Midazolam and 2% propofol in long-term sedation of traumatized critically ill patients: efficacy and safety comparison.

Objective: We proposed to compare the efficacy and safety of midazolam and propofol in its new preparation (2% propofol) when used for prolonged, deep sedation in traumatized, critically ill patients. We also retrospectively compared 2% propofol with its original preparation, 1% propofol, used in a previous study in a similar and contemporary set of patients.

Design: A prospective, randomized, unblinded trial (midazolam and 2% propofol) and a retrospective, contemporary trial (2% propofol and 1% propofol).

Settings: A trauma intensive care unit in a tertiary university hospital.

Patients: A total of 63 consecutive trauma patients, admitted within a period of 5 months and requiring mechanical ventilatory support for >48 hrs, 43 of whom (73%) suffered severe head trauma. We also retrospectively compared the 2% propofol group with a series of patients in whom 1% propofol was used.

Interventions: For the prospective trial, we randomized two groups--a midazolam group with continuous administration of midazolam at dosages 0.1-0.35 mg/kg/hr, and a 2% propofol group with continuous infusion at dosages 1.5-6 mg/kg/hr. Equal dosages of analgesics were administered. Similar management protocols were applied in the 1% propofol group, used in the retrospective analysis with 2% propofol.

Measurements And Main Results: Epidemiologic and efficacy variables were recorded. Hemodynamic and biochemical variables were also monitored on a regular basis. Neuromonitoring was also performed on those patients with head trauma. Sedation adequacy was similar and patient behavior after drug discontinuation was not different in either prospective group (midazolam and 2% propofol). Hemodynamic or neuromonitoring variables were also similar for both groups. Triglyceride levels were significantly higher in the 2% propofol group compared with the midazolam group. A higher number of therapeutic failures because of sedative inefficacy was seen in the 2% propofol group compared with the midazolam group, especially during the first sedation days. When comparing 2% propofol and 1% propofol, a significantly higher number of therapeutic failures because of hypertriglyceridemia were found in the 1% propofol group, as opposed to a major number of therapeutic failures because of inefficacy, found in the 2% propofol group.

Conclusions: Propofol's new preparation is safe when used in severely traumatized patients. Its more concentrated formula improves the lipid overload problem seen with the prolonged use of the previous preparation. Nevertheless, a major number of therapeutic failures were detected with 2% propofol because of the need for dosage increase. This fact could be caused by a different disposition and tissue distribution pattern of both propofol preparations. New studies will be needed to confirm these results.