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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 2  |  Page : 58-63

Effect of sevoflurane with morphine or fentanyl on haemodynamic response to laryngoscopy and tracheal intubation: a prospective, randomised, double-blind study


1 Department of Anaesthesiology and Critical Care Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Anaesthesiology and Critical Care, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Web Publication26-Mar-2019

Correspondence Address:
Madhusudan Mukkara
Associate Professor, Department of Anaesthesiology and Critical Care, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_31_18

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  Abstract 


Background: Multimodal therapy can be used for obtundation of the haemodynamic response to laryngoscopy and tracheal intubation. The current study was undertaken to compare the haemodynamic response to laryngoscopy and tracheal intubation after administration of 0.2 mg/kg morphine or 2 μg/kg fentanyl with 2% end tidal sevoflurane during induction of anaesthesia.
Methods: Sixty patients were randomised into two equal groups to receive either 2% end tidal sevoflurane + fentanyl 2 μg/kg (Group SF) or 2% end tidal sevoflurane + morphine 0.2 mg/kg (Group SM). General anaesthesia technique was standardised for both the groups. Haemodynamic parameters heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded for 15 min.
Results: The maximum increase in HR compared to baseline was statistically significant in Group SM (16.5%, P = 0.0002) which occurred at one min after tracheal intubation. The maximum increases in SBP, DBP and MAP compared to baseline occurred at one min after tracheal intubation in both the groups, Group SF (7.04%, 6.5% and 7.9% respectively) and Group SM (6.2%, 8.2% and 8.1% respectively) which was not statistically significant. The attenuation of haemodynamic response between the two groups was not statistically significant (for HR P = 0.1428, for SBP P = 0.8558, for DBP P = 0.1958 and for MAP P = 0.5303).
Conclusions: With 2% end tidal sevoflurane during induction of anaesthesia, both 0.2 mg/kg morphine and 2 μg/kg fentanyl were equally effective in attenuating haemodynamic response to laryngoscopy and tracheal intubation. However morphine appeared to be less effective in attenuating the chronotropic response resulting in a greater increase in heart rate from baseline.

Keywords: Fentanyl, Haemodynamic response, Intubation, Laryngoscopy, Morphine


How to cite this article:
Bhushanam Padala SA, Anakapalli M, Mangu HR, Mukkara M, Samantaray A. Effect of sevoflurane with morphine or fentanyl on haemodynamic response to laryngoscopy and tracheal intubation: a prospective, randomised, double-blind study. J Clin Sci Res 2018;7:58-63

How to cite this URL:
Bhushanam Padala SA, Anakapalli M, Mangu HR, Mukkara M, Samantaray A. Effect of sevoflurane with morphine or fentanyl on haemodynamic response to laryngoscopy and tracheal intubation: a prospective, randomised, double-blind study. J Clin Sci Res [serial online] 2018 [cited 2019 Aug 22];7:58-63. Available from: http://www.jcsr.co.in/text.asp?2018/7/2/58/254973




  Introduction Top


Laryngoscopy, endotracheal intubation and airway management are essential for anaesthesiologists in maintaining airway during surgery under general anaesthesia. King et al. in 1951 described the circulatory response to laryngeal and tracheal stimulation following laryngoscopy and tracheal intubation as reflex sympathoadrenal stimulation.[1] This results in increase in heart rate (HR) and blood pressure which are short-acting and may have detrimental effects in high-risk patients, especially those with cardiovascular diseases.[2]

Different classes of drugs and techniques have been used to prevent this haemodynamic response.[3] Opioids administered in moderate-to-high dose, have been suggested as a means of blunting this response. Availability of literature on the effect of currently used inhalational agents on the pressor response to laryngoscopy and tracheal intubation is limited. Multimodal therapy rather than a single agent has been recommended to obtund the sympathetic discharge associated with tracheal intubation. The advantage of combining drugs is that side effects of individual agents will be less because of lower doses used.[4] Not many studies have examined the combination of opioids and inhalational anaesthetics for attenuation of the haemodynamic response to laryngoscopy and tracheal intubation. Hence, the current study is undertaken to compare the haemodynamic responses to laryngoscopy and tracheal intubation after administration of 0.2 mg/kg morphine or 2 μg/kg fentanyl with 2% end-tidal (ET) sevoflurane during induction of anaesthesia. The main objective of this study is to know which opioid in combination with 2% ET sevoflurane is better in attenuating intubation response (11 min, i.e.,1 min after intubation).


  Material and Methods Top


After obtaining approval from the Institutional Research and Ethics Committee, a prospective, randomised, double-blind study was conducted at our superspeciality university teaching hospital. The study population comprised 60 patients belonging to the American Society of Anaesthesiologists physical status[5] Grade 1 and Grade 2 (except hypertensives) in the age group of 18–50 years of either sex weighing between 40 and 70 kg posted for elective surgical procedures under general anaesthesia. Patients who were not willing to participate in the study, obese patients with body mass index (BMI) >30 kg/m2, hypertensive patients, pregnant and lactating women were excluded from the study. Patients with known allergic reaction to study drugs, raised intracranial pressure, expected difficult intubation and in whom intubation took more than one attempt were also excluded from the study. After detailed pre-anaesthetic evaluation, each patient was explained about the study and the anaesthesia technique. Written informed consent was obtained from each patient. All patients were pre-medicated with tablet ranitidine 150 mg orally and tablet alprazolam 0.25 mg orally the night before surgery and were kept nil per oral 6 h for solids, 2 h for clear liquids[6] Randomisation and sequence were generated before initiating the study. Patients were randomised into one of the two groups each containing 30 patients by a computer-generated random number table and sealed opaque envelope technique. The double-blind nature of the study was ensured by having an independent anaesthesiologist, not participating in the study, preparing fentanyl or morphine in ready to inject form for a total volume of 10 ml using 0.9% normal saline.

On arrival in the operating room, the patients were monitored by electrocardiogram, pulse oximeter and non-invasive blood pressure (IBP). Baseline values of haemodynamic parameters such as HR, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were noted. Under local anaesthesia, a good intravenous (IV) line with 18G cannula was secured to allow administration of fluids (lactated Ringer's solution at the rate of 300 ml/h) and medication. General anaesthesia technique was standardised for both the groups. Patients were induced by an anaesthesiologist not a part of this study and the observations were recorded by the investigator himself who was blinded to the study drugs. The study drug (either fentanyl or morphine) diluted to 10 ml was administered by slow IV route over 2 min after securing the IV line and starting of administration of the study drug was considered as '0' min. The closed circuit was primed with 2% ET sevoflurane with 50% oxygen (O2) + 50% nitrous oxide (N2O) for the first 5 min. Between 5 and 7 min, patients were induced with thiopentone 4 mg/kg and paralysed by vecuronium 0.1 mg/kg and ventilated with closed circuit which was already primed with 2% ET sevoflurane and fresh gas flows O2 and N2O in a ratio of 50:50. Patients were intubated, 3 min after induction with appropriate size endotracheal tube [Table 1].
Table 1: Study procedure

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Haemodynamic parameters recorded in this study were HR, SBP, DBP and MAP at 2, 5, 8, 9 and 10 min and for 5 min at one min interval after intubation (i.e., 11, 12, 13, 14 and 15 min). During the study period, no other stimulations were given such as bladder catheterisation, nasogastric tube insertion, change in position or surgical incision. Any hypertension (rise in SBP >25% of baseline value) during the study was treated with injection esmolol 5 mg IV, whereas hypotension (fall in SBP >25% of baseline value) was treated with injection ephedrine 3 mg IV or injection phenylephrine 50 μg IV depending on HR. The incidence of tachycardia (HR >120 beats/min) and bradycardia (HR <50 beats/min) were treated with injection esmolol 5 mg IV and injection atropine 0.4 mg IV, respectively. The study period ended in 15 min after starting of administration of study drugs.

Statistical analysis

We used Microsoft Excel 2007 (Microsoft Crop, Redmond USA), GNU PSPP for GNU/Linux (Version 0.8.5, Boston MA) and MedCalc version 11.3.0 for windows 2000/XP/ Vistal 7 (MedCalc Software Bvba, Belgium) software for statistical analysis. Quantitative variables such as age, weight, HR, SBP, DBP and MAP were expressed as mean and standard deviation. Intergroup data were analysed by using unpaired Student's t-test. Intra-group data were analysed using repeated-measures analysis of variance and appropriate post hoc testing. Qualitative data were analysed by using the Chi-square test. P < 0.05 was taken as statistically significant.


  Results Top


The elective spine surgeries requiring general endotracheal anaesthesia such as discectomies, decompressive laminectomies and fusions performed in our institute were included in our study. Three patients were observed to have persistent hypertension and one patient was observed to have persistent tachycardia on the operating table before inducing anaesthesia. One patient desaturated after giving study drug and we immediately intervened with 100% O2 and in one patient, there was an unanticipated difficult intubation in which intubation took two attempts. All the above six cases were excluded from the study. During the conduct of the study, three patients developed hypertension (two patients in Group sevoflurane-fentanyl [SF] and one patient in Group sevoflurane-morphine [SM]), 18 patients developed hypotension (13 patients in Group SF and 5 patient in Group SM), four patients developed tachycardia (two patients each in Group SF and Group SM). They were treated accordingly. None of the patients developed bradycardia.

Demographic variables such as age, weight, height, BMI, gender distribution and Mallampati grade were comparable, and there was no statistically significant difference between the two groups [Table 2].
Table 2: Comparison of demographic variables between the study groups

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We observed statistically significant difference in HR between the two groups, Group SF and Group SM, only at 12 and 13 min [Figure 1] whereas for DBP and MAP only at 12.13 and 14 min (P = 0.0141,0.0328 and 0.0120, respectively, for DBP; 0.0171,0.0126 and 0.0103 for MAP). There was no statistically significant difference in SBP at any time intervals.
Figure 1: Comparison of heart rate between the study groups *Intubation; † P < 0.05

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In our study, the maximum increase in HR compared to baseline value occurred at 11 min (i.e.,1 min after tracheal intubation) in both the groups, Group SF (8.4%, P = 0.2031) and Group SM [16.5%, P = 0.0002; [Figure 1]. It was statistically significant only in Group SM.

The maximum increases in SBP, DBP and MAP compared to baseline values occurred at 11 min (i.e.,1 min after tracheal intubation) in both the groups, Group SF (7.04%, 6.5% and 7.9%, respectively) and Group SM (6.2%, 8.2% and 8.1%, respectively). They were not statistically significant in both the groups.

There was no statistically significant difference between Group SF and Group SM in maintaining the haemodynamics immediately after IV bolus (2 min) and just before induction of anaesthesia (5 min). However, fentanyl appeared to maintain better haemodynamics than morphine as Group SM showed a statistically significant increase in HR from baseline at 2 and 5 min [Figure 1] and statistically significant decrease in DBP and MAP at 5 min (P = 0.0001 and 0.0160, respectively).

There was no statistically significant difference between Group SF and Group SM in maintaining the haemodynamics after induction (8, 9 and 10 min). However, morphine appeared to maintain better chronotropic response than fentanyl after induction as Group SF showed statistically significant decrease in HR from baseline at 10 min [Figure 1]. Both the groups showed statistically significant decreases in SBP, DBP and MAP from baseline after induction, at 8, 9 and 10 min.

The difference in HR between the two groups was statistically significant only at 12 min and 13 min [i.e., 2 and 3 min after intubation; [Figure 1], whereas the difference in SBP between the two groups was not statistically significant at any time intervals. DBP and MAP showed a statistically significant difference only at 12, 13 and 14 min. (2, 3 and 4 min after intubation, respectively) [Figure 2].
Figure 2: Comparison of SBP, DBP and MAP between the study groups.

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Our results showed that with 2% ET sevoflurane during induction of anaesthesia, both 2 μg/kg fentanyl and 0.2 mg/kg morphine were equally effective in attenuating haemodynamic response to laryngoscopy and tracheal intubation. The attenuation of haemodynamic response between the two groups was not statistically significant (for HR P = 0.1428, for SBP P = 0.8558, for DBP P = 0.1958 and for MAP P = 0.5303). However, morphine appeared to be less effective than fentanyl in attenuating the chronotropic response because it resulted in a greater increase in HR from baseline (16.5%), which was statistically significant (P = 0.0002). Adverse events are listed in [Table 3].
Table 3: Adverse events

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  Discussion Top


Laryngoscopy and tracheal intubation are considered to be stressful and cause exaggerated cardiovascular response. Although transient hypertension and tachycardia are usually of little consequence, they may be hazardous, especially in patients with persistent hypertension, limited coronary and myocardial reserve or cerebrovascular diseases.[7],[8] Reflex changes in the cardiovascular system after laryngoscopy and intubation lead to an average increase in blood pressure by 40%–50% and 20% increase in HR.[9] The magnitude of haemodynamic changes observed may be dependent on various factors such as depth of anaesthesia, whether any measure is taken before airway manipulation, the anaesthetic agent used, the duration of laryngoscopy and intubation. Another factor contributing to pressor response is anxiety. To relieve anxiety we have used tablet alprazolam in pre-medication. Tablet alprazolam 0.25 mg orally was administered at bedtime in the night before surgery. Coughing and straining were avoided by adequate muscle relaxation and deeper planes of anaesthesia by maintaining 2% ET sevoflurane concentration ET aneasthetic concentrations.[10]

Numerous pharmacological methods have been recommended to obtund the sympathoadrenal cardiovascular response to laryngoscopy and tracheal intubation. They may be classified as non-specific means achieved by deepening the plane of anaesthesia or by specific means involving various pharmacological preparations. Opioids administered in moderate-to-high dose, have been suggested as a means of blunting this response. A linear relationship exists between increasing opioid dose and reduction in cardiovascular response.[11],[12],[13],[14] Fentanyl is available in our country since 1998 and has various advantages such as no histamine release, no bronchospasm, cardiostability, rapid onset and short duration of action. It produces analgesia and stable haemodynamics by modulating stress response through receptor-mediated actions on hypothalamic-pituitary-adrenal axis. Fentanyl has been tried in various bolus doses for control of haemodynamic changes of laryngoscopy. However, large dose can lead to muscular rigidity, bradycardia, nausea and vomiting. Large doses may also cause post-operative respiratory depression, especially in surgery with short duration (<1 h). Morphine, a prototype opioid analgesic was also used in various studies to obtund the haemodynamic response to laryngoscopy and tracheal intubation. Morphine has been recognised for its hypotensive effect. Previous studies suggest that morphine decreases arterial blood pressure as a result of multiple mechanisms, including decreases in cardiac and renal sympathetic nerve activity, an increase in vagal tone and histamine release.[15],[16],[17]

Availability of literature on the effect of currently used inhalational agents on presser response to laryngoscopy and tracheal intubation is limited. In rabbits, after administration of 1%–4% concentration sevoflurane caused a 50% reduction in MAP without any change in HR. This was due to the baroreflex compensation for the effects of sevoflurane on sympathetic and cardiomotor activity up to a concentration of 3%.[18] The same effect has been observed in clinical studies in humans. Autonomic nerve activity was attenuated by sevoflurane administered with N2O.[19] It has also been postulated that sevoflurane depresses the sympathetic activity without altering the parasympathetic response.[20]

Multimodal therapy rather than a single agent has been recommended to obtund the sympathetic discharge associated with tracheal intubation. The advantage of combining drugs is that side effects of individual agents will be less because of lower doses used.

Hoda and Khan[21] compared the haemodynamic response to laryngoscopy and tracheal intubation after administration of 2 μg/kg fentanyl bolus with a placebo with 2% ET sevoflurane at induction of anaesthesia. In our study, we also used the same dose of fentanyl in Group SF and found comparable results. The maximum rise in HR, SBP, DBP and MAP were 8.4% (vs. 15%), 7.04% (vs. 6%), 6.5% (vs. 11%) and 7.9% (vs. 8%), respectively, which occurred at 11 min, i.e., 1 min after intubation.

Other studies[11],[13] also compared different doses of fentanyl and concluded that fentanyl 2 μg/kg significantly attenuated haemodynamic response during laryngoscopy and intubation as in our study, although higher doses completely abolished these responses.

The maximum rise in HR, SBP and DBP in Group SF in our study were comparable to the fentanyl group in a study[22] in which they compared fentanyl 2 μg/kg IV and nalbuphine 0.2 mg/kg IV for control of haemodynamic changes during endotracheal intubation, i.e., 8.4% (vs. 12.5%), 7.04% (vs. 4.8%) and 6.5%(vs. 4.5%), respectively.

Various authors[23],[24],[25] studied morphine in doses ranging from 0.1 to 0.5 mg/kg for attenuation of haemodynamic response to laryngoscopy and endotracheal intubation. We used morphine 0.2 mg/kg in Group SM in our study and got comparable results to them.

Not many studies have examined the combination of opioids and inhalational anaesthetics for attenuation of the haemodynamic response to laryngoscopy and tracheal intubation. We have studied the changes in haemodynamic parameters in response to laryngoscopy and tracheal intubation in relation to HR, SBP, DBP and MAP after administration of equipotent analgesic doses of fentanyl (2 μg/kg) or morphine (0.2 mg/kg) with 2% ET sevoflurane during induction of anaesthesia. Our rationale was to compare and know which of these combinations better attenuate the haemodynamic response. The combined effect of fentanyl during inhalational induction was observed in different previous studies along with the use of muscle relaxant[21] or without the use of muscle relaxant.[4]

We chose fentanyl 2 μg/kg and 2% ET sevoflurane based on one of the previous studies[21] where this combination attenuated the haemodynamic responses to a maximum of 15% above baseline values. The dose of morphine is selected based on the equipotent analgesic dose of fentanyl. Fentanyl is 100 times more potent than morphine.[26]

The rise in HR in Group SM at 1 min after intubation (11 min) was statistically significant (16.5%, P = 0.0002), whereas the rise in HR in Group SF and the rise in SBP, DBP and MAP in both the groups, Group SF and Group SM post-intubation were not statistically significant, but this might be due to the offset of the fall compared to the baseline in the post-induction period and 2 min following intubation, which lasted until 5 min post-intubation.

There were a few limitations in our study. IBP monitoring was not used due to cost constraints, which would have allowed us for the beat-to-beat recording of the parameters. The age distribution of our patients was between 18 and –50 years which might have affected our results because of the influence of age on the minimum alveolar concentration of inhalational agents.[27] According to the reference based on which we designed our study, the time for onset of action is 5 min. Moreover, the time taken for peak effect to be seen is 10 min.[26] However, some textbooks quote, the time for peak effect to be approximately 20 min or more, which might have affected the attenuation of chronotropic response in Group SM. The patient population included in this study might have associated with chronic pain and might be receiving analgesics. Hence, there might be differences in analgesic requirements in the study population which could have affected our results.

We recommend further studies to assess different concentrations of sevoflurane in combination with different doses of fentanyl and morphine for obtaining an optimum attenuation of the haemodynamic response to tracheal intubation.

From our study, we conclude that fentanyl and morphine were equally effective in attenuating haemodynamic response to laryngoscopy and tracheal intubation. However, morphine appeared to be less effective in attenuating the chronotropic response resulting in a greater increase in HR from baseline.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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King BD, Harris LC Jr., Greifenstein FE, Elder JD Jr., Dripps RD. Reflex circulatory responses to direct laryngoscopy and tracheal intubation performed during general anesthesia. Anesthesiology 1951;12:556-66.  Back to cited text no. 1
    
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Shribman AJ, Smith G, Achola KJ. Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation. Br J Anaesth 1987;59:295-9.  Back to cited text no. 3
    
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