To Compare the Effect of Two Different Doses of Dexmedetomidine on the Attenuation of Airway and Pressor Response during Tracheostomy Tube Change in Traumatic Brain Injury Patients.

BACKGROUND: Tracheostomy tube (TT) change is the common procedure in trauma Intensive Care Unit (ICU) and almost always associated with cough reflex, increase in blood pressure, and heart rate. Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist well studied for the prevention of pressor response during laryngoscopy and extubation, but literature on prevention of pressor response during TT change is lacking. AIMS: The aim of this study is to compare two doses (0.5 and 1.0 μg/kg) of DEX for prevention of cough and pressor response during TT change in traumatic brain injury patients. SETTINGS AND
DESIGN: Prospective randomized, double-blind trial.
MATERIALS AND METHODS: Sixty tracheostomized traumatic brain injury patients in ICU scheduled for TT change were randomized to two equal groups: Group A to receive DEX 0.5 μg/kg and Group B to receive DEX 1.0 μg/kg. Calculated dose of studied drug was given by infusion pump over 10 min after dilution in 50 ml. Hemodynamic parameters, cough reflex, and adverse event were recorded and statistically analyzed. STATISTICAL ANALYSIS: Statistical analysis was done with nonpaired (two tailed, independent) Student's t-test for continuous data. Demographic data were compared using Pearson's χ2 test. P < 0.05 was considered to be statistically significant.
RESULTS: Both doses of DEX were able to attenuate the hemodynamic response of tracheal stimulation and cough reflex. Cough reflex was better controlled with 1.0 μg/kg dose but associated with increased incidence of hypotension and bradycardia.
CONCLUSIONS: We conclude that 0.5 μg/kg dose provides desired attenuation of hemodynamic response during TT change without any significant adverse events.

INTRODUCTION

Tracheostomy is among the most commonly conducted procedures in head injury patients in trauma Intensive Care Unit (ICU). It has many potential advantages such as improved nursing care, reduced laryngeal ulceration, decrease in respiratory resistance, better tolerability, and improved communicability.[12] Tracheostomy tubes (TTs) are periodically changed according to institutional protocol and are almost always associated with tracheal stimulation causing coughing and pressor response leading to sympathoadrenal system stimulation and release of catecholamine. Although this response is transient, it may be detrimental in patients with traumatic brain injury where pressor response due to TT change may cause increase in intracranial pressure (ICP) and poor outcome. The rise in blood pressure (BP) and ICP is usually transient, variable, and unpredictable. To “blunt” this pressor response during tracheal intubation, various methods have been tried including adrenergic blockers, vasodilators, calcium channel blockers, and α2-agonists.[3456] Literature on sedation or analgesia during TT change is scarce, and in many centers, TTs are changed without any sedation or analgesia. In our trauma, intensive care midazolam or opioid is commonly used but not very effective in controlling cough and pressor response. Hence, there is a need of a short-acting drug having property of sedation and analgesia which effectively control the cough and pressor response during TT change.

Dexmedetomidine (DEX), which is widely used in anesthesia and intensive care, possesses properties of sedation, anxiolysis, and analgesia without the development of respiratory depression.[78] It reduces catecholamine's release at the neuroeffector junction, inhibits neurotransmission of sympathetic nerves, and decreases plasma catecholamine's, which results in a slight decrease in BP and lowering of the heart rate (HR).[9] DEX has a relatively high ratio of α2/α1-activity, the α2:α1 binding selectivity ratio 1620:1; therefore, DEX is a highly specific and selective α2-adrenergic receptor agonist.[1011] Previous studies that had used intravenous (IV) boluses of DEX showed decrease in BP and cardiac output after small boluses (0.25–1 μg/kg), which were associated with decrease in serum norepinephrine concentration.[1213] Review of previous literature showed that DEX has been extensively used for attenuation of pressor response during laryngoscopy and tracheal intubation, but literature on attenuation of pressor response during TT change is not available.

The purpose of the present study is to determine the effect of two different doses of DEX on the cough and hemodynamic responses to TT change and associated adverse events.

MATERIALS AND METHODS

After Institutional Ethical approval and written informed consent, sixty tracheostomized traumatic brain injury patients in trauma ICU, aged 18–60 years, of either sex scheduled for TT change were included in this prospective, randomized, double-blinded trial from January 2015 to December 2016. Patients with a history of cervical spine injury, chronic obstructive pulmonary disease, asthma, diabetes, hypertension (mean arterial pressure [MAP] >110 mmHg, systolic BP [SBP] >160 mmHg, or diastolic BP [DBP] >90 mmHg), hypotension (MAP <70 mmHg or SBP <90 mmHg or DBP <50 mmHg), and patient allergic to study drugs were excluded from the study.

All patients were randomly (computer-generated randomization and concealment via sealed opaque envelope technique) assigned to two equal groups: Group A to receive DEX 0.5 μg/kg and Group B to receive DEX 1.0 μg/kg. After dilution in 50 ml normal saline, calculated dose of DEX was infused over 10 min (with infusion pump) before the scheduled procedure in both groups. Under aseptic and antiseptic precaution, TT was changed after IV administration of respective studied drug.

Hemodynamic variables were measured at T0-at the time of starting infusion, T1: 5 min after starting infusion, T2: after infusing the drug, T3: at the moment of TT change, and T4: 5 min after TT change and T5: 10 min after TT change. Grading of cough was noted as a measure of response to tracheal stimulation. Coughing after the change of tube was assessed using a 5-point scale: (1) No cough, easy breathing; (2) Slight coughing (one or two), easy breathing; (3) moderate coughing (three or four); (4) heavy coughing, breathing hard, and (5) laryngospasm, severe coughing, and hardly breathing.

The patient was monitored for any complications. Hypotension (MAP <70 mmHg) was treated with IV blouses of ephedrine. Bradycardia (HR <50 beats/min) was treated with 0.6 mg of IV atropine. Hypoxia was treated with supplementation oxygen or by increasing FiO2.

Statistical analysis

Data were presented as mean ± standard deviations. Variables were tested about normal distribution with Kolmogorov–Smirnov test and Q-Q plots. The parametric test of variance analysis in the above-mentioned subgroups of patients was assessed by nonpaired (two tailed, independent) Student's t-test for continuous data. Demographic data were compared using Pearson's χ2 test. P < 0.05 was considered to be statistically significant.

RESULTS

All patients completed the study successfully [Figure 1]. The two groups were comparable in terms of demographic profile, baseline hemodynamic variables, and Glasgow Coma Scale (GCS) [Table 1].

Figure 1

Flow chart of the patient studied

Table 1

Patient demographic characteristics and baseline parameters (n=30)

The MAP at T2, T3, and T4 showed significant difference between two groups (P < 0.05) [Table 2]. There was significant fall in MAP from baseline values in both groups at all measured time intervals except at T5 in Group A [Table 2].

Table 2

Mean arterial pressure between two groups at different time interval (n=30)

The mean HR shows significant difference between two groups at T2 and T3. There was significant fall in mean HR from baseline values at T2, T3 in Group A, and at T1, T2, T3, T4, and T5 in Group B [Table 3].

Table 3

Comparison of heart rate between two groups at different time interval (n=30)

When comparing cough reflex, in Group B, 30% of patients had Grade 1, and 53.3% of patients had Grade 2 cough reflexes whereas in Group A, 46.3% patient had Grade 3 cough reflex [Table 4]. This shows that severity of cough reflex was less in Group B.

Table 4

Comparison of cough reflex between two groups (n=30)

The severity of hypotension and bradycardia was more in Group B than Group A [Table 5].

Table 5

Incidence of adverse event during procedure (n=30)

DISCUSSION

Tracheal intubation is associated with increase in arterial pressure, HR, and plasma catecholamine concentrations, which are due to intense sympathetic discharge caused by stimulation of upper respiratory tract.[3] Intubation can lead to an average increase in BP by 40%–50% and 20% increase in HR. A similar but slightly less intense response can be seen at the time of TT change due to tracheal stimulation producing coughing and pressor response, and this can be detrimental in head injury patients due to increase in ICP.

It has been observed that DEX used in premedication suppresses the sympathetic activation due to the endotracheal intubation and at the time of the tracheal extubation.[141516] Literature related to use of DEX during TT change is not available, so this study was planned in head injury patients where using DEX during TT change may be helpful. In different studies, different doses of DEX have been used, commonly from 0.5 to 1.0 μg/kg.[17181920] Hence, we have conducted a prospective and comparative study of effect of two different doses (0.5 vs. 1 μg/kg) of DEX for attenuating the hemodynamic and cough response to TT change.

Our study demonstrated that DEX is effective in the prevention of undesirable hemodynamic and cough reflex during TT change. There is blunting of hemodynamic response in both the groups, more with 1 μg/kg dose but associated with increased incidence of adverse effects such as hypotension and bradycardia. Cough reflex is suppressed more effectively with 1 μg/kg as only 13.33% patient develop Grade 3 cough reflex while 46.7% develop with 0.5 μg/kg. More incidences of adverse events were noted in Group B as indicated by more episodes of hypotension (16.6% vs. 3.33%), bradycardia (13.33% vs. 0), and hypoxia (3.33% vs. 0). Hence, DEX can be a good drug for future in the prevention of cough and pressor response during TT change in monitored care facility.

Our study has two main limitations. First is lack of control group, so we did not know the intensity and severity of cough and pressure response without drug. Second is only two doses (0.5 and 1.0 μg/kg) selection, but it may be possible the most appropriate dose may be in between two doses. Future trials are needed to investigate these aspects.

CONCLUSIONS

Thus, we conclude from the present study that DEX is able to suppress hemodynamic response to tracheal stimulation at both doses (statistically significant), there was better suppression of cough response with higher doses, i.e., 1 μg/kg, but with this dose, higher episodes of adverse events were noted. Finally, we conclude that 0.5 μg/kg loading dose provides significant attenuation of hemodynamic responses to TT change and fewer incidences of adverse events, which were observed at 1 μg/kg dose.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.