Norepinephrine causes a pressure-dependent plasma volume decrease in clinical vasodilatory shock.
BACKGROUND
Recent experimental studies have shown that a norepinephrine-induced increase in blood pressure induces a loss of plasma volume, particularly under increased microvascular permeability. We studied the effects of norepinephrine-induced variations in the mean arterial pressure (MAP) on plasma volume changes and systemic haemodynamics in patients with vasodilatory shock.


METHODS
Twenty-one mechanically ventilated patients who required norepinephrine to maintain MAP > or =70 mmHg because of septic/postcardiotomy vasodilatory shock were included. The norepinephrine dose was randomly titrated to target MAPs of 60, 75 and 90 mmHg. At each target MAP, data on systemic haemodynamics, haematocrit, arterial and mixed venous oxygen content and urine flow urine were measured. Changes in the plasma volume were calculated as 100 x (Hct(pre)/Hct(post)-1)/ (1-Hct(pre)), where Hct(pre) and Hct(post) are haematocrits before and after intervention.


RESULTS
Norepinephrine doses to obtain target MAPs of 60, 75 and 90 mmHg were 0.20+/-0.18, 0.29+/-0.18 and 0.42+/-0.31 microg/kg/min, respectively. From 60 to 90 mmHg, increases in the cardiac index (15%), systemic oxygen delivery index (25%), central venous pressure (CVP) (20%) and pulmonary artery occlusion pressure (33%) were seen, while the intrapulmonary shunt fraction was unaffected by norepinehrine. Plasma volume decreased by 6.5% and 9.4% (P<0.0001) when blood pressure was increased from 60 to 75 and 90 mmHg, respectively. MAP (P<0.02) independently predicted the decrease in plasma volume with norepinephrine but not CVP (P=0.19), cardiac index (P=0.73), norepinephrine dose (P=0.58) or urine flow (P=0.64).


CONCLUSIONS
Norepinephrine causes a pressure-dependent decrease in the plasma volume in patients with vasodilatory shock most likely caused by transcapillary fluid extravasation.
Nygren
A
A
Department of Cardiothoracic Anesthesia and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
Redfors
B
B
Thorén
A
A
Ricksten
S-E
SE
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D004231:Diuresis / Q000187:drug effects; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010953:Plasma Volume / Q000187:drug effects*; D011183:Postoperative Complications / Q000188:drug therapy / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D012121:Respiration, Artificial; D012769:Shock / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D006454:Hemoglobins; D014662:Vasoconstrictor Agents; D010100:Oxygen; D009638:Norepinephrine