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Comparison between the
Effect of Dexmedetomidine, Ketamine or Sedation-Analgesia Holiday on
Weaning From Mechanical Ventilation after Sedation-Based Analgesia
with Midazolam And Fentanyl
Ghada Fouad El-Baradey(1) & Soad S. Abd El-all El-Gaby(2)
Department
of Anesthesiology &ICU, Faculty of Medicine, Tanta University(1) &
Department of Anesthesiology &ICU, Faculty of medicine for girls
AL-Azhar University(2), Egypt.
Tanta Med. Sc. J 2009; 4(3):46-59
Original article
| Abstract provided by Publisher |
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Background/Aim: Mechanically ventilated patients in the intensive
care unit (ICU) routinely require sedative and analgesic medications
to manage pain, agitation and anxiety. Continuous infusion of
midazolam and opioid for long term had unpredictable effect as
respiratory depression, ventilator dependance and were associated
with increase in duration of mechanical ventilation, length of ICU
and hospital stays. With start of weaning reduction in the dose of
midazolam and opioid were associated with withdrawal symptoms as
agitation, anxiety, hypertension, tachycardia, tachypnea and
ventilator desynchrony. Both the cumulative effect and the
withdrawal symptoms of these drugs hinder weaning and arose the need
for different protocols, strategies or alternative drugs. The Aim of
the study is to minimize the impact of long term infusion of
midazolam & fentanyl and to suppress their withdrawal symptoms by
comparing their substitution with start of weaning by different
classes of drugs as ketamine or dexmedetomidine or by using
different strategy as daily midazolam & fentanyl interruption
(sedation-analgesia holiday) in order to choose the best method
which help early weaning without complication. Patients & Methods:
This study was carried out on 60 adult patients that expected to
require mechanical ventilation for more than 48 hours after major
surgeries. At end of surgery artificial ventilation continued in ICU
with synchronized intermittent mandatory ventilation (SIMV) with
pressure support (PS) mode. All patients received sedation with
midazolam 0.1-0.5 mg/Kg/h intravenous (IV) & analgesia with fentanyl
0.25-0.5 μg/Kg/h IV infusion was adjusted hourly as required by the
patients based on sedation–agitation scale (SAS) 3 or 4 and pain
intensity score using behavioral pain scale (BPS) 1 or 2. Patients
were randomly allocated into 4 groups: 1) Control group (group C):
Patients received midazolam & fentanyl infusion till weaning
&extubation. 2) Sedation-analgesia holiday group (group H ):
Patients received midazolam & fentanyl continuous IV infusion and
after 24h of mechanical ventilation, daily stopping of midazolam
&fentanyl infusion & will be restarted by 1/2 of previous dose after
patient shows signs of awaking. 3) Dexmedetomidine group (group D):
With start of weaning from mechanical ventilation midazolam &
fentanyl were stopped & dexmedetomidine was started by loading dose
of 1μg/Kg IV over 20 minutes followed by continuous IV infusion of
(0.5-0.7μg/Kg/h) till extubation. 4) Ketamine group (group K): With
start of weaning from mechanical ventilation midazolam & fentanyl
were stopped & ketamine was started by loading dose of 0.5mg/Kg IV
followed by continuous IV infusion of (0.1-0.5 mg/Kg/h) till
extubation. Following parameters recorded: -Total dose of midazolam
& fentanyl used in each group. - Duration of mechanical ventilation
& duration of ICU stay. - Time from start of weaning till
extubation. -The need for supplementary bolus doses of sedatives &
analgesics (eg. fentanyl , midazolam or dexmedetomidine as
clinically indicated). -Adverse effects (eg. self extubation,
hemodynamic instability, failed weaning & need for re-intubation). -
Changes in heart rate (HR), mean arterial pressure (MAP) and
respiratory rate (RR ) (Immediately before start of weaning, 1h and
2h after start of weaning, before extubation and post-extubation).
Results: Duration of mechanical ventilation, duration of ICU stay
and total dose of fentanyl & midazolam requirement showed
significant decrease (P= 0.0001, 0.0005, 0.0012, 0.0002
respectively) in group D (3.18±0.37days, 4.01±0.5 days, 2.14±0.51 mg
& 2.65±0.72 gm respectively) in comparison with the group C
(6.14±0.82 days, 8.1±0.76 days, 4.42±0.72 mg & 4.3±0.69 gm
respectively), group H (4.34±0.91 days, 5.4±1.04 days, 3.11±0.84 mg
& 3.25±0.66 gm respectively) & group K (4.41±0.93 days, 5.1±0.8
days, 3.01± 0.4 mg & 3.19± 0.54 gm respectively). Also, they showed
significant decrease in group K & group H in comparison with group
C. Time from start of weaning till extubation showed significant
decrease (P= 0.0002) in group K (8.6±2.1 h), group D (5.7±1.5 h) &
group H (9.4±1.9 h) in comparison with group C (12.3±2.2 h). Group D
showed the shortest time between start of weaning till extubation in
comparison with the other three groups. Group D showed significant
decrease in HR & MAP (P<0.05) in comparison with group C, group H
&group K. While group K showed insignificant increase in HR & MAP
(P>0.05) in comparison with group C. Respiratory rate showed
significant decrease (P<0.05) in group H, group K & group D in
comparison with group C. Conclusion: Although the strategy of
sedation –analgesia holiday was effective in reducing both
cumulative and withdrawal symptoms of midazolam & fentanyl, it
showed less beneficial effect in comparison with dexmedetomidine. In
our study the strategy of using dexmedetomidine during weaning was
the best as it does not only control withdrawal symptoms but also
had hemodynamic stability without respiratory depression resulting
into early weaning, shorter time of mechanical ventilation and
length of ICU stay. As regard ketamine, its hemodynamic effect
hinders its use as sole sedative agent and need to be combined with
other drugs.
ICID 903260
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