Comparative Evaluation of Different Doses of Intravenous Dexmedetomidine on Hemodynamic Response during Laryngoscopy and Endotracheal Intubation in Geriatric Patients Undergoing Spine Surgeries: A Prospective, Double-Blind Study.

BACKGROUND: Dexmedetomidine, a selective alpha 2 (α2)-adrenergic receptor agonist, has been used to blunt the hemodynamic response associated with laryngoscopy and tracheal intubation, which is a common concern for the anesthesiologist, especially in high-risk patients and geriatric age group. AIM AND
OBJECTIVES: The current study is to evaluate and compare the effects of different doses of dexmedetomidine in controlling hemodynamic response during tracheal intubation in geriatric patients.
MATERIALS AND METHODS: After getting approval from the Ethical Committee, 90 patients of the American Society of Anesthesiologist Physical Status Classes I and II, aged ≥60 years, were randomly assigned into three groups: Group I (normal saline, n = 30), Group II - dexmedetomidine (0.50 μg/kg, n = 30), and Group III - dexmedetomidine (1.00 μg/kg, n = 30). Dexmedetomidine was infused for 10 min before induction. Data were recorded as before infusion (T0), at the end of infusion (T1), before tracheal intubation (T2), at the moment of tracheal intubation (T3) 5 min after tracheal intubation (T4), and 10 min after tracheal intubation (T5). Modified observer's assessment of alertness/sedation scale score was observed at the time of T0 and T1. All statistical analyses were done using SPSS version 22.
RESULTS: Mean systolic blood pressure was statistically significantly (P < 0.05) more among Group I compared to Group II and III at T2, T3, and T4. Mean heart rate (HR) value was significantly (P < 0.05) more among Group I compared to Group III from T1 to T5, whereas there was no significant change in HR between Group I and Group II and at T4 and T5 h was comparable in Group II and Group III.
CONCLUSION: This study concluded that more acceptable hemodynamic changes were seen with 0.50 μg/kg dexmedetomidine when compared with 1.0 μg/kg dexmedetomidine during intubation. A lower dose besides being cost-effective is also free of side effects associated with the higher dose of 1 μg/kg dexmedetomidine.

INTRODUCTION

Direct laryngoscopy during tracheal intubation in patients undergoing general anesthesia is noxious stimuli that produce adverse hemodynamic responses, due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation. Increased plasma catecholamine concentration leads to hypertension, tachycardia, and arrhythmia.[1] The magnitude of hemodynamic response is greater with increasing force and duration of laryngoscopy and endotracheal intubation.[2] In geriatric age group owing to decreased reserve capacity of cardiovascular structure and function, it is important for anesthesiologists to attenuate sympathoadrenal response during tracheal intubation which can be detrimental, especially in geriatric age group if not taken care of.[3]

There is increase in life expectancy due to the better medical facility, which leads to increasing number of patients presenting for surgery in geriatric age group. With increase in age, there is alteration in autonomic system, diminution in physiological reserve, increasing the risk of coexisting cardiac disease, and increased sensitivity to opioids and anesthetic drugs.[45] In the elderly, the responsiveness of heart rate, ejection fraction, and global cardiac output decreases due to blunted β-adrenoceptor. Simultaneously, there is increase in end-diastolic volume, left ventricular size, and myocardial O2 demand. They have reduced or absent preload reserve due to an inelastic venous capacitance system which in combination increases the risk of circulatory failure and that is further augmented as a consequence of diuretic therapy and nil per oral status associated with surgery. Other cardiac comorbidities such as ischemic heart disease, systolic and/or diastolic heart failure, and valvular abnormalities further decrease cardiovascular reserve. Therefore, an alteration of the anesthetic technique is preferable to pharmacological means to blunt the pressor response in this class of patients.

Dexmedetomidine possesses properties of sedation, anxiolysis, and analgesia without the development of respiratory depression.[6] Previous studies showed a decrease in blood pressure and cardiac output after small intravenous (IV) boluses (0.25–1 μg/kg), which were associated with decrease in serum norepinephrine concentration, nevertheless the response to larger boluses (1–4 μg/kg) had been a transient increase in blood pressure and sometimes reflex bradycardia.[789]

Various opioids and drugs have been used as coinduction drug by anesthesiologists exploiting their drug interactions, particularly synergism properties with anesthetic drugs producing an improvement in all phases of anesthesia including induction, maintenance, and recovery.[10] Till date, no perfect drug or drug combination that would blunt the hemodynamic response completely without causing unwanted side effects has been found, but dexmedetomidine promises to be a good option.[11] It was found that patients sedated with dexmedetomidine could be easily aroused for cooperation with procedures, and it may protect against myocardial ischemia and reduces the requirement of opioid analgesia.

Furthermore, the use of dexmedetomidine decreases the dose of induction agents such as propofol for sedation and induction of anesthesia and hemodynamic response to laryngoscopy and intubation.[11121314] The existing comparative studies of different doses of dexmedetomidine in blunting the hemodynamic response have found the use of a higher loading dose of 1 μg/kg to be more effective.[15] However, this advantage may be offset by adverse effects such as hypotension and bradycardia, which are likelier to occur with a higher dose and may be catastrophic in the geriatric age group. A lower dose of dexmedetomidine (0.5 μg/kg), besides blunting the hemodynamic response, may be safer in terms of having a reduced incidence of adverse effects and being more cost-effective.

Therefore, the current study investigated and compared the effects of different doses of dexmedetomidine in controlling hemodynamic response to induction of anesthesia and tracheal intubation, with fewer complications in geriatric age group undergoing spine surgeries.

MATERIALS AND METHODS

The study was approved by the Institutional Ethical Committee in a tertiary care center in North India. This prospective study was conducted in the department of anesthesia from March 2017 to May 2018. A total of 90 patients (30 in each group) were calculated at 80% power and Type 1 error of 0.05 using hemodynamics (heart rate [HR] and mean arterial pressure [MAP]) as primary outcome measure from a previous study done by Turan et al.[16] on dexmedetomidine used in intracranial surgeries. After obtaining written informed consent, 90 patients of the American Society of Anesthesiologists Physical Status Classes I and II, aged ≥60 years, planned for elective spine surgeries were randomly assigned into three groups: Group I (normal saline), Group II (0.50 μg/kg dexmedetomidine), and Group III (1.00 μg/kg dexmedetomidine). Group I patients received normal saline of 10 ml bolus over 10 min intravenously before induction. Group II received a loading dose of 0.5 μg/kg body weight of dexmedetomidine in 10 mL normal saline and Group III received a loading dose of 1 μg/kg body weight of dexmedetomidine in 10 mL normal saline over 10 min intravenously before induction, respectively.

Patients having a history of liver disease, mental illness, allergy, bradycardia, use of alpha-2 agonists or antagonists, and any drug abuse were excluded from the study.

Appropriate preoperative fasting was ensured. All standard monitors such as electrocardiography (ECG), blood pressure, pulse oximeter, and end-tidal carbon dioxide (ETCO2) were attached after securing the 18G IV lines. Patients were premedicated with injection ranitidine 50 mg, injection ondansetron 4 mg, and injection fentanyl 1.5 μg/kg. The prepared drug was infused over 10 min before the induction of anesthesia. Following preoxygenation, anesthesia was induced with IV propofol 2 mg/kg, and IV vecuronium bromide (0.1 mg/kg) was used to facilitate tracheal intubation. Anesthesia was maintained with nitrous oxide (60%) and isoflurane (0.5%–1%) in oxygen and vecuronium bromide (0.05 mg/kg). After proper padding of the eyes, patients were kept in the prone position, and all pressure points were secured. The neuromuscular blockade was reversed by IV neostigmine 0.05 mg/kg with glycopyrrolate 0.01 mg/kg at the end of surgery.

The patient as well as the anesthesiologist performing intubation was not aware of the group to which the patient belonged, and the study drug was prepared by an anesthesiologist who was not participating in the study. Hence, our study was double blinded. However, in case of any adverse event related to the study drug, the anesthesiologist, who prepared the drug, was authorized to reveal the drug.

ECG, HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure, oxygen saturation (SPO2), and -ETCO2 were recorded at point of time before infusion of dexmedetomidine (T0), at the end of infusing dexmedetomidine (T1), before tracheal intubation (T2), at the moment of tracheal intubation (T3) 5 min after tracheal intubation (T4), and 10 min after tracheal intubation (T5). SPO2 and the Modified Observer's Assessment of Alertness/Sedation Scale (OAA/S) score [Table 1] were observed at the time of T0 and T1.

Table 1

Modified Observer's Assessment of Alertness/Sedation Scale

The software used for the statistical analysis was Statistical Package for the Social Sciences for Windows version 22.0 (IBM Corp, Armonk, NY, USA). Data were presented as mean and standard deviation. Continuous variables such as HR and MAP were analyzed using analysis of variance and categorical variables were analyzed using the Chi-square test. P < 0.05 was considered to be statistically significant.

RESULTS

Ninety patients were screened for the present study. The consort diagram of the study is shown in Figure 1. All groups were comparable with respect to age, sex, and weight [Table 2]. Mean HR values were significantly (P < 0.05) more among Group I compared to Group III at the end of infusion, before tracheal intubation, during tracheal intubation, and 5 and 10 min after tracheal intubation, whereas there was no significant change in HR between Group I and Group II. Although there was a significant increase in HR in Group II as compared to Group III at T1, T2, and T3, it became comparable in both the groups at T4 and T5 [Table 3].

Figure 1

Consort diagram of the study

Table 2

Demographic characteristics of all the three groups

Table 3

Mean heart rate among the patients of all the groups

The mean (SBP) value at the end of infusion was comparable in all the three groups, but SBP was significantly (P < 0.05) more among Group I compared to Group II and Group III from T2 to T4. However, SBP was significantly low in Group III as compared to Group II at T4 and T5 [Table 4].

Table 4

Mean systolic blood pressure among the patients of all the groups

Mean DBP was significantly (P < 0.05) less among Group III compared to Group I before tracheal intubation, remain comparable during intubation and significantly lower at T4 and T5. However, it remained insignificant in Group II compared to Group I at all intervals except before tracheal intubation [Table 5].

Table 5

Mean diastolic blood pressure among the patients of all the groups

Mean SPO2 in Group III at T1 (91.63 ± 1.98%) was significantly less compared to T0 (98.75 ± 0.98%). Mean OAA/S at T1 (3.46 ± 0.65) was significantly less compared to T0 (5.0 ± 0.0) in group III [Table 6].

Table 6

Mean oxygen saturation and Observer's Assessment of Alertness/Sedation Scale score among the patients of all the groups

DISCUSSION

Tracheal intubation is associated with catecholamine release and pressor response, leading to an elevation in HR and blood pressure. Many previous studies have reported the use of dexmedetomidine to suppress this response as well as to reduce the dose of anesthetic agent.[17] In our study, dexmedetomidine significantly reduced the hemodynamic response though was not completely abolished.

Intubation can increase blood pressure by 40%–50% and HR by 20%.[18] This transient hypertension and tachycardia can be tolerated in young patients but can be catastrophic in vulnerable patients who are vasoconstricted, volume depleted, or have severe heart block. Geriatric patients are at increased risk because of their aging-associated structural and functional changes in the cardiovascular and cerebrovascular systems, which would affect myocardial and cerebral perfusion.[16] The relatively unstable cardiovascular system in elderly patients owing to lost elastance in the arterial wall, venous vessels, and myocardium leads to hypertensive diseases, especially systolic hypertension with a large pulse pressure, further increasing the systemic vascular resistance.[192021]

Stiffening of the venous system leads to the limited ability to autoregulate preload and myocardial stiffening causes delayed relaxation with impaired early and late diastolic filling, leading to poor tolerability to change in volume and pressure.[22] Therefore, it is important in the geriatric patients to avoid statistically significant hemodynamic changes during tracheal intubation.

Many methods such as nasal intubation and many drugs such as opioids, beta-blockers, calcium channel blockers, and halothane had been tried by various authors for blunting hemodynamic response to laryngoscopy and tracheal intubation. However, all such maneuvers had their own limitations.[23]

Sağıroğlu et al.[15] compared the two different doses of dexmedetomidine to observe the blunting of pressor response to laryngoscopy and intubation and reported that a dose of 1.0 μg/kg was more effective than a dose of 0.5 μg/kg. In our study, the hemodynamic response was sufficiently blunted with both the doses of dexmedetomidine.

Menda et al.[24] demonstrated that SBP, DBP, and MAP were lower at all times in comparison to the baseline values compared to placebo group when dexmedetomidine was used in dose of 1 μg/kg. They also demonstrated that after induction of general anesthesia, the drop in HR was higher in dexmedetomidine group than that of placebo group. At time of induction HR was lower in placebo group as compared to its baseline HR. However, in our study there was decrease in HR in Group III at all time interval when compared to Group I and HR never went below baseline in Group I.

Pipanmekaporn et al.[25] found that hemodynamic parameters (mean HR, SBP, DBP, and MAP) during intubation and 10 min afterward were significantly higher in control group than in the dexmedetomidine group (0.7 μg/kg) except at T1 when there was increase in blood pressure in dexmedetomidine group. These findings were similar to our dexmedetomidine group (1 μg/kg).

Piao and Wu[26] in their meta-analysis assessing dexmedetomidine as an anesthetic agent by the occurrence of adverse effects such as hypotension and bradycardia found them to be significantly higher as compared to controls. Khan et al.[27] in their comparative study of 1.0 μg/kg and 0.5 μg/kg doses of dexmedetomidine reported a higher incidence of hypotension and bradycardia with the use of higher dose of the drug. In our study, the use of lower dose was associated with a lesser incidence of both these side effects. Considering the adequacy of both the low and high doses in blunting the hemodynamic response, the relative safety of lower dose with regard to these adverse effects appears to offer a definite clinical advantage, especially in patients with low cardiac reserve like in geriatric patients.

A possible limitation of our study was that opioids used in all the patients in our study themselves blunted the hemodynamic response to laryngoscopy and intubation. Other limitations are the study being confined to a single center and inability to quantify plasma catecholamine levels.

CONCLUSION

The results of this study indicate a loading dose of 0.50 μg/kg dexmedetomidine prove to be a useful anesthesia adjuvant as has the minimum side effects in reducing the hemodynamic stress response, whereas 1.00 μg/kg dexmedetomidine significantly causes the suppression of the tracheal intubation-related cardiovascular responses, with a significant lowering of blood pressure and HR which occurs before and after intubation. A lower dose of 0.5 μg/kg of dexmedetomidine besides having less side effects can be cost-effective as compared to 1 μg/kg infusion of dexmedetomidine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.