The Influence of Injection Rate on the Hypnotic Effect of Propofol during Anesthesia: A Randomized Trial

Objective: Previous studies suggested that slow injection of propofol may increase the hypnotic effect during induction of anesthesia. The aim of the present study was therefore to investigate whether injection rate of propofol has an influence on its maximum effect. Design: Randomized, single-blind trial. Setting: This study has been carried out in the operating rooms of a university hospital. An anesthesiologist and a resident performed the study with the aid of changing nursing staff. Participants: We investigated 99 unpremedicated patients aged 18 to 60 years with American Society of Anesthesiologists (ASA) physical status 1–3. Interventions: Anesthesia was induced by intravenous injection of propofol (2 mg/kg). Propofol was manually injected in group 1 over a period of 5 s; in group 2 (120-s injection interval), and in group 3 (240-s injection interval), propofol was administered by an injection pump. After loss of consciousness, mask ventilation was performed with 100% oxygen. Bispectral index (BIS) was used to measure the hypnotic effect of propofol. After the decrease of BIS to the minimum value (i.e., maximum hypnotic effect) and the following increase of BIS to 60, the study period was finished and anesthesia was performed according to clinical criteria. Outcome Measures: We analyzed whether injection speed has an influence on the maximum hypnotic effect of a given dose of propofol (2 mg/kg). Results: BISmin marks the maximum electroencephalogram (EEG) effect of the propofol bolus as measured by the BIS. The lowest mean BISmin was measured in group 1 (28.7 ± 10.3). In group 2, BISmin was 33.0 (±13.9), and in group 3, BISmin was 36.4 (±11.0). There were no significant differences between group 2 and groups 1 or 3, but there were significant differences between groups 1 and 3. In group 1, BISmin was reached after 102.91 s (±44.20), in group 2 after 172.33 s (±29.76), and in group 3 after 274.21 s (±45.40). These differences were statistically significant for all comparisons. In summary, the lowest value for BISmin was achieved in the group with the fastest rate of propofol injection (group1, 5 s). The highest BISmin was obtained in the group with the slowest rate of injection (group 3, 240 s). The hemodynamic parameters were not significantly different among groups. Conclusions: The hypnotic peak effect of propofol is lower with extremely slow injection (240 s versus 5 s). For clinically usual injection rates (5 s and 120 s), there was no significant difference in propofol peak effect. Trial Registration: ClinicalTrials.gov NCT00290108 : Background: Propofol is an injectable compound that is commonly used to bring about anesthesia in adults and in children aged more than three years. The rate at which propofol is injected is thought to affect the total dose of the drug that's needed to achieve loss of consciousness and lowered blood pressure during anesthesia. Previous trials have looked at the effect of different injection rates on anesthesia (time taken to lose consciousness, and degree of consciousness). In this trial of 99 patients scheduled for elective surgery, the researchers studied the effect of three different propofol injection rates. Patients were randomized to receive propofol injected over 5 s, 120 s, or 240 s. In each group the total dose of propofol (per kilogram of a patient's bodyweight) was the same. The main measure used to assess anesthetic effect was the bispectral index. This is a method of translating information from an electroencephalogram (graph showing electrical activity in the brain) into a standard measurement that reflects the patient's level of consciousness. The researchers also recorded time to loss of consciousness, i.e., when patients stopped responding to commands, and took blood pressure measurements.