Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?
OBJECTIVE
Hypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass.


METHODS
A total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated.


RESULTS
Hemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study.


CONCLUSIONS
Pretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.
Farstad
M
M
Department of Anesthesia and Intensive Care, University of Bergen, Haukeland University Hospital, Norway.
Heltne
J K
JK
Rynning
S E
SE
Onarheim
H
H
Mongstad
A
A
Eliassen
F
F
Husby
P
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002199:Capillary Permeability / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D004909:Erythrocyte Indices / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006400:Hematocrit; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007295:Inositol Phosphates / Q000494:pharmacology*; D007431:Intraoperative Complications / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008955:Models, Cardiovascular; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000187:drug effects; D010953:Plasma Volume / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D013552:Swine; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D007295:Inositol Phosphates; D012709:Serum Albumin; D001205:Ascorbic Acid; C059368:atrinositol; D008775:Methylprednisolone