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Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 1  |  Page : 111-118  

Evaluation and comparison of fentanyl versus nalbuphine for attenuation of hemodynamic response to laryngoscopy and endotracheal intubation in general anesthesia


Department of Anaesthesiology and Critical Care, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Date of Web Publication7-Mar-2019

Correspondence Address:
Aabid Hussain Mir
Department of Anaesthesiology and Critical Care, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar - 190 011, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.252867

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   Abstract 

Background: General anesthesia administration involves laryngoscopy and endotracheal intubation which are associated with the pressor response and can lead to tachycardia, hypertension, and arrhythmias, which can be deleterious in compromised patients and hence, this response needs to be suppressed. Aims: The aim of the study is to compare the effectiveness of intravenous (i.v) fentanyl and nalbuphine on the suppression of hemodynamic response in patients undergoing surgery under general anesthesia. Setting and Design: This prospective comparative study was conducted in the department of anesthesiology of a tertiary care center, and patients posted for elective surgery under general anesthesia were included. Methods: A total of 100 patients of either sex in the age group of 20–50 years, belonging to the American Society of Anesthesiologists physical status classes I and II undergoing surgery under general anesthesia, were divided into two groups: Group N (n = 50) – who received injection nalbuphine 0.2 mg/kg diluted in 10 mL normal saline i.v and Group F (n = 50) – who received injection fentanyl 2 μg/kg diluted in 10 mL of normal saline i.v over 1 min, 5 min prior to intubation. Technique of anesthesia was standardized for all the patients in the study. Heart rate (HR), blood pressure (systolic, diastolic, and mean arterial pressure [SBP, DBP, and MAP]), and oxygen saturation were recorded at baseline, induction, and at 1, 3, 5, and 10 min after intubation. Statistical Analysis: Descriptive statistics were done using mean with standard deviation for quantitative variables, and categorical variables were presented in frequencies along with respective percentages. The statistical comparisons for quantitative variables were done using Student's t-test and for categorical variables, Chi-square was used according to the data. All statistical analyses were performed using SPSS software (Version 22, SPSS Inc., Chicago, IL, USA). All analyses were two tailed, and results were discussed on 5% level of significance, i.e., P < 0.05 was considered statistically significant. Results: The demographic characteristics were comparable in both groups. HR was statistically insignificant between the two groups at all intervals. Comparing SBP, DBP, and MAP between the two groups, there was a significant increase in nalbuphine group than fentanyl group postintubation and was statistically significant at all intervals of time. Maximum rise in SBP, DBP, and MAP was 5.49%, 6.03%, and 5.80% for fentanyl group and 12.88%, 9.37%, and 10.86% for nalbuphine group, respectively. Comparison of oxygen saturation in two groups was statistically insignificant. Conclusion: Fentanyl is better than nalbuphine in blunting the pressor response of laryngoscopy and endotracheal intubation.

Keywords: Fentanyl, intubation, laryngoscopic response, nalbuphine


How to cite this article:
Khanday SB, Mir AH, Sofi KP, Lone AQ, Shah AN. Evaluation and comparison of fentanyl versus nalbuphine for attenuation of hemodynamic response to laryngoscopy and endotracheal intubation in general anesthesia. Anesth Essays Res 2019;13:111-8

How to cite this URL:
Khanday SB, Mir AH, Sofi KP, Lone AQ, Shah AN. Evaluation and comparison of fentanyl versus nalbuphine for attenuation of hemodynamic response to laryngoscopy and endotracheal intubation in general anesthesia. Anesth Essays Res [serial online] 2019 [cited 2019 May 19];13:111-8. Available from: http://www.aeronline.org/text.asp?2019/13/1/111/252867


   Introduction Top


Laryngoscopy and endotracheal intubation are invariably associated with certain cardiovascular changes such as tachycardia, rise in blood pressure, and a wide variety of cardiac arrhythmias, all of which are categorized as a pressor response. This response may be due to sympathetic reflex provoked by mechanical stimulation of epipharynx and hence increase in plasma catecholamine concentration.[1] These responses are generally of no serious consequence in normotensive patients, but may be exaggerated and hence more hazardous in patients with hypertension, coronary artery disease, cerebrovascular disease, myocardial infarction, thyrotoxicosis, and various other conditions as they result in increased cardiac workload. The other hazards are rise in intraocular and intracranial pressures.[2] Drugs such as opioids, calcium channel blockers, inhalational agents, local anesthetics; vasodilators such as nitroglycerine, magnesium sulfate, and sodium nitroprusside; angiotensin-converting enzyme inhibitors such as enalapril; α2 agonists such as clonidine and dexmedetomidine; β-adrenergic blocking agents such as esmolol; α- and β-adrenergic blockers such as labetalol; and techniques such as local and regional anesthesia have been found to modify this response.[3],[4],[5],[6],[7],[8],[9] Opioids specifically have been found to be useful in attenuation of this cardiovascular response, but may cause respiratory depression and rigidity or may prolong the recovery time. Fentanyl is a synthetic pure μ-receptor agonist with shorter time to peak analgesic effect, larger safety margin, minimal respiratory depression at analgesic doses and rapid termination of effect after small bolus doses, and relative cardiovascular stability.[10] Nalbuphine is a semi-synthetic opioid agonist–antagonist analgesic of phenanthrene series. It has a potent analgesic action equivalent to that of morphine on milligram basis. It binds to μ, kappa, and delta receptors. Nalbuphine may partially reverse or block opioid-induced respiratory depression from the μ-agonist analgesic. Nalbuphine, unlike other agonist–antagonist opioids, for example, pentazocine or butorphanol, does not increase systemic blood pressure, pulmonary artery blood pressure, heart rate (HR), or arterial filling pressure. For this reason, nalbuphine may be useful to provide sedation and analgesia in patients with heart disease, for example, during cardiac catheterization.[11],[12] In the present study, we compared the effectiveness of fentanyl and nalbuphine for blunting of pressor response and safety profile during laryngoscopy and endotracheal intubation for induction of general anesthesia. Various studies have been conducted previously on the current topic. This study aimed to assure the reliability and validity of the results when applied on different individuals and in a different setup and to strengthen the previous research by finding and correcting the limitations so that the results could be generalized. Moreover, it was to inspire new research counting previous findings from related studies which can add to the body of information supporting the discipline.


   Methods Top


This prospective, randomized study was conducted for 2 years from 2016 to 2018 in a tertiary care institute on a total of 100 patients of the American Society of Anesthesiologists (ASA)-physical status (PS) classes I and II of either sex, in the age group of 20–50 years undergoing elective surgeries under general anesthesia. Patients were allocated using computer-generated randomization list into two groups: Group F (fentanyl) and Group N (nalbuphine) of fifty patients each after taking written informed consent and approval from the Institutional Review Board. Uncooperative patients, pregnant patients, patients with allergy to drugs used, patients with opioid addiction, patients requiring emergency surgery, patients with difficult airway or Mallampati score >3, prolonged laryngoscopy (>15 s), and morbidly obese (body mass index (BMI) >40) were excluded from the study. Tablet ranitidine 150 mg and alprazolam 0.25 mg were given as premedication on night prior to surgery. Patients were shifted to operating room, and baseline monitors such as electrocardiogram, noninvasive blood pressure, and oxygen saturation were connected after securing wide-bore (18G) cannula and baseline parameters were recorded. Fentanyl (2 μg/kg diluted in 10 mL normal saline) was given in Group F and nalbuphine (0.2 mg/kg diluted in 10 mL normal saline) was given in Group N slowly over 1 min according to the patients' inclusion number, 5 min prior to intubation. Induction was done with intravenous (i.v) propofol 2–2.5 mg/kg and i.v rocuronium 0.6 mg/kg. Laryngoscopy and intubation were performed 3 min after the administration of rocuronium. All the patients were intubated by a skilled anesthetist with an appropriate sized cuffed endotracheal tube. Anesthesia was maintained with oxygen plus nitrous oxide and isoflurane. Bolus doses of rocuronium 0.1 mg/kg were used to maintain neuromuscular blockade. All patients received injection paracetamol 1 g and 0.5 mg/kg ketorolac i.v. Injection ondansetron 0.1 mg/kg was given 20 min prior to the anticipated time of completion of surgery. At the end of the surgery, isoflurane was stopped, and residual neuromuscular blockade was reversed by injection neostigmine 0.05 mg/kg and injection glycopyrrolate 0.01 mg/kg i.v. Patients were extubated after the extubation criteria are met and shifted to the post anesthesia care unit. HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and oxygen saturation (SpO2) were recorded preinduction (baseline), at induction, and at 1, 3, 5, and 10 min after intubation for both the groups. Any hypotension, bradycardia, and desaturation were treated with i.v fluids, drugs, and oxygen supplementation, respectively. Patients were observed intraoperatively and postoperatively for any complication such as arrhythmias, bradycardia, nausea, vomiting, respiratory depression, sedation, muscular rigidity, and pruritus.

Statistical analysis

Descriptive statistics were done using mean with standard deviation for quantitative variables, and categorical variables were presented in frequencies along with respective percentages. The statistical comparisons for quantitative variables were done using Student's t-test and for categorical variables, Chi-square test was used according to the data. All statistical analyses were performed using SPSS software (Version 22, SPSS Inc., Chicago, IL, USA). All analyses were two tailed, and results were discussed on 5% level of significance, i.e., P < 0.05 was considered statistically significant.


   Results Top


The demographic characteristics (age, weight, male-female ratio, height, BMI, and ASA-PS) were comparable between the two groups [Table 1]. HRs between the two groups was comparable and statistically insignificant at all intervals of time as shown in [Table 2] and [Figure 1], [Figure 2]. There was a drop in HR in both groups at induction and then increase postinduction. Maximum increase was at 1 min postinduction with a mean rate of 94.96 ± 7.25 (12.97%) in Group F and 95.76 ± 9.31 (12.84%) in Group N. Thereafter, the rate decreased in both groups and was comparable at 3, 5, and 10 min with P = 0.685, 0.062, and 0.651, respectively.
Table 1: Comparison of patient characteristics in the two groups

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Table 2: Group comparison for heart rate and their percentage variation from baseline at different intervals of time (beats/min)

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Figure 1: Group comparison for heart rate in beats/minute

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Figure 2: Percentage increase/decrease in heart rate from baseline

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SBP in both the groups was comparable at baseline. At induction, there was 0.28% increase in SBP in fentanyl group and 1.34% decrease in SBP in nalbuphine group and was statistically significant with P = 0.017. At 1, 3, 5, and 10 min postintubation, the increase in SBP was more in nalbuphine group than fentanyl group and was statistically significant at all intervals of time (P < 0.001, 0.001, <0.001, and <0.001, respectively), with a maximum value of 126.10 ± 8.91 (5.49% increase from baseline) in the fentanyl group and 133.72 ± 8.90 (12.88% increase from baseline) in the nalbuphine group at 1 min postintubation time. The increase in SBP in the nalbuphine group persisted for longer period as compared to increase elicited in the fentanyl group. In both the groups, a decrease was noticed at 10 min after intubation as compared to the 5 min; however, the mean values of SBP at 10 min after intubation were higher as compared to those of baseline. The average percent change of SBP from baseline was high in the nalbuphine group as compared to the fentanyl group [Table 3] and [Figure 3], [Figure 4].
Table 3: Group comparison for systolic blood pressure, diastolic blood pressure, and mean arterial pressure and their percentage variation from baseline at different intervals of time (mmHg)

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Figure 3: Group comparison for systolic blood pressure in mmHg

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Figure 4: Percentage increase/decrease in systolic blood pressure from baseline

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On comparing mean DBP between fentanyl and nalbuphine groups, the basal mean DBP was comparable in both the groups. During induction, there was a slight decrease in DBP in both the groups and was comparable. At 1 min after intubation, both groups showed an increase in DBP that was statistically significant (P = 0.009) within and between the groups, with a mean value of 85.86 ± 5.86 in the fentanyl group and 90.06 ± 9.52 in the nalbuphine group. Similarly, at 3, 5, and 10 min after intubation, the mean DBP showed significantly decreasing trend in both the groups, and the difference between the two groups was statistically significant with better control in the fentanyl group [Table 3] and [Figure 5], [Figure 6].
Figure 5: Group comparison for diastolic blood pressure in mmHg

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Figure 6: Percentage increase/decrease in diastolic blood pressure from baseline

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MAP (mmHg) between the two study groups showed significant differences at all the time intervals except at baseline [Table 3] and [Figure 7], [Figure 8]. At induction, MAP (mmHg) between the two groups was lower as compared to baseline; however, the difference between the two groups was statistically significant. At 1 min after intubation, MAP (mmHg) was 99.27 ± 5.31 (+5.80%) and 104.61 ± 6.86 (+10.86%) mmHg as compared to 93.51 ± 6.62 and 93.25 ± 6.29 mmHg at baseline in fentanyl and nalbuphine groups, respectively. In both the groups, the MAP (mmHg) showed a decreasing trend from 3 to 10 min after intubation; however, the differences between the two groups at the above time interval were statistically significant (P < 0.001). The mean oxygen saturation values were comparable in both the groups at all intervals of time [Table 4].
Figure 7: Group comparison for mean arterial pressure in mmHg

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Figure 8: Percentage increase/decrease in mean arterial pressure from baseline

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Table 4: Group comparison for oxygen saturation and their percentage variation from baseline at different intervals of time

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   Discussion Top


Laryngoscopy and endotracheal intubation are associated with the pressor response which leads to variable and transitory hemodynamic changes such as increase in HR and blood pressure and can cause arrhythmias which result from increase in sympathoadrenal activity and is mediated by increase in plasma catecholamines.[13],[14] Studies have shown that narcotics such as fentanyl[15] and nalbuphine[16],[17] are effective in blunting pressor response to laryngoscopy and endotracheal intubation. Narcotics are used as sole or supplementary agents for the induction of anesthesia. The aim of the present study was to select a better drug in terms of attenuation of pressor response during laryngoscopy and endotracheal intubation at the same time without affecting the duration or modality of the anesthetic technique and recovery profile and lesser complications. In the present study, clinical efficacy of fentanyl with nalbuphine was compared. Fentanyl was used at a dose of 2 μg/kg and nalbuphine at a dose of 0.2 mg/kg, and fentanyl was found better in the attenuation of hemodynamic response than nalbuphine. These doses were selected on the basis of their equipotency with morphine.[18] These drugs were given 5 min before endotracheal intubation, and this time was chosen as per the optimal time found by Ko et al.[19] Fentanyl has been tried in various bolus doses for control of hemodynamic changes secondary to laryngoscopy. Kay et al.[20] found complete attenuation of hemodynamic response with 5 μg/kg of fentanyl. However, large dose can lead to muscular rigidity, bradycardia, nausea, and vomiting. Large doses may also cause postoperative respiratory depression, especially in surgery with short duration (<1 h), so a lesser dose was chosen.

Increase in HR and blood pressure has always been a matter of concern during laryngoscopy and intubation. In the present study, at induction (0 min), there was decrease in HR in fentanyl group, which was not different than that of the nalbuphine group. Increase in HR from the baseline was recorded highest as 12.97% and 12.84% at 1 min after intubation in the fentanyl and nalbuphine groups, respectively. However, the variation was statistically nonsignificant (P = 0.748). Thereafter, HR showed a gradual decrease in both the groups over the next 5 min, almost returning to baseline at 10 min after intubation. The results were not significantly different between the two groups. Similarly, Sharma and Parikh[21] did not find any statistically significant difference between fentanyl and nalbuphine at any time interval (P > 0.05). Ahsan-ul-Haq et al.[16] and Kay et al.[22] in their study compared the effects of fentanyl and nalbuphine and found significant rise in HR in patients of nalbuphine group, as compared to patients of fentanyl group. Bhandari et al.[23] stated that mean HR after intubation showed significantly increased value of 88 ± 11.45 beats/min in fentanyl group and 102.68 ± 16.04 beats/min in nalbuphine group and was statistically significant. This significance may be due to the different number of individuals and dose used. Khan and Hameedullah[18] compared nalbuphine with fentanyl after endotracheal intubation and documented 25% rise in HR after intubation in the nalbuphine group when compared with fentanyl group. In accordance with this study, our study also showed increase in HR after intubation with both groups, but comparison between the two groups was statistically insignificant.

The mean SBP shows a significant variation at the time of induction, being higher in fentanyl group (119.52 ± 9.18 vs. 114.96 ± 9.63). At 1 min after intubation, there was a significant rise in the mean SBP in Group N compared to Group F (133.72 ± 8.90 vs. 126.10 ± 8.91). Subsequently, mean SBP revealed a downward trend in both groups, but continued to be significantly higher in nalbuphine group till 10 min after intubation. The reasons behind elevation of the mean SBP might be due to the fact that both fentanyl and nalbuphine have minimal depressive effect on the cardiovascular system and cannot completely attenuate response to endotracheal intubation. Our results suggest better hemodynamic stability with fentanyl compared to nalbuphine. In concordance with our study, Khan and Hameedullah[18] found significant increase in SBP in nalbuphine group, which is similar to our result. Aftab et al.[24] also observed that fentanyl/isoflurane provided better hemodynamic stability than nalbuphine/isoflurane in patients undergoing elective coronary artery bypass surgery. In contrast to our study, Bhandari et al.[23] observed significant attenuation of the hemodynamic changes (SBP) in patients of nalbuphine group as compared to patients of fentanyl group.

In the present study at induction, there was a nonsignificant decrease in mean DBP in the fentanyl and nalbuphine groups at induction. On the other hand, at 1 min after intubation, the mean DBP was increased to 85.86 ± 5.86 mmHg and 90.06 ± 9.52 mmHg in fentanyl and nalbuphine groups, respectively, and the variation was found to be statistically significant (P = 0.009). Thereafter, DBP showed a progressive fall till 10 min postintubation in both groups. However, the drop was seen to be more in fentanyl group compared to nalbuphine group with statistically significant difference. The results of Park et al.[25] are in close agreement with the current findings who found significant increase in blood pressure (DBP) after intubation in patients receiving fentanyl 1 μg/kg given 15 min before intubation. DBP increased to 40% above baseline in fentanyl group 30 s after intubation. The inadequate effect of fentanyl to attenuate the hemodynamic response in this study may be related to the lower dose used and longer-than-optimal time lag from administration to laryngoscopy. Khan and Hameedullah[18] also observed increase in DBP with both fentanyl and nalbuphine but more in nalbuphine, similar to our study. Channaiah et al.[26] observed attenuation of SBP and DBP in response to intubation in fentanyl at all measured times. The greatest attenuation in SBP and DBP was observed at intubation with a significant difference from the control group (P < 0.001) in contrast to our study where there is more consistent decrease in DBP after 1 min of intubation. Sharma and Parikh[21] did not observe any difference between the two groups in DBP.

MAP is a derived value and is important in relation to the autoregulatory responses of the heart, brain, and kidneys. In the present study, there was a significant fall at induction in MAP from baseline in patients of both fentanyl and nalbuphine groups. At 1 min after intubation, mean MAP in fentanyl and nalbuphine groups differed significantly, and their values were higher as compared at induction [Table 3]. Thereafter, there was a decrease in MAP in both the groups. However, fentanyl group exhibited more decrease as compared to nalbuphine group till 10 min after intubation with a significant difference between fentanyl and nalbuphine groups. Our results have shown that MAP control after laryngoscopy and intubation is better in fentanyl group than that in nalbuphine group. In accordance with our study, Channaiah et al.[26] noted that intergroup MAP yielded significant attenuation in the fentanyl group for all recorded time periods. Chawda et al.[27] observed significant increase in MAP after intubation in placebo compared to nalbuphine. Similarly, Ahsan-ul-Haq et al.[16] noticed increase in MAP just after induction in placebo group which was significant whereas nalbuphine prevented this rise, in contrast to our study where nalbuphine could not attenuate the rise in MAP completely.

In the present study, mean SpO2 level shows a nonsignificant variation at all study stages. However, the level remained within the normal limits at all times, and respiratory depression was not seen in any of the patients. Chung et al.[28] observed that pure agonists can cause complications such as respiratory depression, which can be dangerous in the recovery room. On the other hand, nalbuphine is an agonist–antagonist opioid and causes less respiratory depression by activating the supraspinal and spinal kappa receptors.

In general, SBP, DBP, and MAP were significantly elevated after the endotracheal intubation in both the groups, and higher values were noted in nalbuphine group as compared to the fentanyl group. The elevation persisted mostly for 3 min and subsequently, the parameters returned to the preintubation values in case of fentanyl. These results are similar to those stated by Miller[29] that, in normotensive patients, laryngoscopy and insertion of a tracheal tube are immediately followed by an average increase in MAP of 25 mmHg. Nalbuphine binds to μ, kappa, and delta opioid receptors and is primarily kappa agonist and μ antagonist.[30] In Group N, the initial fall in all the hemodynamic parameters is because of its strong and predominant kappa agonistic action. Rise in hemodynamic parameters after intubation is due to sympathoadrenal stimulation.[31] Fentanyl is a pure μ-agonist and is known to cause a decrease in arterial blood pressure, HR, systemic vascular resistance, and blood catecholamine levels while depressing the myocardial contractility and decreasing the cardiac workload, which may be the cause of the steady fall in all the hemodynamic parameters in the fentanyl group after 1 min of intubation. None of the patients involved in the study had any complication such as respiratory depression, bradycardia, arrhythmias, nausea, vomiting, or pruritus.

Limitations

The study was not blinded which may have added to observational bias. The levels of catecholamines were not measured which would have shown more accurate attenuation, and the study was carried out on ASA-PS classes I and II with no compromised state and hence, the population at potential risk was not included.

Strengths

This study adds to the literature that fentanyl at the dosage of 2 μg/kg is better at the attenuation of hemodynamic pressor response to laryngoscopy and endotracheal intubation than nalbuphine used at a dosage of 0.2 mg/kg. It also determines the efficacy and safety of the drugs at this dosage as none of the patients had respiratory depression, chest wall rigidity, or hypotension, which can have implications on cardiac and respiratory compromised patients. Our study has shown fentanyl as the drug of choice for blunting of pressor response in such patients. Further studies with a larger sample size and which will overcome our limitations may be required to generalize the results and strengthen the literature.


   Conclusion Top


We concluded that fentanyl is better than nalbuphine in blunting the pressor response of laryngoscopy and endotracheal intubation. Fentanyl is better in the control of SBP, DBP, and MAP; however, control of HR is equal with both the drugs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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