Esmolol Hydrochloride and Dexmedetomidine on Pressure Response during Laryngoscopy, Intubation and Pneumoperitoneum in Laparoscopic Surgery
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Original Article - Journal of Patuakhali Medical College Volume 2 Number 2 July 2023 A.K.M Fakhrul Alam1, Md. Mahbub-Ur-Rahman2, Md. Nazmul Ahsan3, Kaneez Fatema4, Md. Salim Matber5 1. Dr. A.K.M Fakhrul Alam, Assistant Professor, Anaesthesia, Analgesia & ICU Department, Patuakhali Medical College, Patuakhali, Bangladesh 2. Dr. Md. Mahbub-Ur-Rahman, Assistant Professor, Anaesthesia, Analgesia & ICU Department, Sher-e-Bangla Medical College, Barishal, Bangladesh 3. Dr. Md. Nazmul Ahsan, Assistant Professor, Anaesthesia, Analgesia & ICU Department, Sher-e-Bangla Medical College, Barishal, Bangladesh 4. Dr. Kaneez Fatema, Assistant Professor, Anaesthesia, Analgesia & ICU Department, Sher-e-Bangla Medical College Barishal, Bangladesh 5. Md. Salim Matber, Assistant Professor, Department of Ortho-surgery, Patuakhali Medical College, Patuakhali, Bangladesh Correspondence: Dr. A.K.M Fakhrul Alam, Assistant Professor, Anaesthesia, Analgesia & ICU Department, Patuakhali Medical College, Patuakhali, Bangladesh, Email: [email protected] Received: 06 May 2023 Revised: 26 May 2023 Accepted: 15 June 2023 ABSTRACT Background: Laparoscopy procedures require pneumoperitoneum for adequate visualisation and operative manipulations which affects many homeostatic systems causing alterations in acid-base status, cardiovascular system, stress response and pulmonary physiology. This study was conducted to compare the effect of esmolol and dexmedetomidine on pressure response during laryngoscopy, intubation and pneumoperitoneum in laparoscopic surgery. Methods: This was a randomized open labelled, prospective control type of study was conducted at Anaesthesia, Analgesia & ICU Department, Sher-e-Bangla Medical College Hospital, Barishal, Bangladesh from July 2020 to December 2020. Eighty Four patients aged between 25-60 years, belonging to ASA I or II of either sex posted for elective laparoscopic surgery under general anaesthesia were selected for the study. Patients were allocated randomly in to three groups (28 patients in each group).Patients of group-A received dexmedetomidine (0.5 mcg/kg) IV as loading dose over 10min, followed by 0.4mcg/kg/hr till the end of pneumoperitoneum and patients of group-B received esmolol (0.5mg/kg) IV as loading dose over 5 min followed by 50mcg/kg/min till the end of pneumoperitoneum. Patients of group-C received same volume of normal saline. During laryngoscopy, intubation, pneumoperitoneum, at reversal and extubation HR, MAP, oxygen saturation were observed. Recovery in terms of time to respond to oral-commands, extubation and full orientation was noted along with any adverse effects. Results: In control group, there was significant increase in HR and MAP during intubation, extubation and pneumoperitoneum. In dexmedetomidine group we observed better control of HR and MAP as compare to esmolol and control groups. Conclusion: Both dexmedetomidine hydrochloride and esmolol hydrochloride were effective in attenuating pressure response to laryngoscopy, intubation and pneumoperitoneum in patients undergoing laparoscopic surgeries. Dexmedetomidine was more effective to control HR and MAP as compared to esmolol. With dexmedetomidine, the recovery from anaesthesia was prolonged than esmolol. Key words: Laryngoscopy, Laparoscopic Surgery, Pneumoperitoneum, Hemodynamic Response, Dexmedetomidine, Esmolol. INTRODUCTION Laparoscopy procedures require pneumoperitoneum for adequate visualisation and operative manipulations which affects many homeostatic systems causing alterations in acid-base status, cardiovascular system, stress response and pulmonary physiology. Laparoscopic procedures include smaller incisions, lower risk of wound complications, reduced postoperative pain and pulmonary complications, shorter hospital stay, more rapid return to normal activity which in turn reduces cost to the patient. These hemodynamic responses are mainly due to increased release of catecholamines, vasopressin, or both. Esmolol, an ultrashort-acting cardioselective β1 adrenoceptor antagonist, has been used to control tachycardia and hypertension. They cause increase in systemic vascular resistance which increases mean arterial pressure, decreases cardiac output and compromise tissue perfusion. Various pharmacological agents like nitroglycerine1, opioids2, gabapentin3, pregabalin4, magnesium sulfate5, clonidine6, dexmedetomidine7 and beta blocker8 has been used to maintain hemodynamic during pneumoperitoneum. Dexmedetomidine by its agonist effect on α2- adrenergic receptor thereby inhibiting the release of catecholamine and vasopressin released during laparoscopic surgery9 controls hemodynamic response of pneumoperitoneum. Esmolol, an ultra-short acting cardio-selective β1- receptor antagonist, blunts hemodynamic responses to perioperative noxious stimuli during laryngoscopy, intubation and pneumoperitoneum.8 Dexmedetomidine, an α2 adrenergic receptor agonist, possesses hypnotic, sedative, anxiolytic, sympatholytic, and analgesic properties without producing significant respiratory depression.10 Its sympatholytic effect decreases mean arterial pressure (MAP) and heart rate (HR) by reducing norepinephrine release.11 Bhattacharjee et al 12 have shown that dexmedetomidine is effective in attenuating the adverse hemodynamic response to CO2 pneumoperitoneum. Anaesthetic manoeuvres like direct laryngoscopy, tracheal intubation, extubation, pneumoperitoneum and CO2 insufflations necessary in laparoscopic surgeries causes increase in plasma stress hormone which leads to increase in heart rate (HR), mean arterial blood pressure (MAP), systemic and pulmonary vascular resistance and decrease cardiac output. In this randomized open labeled observer blinded study, we compared effect of esmolol and dexmedetomidine to attenuate pressure response to laryngoscopy, intubation and pneumoperitoneum during laparoscopic surgery. Our aim of study was to compare the effectof esmolol and dexmedetomidine on pressure response during laryngoscopy, intubation and pneumoperitoneum in laparoscopic surgery.
METHODS This was a randomized open labelled, prospective control type of study conducted at Anaesthesia, Analgesia & ICU Department, Sher-e-Bangla Medical College Hospital, Barishal, Bangladesh from July to December 2020. Eighty Four patients aged between 25-60 years, belonging to ASA I or II of either sex posted for elective laparoscopic surgery under general anaesthesia were selected for the study. Patients who refuses or with history of hypertension, diabetes mellitus, morbid obesity, allergy to study drugs, renal and hepatic insufficiency, cardiopulmonary or respiratory disease, patients on beta blocker drugs, anticipated difficult intubation, pregnant or breast feeding female were excluded from the study. Patients were allocated randomly in to three groups (28 patients in each group). Group-A: Inj. Dexmedetomidine hydrochloride. Group-B: Inj. Esmolol hydrochloride. Group-C: Inj. 0.9% normal saline was administered to the control group. Pre-anaesthesia check-up was conducted and a detailed history and complete physical examination was done. Routine investigations like complete blood count, random blood sugar, renal function test, liver function test, chest x-ray and electrocardiogram were done. Monitors for pulse oximetry, NIBP and multipara monitor. Baseline values of heart rate (HR), non-invasive blood pressure (NIBP) were recorded. Intravenous access was secured. All the patients were premedicated with intravenous Inj. glycopyrrolate 0.004 mg/kg, Inj. ondansetron 0.01 mg/kg, Inj. Omeprazole and antibiotic. Group-A: Inj. Dexmedetomidine hydrochloride intravenously (IV) bolus of 0.5 μg/kg was given over 10 minutes by infusion pump starting 5 minutes before induction following which infusion rate was set at 0.4 mcg/kg/hr till the end of pneumoperitoneum. Group-B: Inj. Esmolol hydrochloride IV bolus of 0.5 mg/kg was given over 5 minutes by infusion pump starting 2 minutes before induction, followed by infusion was set at 50 mcg/kg/min till the end of pneumoperitoneum. Group-C: 0.9% normal saline was given as bolus 3 ml/min starting 5 min before induction by infusion pump following which infusion was continued till the end of pneumoperitoneum. The patients were pre oxygenated with 100% oxygen by face mask for 3 min. Anaesthesia was induced with intravenous Inj. fentanyl 2 mcg/kg, Inj. thiopentone 6mg/kg and Inj. Vecuronium 0.1mg/kg to facilitate intubation. Oro-tracheal intubation with Macintosh laryngoscope was done with an appropriate sized portex cuffed endotracheal tube. Intubation was done by experienced anaesthesiologist. Patients were maintained with oxygen, nitrous oxide (O2:N2O, 40:60), Halothen* 7 MAC and intermittent boluses of Inj. vecuronium (0.01 mg/kg). Patients were ventilated manually with tidal volume 500-550 ml/kg and respiratory rate 12–14 breaths/min. Intraabdominal pressure was maintained to 12-14 mm of Hg. CO2 insufflation flow was maintained at the rate of 6 L/min. HR, oxygen saturation (SpO2), urine output and blood loss was monitored. As soon as the pneumoperitoneum was released, study drug infusion was stopped. At the end of procedure, residual neuromuscular blockade was reversed with IV glycopyrrolate (.004mg/kg) and neostigmine (0.05 mg/kg). HR, MAP and SpO2 were recorded at baseline, after study drug administration, after induction, immediately after intubation, at the time of gas insufflation, at every 5 minute interval after pneumoperitoneum, at the end of pneumoperitoneum, at the time of reversal and at the time of extubation. Hypertension (MAP >110 mmHg) was treated with intermittent bolus of Inj. Propofol. Bradycardia (HR<50/min) was treated with inj. atropine 0.6mg IV. Any case of failure to intubate within 15 second, massive blood loss, laparoscopic surgery converted to open laparotomy and surgical time extended more than 3 hr was excluded from the study. Statistical Analysis: Statistical analysis was carried out using the Graph pad prism 8.0 statistical software. Results of continuous measurements were presented as Mean±SD and results of categorical measurements are presented in number and percentage (%). Patient characteristic data were analysed with one-way analysis of variance (ANOVA) for continuous variables and Chi-square test for categorical variables. Inter group comparison of HR; MAP was done with ANOVA, followed by an unpaired t-test. A p-value of <0.05 was considered statistically significant.
RESULTS Our study included 84 adult patients of ASA grade I and II posted for laparoscopic surgery. They were randomly assigned into three groups of 28 patients in each. None of the patient was excluded from the study. As shown in Table 1 there was no significant difference in age, sex, weight, duration and type of surgery (P value >0.05) in all groups. Table-2 shows, there was no significant difference in baseline HR between the groups. After administration of the study drugs and induction agent, there was a significant decrease in HR in group-B and group-C as compared to group-A (p<0.05).
Table 1: Demographic Data (N=84)
Table-2: Comparison of heart rate at various time intervals (N=84)
Gas insufflation caused an increase in HR from baseline values in group-C, however this increase was not seen in group-B and group-A (P<0.001). In group-C, HR was maintained near baseline values and below baseline value in group-B. However HR was statistically lower in group-A (p<0.05). In group-A there was significant rise from baseline value in the HR immediately after intubation and remained higher till the end of pneumoperitoneum. In group-B, after loading dose HR was decrease from baseline value and remained decreased at all-time intervals till the end of surgery. In group-C, there was minimal increase in HR from baseline value immediately after intubation which came to baseline values within 3 min after intubation and remained near baseline values till the end of pneumoperitoneum.
Table-3: Comparison of mean arterial blood pressure at various time intervals (N=84)
Table-3 shows, there was no statistically significant difference in baseline MAP between the groups but after administration of the study drugs and induction agent, significant decrease was seen in MAP in group-A, while no significant difference between group-A and group-B (P>0.05) was found. The rise in MAP immediately after intubation was 25% in group-A and 15% in group-B. Gas insufflation caused an increase in MAP from baseline values in group-A, it was not seen in group-A and group-C (P<0.001). There was significant difference in MAP values between all the groups during pneumoperitoneum (p<0.001). During pneumoperitoneum MAP was higher in group-A at all-time intervals as compared to baseline values. Where as in group-A, MAP was maintained near baseline values, while it was below baseline value in group-C. There was no significant difference in MAP values between group-A and group-C at the end of gas insufflation, at the time of reversal and at the time of extubation (P>0.05), however MAP was statistically lower in group-A (P<0.05). While comparing group-A and group-C, there was significant difference between the groups in MAP at all-time interval during pneumoperitoneum (P<0.001). In group-A and group-B, statistically significant increase in MAP after intubation and during pneumoperitoneum was observed. Decrease in MAP was found in group-A after administration of dexmedetomidine, which was persisted till the end of surgery and extubation.
Table-4: Post-operative complications
Table-4 shows bradycardia was found in 5 patients of group-A and 3 patients in group-B which responded to inj. atropine (0.6mg) IV stat. Hypotension was found in 4 patients of group-A and 1 patient of group-B. Respiratory depression was found in 1 patient of group-A. As shown in table-5, time to respond to oral commands was longer in dexmedetomidine (8.5±1.3 min) as compared to esmolol group (5.8±0.99 min) and control group (5.7±0.97 min) which is statistically Significant (P<0.001).
Table-5: Recovery profile.
There was no significant difference in time to respond to oral commands between esmolol group and control group (P>0.05). The time to extubation was longer in dexmedetomidine group (11±1.86 min) as compared to esmolol group (8.7±1.4 min.) and control group (8±1.03 min) which is statistically significant (P<0.01). There was no significant difference in time to extubation between esmolol group and control group in our study. Time to full orientation was longer in dexmedetomidine (14.03±2.78min) as compared to esmolol group (10.43±1.45min) and control group (10.2±1.32min) which is statistically significant (P<0.001). There was no significant difference in time to full orientation between esmolol group and control group (P>0.05). In group-A decrease in respiratory rate (RR) 10/min and tidal volume (300 ml) was found in one patient. Patient was observed in operation theatre, RR was improved to 14/min and tidal volume to 500 ml within 30 min.
DISCUSSION For laparoscopic procedures, CO2 is used to create pneumoperitoneum because of which intra-abdominal pressure increases, which causes stretching and stimulation of peritoneum by CO2 which leads to activation of sympathetic nervous system which in turn increases plasma catecholamine and vasopressin level, which further activates renin angiotensin aldosterone system leading to abrupt increase in HR, MAP, cardiac output and systemic vascular resistance.13 Administration of general anaesthesia, laryngoscopy, tracheal intubation and extubation are one of the critical events which lead to transient yet marked sympathoadrenal response leading to hypertension and tachycardia.14 This can leads to complications like myocardial ischemia, infarction, etc. Bon Sebastian et al15 conducted study for an optimal bolus dose of dexmedetomidine by comparing two doses 0.5mcg/kg and 0.75 mcg/kg with placebo to attenuate stress response during laryngoscopy and endotracheal intubation and found that both the doses were effective in attenuating the pressure response. If dexmedetomidine given as rapid infusion, it leads to a biphasic response on blood pressure which is initial hypertension followed by fall in blood pressure due to stimulation of α2 receptors in vascular smooth muscles.16 In our study, we choose lower dose 0.5 μg/kg and administered slowly as an infusion over 10 min as bolus and found it effective to control pressure response during laryngoscopy and intubation as compared to control group. Siddareddigari Reddy et al.17 compared dexmedetomidine (1mcg/kg) and esmolol (2mg/kg) for attenuating hemodynamic response and found esmolol effectively control HR after intubation but no effect on systolic blood pressure whereas, dexmedetomidine suppressed both HR as well as MAP to laryngoscopy and tracheal intubation. In our study, we found that both the drugs blunted HR response to laryngoscopy and intubation significantly (P<0.001). We used low dose dexmedetomidine infusion (0.4mcg/kg/hr) and found it effective to control the hemodynamic changes due to pneumoperitoneum during laparoscopic surgeries. Similar to our study, Gourishankar Reddy et al.18 studied dexmedetomidine (0.4mcg/kg/hr) infusion for hemodynamic stability and found it effective in attenuating hemodynamic stability. Decrease in MAP was significant only at higher dose. In our study, bolus dose of 0.5mg/kg esmolol significantly blunted rise in HR but did not blunted blood pressure response. The rise in HR during intubation was 4% inesmolol group whereas; the rise in blood pressure during intubation was 14% in esmolol group. Similar to this, A. M. Koivusalo et al.8 studied effects of esmolol (1mg/kg bolus followed by 200 mcg/kg/min infusion) on hemodynamic response to CO2 pneumoperitoneum for laparoscopic surgery. They concluded that esmolol effectively prevent the pressure response to induction and maintenance of CO2 pneumoperitoneum. In our study, we found effective control of HR and MAP throughout the pneumoperitoneum with esmolol 0.5mg/kg bolus followed by 50mcg/kg/min infusion as compared to control group without intra-operative complication. Effect on HR was faster while control of MAP was delayed, which may be related to the gradual decline in the plasma renin activity occurring with a half- life of 11.9 minutes. Ahmed nabil ibrahim et al.19 compared the efficacy of clonidine (2mcg/kg bolus) versus esmolol (1.5mg/kg bolus followed by 10 mcg/kg/min infusion) on the hemodynamic response during laparoscopic cholecystectomy and concluded that esmolol and clonidine both provided hemodynamic stability in laparoscopic cholecystectomy but clonidine was associated with postoperative sedation. We compared esmolol with dexmedetomidine and found more sedation in dexmedetomidine group with better control of hemodynamic response to laryngoscopy, intubation and pneumoperitoneum. In accordance to our study, Nirav kotak et al.20 also compared dexmedetomidine and esmolol in similar dose for attenuation of pressure response during pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. However, MAP was not significantly controlled during intubation but values were lower compared to control group. Study done by Vinit K. Srivastava et al.21 with dexmedetomidine (bolus dose of 1mcg/kg followed by 0.5mcg/kg/h infusion) and esmolol (bolus dose of 1mg/kg followed by 0.5mg/kg/h infusion) during laparoscopic cholecystectomy also showed dexmedetomidine is better than esmolol for attenuation of hemodynamic response to pneumoperitoneum. Kol et al.22 studied desflurane with esmolol or dexmedetomidine for controlled hypotension during tympanoplasty. They found significantly shorter extubation and recovery times and significantly less postoperative sedation in esmolol group as compare to dexmedetomidine. In accordance to our study Ibraheim et al.23 compared esmolol and dexmedetomidine in similar dose and found dexmedetomidine was associated with prolonged recovery as compared to control group. In consistent to above studies we also found prolong recovery time with dexmedetomidine as compared to control and esmolol group. The study by Islam M. Massad et al.24 and Necla Dereli et al.25 demonstrated less postoperative nausea and vomiting with dexmedetomidine and esmolol infusion during laparoscopic surgery respectively. Similarly we also found less incidence of nausea and vomiting with both dexmedetomidine and esmolol group as compared to control group.
CONCLUSION In concluded, both dexmedetomidine hydrochloride and esmolol hydrochloride were effective in attenuating pressure response to laryngoscopy, intubation and pneumoperitoneum in patients undergoing laparoscopic surgeries. Dexmedetomidine was more effective to control HR and MAP as compared to esmolol. With dexmedetomidine, the recovery from anaesthesia was prolonged than esmolol. Conflict of Interest: None. Source of Fund: Nil.
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DOI How to cite this Alam AKMF, Rahman MMU, Ahsan MN, Fatema K, Matber MS. Esmolol Hydrochloride and Dexmedetomidine on Pressure Response during Laryngoscopy, Intubation and Pneumoperitoneum in Laparoscopic Surgery. Journal of Patuakhali Medical College. 2023 July;2(2):1-2. Issue Section Original Article |
Esmolol Hydrochloride and Dexmedetomidine on Pressure Response during Laryngoscopy, Intubation and Pneumoperitoneum in Laparoscopic Surgery
