the fentanyl group ([Table 3]).
Table 3 Mean arterial blood pressure (mmHg) changes in different studied groups

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Regarding Ramsay sedation score, there was no significant difference between groups, at preinduction, after premedication, and 20 min after extubation. However, patients in the fentanyl group showed greater degree of sedation during suctioning of airway, extubation, and 5 min and10 min after extubation when compared with the other groups ([Table 4]).
Table 4 Ramsay sedation score in different studied groups

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Regarding respiratory rate, there were no clinically significant decreases in respiratory rate in all groups after extubation. In fentanyl group, patients were sedated, but respiratory rate was not affected ([Table 5]).
Table 5 Respiratory rate in different studied groups

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Regarding oxygen saturation (SpO2), there was no clinically significant decreases in respiratory rate in all groups after extubation. In fentanyl group, patients were sedated, but oxygen saturation was not affected ([Table 6]).
Table 6 Oxygen saturation in different studied groups

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  Discussion Top


Induction and emergence from general anesthesia is always associated with stress response. Many theories have been put forward to explain the sudden increase in HR and BP during extubation such as a rise in catecholamine, airway irritation owing to suction, and intense pain from surgical wounds and emergence [8].

However, much attention has been paid to attenuate stress response during intubation when compared with extubation.

This study aimed to compare the efficacy and preventative effects of labetalol, fentanyl, and lidocaine in controlling BP and pulse rate during emergence from general anesthesia in elective surgery.

Patients in all groups were similar in demographic variables including age, sex, weight, and duration of anesthesia, as these factors can affect the results.

In our study, HR and MAP were comparable in all the groups until 10 min before extubation. Later, there was an increase in HR and MAP in lidocaine and saline groups. There was a statistically significant decrease in HR and MAP in labetalol and fentanyl groups at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with lidocaine and saline groups.

Moreover, there was a statistically significant decrease in HR and MAP in labetalol group at 5 min before extubation, at extubation, and 5 and 10 min after extubation, in comparison with fentanyl group.

In agreement with the current result, two studies were conducted by Babita et al. [9] and Meftahuzzaman et al. [10] to examine attenuation of stress response during intubation. On comparison of the efficacy of labetalol and fentanyl to attenuate sympathetic response to tracheal intubation, they concluded that both fentanyl and labetalol effectively blunt the hemodynamic response to tracheal intubation and can be safely used. However, in lower doses, labetalol 0.25 mg/kg is a better agent than fentanyl 2.0 µg/kg in attenuating the sympathomimetic response to laryngoscopy and intubation [9],[10].

Nishina et al. [11] examined the effect of i.v. fentanyl (1 or 2 µg/kg) on hemodynamic changes during tracheal extubation and emergence from anesthesia, and they concluded that a bolus dose of i.v. fentanyl 2 µg/kg given at the time of peritoneal closure was of value in attenuating the cardiovascular changes associated with tracheal extubation and emergence from anesthesia.

Moreover, in agreement with our result, Jee and Park [12] investigated whether lidocaine sprayed down the ETT would attenuate airway-circulatory reflexes during emergence. They compared the reflex responses after endotracheal or i.v. lidocaine in 75 patients receiving a standardized anesthetic protocol. At the end of surgery, the patients were divided into three groups (n=25 for each group): given no drug (group 1), given 1 mg/kg of 2% lidocaine sprayed down the ETT 5 min before extubation (group 2), or given the same dose i.v. 3 min before extubation (group 3). The results indicate that lidocaine sprayed down the ETT suppresses the reflexes, whereas using the same i.v. dose does not suppress the reflexes, which is probably attributable to the mucosa-anesthetizing effect of lidocaine [12].

In contrary to our result, Shabnum et al. [13] investigated whether intratracheal lidocaine 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 i.v. and placebo groups. They conclude that both i.v. and intratracheal lidocaine are effective in attenuation of hemodynamic response if given within 20 min from skull pin removal to extubation, [13] but in neurosurgery, other factors affect stress response to tracheal extubation as the patient is always extubated in deep plane of anesthesia.

Consistent with our result, one study conducted by Attari et al. [14] compared the efficacy of morphine and labetalol in controlling BP and pulse during emergence from anesthesia in brain tumors craniotomy and found that patients receiving labetalol had lower systolic pressure and diastolic pressure at the time of extubation. Patients receiving labetalol had better hemodynamic stability, but in morphine group, some fluctuations in BP and HR were observed [14].

The results of our study reveal that there were no clinically significant decreases in respiratory rate or SpO2 in all groups after extubation. Patients in fentanyl group showed greater degree of sedation during suctioning of airway in comparison with other groups.

Comparable with our result, a study conducted by Nishina et al. [11] examined the effects of i.v. fentanyl (1 or 2 µg/kg) on hemodynamic changes during tracheal extubation and found that a bolus dose of i.v. fentanyl 2 µg/kg attenuates the cardiovascular changes, without delay in recovery.

Moreover, another two studies conducted by Rani et al. [15] and Aksu et al. [16] compared the efficacy of dexmedetomidine and fentanyl in attenuation of hemodynamic and airway reflexes during emergence and extubation, and they observed that both groups had a similar duration of recovery from anesthesia without delay in emergence.

In contrary to our result, one study conducted by Attari et al. [14] compared the efficacy of morphine and labetalol in controlling BP and pulse during emergence from anesthesia in brain tumors craniotomy, and they found that the extubation time and the emergence from anesthesia were shorter, and the awareness of patients was rapider in labetalol group [12] but this was owing to the strong sedative effect of morphine.


  Conclusion Top


We conclude that both labetalol and fentanyl effectively blunt the hemodynamic response to tracheal extubation in patients undergoing elective surgeries under general anesthesia and can be safely used. Labetalol at dose of 0.25 mg/kg is a better agent than fentanyl (2.0 µg/kg) and xylocaine (1.5 mg/kg) in attenuating the sympathetic response to tracheal extubation. However, patients in fentanyl group showed greater degree of sedation without any deleterious effects.

Recommendation

In our study, we used single dose of studied drugs. In another study, we recommend the use several doses of studied drugs to obtain good result without adverse effect.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Minogue SC, Ralph J, Lampa MJ. Laryngotracheal topicalization with lidocaine before intubation decreases the incidence of coughing on emergence from general anesthesia. Anesth Analg 2004; 99:1253–1257.  Back to cited text no. 1
    
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Hartley M, Vaughan RS. Problems associated with tracheal extubation. Br J Anaesth 1993; 71:561–568.  Back to cited text no. 2
    
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Kanto J, Allonen H, Kleimola T. Pharmacokinetics of labetalol in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1981; 19:41–44.  Back to cited text no. 3
    
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Stoelting RK, Hillier SC. Pharmacology & physiology in anesthetic practice. In: Robert KS, Simon CH, editors. Handbook of pharmacology and physiology in anesthetic practice. 2nd ed. Philadelphia, USA: Lippincott Williams & Wilkins 2006. 347. 87–342.  Back to cited text no. 4
    
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Martin DE, Rosenberg H, Auk burg SJ, Bartkowski RR, Edwards MWJr. Low-dose fentanyl blunts responses to tracheal intubation. Anesth Analg 1982; 61:680–684.  Back to cited text no. 5
    
6.
De Oliveira CM, Issy AM, Sakata RK. Intra operative intravenous lidocaine. Rev Bras Anestesiol 2010; 60:325–333.  Back to cited text no. 6
    
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Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J 1974; 2:656–659.  Back to cited text no. 7
    
8.
Nishina K, Mikawa K, Maekawa N, Obara H. Attenuation of cardiovascular responses to tracheal extubation with diltiazem. Anesth Analg 1995; 80:1217–1222.  Back to cited text no. 8
    
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Babita SB, Saiyed A, Meena R, Verma I. A comparative study of labetalol and fentanyl on the sympathomimetic response to laryngoscopy and intubation in vascular surgeries. Karnataka Anesth J 2015; 1:64–68.  Back to cited text no. 9
    
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Meftahuzzaman SM, Islam MM, Ireen ST, Islam MR, Kabir H. Comparison of efficacy of labetalol and fentanyl for attenuating reflex responses to laryngoscopy and intubation. Mymensingh Med J 2014; 23:242–248.  Back to cited text no. 10
    
11.
Nishina K, Mikawa K, Maekawa N, Obara H. Fentanyl attenuates cardiovascular responses to tracheal extubation. Acta Anaesthesiol Scand 1995; 39:85–89.  Back to cited text no. 11
    
12.
Jee D, Park SY. Lidocaine sprayed down the endotracheal tube attenuates the airway-circulatory reflexes by local anesthesia during emergence and extubation. Anesth Analg 2003; 96:293–297.  Back to cited text no. 12
    
13.
Shabnum T, Ali Z, Naqash IA. Effects of lignocaine administered intravenously or intratracheally on airway and hemodynamic responses during emergence and extubation in patients undergoing elective craniotomies in supine Position. Anesth Essays Res 2017; 11:216–222.  Back to cited text no. 13
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14.
Attari MA, Tayyari F, Narimani N. Comparing the effect of labetalol versus morphine on controlling blood pressure and pulse rate during emergence from anesthesia after craniotomy. Adv Biomed Res 2017; 6:127.  Back to cited text no. 14
    
15.
Rani P, Hemanth Kumar VR, Ravishankar M, Sivashanmugam T, Trilogasundary M. Rapid and reliable smooth extubation − comparison of fentanyl with dexmedetomidine: a randomized, double-blind clinical trial. Anesth Essays Res 2016; 10:597–601.  Back to cited text no. 15
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16.
Aksu R, Akin A, Biçer C, Esmaoğlu A, Tosun Z, Boyaci A. Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes and hemodynamic responses to tracheal extubation during rhinoplasty: a double-blind, randomized, controlled study. Curr Ther Res Clin Exp 2009; 70:209–220.  Back to cited text no. 16
    



 
 
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