Continuous infusion of pyridoxalated hemoglobin polyoxyethylene conjugate in hyperdynamic septic sheep.
Cell-free hemoglobin solutions can scavenge nitric oxide and therefore increase mean arterial pressure (MAP). The present study investigated the effects of a continuous low-dose infusion of modified hemoglobin during ovine hyperdynamic sepsis. 13 sheep received a continuous infusion of live Pseudomonas aeruginosa bacteria for 48 h. Animals that survived the first 24 h of sepsis (n=12) were randomly assigned either to a treatment group that received 20 mg x kg(-1) x h(-1) pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) for 20 h or to a control group that received the same volume of the vehicle for 20 h. MAP increased in the treatment group during 4 h of PHP infusion 12.7+/-1.7 mmHg (p < .05) and after 20 h of PHP infusion MAP was still 12.4+/-2.1 mmHg above the MAP before starting PHP (p < .05). MAP in the control group did not change significantly from 24 h to 48 h of sepsis. No differences in regional blood flow were seen between groups. Bacterial counts in the spleen and kidney were lower in the treatment group than in the control group. Continuous low-dose infusion of PHP can normalize systemic vascular resistance and MAP for long periods without deterioration of regional blood flow or bacterial clearance.
Department of Anesthesiology and Intensive Care Medicine, Westfälische-Wilhelms-Universität, Münster, Germany.
H G
HG
Bone
S R
SR
Fischer
P J
PJ
Schenarts
R
R
McGuire
L D
LD
Traber
D L
DL
Traber
D000818:Animals; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008168:Lung / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa; D012039:Regional Blood Flow / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D012756:Sheep
D006454:Hemoglobins; C050907:pyridoxalated-hemoglobin-polyethylene glycol conjugate; D011092:Polyethylene Glycols