Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial.
OBJECTIVE
To compare the effectiveness, characteristics, duration of action, hemodynamic and biochemical effects, and side effects of propofol and midazolam used for continuous intravenous sedation of ventilated critically ill patients.


METHODS
Multicenter, prospective, randomized, nonblinded study.


METHODS
Nine Spanish general intensive care units (ICUs).


METHODS
Ninety-eight patients admitted to the ICU who were mechanically ventilated and required sedation for a minimum of 48 hrs.


METHODS
Propofol or midazolam was used for induction and maintenance of continuous intravenous sedation for a maximum of 5 days. The effectiveness of those two regimens was assessed according to their effects on ventilatory management and the presence of agitation.


RESULTS
In 93% of the patients studied, there was a medical cause necessitating mechanical ventilation. The mean (+/-SD) duration of sedation was 81 +/- 25 hrs and 88 +/- 27 hrs for the propofol and midazolam groups, respectively. The induction dose was 2.24 +/- 0.43 mg/kg over 318 +/- 363 secs for propofol, and 0.22 +/-0.07 mg/kg over 33 +/-29 secs for midazolam. The maintenance dose was 2.8 +/-1.1 mg/kg/hr for propofol and 0.14 +/- 0.10 mg/kg/hr for midazolam. There was no difference regarding the opiate and muscle relaxant requirements between the two groups. Sedation with propofol was more effective in achieving patient-ventilator synchrony than that with midazolam after the first hour of treatment (p < .01). Patients sedated with propofol awoke more rapidly and with less variability that those patients sedated with midazolam (23 +/- 16 mins vs. 137 +/- 185 mins, respectively, p < .05), particularly in those patients requiring deep sedation (27 +/- 16 mins vs. 237 +/- 222 mins, respectively, p < .01). No hemodynamic or biochemical changes were detected in any of the treatment groups. During induction, five patients in the propofol group and two patients in the midazolam group had hypotension.


CONCLUSIONS
In this population of critically ill patients, propofol is an effective and safe alternative for sedation, with some advantages, such as short duration of action and high effectiveness over the conventional regimen with benzodiazepines and opiates.
Chamorro
C
C
Intensive Care Units, Clínica Puerta de Hierro, Madrid, Spain.
de Latorre
F J
FJ
Montero
A
A
Sánchez-Izquierdo
J A
JA
Jareño
A
A
Moreno
J A
JA
Gonzalez
E
E
Barrios
M
M
Carpintero
J L
JL
Martín-Santos
F
F
Otero
B
B
Ginestal
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D016292:Procedural Sedation / Q000145:classification; D003422:Critical Care; D016638:Critical Illness; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008874:Midazolam / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D012121:Respiration, Artificial
D006993:Hypnotics and Sedatives; D008874:Midazolam; D015742:Propofol