Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study

Abstract

IntroductionMidazolam and propofol used alone for long-term sedation are associated with adverse effects. Sequential use may reduce the adverse effects, and lead to faster recovery, earlier extubation and lower costs. This study evaluates the effects, safety, and cost of midazolam, propofol, and their sequential use for long-term sedation in critically ill mechanically ventilated patients.MethodsA total of 135 patients who required mechanical ventilation for >3 days were randomly assigned to receive midazolam (group M), propofol (group P), or sequential use of both (group M-P). In group M-P, midazolam was switched to propofol until the patients passed the spontaneous breathing trial (SBT) safety screen. The primary endpoints included recovery time, extubation time and mechanical ventilation time. The secondary endpoints were pharmaceutical cost, total cost of ICU stay, and recollection to mechanical ventilation-related events.ResultsThe incidence of agitation following cessation of sedation in group M-P was lower than group M (19.4% versus 48.7%, P = 0.01). The mean percentage of adequate sedation and duration of sedation were similar in the three groups. The recovery time, extubation time and mechanical ventilation time of group M were 58.0 (interquartile range (IQR), 39.0) hours, 45.0 (IQR, 24.5) hours, and 192.0 (IQR, 124.0) hours, respectively; these were significantly longer than the other groups, while they were similar between the other two groups. In the treatment-received analysis, ICU duration was longer in group M than group M-P (P = 0.016). Using an intention-to-treat analysis and a treatment-received analysis, respectively, the pharmaceutical cost of group M-P was lower than group P (P <0.01) and its ICU cost was lower than group M (P <0.01; P = 0.015). The proportion of group M-P with unbearable memory of the uncomfortable events was lower than in group M (11.7% versus 25.0%, P <0.01), while the proportion with no memory was similar (P >0.05). The incidence of hypotension in group M-P was lower than group (P = 0.01).ConclusionSequential use of midazolam and propofol was a safe and effective sedation protocol, with higher clinical effectiveness and better cost-benefit ratio than midazolam or propofol used alone, for long-term sedation of critically ill mechanically ventilated patients.Trial registrationCurrent Controlled Trials ISRCTN01173443. Registered 25 February 2014.

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

“…Seven trials (n = 357) (191)(192)(193)(194)(195)(196)(197) reported shorter time to light sedation with propofol when compared with a benzodiazepine (MD, -7.2 hr; 95% CI, -8.9 to -5.5; low quality). Nine trials (n = 423) (191,(196)(197)(198)(199)(200)(201)(202) reported shorter time to extubation with propofol compared with a benzodiazepine (MD, -11.6 hr; 95% CI, -15.6 to -7.6; low quality). Only one RCT assessed delirium and found no difference (196).…”

Effects of Propofol on Intracranial Pressure and Prognosis in Severe Neuropathy Patients Undergoing Endotracheal Suctioning

“…This bene cial action of propofol depends on its ability to activate the GABA receptor chloride complex and decrease the stress response of the body caused by ES. Moreover, propofol can reduce cerebral blood ow, ICP, and CMRO2 [18][19][20][21][22][23][24][25][26].…”

“…In the present investigation, we have applied the concept of enhanced recovery after surgery (ERAS) and consulted relevant literature [24][25][26][27][28][29] to determine that an appropriate dose of sedatives was given before ES according to the weight of the patient. The results showed that propofol did not cause adverse reactions and complications.…”

“…Propofol, a short-term acting sedative, can reduce cerebral blood ow, ICP, and cerebral metabolic rate of oxygen (CMRO2). The action of propofol is characterized by a fast onset time of approximately 30-60 seconds, a short halflife of 10-15 minutes, and a fast wake-up time after drug withdrawal, which facilitates the evaluation of the nervous system [18][19][20][21][22][23][24][25][26]. During ES, propofol can directly dilate bronchial smooth muscles, inhibit the pharyngeal re ex, and reduce the airway hyperresponsiveness [18][19][20]25].…”

“…In addition, it exerts amnestic and anticonvulsant effects, increasing the comfort of patients [21-22, 28, 29]. Moderate or slow infusion (respectively, 40 mg/10s or 20-50 mg/min in generally healthy adults) has no signi cant effect on vital signs of patients [18,19,[24][25][26][27][28][29].…”