Propofol does not induce pulmonary dysfunction in stressed endotoxic pigs receiving Intralipid.
OBJECTIVE
To assess the effect of diisopropyl phenol (propofol), with and without Intralipid, on the cardiopulmonary system and on thromboxane production in endotoxic pigs.


METHODS
Prospective, randomized animal study.


METHODS
Animal research laboratory at a major teaching hospital.


METHODS
Twenty-four pigs, divided into three groups (n = 8).


METHODS
Pulmonary arterial catheters and arterial cannulas were inserted into all pigs. Each pig received a 30 ng/kg bolus of endotoxin at 1 hr, followed by a continuous infusion of endotoxin at 24 ng x kg-1 x hr-1. Diisopropyl phenol at 25, 75, and 200 microg x kg-1 x min-1 was administered to all pigs, beginning at 1, 2, and 3 hrs, respectively. The pigs were divided into three groups to receive 0.25 g x kg-1 x hr-1, 0.08 g x kg-1 x hr-1, or no Intralipid, starting at time t = 0. Heart rate and mean arterial, central venous, and pulmonary arterial pressures were recorded continuously. Core temperature, arterial blood gases, mixed venous oxygen saturation, pulmonary arterial occlusion pressure, and cardiac output were measured intermittently. Thromboxane B(2) concentrations were measured at baseline and at 60, 75, 120, 135, 180, 195, and 240 mins. Data are expressed as mean +/- sd. Groups were compared by using repeated analysis of variance, with p <.05 used for statistical significance.


RESULTS
All pigs completed the 4-hr study. Marked variabilities were noted for individual pigs. Following the infusion of endotoxin, compared with baseline, there was a significant increase in pulmonary vascular resistance and a decrease in Pao(2) (p <.001 and p <.008, respectively). This response was not affected by the increasing dose of diisopropyl phenol, nor were there differences between the Intralipid and control groups. Pao(2) remained significantly lower in all groups, compared with the baseline measurements (p <.001) over the 4 hrs of the experiment. Thromboxane B(2) concentrations remained elevated compared with baseline and were significantly higher (p <.05) in the high-dose Intralipid group, compared with the low-dose and the control groups, during the last hour of the experiment.


CONCLUSIONS
Small doses of endotoxin, when given to pigs, induce major perturbations of cardiopulmonary function. Neither Intralipid, high vs. low dose, nor diisopropyl phenol, at sedating vs. anesthetizing doses, worsened the physiologic derangement associated with the stress of low-dose endotoxemia.
Ziser
Avishai
A
Rambam Medical Center, Haifa, Israel.
Strickland
Robert A
RA
Murray
Michael J
MJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000098:blood supply; D008297:Male; D015742:Propofol / Q000633:toxicity*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D005217:Fat Emulsions, Intravenous; D013929:Thromboxane B2; D015742:Propofol