Discussion:
In this study, dexmeditomidine was shown to be well tolerated when
delivered intravenously to mechanically ventilated patients in intensive
care as well as to non-intubated patients for the purpose of procedural
sedation in the operating room. The data on tolerability from the
clinical studies described in Section 4 as well as data from pooled
analyses derived from the prescribing information provided by
Dexmeditomidine’s manufacturer in the United States will be the focus of
this section, which will be updated as new data becomes available. The
postoperative delirium of patients who were mechanically ventilated
following surgery was also evaluated to determine whether they had the
condition.
Clinical investigations, on the other hand, discovered that just 2
percent of patients developed treatment-related side effects such as
bradycardia, oral dehydration, and hypotension.
Patients with a high vagal tone have experienced clinically significant
bouts of bradycardia and sinus arrest with Dexmeditomidine treatment,
and this has been recorded in healthy individuals as well as in patients
with low vagal tone.
According to a recent study, the use of intravenous Dexmeditomidine as a
primary sedative in intensive care patients following surgery was
generally well tolerated by the participants. Patients who received
dexmeditomidine were more likely than those who received a placebo to
have hypotension, nausea, and bradycardia as a result of their
treatment. Luise Jessen Lundrof describes it in this way:
In the pooled trial, Dexmeditomidine was shown to have a tolerability
profile that was consistent with that of past clinical investigations.
The patients who received Dexmeditomidine experienced at least one
treatment-related adverse event, whereas the patients who received the
control medicine experienced none. A large proportion of adverse events
were mild or moderate in intensity, as revealed by the data. Comparing
dexmeditomidine-induced sedation to placebo-induced sedation,
hypotension (30 percent compared to 10%) and bradycardia (9 percent
compared to 2%) were statistically substantially (p 0.005) higher in
the dexmeditomidine-induced sedation group.
The majority of patients who developed hypotension after receiving a
loading dose of Dexmeditomidine did so within a few minutes of receiving
the medication. Many of these episodes went away on their own, without
the need for medication, water, or any other form of treatment. In this
study, dexmeditomidine induced severe hypotension in 5% of patients,
whereas a placebo caused severe hypotension in 2% of patients,
necessitating pharmacological intervention (e.g., inotropic support).
Bradycardia was experienced by seven of the eighteen patients who had it
while receiving Dexmeditomidine within the first hour of treatment, with
five of those patients experiencing it during the loading dose infusion.
When Dexmeditomidine was administered to the 18 patients who got it, six
incidences of severe bradycardia were observed, as well as 12 episodes
of bradycardia. It is possible that these incidents were caused by the
medicine or were unrelated to it. Bradycardia was reported by three of
the four participants who got a placebo, but it was not thought to be
severe enough to justify further investigation in this case. Patients
with bradycardia were treated in both therapy groups, either by natural
means or through the use of medication (such as atropine).
Patients receiving Dexmeditomidine experienced mild to moderate
hypertension during the loading dose infusion, which lasted less than an
hour and then resolved on its own.
According to preliminary findings, dexmeditomidine appears to have no
effect on respiratory rate or saturation of oxygen in the blood. There
were no statistically significant differences in mean respiratory rate
following extubation or oxygen saturation variability during the study
medication infusion period, despite the fact that 11 percent of
Dexmeditomidine recipients and 14 percent of placebo recipients
experienced treatment-emergent respiratory system adverse events. When
the patients were extubated, the oxygen saturation levels in both
treatment groups remained within normal limits.
When asked why they stopped taking the drug, more than one-third of
dexmedetomidine and placebo patients said it was because they blamed the
treatment for their decision to stop taking it. Severe treatment-related
adverse events occurred in 12 percent of the participants in each
therapy group. There was one thing that was discovered about each of the
four patients who died during the experiment: they all died for reasons
that were unrelated to the medicine under investigation (three of them
received Dexmeditomidine and one received a placebo).
Following cardiac valve surgery with cardiopulmonary bypass,
dexmeditomidine was found to have a lower rate of postoperative delirium
than either midazolam or propofol in a randomised, non-blind study of
mechanically ventilated patients who received cardiopulmonary bypass. A
total of half of the patients received midazolam (0.5–2 mg/hour) and
half received propofol (25–50 g/kg/minute) [both p 0.0001], while
the other half received no medication. Midazolam (0.5–2 mg/hour),
propofol (0.4 g/kg infused over 10 minutes), and midazolam/propofol (0.4
g/kg infused over 10 minutes) infusions were given to 3 percent of the
patients at rates ranging from 0.2–0.7 g/kg/hour. DSM-IV-TR (Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition, Text
Revision) criteria were used to diagnose delirium. Individuals suffering
from delusions spent much longer time in the intensive care unit (4.1
days as opposed to 1.9 days) and in the hospital (10.1 days as opposed
to 7.1 days) than other patients.” (Source: Jon.H Salicatch)
An review of two randomised controlled studies addressed later in this
section found that hypotension was the most common treatment-emergent
adverse event associated with intravenous Dexmeditomidine as the major
sedative during procedural sedation. In this pooled analysis, adverse
events that occur more than 2 percent of the time in a group of people
receiving therapy are assessed and categorised as severe. Only a few of
these incidents were deemed to be life-threatening by medical
professionals.
There was a clear distinction between what was deemed dysrhythmia, what
was called hypertension, and what was considered hypotension, as well as
between what was regarded a decline in DBP of 30% from baseline. If DBP
dropped by 10%, it was considered hypoxia; if DBP increased by 30%, it
was considered hyperoxia, according to the researchers.
Only 63,63 percent of individuals in the AFOI study who received
Dexmeditomidine or a placebo had treatment-related adverse events. Those
who received a placebo accounted for 29.50 percent of the total, with no
statistically significant difference between the two groups of persons.
When it comes to treatment-related adverse events, the MAC study
discovered that there were no statistically significant differences
between the two treatment groups.
Patients who received Dexmeditomidine experienced hypotension, which was
defined as a decrease in both systolic and diastolic blood pressures as
well as heart rate. Patients receiving dexmeditomidine in the AFOI study
exhibited a significantly higher rate of protocol-defined hypotension
when compared to those receiving placebo, whereas their rates of
protocol-defined tachycardia were significantly lower when compared to
those receiving placebo (7.3 percent). (Additional information can be
found in the definitions.) Participants who received dexmeditomidine
were more likely (7.3 percent) than those who received a placebo to have
protocol-defined bradycardia during the study (0 percent ). In
comparison to those who received a placebo (23.6 percent), a higher
number of them developed hypertension (28.0 percent ).
During the infusion phase of the MAC research, loading doses of
Dexmeditomidine of 0.5 or 1.0 g/kg were found to significantly minimise
respiratory depression (p = 0.018) when compared to placebo.
Dexmeditomidine used with fentanyl or midazolam did not result in an
increase in bradycardia, hypotension, or respiratory depression in the
MAC study, and no patient required a midazolam or opioid reversal
medication as a result of this combination. According to the results,
when Dexmeditomidine was administered to persons who were already using
long-term antihypertensive medication, there was no statistically
significant increase in bradycardia or hypotension. In the AFOI study,
there were 18 Dexmeditomidine recipients who got long-term -adrenergic
receptor antagonist medication, and one of them exhibited bradycardia as
indicated by the protocol.
The incidence of intervention (titration of the study medication or
intravenous fluid or pharmacological therapy) for bradycardia,
hypertension, hypotension, and/or tachycardia during the study
medication administration period was not significantly different between
the Dexmeditomidine loading doses of 0.5 and 1 g/kg; intervention was
required in 0.9 percent, 0.8 percent, and 4.8 percent of patients,
respectively, during the study medication administration period.
Patients who received the loading dose of 0.5 g/kg of Dexmeditomidine
required more intervention for hypotension than those who received the
placebo (11.9 percent of those in the group required treatment; 3.2
percent required treatment; and in the group receiving the loading dose
of 1.0 g/kg of Dexmeditomidine, the incidence of hypotension was not
statistically different from that in the placebo) (11.9 percent
[16/134] vs. 3.2 percent [2/63]. Following the outcomes of this
study, no respiratory depressants were administered in the course of
this examination.
It was found in the AFOI study that there was no statistically
significant difference between Dexmeditomidine and placebo recipients in
the proportion of patients who required intravenous fluids or medication
(such as Ephedrine, Esmolol, Nicardipine, or Phenylephrine) for high
blood pressure or heart rate during the infusion of the study medication
during the infusion of the study medication.
All participants in the trial who received Dexmeditomidine 0.5 mg/kg
loading doses or 1.0 mg/kg loading doses achieved treatment
discontinuance after receiving the Dexmeditomidine loading doses.
Due to hypertension, one patient in each treatment group in the AFOI
trial discontinued taking the study drug over the course of the study.
While participating in the MAC trial, three patients (one from each
treatment group) experienced major treatment-emergent adverse events
that were later determined by the investigators to be unrelated to the
study medication. These events occurred during the 24-hour follow-up
phase of the study. In the AFOI study, only modest treatment-related
problems were reported, and they were all minor. It was determined that
neither inquiry resulted in any fatalities.
There were no statistically significant differences between the
Dexmeditomidine and placebo treatment groups in terms of cardiac
monitoring, laboratory profiles, or electrocardiogram recordings,
according to the MAC study.