|Year : 2018 | Volume
| Issue : 4 | Page : 778-785
Intravenous low dose fentanyl versus lignocaine in attenuating the hemodynamic responses during endotracheal intubation: A randomized double-blind study
Ranjithkumar R Thippeswamy, Supreeth R Shetty
Department of Anaesthesiology and Critical Care, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
|Date of Web Publication||18-Dec-2018|
Dr. Supreeth R Shetty
Department of Anaesthesiology and Critical Care, SDM College of Medical Sciences and Hospital, Sattur, Dharwad - 580 009, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The laryngotracheal stimulation is known to cause reflex sympathoadrenal response with a marked increase in heart rate and blood pressure. Arrhythmias can be precipitated. The harmful nature of this response has been noted in patients at risk. Therefore, it is important to find an effective means of attenuating sympathetic response to laryngoscopy and intubation. The present study is undertaken to determine the efficacy of intravenous low dose fentanyl (2 μg/kg) and lignocaine (1.5 mg/kg) in attenuating hemodynamic response to laryngoscopy and tracheal intubation. Aim: The aim of this study is to compare the efficacy of intravenous low dose fentanyl (2 μg/kg) versus lignocaine (1.5 mg/kg) in attenuating the hemodynamic responses during endotracheal intubation. Settings and Design: This was double-blinded randomized controlled study. Materials and Methods: After obtaining institutional ethical clearance and informed consent, a total of 90 patients, with the American Society of Anaesthesiologists Physical Status I and II scheduled for elective surgeries, were selected randomly and divided into three groups of 30 each. The general anesthesia technique was standardized for all three groups as follows: Group 1 (control-received normal saline), Group 2 (Lignocaine 1.5 mg/kg), and Group 3 (Fentanyl 2 μg/kg). Heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were recorded preinduction, postinduction and 1,3,5,7, and 10 min after endotracheal intubation. Statistical Analysis: Descriptive data presented as mean ± standard deviation and in percentage. Multiple group comparisons were made using one-way ANOVA followed by unpaired “t” test for pairwise comparison. “P” <0.05 was considered for statistical significance. Results: The fentanyl group showed significantly lesser rise (26%) in heart rate compared to lignocaine (33%) (P = 0.018) and control group (42.5%) (P = 0.000). The lignocaine group showed lesser rise in systolic blood pressure (14.5%) compared to control group (20%) (P = 0.000) at intubation. The fentanyl group showed a significant decrease in systolic blood pressure after administration, which came back to normal at 7 min following intubation and again decreased 10 min after intubation. Conclusion: Lignocaine and fentanyl both attenuated the rise in heart rate, though fentanyl was better. Lignocaine attenuated the rise in blood pressure with intubation whereas fentanyl prevented it totally. Of the two drugs low dose fentanyl 2 μg/kg i. v. bolus provides a consistent, reliable, and effective attenuation as compared to lignocaine 1.5 mg/kg i. v. bolus.
Keywords: Attenuation, intubation, laryngoscopy, lignocaine
|How to cite this article:|
Thippeswamy RR, Shetty SR. Intravenous low dose fentanyl versus lignocaine in attenuating the hemodynamic responses during endotracheal intubation: A randomized double-blind study. Anesth Essays Res 2018;12:778-85
|How to cite this URL:|
Thippeswamy RR, Shetty SR. Intravenous low dose fentanyl versus lignocaine in attenuating the hemodynamic responses during endotracheal intubation: A randomized double-blind study. Anesth Essays Res [serial online] 2018 [cited 2019 May 20];12:778-85. Available from: http://www.aeronline.org/text.asp?2018/12/4/778/247631
| Introduction|| |
The circulatory responses to laryngeal and tracheal stimulation following laryngoscopy and tracheal intubation were documented by Reid and Brace, 1940 and King et al., 1951 and interpreted as reflex sympathoadrenal stimulation.” Increase in mean arterial pressure of an average of 25 mm Hg was observed in normotensive patients following laryngoscopy and intubation under anesthesia with thiopentone, nitrous oxide, oxygen, and suxamethonium.
Although the increase in heart rate and blood pressure due to sympathoadrenal response are short-lived, they might have detrimental effects in high-risk patients, especially those with cardiovascular diseases, increased intracranial pressure or anomalies of cerebral vessels.
Postintubation pressor responses have been associated with ST-segment changes and ventricular arrhythmias. Catecholamine levels change significantly. Norepinephrine levels may double and continue for 4–8 min; epinephrine levels may quadruple. The endocrine stress response is also seen. Some authors, in fact, consider the intubation period one of the periods of greatest risk in surgical patients with coronary artery diseases. Although the response may be transient, it is invariable, significant, often persistent, and of great concern.
Laryngoscopy and tracheal intubations are also employed for nonanesthetic purposes. Diagnostic direct laryngoscopy and fiberoptic bronchoscopy for diagnosis or intubation are being commonly used. Endotracheal intubation may be required for prevention of aspiration and protection of airway and mechanical ventilation. All these procedures can also produce sympathetic responses. Many of these patients are at increased risk or critically ill.
Hassani et al. compared fentanyl and fentanyl plus lidocaine effectively decreased the hemodynamic response to tracheal intubation, however, neither fentanyl nor fentanyl plus lidocaine, could inhibit all hemodynamic responses, moreover fentanyl plus lidocaine was not more effective than fentanyl alone.
Gurulingappa et al. showed attenuation of pressor response is seen both with lignocaine and fentanyl. Of the two drugs fentanyl 4 μg/kg intravenous (iv) bolus provides a consistent, reliable and effective attenuation as compared to lignocaine 1.5 mg/kg iv Bolus.
With advances in medicine, the number of high-risk patients coming for surgeries has steadily increased.
Therefore it is important to find an effective means of attenuating sympathetic response to laryngoscopy and intubation.
The present study is undertaken to determine the efficacy of iv low dose of fentanyl (2 μg/kg) and lignocaine (1.5 mg/kg) in attenuating sympathetic response to laryngoscopy and tracheal intubation.
The superiority of fentanyl over lignocaine or vice versa will also be determined.
| Materials and Methods|| |
A double-blind randomized controlled comparative study was carried out in the Department of Anaesthesia, Navodaya Medical College and Hospital, Raichur from June 2012 to June 2014 in 90 patients posted for elective orthopedic, gynecological and General surgeries after obtaining institutional ethical clearance and written informed consent. General anesthesia was provided with endotracheal intubation for all the patients.
- Patients scheduled for elective surgeries
- Age between 18 and 60 years of both the sexes
- Patients with the American Society of Anaesthesiologists (ASA) Grade I or II
- Mallampatti airway assessment of Grade I and II.
- Unwilling patients
- Emergency surgeries
- Anticipated difficult intubation
- Patients with ASA Grade III or more
- Patients with cardiovascular diseases
- Patients on beta blockers or calcium channel blockers
- Patients undergoing procedures requiring the head/neck manipulations, nasogastric tube insertion, throat packing.
All the patients falling under inclusion criteria were numbered and every nth patient was selected by systemic random sampling procedure. The patients were randomly allocated into three groups of 30 each, Group-I (Control Group), Group-II (Lignocaine Group), and Group-III (Fentanyl Group) using sealed envelope technique which were opened just before shifting the patient to the operation theater. Trained anesthetist who had not participated in the study generated the random allocation sequence, enrolling participants and assigned participants to the interventions.
Sample size calculation
Using the results of the previously conducted study and substituting the values below stated formula the sample size of 30 in each group was arrived at:
Where, Zα = 1.65, Zβ = 0.84, Power = 80%
S1 = Standard deviation of lignocaine group
S2 = Standard deviation of fentanyl group
X1 = Mean deviation of lignocaine group
X2 = Mean deviation of fentanyl group
A careful preanesthetic evaluation was done by taking history and by clinical examination. Patients pulse rate, blood pressure, respiratory rate, and relevant clinical signs and symptoms were noted. All the patients received tablet Alprazolam 0.5 mg orally at night on the day before surgery.
The following investigations were done in elective cases:
- Blood: Hemoglobin %, bleeding time, clothing time, platelet count
- Total blood cell count and differential white blood count
- Blood grouping and cross matching
- Urine: Sugar, protein, and microscopy
- HIV test and hepatitis B virus surface antigen test
- Chest X-ray and electrocardiogram (ECG)
- Renal function test-blood urea, serum creatinine.
- Liver function tests
- Allocation of the patients: All the selected patients were allocated into three groups consisting of 30 patients each.
- Group-I was control group. In this group, no drug was administered for attenuating sympathetic response to laryngoscopy and intubation
- Group-II was lignocaine group. Here, patients received 1.5 mg/kg lignocaine IV, 3 min before laryngoscopy and intubation
- Group-III was fentanyl group. All the patients in this group received 2 μg/kg of fentanyl IV, 5 min before laryngoscopy and intubation.
Preparation in the operation theater
All drugs and equipment were checked and kept ready before starting the anesthetic procedure. On the day of surgery IV line was secured with 18G cannula. On entering the OT, pulse oximeter, noninvasive blood pressure, ECG, and End-tidal (ET) CO2 monitors were connected. A preinduction Heart rate, systolic and diastolic blood pressure were recorded. Preloading with IV infusion of the crystalloid solution was started.
All the patients were preoxygenated with 100% oxygen for 3 min before induction using Bain's circuit with a close-fitting face-mask.
Induction was achieved with injection thiopentone sodium 5 mg/kg IV given in 2.5% solution. After induction (loss of eyelash reflex), bag and mask ventilation checked. Depolarizing muscle relaxant injection succinylcholine 2 mg/kg IV was administered. Oral laryngoscopy and endotracheal intubation were done with appropriate sized, disposable, high volume low pressure cuffed ET tube within 15–20 s.
All patients were ventilated with 4 L/min of oxygen and 6 L/min of nitrous oxide. No additional agents were given for the first 10 min postintubation nor any surgical stimulus was given to these patients. All patients who required the second attempt at intubation were excluded from the study.
The heart rate, blood pressure, and SpO2 were recorded at the following time intervals.
After Laryngoscopy and intubation:
- 1 min after intubation
- 3 min after intubation
- 5 min after intubation
- 7 min after intubation
- 10 min after intubation.
At the end of 10 min monitored period during which time the patient has been cleaned and draped, surgery is commenced.
Patients were connected to Bain's circuit, and anesthesia was maintained with oxygen (33%), N2O (67%), halothane 0.5% and nondepolarizing muscle relaxant vecuronium bromide at a dose of 0.05 mg/kg IV and intermittent positive pressure ventilation.
Adequacy of ventilation was monitored clinically, SpO2 was maintained at 99%–100% and ETCO2 was maintained between 35 and 45 mm of Hg.
Positioning, epinephrine infiltration throat packing, and surgery were withheld until the completion of recording.
At the end of the surgery reversal was done with Injection neostigmine 0.05 mg/kg and Injection glycopyrrolate 0.008 mg/kg IV.
An observation was made related to adverse effects of drugs and anesthesia related problems and was attended to appropriately.
Descriptive data presented as mean ± SD and in percentage. Multiple group comparisons were made by one-way analysis of variance (ANOVA) followed by unpaired “t” test for pairwise comparison. For all the tests, a “P” < 0.05 was considered for statistical significance. Statistical software SAS 9.2, SPSS 19.0 (IBM Corp, Armonk, NY, USA), were used for the analysis of data and Microsoft Word and Excel have been used to generate graphs and tables.
| Observation and Results|| |
A total of 90 ASA 1 and two patients aged 18–60 years posted for elective gynecological, surgical and orthopedics surgeries were randomly selected.
[Figure 1] shows age distribution in control and study groups. The age range was 18–60 years for control and study groups. The mean values of age with standard deviations are 42.63 ± 9.27, 43.17 ± 11.7, and 44.93 ± 9.78 for control, lignocaine, and fentanyl groups respectively. There was no significant difference between the three groups (P > 0.05) [Figure 1].
- In the control group, 60% of the patients were male and 40% of the patients are female
- Lignocaine group had 53% of male and 47% of female patients
- Fentanyl group contained 60% of male and 40% of female patients [Figure 2].
No significant difference was observed in sex-wise distribution of the cases between three groups (P > 0.05).
Weight range in the control group is 40–70 kg. Mean value of weight is 53.33 with a standard deviation of ± 5.72.
In study groups, weight ranges for lignocaine and fentanyl groups are 40–70 kg respectively. Mean values and standard deviations of weight are 56.3 ± 6.83 and 55 ± 5.8 kg, respectively.
With regard to weight, the difference between the three groups is not statistically significant (P > 0.05).
One-way ANOVA study showed significant variations in heart rate before and after induction and at time intervals of 1, 3, 5, 7, and 10 min from the onset of laryngoscopy and intubation (P < 0.001 and P < 0.01) [Table 1].
The difference in heart rate between control and lignocaine groups remains highly significant at all times of assessment (P < 0.001).
The maximum increase in heart rate is 42.5% in the control group and 33% in lignocaine group. It is statistically highly significant (P < 0.001) [Table 1].
It reaches to a level which is clinically less significant by the end of 7 min in the control group and 5 min in lignocaine group.
The difference in heart rate between control and fentanyl group remains statistically significant at all times of assessment (P <.001).
The maximum increase in heart rate is 42.5% in control group and 26% in fentanyl group. Attenuation of heart rate by fentanyl when compared with control group is highly significant (P < 0.001) [Table 1].
Increase in heart rate remains clinically significant until the end of 5 min in control group and 3 min in the fentanyl group from the onset of laryngoscopy and intubation.
There appeared no significant difference in heart rate at pre and postinduction levels between lignocaine and fentanyl groups (P = 0.42 and 0.97).
The heart rate response between lignocaine and fentanyl group is clinically and statistically highly significant at 1 and 3 min (P < 0.001) and significant at 5 min (P < 0.01).
No clinical or statistical significance appears between lignocaine and fentanyl at 7 and 10 min (P = 0.13 and 0.64).
A statistically significant difference is observed among all the groups at subsequent assessments (P < 0.001 and P < 0.05) [Table 1].
Attenuation of the rise in systolic blood pressure is significant in lignocaine group. A rise of only 14.5% is observed when compared with 20% in control group (P < 0.05) [Table 2].
A similar attenuation is highly significant with the fentanyl group. There was only 7.2% rise in systolic blood pressure (P < 0.001).
It returned nearer to basal values earlier in both lignocaine and fentanyl groups (5 min) than in the control group (7 min).
Attenuation of systolic blood pressure is highly significant with fentanyl when compared with lignocaine. A maximum rise of only 7.2% was seen (P < 0.001) [Table 2].
One-way ANOVA shows no significant difference among all the groups at pre- and post-induction levels (P = 0.81; P = 0.29).
A significant difference is observed in all the groups at subsequent assessments up to 7 min. P < 0.001 to P < 0.01.
Suppression of maximum rise in diastolic blood pressure by lignocaine is statistically significant (P < 0.01). Maximum rise is 12.6% in lignocaine group and 18% in control group [Table 3].
Fentanyl is also efficient in attenuating the rise in diastolic blood pressure. The maximum rise was only 6%. Statistically, it is highly significant (P = 0.001).
When compared with lignocaine fentanyl shows highly significant suppression of diastolic blood pressure. The maximum rise was 12.6% and 6% in lignocaine and fentanyl groups, respectively (P < 0.001) [Table 3].
One-way ANOVA shows no significant difference among three groups before and after induction (P = 0.47 and P = 0.24).
A significant difference is seen in all the groups at 1, 3, 5, and 7 min interval (P < 0.01 to P < 0.001).
Attenuation of pressure response by lignocaine when compared with control is significant (P < 0.01). The maximum rise is 13.8% in lignocaine group whereas it is 19% in control group [Table 4].
When compared with control fentanyl is highly significant in attenuating pressure response. The fentanyl group shows 6.5% increase while control shows 18.8% (P < 0.001) [Table 4].
Among the two study groups, fentanyl is highly significantly in attenuating pressure response. Lignocaine shows 13.8% increase in mean arterial pressure. But fentanyl shows only 6.5% increase (P < 0.001) [Table 4].
| Discussion|| |
Fentanyl and lignocaine (xylocaine) have undergone many clinical trials in combination with other drugs in relation to attenuation of the cardiovascular response to laryngoscopy and intubation.
The present study was done to evaluate the efficiency of fentanyl and lingnocaine versus control in attenuation the cardiovascular response induced, rise of blood pressure and heart rate during direct laryngoscopy and endotracheal intubation in ASA Grade-I and II patients.
In our study, heart rate increased by 42.3% when compared with preinduction value in control group (P < 0.001). Similar increase with lignocaine was 33%, and fentanyl was 26%. Both lignocaine and fentanyl attenuated the heart rate highly significantly (P < 0.001). It reaches to a level which is clinically less significant by the end of 7 min in control group, and 5 min in lignocaine and fentanyl groups. Suppression of maximum rise in heart rate by fentanyl is statistically highly significant when compared with lignocaine (P < 0.001). It remains significant until 5 min.
In control group, systolic blood pressure increased maximally after 1 min from the onset of laryngoscopy and intubation. It gradually decreased to preinduction level over 10 min. With administration of lignocaine maximum increase compared to preinduction value was 14.5% and with fentanyl it was only 7.2%. Both when compared with control showed significant suppression (P < 0.05 and P < 0.001). Among the two drugs, fentanyl showed the better result (P < 0.001).
The maximum increase in diastolic blood pressure was 18% when compared with preinduction value in control group (P < 0.001). It was 12.6% and 6% in lignocaine and fentanyl groups, respectively. “P” < 0.01 with lignocaine and < 0.001 with fentanyl was obtained. Both were statistically significant. Attenuation by fentanyl is highly significant than lignocaine (P < 0.001).
Similarly, mean arterial pressure increased by 19% from the preinduction value in control group at 1 min (P < 0.001) and gradually reached a basal level over 10 min. Lignocaine limited the maximum rise to 13.8% (P < 0.01) while fentanyl to only 6.5% (P < 0.001). It reached preinduction level over 7 min in lignocaine group and 5 min in fentanyl group. The attenuation of mean arterial pressure by fentanyl is highly significant when compared with lignocaine (P < 0.001).
The efficacy of fentanyl over lignocaine has been verified in many other studies.,, Both lignocaine and fentanyl together are also recommended to suppress the pressor response. Many factors affect the cardiovascular changes associated with laryngoscopy and intubation. Age, drugs, type, and duration of procedures, depth of anesthesia, hypoxia, and hypercarbia influence the hemodynamic response.
Different drugs used for premedication, induction, relaxation, and maintenance of anaesthesia influence the sympathetic response to laryngoscopy and intubation. Thiopentone was selected for induction because it continues to be the most popular anesthetic agent. In normovolemic patients thiopentone of 5 mg/kg IV can transiently decrease 10–20 mmHg blood pressure and increase the heart rate by 15-20 beats/min. There is an increase in catecholamine levels; both noradrenaline and adrenaline. Blood pressure is usually offset by increase in heart rate.
Succinylcholine has negative inotropic and chronotropic effect. It acts on the muscarinic receptors of the SA node. These are attenuated by prior glycopyrollate premedication. A marked pressure and noradrenergic response were noted when intubation was performed under succinylcholine.
Nitrous oxide may increase the tone of the sympathetic nervous system. The direct action of N20 is negative inotropism which is offset by increased sympathetic tone. Halothane has the potency to decrease the heart rate, but it does not appreciably change the heart rate. It reduces afterload by affecting the mechanical properties of the arterial tree.
Nasotracheal intubation comprises three distinct stages as follows: (a) nasopharyngeal intubation (b) direct laryngoscopy to identify the vocal cords and (c) passage of the tracheal tube into the trachea. The nasopharyngeal intubation causes a significant pressor response. This response is increased with the passage of the tracheal tube into the larynx and trachea. Direct laryngoscopy did not increase the response significantly in the study of Singh and Smith. We included only laryngoscopy and orotracheal intubation in our study.
The most important laryngoscopic factor influencing the cardiovascular response is found to be the duration of laryngoscopy. A linear increase in heart rate and mean arterial pressure during first 45 s has been observed. Further prolongation has little effect. As the duration of laryngoscopy is normally <30 s the result of studies in which it takes longer than this have less clinical relevance. The force applied during laryngoscopy has only minor effect. In our study, the duration of laryngoscopy and intubation was limited to 20 s.
Bachofen stated the criteria for selection of an appropriate drug to prevent sympathetic response. The drug must be applicable regardless of patient collaboration, prevent impairment of cerebral blood flow, and avoid arousal of the patient. It should neither be time-consuming nor affect the duration or modality of the ensuing anesthesia. iv lignocaine and fentanyl appear to best fulfil the above criteria.
Though lignocaine failed to attenuate the cardiovascular response to laryngoscopy and tracheal intubation in a study designed by Miller CD and Warren SJ, its usefulness was noted by others.,,,, Lignocaine also prevents rise in intracranial pressure, the rise in intraocular pressure associated with laryngotracheal stimulation. It suppresses a cough related to extubation. It is recommended to use at a dose of 1.5 mg/kg Optimal time of administration is 3 min before laryngoscopy and intubation.
Fentanyl is advocated for attenuation of the sympathetic response to laryngoscopy and intubation.,
Dahlgren and Messeter conducted a study in 15 patients scheduled for elective neurosurgery. All the patients were above 15 years of age and were divided into two groups. Group I received Fentanyl 5 μg/kg Group II received placebo (saline). After laryngoscopy and intubation, the blood pressure response in very high in the control group (by about 50 mmHg), while there was no significant rise in fentanyl group (by about 14 mm Hg). The change in heart rate in response to laryngoscopy and intubation followed the same pattern. In our study, fentanyl effectively blunts the systolic blood pressure response during laryngoscopy and intubation (only 0.3% increase from the baseline value against 30.76% increase from the baseline value in control group).
Flacke et al. have postulated that cardiovascular system depression after fentanyl is due to inhibition of central sympathetic outflow that is apart from analgesia or other Sensory depressant effect of fentanyl. Some central cardiovascular regulatory mechanisms are opioid sensitive. Hypotension produced by fentanyl was indirect. Fentanyl also modulates nociceptive input and provides effective blunting of responses to laryngoscopy and intubation. However in our study, both fentanyl and xylocaine attenuate cardiovascular response to laryngoscopy and intubation. However, fentanyl attenuates better when compared with xylocaine.
Smith et al. in their study, they compared fiber optic intubation with fentanyl (6 μg/kg) and without fentanyl and traditional Macintosh intubation with fentanyl. Fentanyl attenuates the pressor response to fiber optic as well as Macintosh intubation under GA. In the present study, fentanyl attenuated the BP response effectively during laryngoscopy and intubation.
However, the present study has the following limitations.
- Adequate depth of anesthesia and neuromuscular relaxation was monitored only by clinical observations.
- Variations in parameters can occur as the patient starts to come out of the effect of succinylcholine and before the action of supplemented vecuronium sets in.
- Hemodynamic changes associated with two stages, i.e., direct laryngoscopy and passage of the tracheal tube into trachea were not studied separately.
| Conclusion|| |
In patients with no drugs to attenuate the sympathetic response to laryngoscopy and intubation the maximum rise of heart rate, systolic, diastolic, and mean arterial blood pressures are 42.5%, 20%, 18%, and 19%, respectively, when compared with preinduction values.
Lignocaine significantly attenuates the sympathetic response to laryngoscopy and intubation.
Fentanyl also significantly attenuates the sympathetic response.
Fentanyl is more effective than lignocaine in attenuation of the sympathetic response to laryngoscopy and intubation.
A low dose of fentanyl at 2 μg/kg IV, administered 5 min before laryngoscopy and intubation can be recommended to attenuate the sympathetic response to laryngoscopy and intubation without any side effects of the drug.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]