Alleviating Stress Response to Tracheal Extubation in Neurosurgical Patients: A Comparative Study of Two Infusion Doses of Dexmedetomidine

INTRODUCTION

Intracranial surgery requires the method of anesthesia that ensures hemodynamic stability and fast recovery to allow immediate neurological evaluation. Tracheal extubation is always associated with hemodynamic changes because of sympathetic discharge due to epipharyngeal and laryngeal stimulation.[1] This increase in sympathetic activity may result in hypertension, tachycardia, and arrhythmias.[12] The increase in blood pressure (BP) and heart rate (HR) is transitory, variable but unpredictable and is more hazardous to the patient with preexisting hypertension, myocardial insufficiency, or cerebrovascular diseases.[3] Hypertension can result in increase of brain edema or intracranial hematoma formation which may give rise to herniation. The occurrence of hypertension during emergence has been reported to be more than 90% in neurosurgical patients.[45] Thus, to prevent and control the hemodynamic response to nociceptive stimuli is of utmost importance to preserve cerebral homeostasis in these patients. Airway irritation appearing during tracheal extubation may cause cough or difficulties in breathing. Smooth extubation requires the absence of straining, movement, coughing, breath holding, or laryngospasm.[6]

Various techniques and antihypertensive drugs are available to reduce airway and circulatory responses during extubation, but none have been completely successful.[56789] Attempts have been made to oppose the hemodynamic response by the use of drugs such as narcotic analgesics,[7] deepen the plane of anesthesia by inhalation agents,[6] vasodilator agents,[8] local anesthetics[910] and adrenoceptor blockers. Studies have been carried out with the use of lignocaine,[2910] esmolol,[51112] nicardipine,[13] labetalol,[5] diltiazem,[123] opioids,[14] clonidine[15] as single dose, or in comparison with each other. Among the anesthetics, propofol has been shown to be very effective in attenuating the sympathetic response to tracheal extubation in cardiac patients.[1617]

Dexmedetomidine, a potent, highly selective alpha-2 receptor agonist that has sedative, analgesic, anxiolytic, and amnesic effects without causing significant respiratory depression.[18] It also has a sympatholytic effect, similar to clonidine, causing decrease in the concentration of norepinephrine. This in turn decreases the BP and the HR. It may thus be theoretically appropriate for reducing airway and circulatory reflexes during emergence from anesthesia. It has also been studied as been given as single bolus dose to attenuate airway, circulatory reflexes, and recovery responses during tracheal extubation.[1819] According to the mathematical model of drug pharmacokinetics, infusion of a drug at a constant rate produces a steady-state drug concentration which is more uniform than the bolus administration of the same drug. Thus, we hypothesize that the infusion of dexmedetomidine may produce more stable hemodynamics during tracheal extubation as compared to boluses.

MATERIALS AND METHODS

After taking approval from the Institute Ethics Committee (IRB No. IESC/T-188/04.05.2012) by Dr. Rakesh Yadav (Chairperson, Ethics Committee, All India Institute of Medical Sciences, New Delhi,) on May 7, 2012, 90 adult patients with the American Society of Anesthesiologists (ASA) physical Status I–II, aged between 18 and 65 years undergoing elective intracranial surgeries such as brain tumor and epilepsy surgeries who were likely to get tracheally extubated at the end of surgery were included in the study.

RESULTS

Ninety adult patients who were initially screened were enrolled in this study. There were no dropouts. The demographic details have been listed in Table 1 and perioperative and recovery characteristics in Table 2. The period of study drug infusion varied in the three groups which was longer in the placebo group as compared to the other two dexmedetomidine groups (P = 0.002), probably due to longer closure time in the placebo group. The emergence time in D_0.4 group patients was 11.4 ± 4.1 min which was longer than the patients in the D_0.2 group where emergence time was 8.2 ± 2.6 min (P < 0.0001). However, emergence time between the D_0.2 and placebo group was comparable.

Table 1 Demographic characteristics of patients in the 3 study groups (mean±standard deviation) or n

Table 2 Perioperative and recovery characteristics of patients in the 3 study groups (mean±standard deviation)

Hemodynamics

The perioperative trend of HR and MAP has been graphically shown in Figures 1 and 2, respectively. The HR and MAP values were higher in placebo group as compared to D_0.2 and D_0.4 groups, especially at the time of tracheal extubation.

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Figure 1

Perioperative trend of heart rate in the 3 study groups expressed as mean standard deviation. HR: Heart rate, HR_BL: Baseline heart rate, HR 5, HR 10, HR 15, HR 20, HR 25, HR 30, HR 35, HR 40, HR 45, HR 50, HR 55, HR 60: Heart rates at 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 min from the start of drug administration, HR_BE: Heart rate just before tracheal extubation, HR PE: Heart rate immediately posttracheal extubation, HR PE1, HR PE2, HR PE3, HR PE4, HR PE5, HR PE6, HR PE7, HR PE8, HR PE9, HR PE10: Heart rates postextubation at 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 min, respectively, Group D_0.2 – dexmedetomidine 0.2 μg/kg/h infusion group, Group D_0.4 – dexmedetomidine 0.4 μg/kg/h infusion group, Group P – Placebo group

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Figure 2

Perioperative trend of mean arterial pressure in the 3 study groups expressed as Mean standard deviation. MAP: Mean arterial pressure, MAP_BL: Baseline MAP, MAP 5, MAP 10, MAP 15, MAP 20, MAP 25, MAP 30, MAP 35, MAP 40, MAP 45, MAP 50, MAP 55, MAP 60: Mean arterial pressures at 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 min from the start of drug administration, MAP_BE: MAP just before tracheal extubation, MAP PE: MAP immediately post tracheal extubation, MAPPE1, MAPPE2, MAPPE3, MAPPE4, MAPPE5, MAPPE6, MAPPE7, MAPPE8, MAPPE9, MAPPE10: MAP postextubation at 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 min, respectively, Group D_0.2 – dexmedetomidine 0.2 μg/kg/h infusion group, Group D_0.4 – dexmedetomidine 0.4 μg/kg/h infusion group, Group P – Placebo group

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Cardiovascular complications

The cardiovascular complications such as emergence hypertension, tachycardia, and hypotension have been graphically shown in Figure 3. Around 73.3% patients in the placebo group suffered both hypertension and tachycardia during emergence, and 23.3% patients had emergence hypertension only; one patient in D_0.4 group had emergence hypertension alone, and one patient had both hypertension and tachycardia. One patient in the D_0.2 group had hypotension whereas no patient in this group had any episode of hypertension and tachycardia.

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Figure 3

Cardiovascular complications in the 3 study groups expressed as n (%). Group D_0.2 – dexmedetomidine 0.2 μg/kg/h infusion group, Group D_0.4 – dexmedetomidine 0.4 μg/kg/h infusion group, Group P – Placebo group

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Cough

No patient coughed during emergence in Group D_0.4 while in Group D_0.2, absence of coughing was observed in 80% subjects. About 33.3% patients had mild cough in the placebo group whereas 20% patients had mild cough in Group D_0.2. Around 40% and 3.3% patients in the placebo group had moderate and severe cough, respectively, as compared to dexmedetomidine group where no patient suffered moderate or severe cough [Figure 4].

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Figure 4

Cough grade in patients in the 3 study groups expressed as n (%). Group D_0.2 – dexmedetomidine 0.2 μg/kg/h infusion group, Group D_0.4 – dexmedetomidine 0.4 μg/kg/h infusion group, Group P – Placebo group

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No patient had respiratory complications, and none reported any intraoperative awareness. Twenty-five patients (83.3%) in the D_0.4 group, 26 patients in Group D_0.2 and 24 patients (80%) in the placebo group were cooperative and well oriented on emergence. Only one patient (3.3%) in Group D_0.4 showed brisk response to stimulus (Ramsay sedation scale 4) and was deeply sedated. However, rest of the patients had a good recovery with an Aldrete score of 8–10 in the Intensive Care Unit, noted within 1 h postsurgery.

DISCUSSION

The hemodynamic responses to intracranial surgery are most often elicited at the beginning or at the end of the surgical procedure. These responses are transitory, variable, and unpredictable, more pronounced in hypertensive patients than in normotensive individuals. This hemodynamic stimulus is associated with increase in plasma adrenaline concentration parallel with the increase in BP.[23] The increase in adrenaline concentration during and after surgery may represent a physiological response to trauma and surgery. Transitory hypertension and tachycardia are probably of no consequence in healthy individuals, but either or both may be hazardous to those with hypertension, myocardial insufficiency, or cerebrovascular disease.

Our study demonstrates that dexmedetomidine in infusion doses of 0.2 and 0.4 μg/kg/h significantly alleviates hemodynamic responses to tracheal extubation without delaying emergence. In our study, there was a significant reduction in HR and MAP just before tracheal extubation and up to 10 min postextubation in both D_0.2 and D_0.4 groups (P < 0.001). Patients in D_0.2 group had a faster emergence (8.2 ± 2.6 min), similar to the control group (9.9 ± 2.7 min) than those in D_0.4 group (11.4 ± 4.1 min) though it was not clinically significant. There were no adverse reactions to the drug, no intraoperative awareness or any respiratory or airway complications. Modified Aldrete score and Ramsay sedation scale were also comparable in the three groups suggesting that dexmedetomidine could be safely used in neurosurgical patients without affecting the sensorium.

In neurosurgical patients, the use of agents that relax vascular smooth muscle to control the increase in arterial pressure at extubation should be avoided, as the resultant cerebral vasodilatation may increase cerebral blood volume and thus intracranial pressure. Various drugs which are alpha and beta adrenergic receptor antagonists have been advocated in such patients. Dexmedetomidine is a highly specific and selective α₂-adrenergic agonist with sedative, anxiolytic, and analgesic effects.

Turan et al.[19] examined the effects of dexmedetomidine given at the end of procedure to prevent hyperdynamic responses during extubation and to allow a comfortable and high-quality recovery. Forty ASA I–III patients having elective intracranial surgery were included in the study. They found that dexmedetomidine 0.5 μg/kg administered 5 min before the end of surgery stabilized hemodynamics, allowed easy extubation, provided a more comfortable recovery, and early neurological examination following intracranial operations. Our findings are in accordance to the study by Turan et al.

Lawrence and De Lange[20] investigated the effect of a single preinduction intravenous dose of dexmedetomidine 2 μg/kg on anesthetic requirements and perioperative hemodynamic stability in 50 patients undergoing minor orthopedic and general surgery. Patients were anesthetized with nitrous oxide/oxygen/fentanyl, supplemented if necessary with isoflurane. The mean intraoperative isoflurane concentration was lower in the dexmedetomidine-treated patients than controls (0.01 [0.03]% compared to 0.1 [0.1]%; P = 0.001) although six of the 25 treated patients required isoflurane at some stage. The hemodynamic response to tracheal intubation and extubation was reduced in the dexmedetomidine group which was comparable to our study as was intraoperative HR variability; postoperative analgesic and antiemetic requirements, and perioperative serum catecholamine concentrations were lower in the dexmedetomidine group.

Guler et al.[21] studied the effect of a single bolus dose of dexmedetomidine 0.5 μg/kg as bolus intravenously over 60 s in comparison to a placebo in 60 ASA I–III patients undergoing intraocular surgery. Five minutes before the end of surgery, they were randomly allocated to receive either dexmedetomidine 0.5 μg/kg or saline intravenously over 60 s in a double-blind design. The blinded anesthetist awoke all the patients, and the number of coughs per patient was continuously monitored for 15 min after extubation; coughing was evaluated on a 4-point scale. Median coughing scores were 1 (1–3) in dexmedetomidine group and 2 (1–4) in placebo group (P < 0.05), but there were no differences between the groups in the incidence of breath holding or desaturation. The HR, systolic, and diastolic arterial pressures increased at extubation in both groups, but the increase was less significant with dexmedetomidine. The time from tracheal extubation and emergence from anesthesia were similar in both groups. Their findings suggested that a single bolus dose of dexmedetomidine before tracheal extubation attenuated cough and hemodynamic responses during extubation which was comparable to our study.

In 54 patients undergoing surgery for supratentorial brain tumors, Tanskanen et al.[24] demonstrated that the decrease in the hypertensive response to extubation was related to dexmedetomidine dose. Dexmedetomidine plasma target doses of 0.2 and 0.4 ng/ml were compared to placebo. Dexmedetomidine decreased the hemodynamic responses caused by stimuli during anesthesia; a higher dose was more effective than a lower dose which was in accordance with our study findings. In addition, the perioperative systemic infusion of dexmedetomidine at 1 μg/kg/h reduced patient-controlled epidural analgesia (PCEA) bolus consumption, prolonged the time for first request of rescue analgesia through the PCEA pump, and postoperative pain scores without severe side effects.

Our study also revealed that postextubation cough is effectively suppressed by both the infusion doses (0.2 and 0.4 μg/kg/h) of dexmedetomidine which was significantly lower than the control group. This may be due to the sedative action of dexmedetomidine and also because it relaxes the bronchial smooth muscle and prevents airway irritation. It may be advantageous as it decreases the postoperative hoarseness and irritation due to tracheal tube. Further studies may be required to assess these airway-related complications and their relation to get suppressed effectively by varying the doses of dexmedetomidine.

Another important concern which our study highlighted was emergence as it is of utmost importance to conduct a neurological examination as early as possible postemergence. Our study revealed that dexmedetomidine infusion in a dose of 0.2 μg/kg/h did not delay emergence as compared to the placebo group though it did alleviate the stress and airway responses by effectively suppressing the cough and hemodynamic pertubations. However, as the infusion dose, was increased to 0.4 μg/kg/h; there was a delay in the emergence which was statistically, but not clinically significant. Further dose response studies may be required to determine the optimal infusion dose of dexmedetomidine in neurosurgical patients.

Shukry et al.[23] studied effects of infusions of dexmedetomidine (0.2 μg/kg/h) during surgery on the incidence of emergence delirium in 50 children aged 1–10 years scheduled for sevoflurane-based general anesthesia. Following inhalation induction, the children were randomly assigned to dexmedetomidine or placebo groups, respectively. The infusion of 0.2 μg/kg/h dexmedetomidine or equal volume of saline was started after securing the airway. The authors found that the incidence of emergence agitation decreased from 61% to 26%. In this study, the time to extubation and eye-opening were not different with dexmedetomidine versus placebo which was similar to our study.

Many studies have shown that dexmedetomidine, such as all other alpha-2 adrenoceptor agonists, has very little effect on ventilation, and there is no difference in respiratory function in patients who received dexmedetomidine compared to ones who received placebo following extubation.[252627] Our study also did not reveal respiratory complications or any difference in ventilation and respiratory function in the three study groups following extubation.

CONCLUSION

Our study in 90 patients undergoing craniotomy for various neurosurgical indications, demonstrates that dexmedetomidine infusion in doses of 0.2 and 0.4 μg/kg/h, effectively suppresses cough and attenuates hemodynamic responses to tracheal extubation without delaying emergence when compared to placebo.