Section : Anaesthesiogy

Original Research Article A COMPARATIVE STUDY OF DEXMEDETOMIDINE

AND MIDAZOLAM FOR SEDATION IN PATIENTS
ON MECHANICAL VENTILATION IN ICU

Sampurnanand1, Deep Chilana2, A.K. Sinha3

Received : 20/03/2023
Received in revised form : 15/04/2023 1 rd
Accepted : 25/04/2023 3 year Postgraduate student, Department of Anaesthesiology, Critical Care, Pain and Palliative
Medicine, GMC, Haldwani, Uttarakhand, India
2
Assistant Professor, Department of Anaesthesiology, Critical Care, Pain and Palliative Medicine,
Keywords: Intensive Care Unit, GMC, Haldwani, Uttarakhand, India
Richmond agitation sedation score, 3
Professor, Department of Anaesthesiology, Critical Care, Pain and Palliative Medicine, GMC,
Dexmedetomidine, Midazolam Haldwani, Uttarakhand, India
Corresponding Author:
Dr. Deep Chilana Abstract
Email: [email protected] Background: The use of non-benzodiazepine sedatives over benzodiazepines,
DOI: 10.47009/jamp.2023.5.3.219 is now advocated in light of recent evidences, in order to improve outcome of
the patients in ICU sedation. However, very few studies in the literature have
Source of Support: Nil,
Conflict of Interest: None declared compared these two most commonly used ICU Sedation agents. In present
study we aim to assess and compare the efficacy of dexmedetomidine and
Int J Acad Med Pharm
2023; 5 (3); 1070-1074
midazolam for sedation in critically ill patients admitted in ICU. Materials
and Methods: A Prospective Randomized Comparative Study including adult
patients of age >18 to <65 years with a sample size of 90 of either sex
admitted to the ICU requiring mechanical ventilation in ICU. Result: Out of
90 a total of 4 patients were excluded from the study due to non-survival up to
24 hrs while one cases was excluded from dexmedetomidine group due to
discontinuation of drug, as it caused severe bradycardia and hypotension. So
final analysis was done on 85 cases, 43 in dexmedetomidine group and 42 in
midazolam group. Both the groups were comparable with regards to pulse rate,
SBP, DBP, O2 saturation at baseline and also throughout the follow up
duration of 24 hours (p>0.05). Conclusion: Extubation was possible
significantly earlier in cases managed by dexmedetomidine as compared to
midazolam (3.34 vs 5.52 hrs; p<0.01). Incidence of delirium was significantly
higher in cases managed by midazolam as compared to dexmedetomidine
(50% vs 25.6%; p<0.01).

INTRODUCTION asynchrony.[4] Hence, the international guidelines

recommend routine use of sedative drug to reach
The ICU environments are filled with and sustain optimal level of comfort to prevent these
uncomfortable procedures both invasive and non- stressful effects.[5] Therefore sedation and analgesia
invasive which may include, but are not limited to are the integral part of management of critically ill
endotracheal intubation, central venous patients in ICU. Sedation is the process of relieving
catheterisation, change in positioning and physical anxiety and establishing a state of calm. This
restraints. Also, ICU is a noisy atmosphere which process may include general supportive measures
aggravates anxiety in a conscious patient.[1] Clinical (like frequent communication with patients and
outcome of the patients can be worsened by ICU families), and drug therapy. The drugs used most
related stress and anxiety; and prevention of often for sedation in ICUs are benzodiazepines
exposure to this can help enhancement of (midazolam and lorazepam), propofol,
outcome.[2] dexmedetomidine, haloperidol etc.
Mechanical ventilation, invasive and non-invasive Midazolam and Dexmedetomidine are most
interventions, pain, anxiety are the major external commonly used sedatives in ICU.
and internal stimuli that may lead to patient Midazolam is a short acting GABA agonist
discomfort, anxiety and agitation in intensive care benzodiazepine, which has been used for many
unit(ICU). Inadequate sedation and analgesia cause years, as one of the ICU sedative drugs.[6,7] It has
unnecessary sympathetic activation, hence leading rapid recovery and minimum respiratory and
to negative impact on the outcome of a critically ill hemodynamic depression. Repeated dosing and
patient.[3] In mechanically ventilated patients, continuous infusion in ICU can lead to prolong
inadequate sedation can cause patient ventilator sedation and delayed recovery.[8] Because of their

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well known adverse effects associated with prolong ventilation were selected for the study and randomly
use, the paradigm is now changing towards use of divided into two groups using computer generated
non-benzodiazepine drugs for ICU sedation. random numbers table: Demedetomidine group
Dexmedetomidine is alpha 2 adrenergic receptor (group D) and Midazolam group (group M). A
agonist, which acts in the central nervous system detailed history and complete physical examination
producing sedative, anxiolytic, and sympatholytic was done for all the patients.Group D received
effects with minimum heamodynamic and Dexmedetomidine infusion started with a bolus of
respiratory depression. In contrast to 1micrograms/kg within 10 mins and then 0.1 to 0.6
benzodiazepines, dexmedetomidine also has micrograms/kg/hr as infusion. Group M received
analgesic action, that acts via spinal cord receptor Midazolam infusion started with a bolus of 0.05
and thereby deceasing the need for opioid analgesia. mg/kg within 1 to 5 minutes followed by continuous
The use of non-benzodiazepine sedatives over infusion with the dose of 1 to 2 mg/hr as per need.
benzodiazepines, is now advocated in light of recent The rate of the maintenance infusion was adjusted to
evidences, in order to improve outcome of the achieve the target RASS score of 0 to -3. Both
patients in mechanical ventilation.[9] So we groups are monitored for period of 24 hours.
conducted this study to assess and compare the Patients in either group not adequately sedated
efficacy of Dexmedetomidine and midazolam for received Fentanyl 0.5 to 1 micrograms/kg
sedation in critically ill patients admitted in ICU, as intravenously as the rescue drug for agitation.
guided by RASS and study the various
hemodynamic responses to administration of
Dexmedetomidine and compare them with those of
Midazolam.

MATERIALS AND METHODS

A Prospective Randomized Comparative Study was
conducted in Department of Anaesthesiology and
Critical Care, Dr. Sushila Tiwari Government
Hospital, Haldwani, Uttarakhand. A sample size of
90 patients was taken for a study duration of 18
months.
Inclusion Criteria
1. Both genders
2. Patients >18 and <65 years of age.
3. Patients with need of mechanical ventilation
Exclusion Criteria *Consolidated Standards of Reporting Trial 2010
1. Patients who are hemodynamically unstable –
bradycardia (heart rate<50bpm) or hypotension
RESULTS
(mean arterial pressure <60 mm hg) despite
appropriate intravenous volume replacement and
Table 1: Distribution of cases as per study drug
vasopressors. Group N
2. Patients with neurological disease and active Dexmedetomidine (D) 45
seizures. Midazolam (M) 45
3. Patients with acute myocardial ischemia, second-
and third-degree heart block etc. Present study included 90 critically ill patients,
4. Diabetic patients with uncontrolled blood sugar admitted in ICU and requiring mechanical
level. ventilation. The patients were allocated using table
5. Morbidly obese patients. of random numbers into two groups for receiving
6. Patients under 18 years and over 65 years of age. different drugs for sedation:
7. Known allergy to the drug. • GROUP D: received Dexmedetomidine
8. Pregnancy • GROUP M: received Midazolam
9. Patients with chronic liver disease. A total of 4 patients were excluded from the study
10. Patients on chronic opioid therapy or use of due to non-survival up to 24 hrs (1 in
alpha 2 agonists or antagonist 24 hours prior to Dexmedetomidine and 3 in midazolam group) while
admission. one cases was excluded from dexmedetomidine
A Prospective Randomized Comparative Study was group due to discontinuation of drug, as it caused
commenced after approval from the institutional severe bradycardia and hypotension. So final
ethical committee. After taking written informed analysis was done on 85 cases, 43 in
consent from the accompanying attendants, 90 dexmedetomidine group and 42 in midazolam
patients of age >18 to <65 years of either sex group.
admitted to the ICU requiring mechanical

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Mean age of the cases was 54.5 years with no
difference between study groups (p-0.53).
Out of the total 90 cases studied, 55.29% were
males and 44.71% were females. Both the groups
were comparable with regards to gender distribution
(p-1.0).
A total of 68.9% were in ASA grade I while 31.1%
were in ASA grade II. Both the groups were
comparable with regards to ASA grade distribution
(p-1.0).
Both the groups were comparable with regards to
diastolic blood pressure at baseline and also
throughout the follow up duration of 24 hours
(p>0.05).

Both the groups were comparable with regards to

oxygen saturation at baseline and also throughout
the follow up duration of 24 hours (p>0.05).

Both the groups were comparable with regards to

pulse rate at baseline and also throughout the follow
up duration of 24 hours (p>0.05). The rate of the maintenance infusion was adjusted to
achieve the target RASS score of 0 to -3. Mean time
spent in RASS range was 80% in cases of
dexmedetomidine group while it was 75.1% in cases
of midazolam group respectively (p-0.26).
Extubation was possible significantly earlier in
cases managed by dexmedetomidine as compared to
midazolam (3.34 vs 5.52 hrs; p<0.01).
Patients in either group not adequately sedated
received Fentanyl 0.5 to 1 micrograms/kg
intravenously. Additional sedatives were required in
34.88% cases in dexmedetomidine group as
compared to 52.38% cases of midazolam group (p-
Both the groups were comparable with regards to 0.12).
systolic blood pressure at baseline and also
throughout the follow up duration of 24 hours
(p>0.05).

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 DISCUSSION
Present study included 90 critically ill patients,
admitted in ICU and requiring mechanical
ventilation. The patients were allocated using table
of random numbers into two groups (45 each) for
receiving different drugs for sedation: GROUP D:
received Dexmedetomidine, and; GROUP M:
received Midazolam. A total of 4 patients were
excluded from the study due to non-survival up to
24 hrs (1 in Dexmedetomidine and 3 in midazolam
group) while one cases was excluded from
dexmedetomidine group due to discontinuation of
drug, as it caused severe bradycardia and
hypotension. So final analysis was done on 85 cases,
43 in dexmedetomidine group and 42 in midazolam
group.
Mean age of the cases was 54.5 years with 55.29%
males and 44.71% females.
A total of 69.41% were in ASA grade I while
30.59% were in ASA grade II. Both the groups were
comparable with regards to demography and ASA
grade distribution (p>0.05).
Sedation Characteristics
In present study, we adjusted the rate of
maintenance infusion to achieve the target
Richmond Agitation Sedation Scale (RASS) score
Both dexmedetomidine and midazolam groups were
between 0 to -3. Mean time spent in RASS range
comparable (p>0.05) with regards of incidence of
was 80% in cases of dexmedetomidine group while
adverse reactions like PONV (7% vs 4.8%),
it was 75.1% in cases of midazolam group
hypotension (4.7% vs 9.5%) bradycardia (9.3% vs
respectively (p-0.26). Additional sedatives were
2.4%) and tachycardia (2.3% vs 9.5%).
required in 35.6% cases in dexmedetomidine group
Incidence of delirium was significantly higher in
as compared to 55.6% cases of midazolam group (p-
cases managed by midazolam as compared to
0.09).
dexmedetomidine (50% vs 25.6%; p<0.01).
Ruokonen E et al,[10] compared dexmedetomidine
(DEX) with standard care (SC, either propofol or
midazolam) for long-term sedation. Target
Richmond agitation-sedation score (RASS) was
reached a median of 64% (DEX) and 63% (SC) of
the sedation time (ns). The study suggests that in
long-term sedation, DEX is comparable to SC in
maintaining sedation targets of RASS 0 to -3.
Richard R. Riker et al,[11] compared the efficacy and
safety of prolonged sedation with dexmedetomidine
vs midazolam for mechanically ventilated patients.
There was no difference in percentage of time
within the target RASS range (77.3% for
dexmedetomidine group vs 75.1% for midazolam

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group; difference, 2.2% [95% confidence interval Dexmedetomidine as a drug of choice for ICU
{CI}, -3.2% to 7.5%]; P = 0.18). Sedation.
Extubation Time
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ISSN (O): 2687-5365; ISSN (P): 2753-6556