|Year : 2021 | Volume
| Issue : 2 | Page : 72-77
Comparing different doses of dexmedetomidine in attenuating extubation response in hypertensive patients undergoing laparoscopic cholecystectomy
Vatika Bhardwaj1, Dheeraj Singha2, Anshit Pathania1, Usha Chaudhary3, Sudarshan Chaudhary2
1 Department of Anaesthesia, Shri Lal Bahadur Shastri Government Medical College, Mandi, Himachal Pradesh, India
2 Department of Anaesthesia, Dr Rajendra Prasad Government Medical College, Kangra, Himachal Pradesh, India
3 Department of Anaesthesia, Indira Gandhi Government Medical College, Shimla, Himachal Pradesh, India
|Date of Submission||29-Aug-2020|
|Date of Decision||07-Dec-2020|
|Date of Acceptance||19-Dec-2020|
|Date of Web Publication||16-Apr-2021|
Dr. Usha Chaudhary
Department of Anaesthesia, Indira Gandhi Government Medical College, Shimla - 171 001, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Background: Tracheal extubation is always linked with hypertension, tachycardia, and high-plasma catecholamine levels. These hemodynamic fluctuations are seen more often in hypertensive patients than in normotensives. The present study evaluates the effects of three different doses of dexmedetomidine in hypertensive patients relative to each other in attenuating extubation response. Patients and Methods: In this randomized, controlled, triple-blinded study, 105 controlled hypertensive patients of either sex on antihypertensive drugs in the age group of 30–70 years, scheduled for laparoscopic cholecystectomy were included. They were randomized into Groups A, B, and C receiving 0.5 μg/kg, 0.75 μg/kg, and 1 μg/kg of dexmedetomidine 10 ml infusion 10 min before extubation. Hemodynamic parameters in form of pulse rate, systolic and diastolic blood pressure, mean arterial pressure (MAP), oxygen saturation, and bispectral index (BIS) were noted. Extubation time, quality, and sedation were evaluated. Any side effects in form of postoperative nausea, vomiting, and bradycardia were noted. Results: There was significant attenuation of rise in heart rate, systolic, diastolic, and MAPs after 4 min of starting infusion between the three groups. At extubation, the values of hemodynamic parameters and BIS were significant between the three groups (P < 0.001). While the quality of extubation improved and the sedation scores increased with the increase in the dose of dexmedetomidine, the incidence of bradycardia was more with dose of 1 μg/kg as compared to 0.75 μg/kg and 0.5 μg/kg. Conclusion: It was found that 0.75 μg/kg was the optimal dose for extubation as it facilitated smooth extubation and maintained hemodynamic stability in patients without causing undue sedation.
Keywords: Bispectral index, dexmedetomidine, extubation response, hemodynamic, hypertension, sedation
|How to cite this article:|
Bhardwaj V, Singha D, Pathania A, Chaudhary U, Chaudhary S. Comparing different doses of dexmedetomidine in attenuating extubation response in hypertensive patients undergoing laparoscopic cholecystectomy. Bali J Anaesthesiol 2021;5:72-7
|How to cite this URL:|
Bhardwaj V, Singha D, Pathania A, Chaudhary U, Chaudhary S. Comparing different doses of dexmedetomidine in attenuating extubation response in hypertensive patients undergoing laparoscopic cholecystectomy. Bali J Anaesthesiol [serial online] 2021 [cited 2021 Jun 23];5:72-7. Available from: https://www.bjoaonline.com/text.asp?2021/5/2/72/313881
| Introduction|| |
Hypertension is the most common comorbidity encountered in the preanesthesia clinics. The impulsive hemodynamic variations at extubation are well tolerated by healthy individuals, but may be detrimental in hypertensive patients. Tracheal extubation has always received less weightage than intubation when attenuation of hemodynamic responses is considered. It causes 10%–30% increase in blood pressure and heart rate (HR) because of high plasma catecholamine levels which can further add on to already existing high blood pressure., The above events lead to increased oxygen demand which can cause myocardial ischemia and infarction. Myocardial oxygen demand, especially in hypertensive patients is often increased owing to myocardial hypertrophy and decreased perfusion to coronary, further making these patients a high risk for adverse events. Moreover, thereby it is logical to consider preventive methods to attenuate these undesirable responses during extubation.
Ample studies have been carried out in the past with highly selective alpha-2 (α-2) agonist dexmedetomidine with varying results and have been found advantageous.,, Data on the use of dexmedetomidine at extubation are sparse, especially in hypertensive patients and laparoscopic surgery. The aim of this study was to identify an optimal dose of dexmedetomidine required to attenuate the hemodynamic stress response to endotracheal extubation in hypertensive patients with minimal adverse event.
| Patients and Methods|| |
The research has been performed in accordance with the declaration of Helsinki and was approved by the Institutional Ethics Committee and registered in Clinical Trials Registry (CTRI/2017/08/009486 dated 24/08/2017). The study was a retrospective, randomized, triple-blinded trial.
The study included 105 hypertensive patients aged 30–70 years, of either sex who were well controlled on antihypertensives, American Society of Anesthesiologists physical status I or II, body mass index ≤30 kg/m2, and scheduled for elective laparoscopic cholecystectomy.
The exclusion criteria included untreated hypertension, users of beta-blockers, history of cardiovascular or renal disease, diabetes mellitus, cerebrovascular disease or abnormal electrocardiography, hypersensitivity to drug, and patient's refusal for participation. If at any time during the study period, bradycardia occurs (HR <50 bpm) or systolic blood pressure (SBP) come to be <80 or more than 180 mmHg or the surgery was not completed within 10 min of starting infusion, patients were excluded from the study, and adequate management was carried out.
Patients were randomized using a computer-generated random table in sequentially numbered, sealed, opaque envelopes into three equal groups. The envelop was opened after the patient is taken inside operating theater (OT) by the first anesthesiologist. The code was given to the second anesthesiologist who prepared the study drugs in 10 ml syringe and was sent to the OT anesthesiologist (the third anesthesiologist) who did drug administration and observations.
Group A received 0.5 μg/kg, Group B received 0.75 μg/kg, and Group C received 1 μg/kg dexmedetomidine diluted to 10 ml in 0.9% normal saline over a period of 10 min. Patients were kept fasting for 8 h before planned procedure and were advised to continue their antihypertensive medication. On arrival to operation theater, five-lead electrocardiography, noninvasive blood pressure, pulse oximetry (SpO2), bispectral index (BIS), temperature probe, and neuromuscular transmission (Infinity Trident neuromuscular transmission Smart Pod-Drager) were attached, and baseline parameters were noted.
Intravenous access was secured, and induction was done with 5 mg/kg thiopentone, 2 μg/kg fentanyl, 0.1 mg/kg vecuronium, and preservative free lignocaine 2% 1.5 mg/kg. When there was no response to train-of-four (TOF) stimulation and BIS ≤60, trachea was intubated with endotracheal tube of appropriate size. Anesthesia was maintained with 0.5%–1.5% isoflurane, 60% nitrous oxide in oxygen, and intermittent boluses of vecuronium (0.02 mg/kg). BIS was kept between 40 and 60. The end-tidal carbon dioxide pressure was maintained between 30 and 40 mm Hg.
All participants were given diclofenac 75 mg intravenously and infusion paracetamol 1 g. At the beginning of closure of ports of the laparoscopic surgery, isoflurane was discontinued and dexmedetomidine diluted to 10 ml in normal saline was infused in all three groups over 10 min using infusion pump. BIS monitoring was continued till the patient was extubated. Nitrous oxide was discontinued after the completion of dexmedetomidine infusion. Reversal of residual muscle relaxation was done with neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg. The patient was extubated when ratio of TOF was >0.9, and patient's spontaneous respirations were considered adequate.
The primary outcome included the hemodynamic parameters, pulse rate, SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), oxygen saturation (SpO2), and BIS which were noted every 1 min after start of infusion till extubation. Extubation time was noted, and extubation quality was rated using extubation quality 5-point scale with a score of 1–5.
The secondary outcomes included the time to extubation, postoperative sedation, and any hemodynamic adverse event (bradycardia, hypotension, or hypertension). Time to extubation was noted from the end of dexmedetomidine infusion until extubation. Patients were kept in postanesthesia care unit for 2 h, supplemental oxygen was given to every patient at 5 L/min via Hudson mask for 30 min post extubation and hemodynamic parameters were recorded every minute until 5 min and thereafter every 15 min until 2 h. Sedation was recorded using the Ramsay Sedation Scale (RSS), which was recorded at 5-min interval until 30 min and thereafter at 30-min interval for the next 90 min.
All data were collected in MS Excel. Statistical analysis was performed using the Epi info version 7 for Windows (by CDC, USA). Normally, distributed data were analyzed using a repeat-measures general linear model analysis of variance followed by Tukey post hoc test to find pairwise significance and categorical data was analyzed using Chi-square or Fisher exact test whichever was applicable. Continuous measurements are presented as mean and standard deviation. Categorical measurements are presented in number with percentage. P ≤ 0.05 was accepted as statistically significant.
| Results|| |
One hundred and five patients fulfilling the eligibility criteria planned for laparoscopic cholecystectomy were enrolled in our study and randomly allocated into three groups [Figure 1]. The demographic profile was comparable between the three groups [Table 1]. The intraoperative monitored parameters were comparable before the start of dexmedetomidine infusion in the three groups.
The mean HR at peak concentration of dexmedetomidine (T10 min was 82.23 ± 10.56, 73.57 ± 10.51, and 62.77 ± 7.23 bpm in Groups A, B, and C, respectively (P < 0.001). HR in group A was higher as compared to Groups B and C, and it was higher when Group B was compared to Group C. Bradycardia was seen in two, three, and ten patients in Groups A, B, and C, respectively, during dexmedetomidine infusion. Instantly, the infusion was stopped and atropine 20 μg/kg was administered intravenously. These patients were excluded from the study as intervention was not completed. The comparison of SpO2 was statistically not significant between the three groups. The mean saturation remained above 97 throughout in the three groups. The values of BIS were above 70 in all three groups during infusion and group C patients were more sedated than B as shown in [Figure 2].
|Figure 2: Graph showing trends of bispectral index during dexmedetomidine infusion|
Click here to view
Time to extubation was 8.60 ± 0.51, 8.83 ± 0.51, and 9.34 ± 0.48 min in Groups A, B, and C, respectively (P = 0.058). Quality of extubation and hemodynamic at extubation are shown in [Table 2]. In Group C, 66.6% patients had no coughing at the time of extubation (Grade 1) as compared to 56.6% patients in Group B and 23.3% in Group A. Each group A and B showed that 30% patients had a smooth extubation (grade 2), compared to Group C (23.3%).
|Table 2: Quality of extubation and hemodynamic parameter at extubation of the three groups|
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After extubation [Figure 3], the overall difference between the three groups is statistically significant (P < 0.001). After 10 min from extubation, there was no difference in HR between Groups A and B (P = 0.025); however, there was significant difference between Groups B and C (P < 0.001). SBP, DBP, and MAP were significantly higher in Group A as compared to Groups B and C. This shows that good attenuation of pressor response was done with higher doses as compared to lower dose, and Group B had more stable hemodynamic without any undue variations.
Patients in Group C had a delayed recovery compared to Group B [Figure 4]. Sedation score was seen maximum in Group C (RSS 4–5) and minimum in Group A (RSS 2–3). RSS in Group B was between 3 and 4. No patient had RSS of 1 or 6 after extubation. After an hour though, sedation scores were comparable in all the three groups.
| Discussion|| |
It is a well-established fact that when compared to intubation complications are three times higher in frequency during and after extubation.,, There is a strong recommendation to maintain hemodynamic during extubation within 20% of normal awake value particularly in high risk patients. The cardiovascular changes to these critical points are more brisk in poorly controlled hypertensives than do normotensives or well-controlled hypertensives.
Dexmedetomidine mitigates this sympathoadrenal response and decreases intensity of hemodynamic fluctuations during these events.,, It also provides sedation and gives us a superb quality of extubation. It depresses the gag reflex and improves tracheal tolerance as compared to other sedative drugs. The main objective of the study was to find the optimal dose of dexmedetomidine in attenuating the extubation response in hypertensive patients. The optimal dose would be the one which provides stable hemodynamic during and after extubation, quality of extubation with no or minimal coughing along with a calm cooperative patient in the postextubation period.
In our study, during and after extubation, HR, SBP, DBP, and MAP were higher with low-dose dexmedetomidine (0.5 μg/kg) as compared to the higher doses (0.75 μg/kg or 1 μg/kg). In contrast, Guler et al. found all doses to be equally effective in normotensive patients. Basic behind this is that α-2 receptors when activated in the central nervous system leads to sedation, reduction of tonic levels of sympathetic outflow, and an augmentation in cardiac-vagal activity net result being decrease in HR and cardiac output.
In addition, activation in the spinal cord provides some extent of analgesia also making it superior to other agents.,, Sezen et al. and Franklin studied hypertensive patients in which dexmedetomidine premedication of 0.5 μg/kg showed similar results as ours., They also concluded that dexmedetomidine provided superior hemodynamic stability and decreases antihypertensive requirements.
In a study done by Bilgi et al. where dexmedetomidine (1 μg/kg), when compared to fentanyl (1 μg/kg), HR in both groups were not raised significantly from the baseline value. Similarly, in our study, during the postextubation period, all the hemodynamic parameters were decreased with higher doses but remained in normal range. New data prove that brief hypotensive episodes can have a significant impact on outcome in the perioperative period.
Chronic hypertensive patient's autoregulation of cerebral and renal perfusion is usually shifted to a higher range so it is of utmost importance to maintain a MAP within the required range. The vital organs such as brain and kidneys are more vulnerable to hypoperfusion when there is sudden and rapid decrease in blood pressure, but none of the patient in our study had MAP below 65 mm Hg, thus maintaining the autoregulation similar to study done by Liyakhath et al. The saturation remained >97 in the three groups suggesting that dexmedetomidine does not depress the respiration which is its unique property.
The explicit recall is remarkably diminished as BIS falls below 70, we found that during and postextubation BIS >70 in all groups showing that patients were sedated and had delayed recovery with higher doses as compared to 0.5 μg/kg dose which was similar to other studies.,, However, Elias et al. reported that during wakefulness BIS >80 with 0.1–0.4 μg/kg/h dexmedetomidine (unmedicated state) suggesting that lower dose causes less decrease in BIS values.
Supported by other studies, the quality of extubation was better with dose of 0.75 μg/kg and 1 μg/kg as compared to the dose of 0.5 μg/kg.,, Antony et al. found 90% of patients in group with dexmedetomidine (0.5 μg/kg), 93.3% (1 μg/kg), and 16.7% (saline) could be extubated smoothly. Fan et al. also found 0.7 μg/kg dose superior to 0.5 μg/kg dose of dexmedetomidine for smooth extubation.
Dexmedetomidine shows dose-related sedation with peak after 45–60 min but with a dose of 1–2 μg/kg. Oxygen supplementation is often required as there is irregular breathing and episodes of apnea. In our study, similar to other studies, none of the patients was deeply sedated, was arousable, and did not require any intervention.,,, Furthermore, patient safety is one of the major concerns in anesthesia, taking into account that elimination half-life of dexmedetomidine is 2 h, we observed patients for a period of about 120 min.
The incidence of hypotension and bradycardia reported with dexmedetomidine sedative doses is above 50% being more with higher doses. These adverse effects are more marked in hypovolemic patients, elderly, diabetes mellitus, or chronic hypertension. Bradycardia was observed in our study in a dose-dependent manner with 2, 3, and 10 patients in Groups A, B and C, respectively. Sezen et al. found the frequency of bradycardia (defined as HR <45 bpm) was 60% in hypertensive and 38% in normotensive patients using 0.5 μg/kg dose. Bindu et al. reported that dexmedetomidine (0.75 μg/kg) led to higher incidence of bradycardia (defined as HR <60 bpm), whereas Aksu et al. reported dexmedetomidine (0.5 μg/kg) use caused bradycardia in only two patients.,
Limitation of our study was that we did not have control group to compare the attenuation of extubation response with 0.5 μg/kg dose.
| Conclusion|| |
We concluded that 0.75 μg/kg and 1 μg/kg doses were able to attenuate extubation response better than 0.5 μg/kg dose and provided better hemodynamic stability during emergence from anesthesia. The dose of 1 μg/kg dexmedetomidine had more sedation and side effects, thus making 0.75 μg/kg dose the single best dose in hypertensive patients for attenuation of hemodynamic responses at extubation. We also recommend further studies with a larger study population and with co-existing morbidities to authenticate our study results.
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| References|| |
Anchala R, Kannuri NK, Pant H, Khan H, Franco OH, Di Angelantonio E, et al
. Hypertension in India: A systematic review and meta-analysis of prevalence, awareness, and control of hypertension. J Hypertens 2014;32:1170-7.
Howell SJ, Sear JW, Foëx P. Hypertension, hypertensive heart disease and perioperative cardiac risk. Br J Anaesth 2004;92:570-83.
Turan G, Ozgultekin A, Turan C, Dincer E, Yuksel G. Advantageous effects of dexmedetomidine on haemodynamic and recovery responses during extubation for intracranial surgery. Eur J Anaesthesiol 2008;25:816-20.
Lapage KG, Wouters PF. The patient with hypertension undergoing surgery. Curr Opin Anaesthesiol 2016;29:397-402.
Manne GR, Upadhyay MR, Swadia V. Effects of low dose dexmedetomidine infusion on haemodynamic stress response, sedation and post-operative analgesia requirement in patients undergoing laparoscopic cholecystectomy. Indian J Anaesth 2014;58:726-31.
] [Full text]
Bilgi KV, Vasudevan A, Bidkar PU. Comparison of dexmedetomidine with fentanyl for maintenance of intraoperative hemodynamics in hypertensive patients undergoing major surgery: A randomized controlled trial. Anesth Essays Res 2016;10:332-7.
] [Full text]
Bindu B, Pasupuleti S, Gowd UP, Gorre V, Murthy RR, Laxmi MB. A double blind, randomized, controlled trial to study the effect of dexmedetomidine on haemodynamic and recovery response during tracheal extubation. JAnaesthesiol Clin Pharmacol 2013;29:162-7.
Ramsay MA, Huddleston P, Hamman B, Tai S, Matter G. The patient state index correlates well with the Ramsay sedation score in ICU patients. Anesthesiology 2004;101:A338.
Antony D, Davies CV, Thomas MK, Shenoy U, Mahesh V, Puthumana KJ. The effect of two different doses of dexmedetomidine to attenuate cardiovascular and airway responses to tracheal extubation: A double blind randomized controlled trial. Int J Med Res Rev 2016;4:1392-403.
Charlson ME, MacKenzie CR, Gold JP, Ales KL, Topkins M, Shires GT. Preoperative characteristics predicting intraoperative hypotension and hypertension among hypertensives and diabetics undergoing noncardiac surgery. Ann Surg 1990;212:66-81.
von Delius S, Thies P, Rieder T, Wagenpfeil S, Herberich E, Karagianni A, et al
. Auditory evoked potentials compared with bispectral index for monitoring of midazolam and propofol sedation during colonoscopy. Am J Gastroenterol 2009;104:318-25.
Keniya VM, Ladi S, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic requirement. Indian J Anaesth 2011;55:352-7.
] [Full text]
Guler G, Akin A, Tosun Z, Eskitasoglu E. During the extubation the effects of dexmedetomidine on cardiovascular changes and quality of extubation in the old patients undergoing cataract surgery. Turkish J Anaesthesia 2005;33:18-23.
Moustafa AM, Atalla H, Koptan HM. Comparison of dexmedetomidine, lidocaine, and their combination in attenuation of cardiovascular and catecholamine responses to tracheal extubation and anaesthesia emergence in hypertensive patients. Res Opin Anesth Intensive Care 2015;2:1-6. [Full text]
Sebastian B, Talikoti AT, Krishnamurthy D. Attenuation of haemodynamic responses to laryngoscopy and endotracheal intubation with intravenous dexmedetomidine: A comparison between two doses. Indian J Anaesth 2017;61:48-54.
] [Full text]
Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes. Anesthesiology 1992;77:1134-42.
Sezen G, Demiraran Y, Seker IS, Karagoz I, Iskender A, Ankarali H, et al
. Does premedication with dexmedetomidine provide perioperative hemodynamic stability in hypertensive patients? BMC Anesthesiol 2014;14:113.
Franklin S. Comparison of dexmedetomidine infusion with saline placebo for smooth extubation in hypertensive patient for major surgery. IJIRMS 2017;8:1133-37.
Varon J, Marik PE. Perioperative hypertension management. Vasc Health Risk Manag 2008;4:615-27.
Liyakhath A, Siddhram J, Jagadish MB. Attenuation of haemodynamic stress response during emergence from general Anaesthesia: A prospective randomized controlled study comparing fentanyl and dexmedetomidine. JEMDS 2014;62:13686-97.
Mahajan L, Kaur M, Gupta R, Aujla KS, Singh A, Kaur A. Attenuation of the pressor responses to laryngoscopy and endotracheal intubation with intravenous dexmedetomidine versus magnesium sulphate under bispectral index-controlled anaesthesia: A placebo-controlled prospective randomised trial. Indian J Anaesth 2018;62:337-43.
] [Full text]
Kasuya Y, Govinda R, Rauch S, Mascha EJ, Sessler DI, Turan A. The correlation between bispectral index and observational sedation scale in volunteers sedated with dexmedetomidine and propofol. Anesth Analg 2009;109:1811-5.
Shah V, Patel J, Patel K. Comparison of Dexmedetomidine and Propofol for haemodynamic changes and depth of anaesthesia (using BIS monitor) during laparoscopic surgery. NHL J Med Sci 2015;4:44-8.
Elias WJ, Durieux ME, Huss D, Frysinger RC. Dexmedetomidine and arousal affect subthalamic neurons. Mov Disord 2008;23:1317-20.
Aksu R, Akin A, Biçer C, Esmaoğlu A, Tosun Z, Boyaci A. Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes and hemodynamic responses to tracheal extubation during rhinoplasty: A double-blind, randomized, controlled study. Curr Ther Res Clin Exp 2009;70:209-20.
Fan Q, Hu C, Ye M, Shen X. Dexmedetomidine for tracheal extubation in deeply anesthetized adult patients after otologic surgery: A comparison with remifentanil. BMC Anesthesiol 2015;15:106.
Shrirang R, Somasekharam P, Dinesh K and Ravi M. Effect of bolus dose of dexmedetomidine on haemodynamic responses and airway reflexes during tracheal extubation: Double blind, randomized, controlled trial study. World J Pharm Pharm Sci 2015;4:731-40.
Rani P, Hemanth Kumar VR, Ravishankar M, Sivashanmugam T, Sripriya R, Trilogasundary M. Rapid and reliable smooth extubation-Comparison of fentanyl with dexmedetomidine: A randomized, double-blind clinical trial. Anesth Essays Res 2016;10:597-601.
] [Full text]
Anjum N, Tabish H, Debdas S, Bani HP, Rajat C, Anjana Basu GD. Effects of dexmedetomidine and clonidine as propofol adjuvants on intra-operative hemodynamics and recovery profiles in patients undergoing laparoscopic cholecystectomy: A prospective randomized comparative study. Avicenna J Med 2015;5:67-73.
] [Full text]
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]