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J Russell Norton

Publications and source records attributed to J Russell Norton.

3 recordsLinked to original sources

Differences between midazolam and propofol sedation on upper airway collapsibility using dynamic negative airway pressure.

BACKGROUND: Upper airway obstruction (UAO) during sedation can often cause clinically significant adverse events. Direct comparison of different drugs' propensities for UAO may improve selection of appropriate sedating agents. The authors used the application of negative airway pressure to determine the pressure that causes UAO in healthy subjects sedated with midazolam or propofol infusions. METHODS: Twenty subjects (12 male and 8 female) completed the study. After achieving equivalent levels of sedation, the subjects' ventilation, end-tidal gases, respiratory inductance plethysmographic signals, and Bispectral Index values were monitored for 5 min. Negative airway pressure was then applied via a facemask in steps of 3 cm H(2)O from -3 to -18 cm H(2)O. UAO was assessed by cessation of inspiratory airflow and asynchrony between abdomen and chest respiratory inductance plethysmographic signals. RESULTS: Equivalent levels of sedation were achieved with both drugs with average (+/- SD) Bispectral Index levels of 75 +/- 5. Resting ventilation was mildly reduced without any changes in end-tidal pressure of carbon dioxide. There was no difference between the drugs in the negative pressure resulting in UAO. Five female subjects and one male subject with midazolam and four female subjects and one male subject with propofol did not show any UAO even at -18 cm H(2)O. Compared with males, female subjects required more negative pressures to cause UAO with midazolam (P = 0.02) but not with propofol (P = 0.1). CONCLUSIONS: At the mild to moderate level of sedation studied, midazolam and propofol sedation resulted in the same propensity for UAO. In this homogeneous group of healthy subjects, there was a considerable range of negative pressures required to cause UAO. The specific factors responsible for the maintenance of the upper airway during sedation remain to be elucidated.

Adult↗

Pharmacodynamics and pharmacokinetics of propofol in a medium-chain triglyceride emulsion.

BACKGROUND: Because propofol is water insoluble, current formulations of propofol use a soybean oil emulsion. These soybean emulsions cause elevated plasma triglycerides and support bacterial growth. This study compares an alternative formulation of propofol as a 2% emulsion in a medium-chain triglyceride solution (IDD-D Propofol) with Diprivan. METHODS: This double-blind, crossover, phase 1 study compared IDD-D Propofol with Diprivan using two consecutive protocols of 12 subjects each. Subjects in protocol 1 received a single bolus of 2.5 mg/kg, and those in protocol 2 received the same induction dose followed by a 30-min infusion at 0.2 mg. kg(-1).min(-1). Venous samples were taken for propofol concentration and biochemical measurements. Induction and emergence times were measured by termination of voluntary counting and responding to command, respectively. RESULTS: Plasma concentrations were not different between the two formulations. Induction time was 14% longer with IDD-D Propofol than with Diprivan (N = 24, protocols 1 and 2 combined, 53.3 +/- 12.1 s and 46.9 +/- 7.8 s, respectively; P = 0.002). Emergence time was not significantly different for protocol 1 but was marginally longer (P = 0.04) for IDD-D Propofol in protocol 2 (1,197 +/- 445 s [n = 11] and 1,254 +/- 468 s [n = 12], respectively). As expected because of the inherent characteristics of the formulations, plasma triglycerides were elevated for Diprivan but not for IDD-D Propofol; octanoate, a metabolite of medium-chain triglycerides, was elevated only with IDD-D Propofol. Octanoate was elevated to concentrations below those considered toxic. Plasma concentrations of other biochemical markers of medium-chain triglyceride metabolism, ketones, showed no significant changes. Interestingly, there were significant differences between male and female subjects in the propofol plasma concentrations and time to awakening with both drugs. CONCLUSIONS: Differences between the two propofol formulations were slight and not clinically significant. Similar gender differences in plasma concentrations and awaking times were found for both formulations.

Adult↗