Fluid Extravasation Rate Research Articles

Microvascular fluid exchange during CPB with deep hypothermia circulatory arrest or low flow.

Use of deep hypothermic low-flow (DHLF) cardiopulmonary bypass (CPB) has been associated with higher fluid loading than the use of deep hypothermia circulatory arrest (DHCA). We evaluated whether these perfusion strategies influenced fluid extravasation rates and edema generation differently per-operatively. Twelve anesthetized pigs, randomly allocated to DHLF (n = 6) or DHCA (n = 6), underwent 2.5 hours CPB with cooling to 20°C for 30 minutes (min), followed by 30 min arrested circulation (DHCA) or 30 min low-flow circulation (DHLF) before 90 min rewarming to normothermia. Perfusion of tissues, fluid requirements, plasma volumes, colloid osmotic pressures and total tissue water contents were recorded and fluid extravasation rates calculated. During the experiments, cerebral microdialysis was performed in both groups. Microvascular fluid homeostasis was similar in both groups, with no between-group differences, reflected by similar fluid extravasation rates, plasma colloid osmotic pressures and total tissue water contents. Although extravasation rates increased dramatically from 0.10 (0.11) ml/kg/min (mean with standard deviation in parentheses) and 0.16 (0.02) ml/kg/min to 1.28 (0.58) ml/kg/min and 1.06 (0.41) ml/kg/min (DHCA and DHLF, respectively) after the initiation of CPB, fluid filtrations during both cardiac arrest and low flow were modest and close to baseline values. Cerebral microdialysis indicated anaerobic metabolism and ischemic brain injury in the DHCA group. No differences in microvascular fluid exchange could be demonstrated as a direct effect of DHCA compared with DHLF. Thirty minutes of DHCA was associated with anaerobic cerebral metabolism and possible brain injury.

Fluid filtration and vascular compliance during cardiopulmonary bypass: effects of two volatile anesthetics.

As intraoperative fluid accumulation may negatively impact post-operative organ function, strategies minimizing edema generation should be sought for. During general anesthesia, isoflurane in contrast to sevoflurane has been associated with increased fluid extravasation and edema generation. In this study, we tested sevoflurane against isoflurane with focus on vascular compliance and fluid shifts in an experimental cardiopulmonary bypass (CPB) model. Sixteen pigs underwent 120 min of cardiopulmonary bypass with isoflurane or sevoflurane anesthesia. Net fluid balance, plasma volume, serum-electrolytes, serum-albumin, serum-protein, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded. Intra-abdominal and intracranial pressures were measured directly, and fluid extravasation rates were calculated. Fluid extravasation rate increased dramatically in both groups during initiation of cardiopulmonary bypass, with no group differences. The animals of the sevoflurane group needed significantly more fluid supplementation to maintain a constant reservoir volume in the CPB circuit during bypass. Plasma volumes prior to bypass were 56.5 ± 7.9 ml/kg (mean ± SD) and 58.7 ± 3.8 ml/kg in the isoflurane group and sevoflurane group, respectively. During bypass, plasma volumes in the isoflurane group decreased about 25%, and remained significantly lowered when compared to the sevoflurane group, where the values remained stable. No differences in fluid extravasation rates were observed between sevoflurane and isoflurane. The increased net fluid balance in the sevoflurane group during cardiopulmonary bypass was not associated with edema generation. Plasma volume was retained in the sevoflurane group, in contrast to the isoflurane group.

Does insulin impact cold-induced fluid- and protein-extravasation?

BackgroundInsulin has been shown to stabilize the endothelial barrier via inactivation of the endothelial contractile machinery and enhancement of cell–cell adhesions. Here we explored if insulin by its endothelial-stabilizing and anti-inflammatory properties could influence the increase of fluid- and protein-extravasation during hypothermia. MethodsTwo groups of animals (n=10, each) were cooled to 28°C, with insulin-infusion (I-group) or without (C-group), in a randomly controlled study. Fluid balance, hemodynamics, plasma volume (PV), colloid osmotic pressures in plasma (COPp) and interstitial fluid (COPi), hematocrit (Hct), cytokine profiles, serum-albumin- and protein-concentrations were measured and fluid extravasation rate (FER) and albumin-and protein-masses calculated. ResultsDuring 240min of hypothermia the albumin- and protein-masses together with COPp decreased significantly in both groups. COPi remained essentially unchanged. Plasma volume decreased significantly in the C-group, whereas only a decreasing trend was present in the I-group. Hemoconcentration was significant in both study groups reflected by the Hct-values. A slight increasing trend of FER was seen in both groups from 0.10 (0.04)ml/kg/min and 0.09 (0.05)mg/kg/min, C-group and I-group, respectively, to 0.14 (0.05)mg/kg/min and 0.12 (0.03)mg/kg/min, during the hypothermic period. Between-group differences were absent for all listed parameters including FER. ConclusionInsulin administration does not impact fluid and protein extravasation significantly in animals undergoing cooling and prolonged hypothermia.

Acute elevation of intra-abdominal pressure contributes to extravascular shift of fluid and proteins in an experimental porcine model.

BackgroundIntra-abdominal hypertension and abdominal compartment syndrome contribute significantly to increased morbidity and mortality in critically ill patients. This study describes pathophysiologic effects of the acutely elevated intra-abdominal pressure on microvascular fluid exchange and microcirculation. The resulting changes could contribute to development of organ dysfunction or failure.Methods16 pigs were randomly allocated to a control-group (C-group) or an interventional group (P-group). After 60 min of stabilization, intra-abdominal pressure of the P-group animals was elevated to 15 mmHg by Helium insufflation and after 120 min to a level of 30 mmHg for two more hours. The C-group animals were observed without insufflation of gas. Laboratory and hemodynamic parameters, plasma volume, plasma colloid osmotic pressure, total tissue water content, tissue perfusion, markers of inflammation and cerebral energy metabolism were measured and net fluid balance and fluid extravasation rates calculated. Analysis of variance for repeated measurements with post-tests were used to evaluate the results with respect to differences within or between the groups.ResultsIn the C-group hematocrit, net fluid balance, plasma volume and the fluid extravasation rate remained essentially unchanged throughout the study as opposed to the increase in hematocrit (P < 0.001), fluid extravasation rate (P < 0.05) and decrease in plasma volume (P < 0.001) of the P-group. Hemodynamic parameters remained stable or were slightly elevated in the C-group while the P-group demonstrated an increase in femoral venous pressure (P < 0.001), right atrial pressure (P < 0.001), pulmonary capillary wedge pressure (P < 0.01) and mean pulmonary arterial pressure (P < 0.001). The protein mass decreased in both study groups but was significantly lower in the P-group as compared with the C-group, after 240 min of intervention. The increased intra-abdominal pressure was associated with elevated intracranial pressure and reduced tissue perfusion of the pancreas and the gastric- and intestinal mucosa.ConclusionElevation of intra-abdominal pressure has an immediate impact on microvascular fluid extravasation leading to plasma volume contraction, reduced cardiac output and deranged perfusion of abdominal organs.

Isoflurane in Contrast to Propofol Promotes Fluid Extravasation during Cardiopulmonary Bypass in Pigs

A highly positive intraoperative fluid balance should be prevented as it negatively impacts patient outcome. Analysis of volume-kinetics has identified an increase in interstitial fluid volume after crystalloid fluid loading during isoflurane anesthesia. Isoflurane has also been associated with postoperative hypoxemia and may be associated with an increase in alveolar epithelial permeability, edema formation, and hindered oxygen exchange. In this article, the authors compare fluid extravasation rates before and during cardiopulmonary bypass (CPB) with isoflurane- versus propofol-based anesthesia. Fourteen pigs underwent 2 h of tepid CPB with propofol (P-group; n = 7) or isoflurane anesthesia (I-group; n = 7). Fluid requirements, plasma volume, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded, and fluid extravasation rates calculated. Fluid extravasation rates increased in the I-group from the pre-CPB level of 0.27 (0.13) to 0.92 (0.36) ml·kg·min, but remained essentially unchanged in the P-group with significant between-group differences during CPB (pb = 0.002). The results are supported by corresponding changes in interstitial colloid osmotic pressure and total tissue water content. During CPB, isoflurane, in contrast to propofol, significantly contributes to a general increase in fluid shifts from the intravascular to the interstitial space with edema formation and a possible negative impact on postoperative organ function.

Microvascular fluid exchange during pulsatile cardiopulmonary bypass perfusion with the combined use of a nonpulsatile pump and intra-aortic balloon pump

To evaluate how pulsed versus nonpulsed cardiopulmonary bypass influences microvascular fluid exchange in an experimental setup combining a nonpulsatile perfusion pump and an intra-aortic balloon pump. A total of 16 pigs were randomized to pulsatile cardiopulmonary bypass perfusion with an intra-aortic balloon pump switched to an automatic 80 beats/min mode after the start of cardiopulmonary bypass (pulsatile perfusion [PP] group, n=8) or to nonpulsatile cardiopulmonary bypass with the pump switched to the off position (nonpulsatile [NP] group, n=8). Normothermic cardiopulmonary bypass was initiated after 60 minutes of stabilization and continued for 3 hours. The fluid needs, plasma volume, colloid osmotic pressure in plasma, colloid osmotic pressure in interstitial fluid, hematocrit, and total tissue water content were recorded, and the protein masses and fluid extravasation rates were calculated. After cardiopulmonary bypass was started, the mean arterial pressure increased in the PP group and decreased in the NP group. At 180 minutes, the mean arterial pressure of the PP and NP groups was 70.9 ± 2.7 mm Hg and 55.9 ± 2.7 mm Hg, respectively (P=.004). The central venous pressure (right atrium) had decreased in the NP group (P=.002). A decreasing trend was seen in the PP group. No between-group differences were present. The hematocrit and colloid osmotic pressure in plasma and interstitial fluid had decreased similarly in both study groups during cardiopulmonary bypass. The plasma volume of the PP group had decreased initially but then returned gradually to precardiopulmonary bypass levels. In the NP group, the plasma volume remained contracted (P=.02). No significant differences in the fluid extravasation rate were obtained. The fluid extravasation rate of the PP group tended to stay slightly higher than the fluid extravasation rate of the NP group at all measurement intervals. The total tissue water content increased significantly in a number of organs compared with that in the control animals. However, differences in the total tissue water content between pulsed and nonpulsed perfusion were absent. No significant differences in the fluid extravasation rates were present between pulsed and nonpulsed cardiopulmonary bypass perfusion in the present experimental setup.

Does β2-adrenergic stimulation attenuate fluid extravasation during hypothermic cardiopulmonary bypass? An experimental study in pigs

Hypothermic cardiopulmonary bypass (CPB) is associated with increased fluid filtration, edema formation and, occasionally, organ dysfunction. Cold-induced reduction in endothelial barrier function may play a role. β(2)-adrenergic activation elevates cellular cyclic adenosine monophosphate (cAMP) which maintains endothelial barrier properties. In this study, we tested whether β-adrenergic stimulation could influence the increase in fluid extravasation observed during hypothermic CPB. Fourteen pigs randomly received terbutaline infusion (T-group) (n=7) or a control infusion (C-group) (n=7). All animals were given 60 min of normothermic CPB, followed by 90 min of hypothermic CPB. Fluid input and losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum proteins and total tissue water content were measured and the fluid extravasation rates (FER) calculated. by SPSS. Values presented as mean ± SD. Repeated measure analysis of variance was performed and a t-test used when appropriate. The commencement of normothermic CPB resulted in a 20% hemodilution, with an abrupt increase in fluid requirements during the first 10 min. FER increased from 0.18 (0.06) pre-bypass to 0.78 (0.27) ml/kg/min (T-group) (p=0.002) and from 0.16 (0.05) to 0.93 (0.26) ml/kg/min (C-group) (p<0.001) with no between-group differences. Thereafter, FER stabilized at a level of 0.32 (0.13) and 0.27 (0.14) ml/kg/min in the T-group and C-group, respectively. After the start of cooling, FER increased in the T-group to 0.55 (0.12) ml/kg/min (P=0.046) and in the C-group to 0.54 (0.13) ml/kg/min (P=0.006), with no between-group differences (P=0.738). In the present experimental study, we were unable to demonstrate any clinically relevant modulating effect of terbutaline on fluid extravasation during hypothermic cardiopulmonary bypass.

Surface cooling versus core cooling: Comparative studies of microvascular fluid- and protein-shifts in a porcine model

To describe how surface cooling compared with core cooling influences fluid and protein distribution, vascular capacity and hemodynamic variables. 14 anesthetized piglets were, following 60 min normothermic stabilization, randomly cooled by surface cooling (ice-sludge) (n=7) or core cooling (endovascular cooling) (n=7) to about 28 degrees C. Fluid balance, hemodynamic variables, colloid osmotic pressures (plasma/interstitial fluid), hematocrit, serum-albumin and -protein concentrations, intracranial pressure (ICP) and cerebral metabolic markers of ischemia were measured. Fluid shifts and changes in albumin and protein masses were calculated. At the end total tissue water content was assessed and compared with a normothermic control group. Both cooling modes induced an increase in fluid extravasation rate from 33.9 (31.9) and 27.8 (28.0) to 109.0 (16.5) (P=0.006) and 95.6 (29.1) ml/kg/min x 10(-3) (P=0.024) in the surface-cooled and core-cooled groups, respectively. Albumin extravasation was reflected by a significant drop in the albumin mass from 148.8 (11.7) to 111.4 (10.3) (P=0.000) and from 163.4 (27.8) to 136.8 (19.0) g/kg x 10(-2) (P=0.001) in the surface-cooled and core-cooled animals, respectively. Similar findings were obtained concerning serum-protein masses. The total tissue water content increased in most organs including brain in both study groups compared with a control. ICP and cerebral metabolic markers remained normal in both groups. Rapid lowering of body core temperature results in extravasation of water and proteins. The amount of extravated fluid and proteins is similar either cooling is a result of surface cooling or core cooling. Cold-induced fluid extravasation is associated with edema in most tissues including brain.

A hyperosmolar-colloidal additive to the CPB-priming solution reduces fluid load and fluid extravasation during tepid CPB

Cardiopulmonary bypass(CPB) is associated with fluid overload. We hypothesized that fluid gain during CPB could be reduced by substituting parts of a crystalloid prime with 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution (HyperHaes). 14 animals were randomized to a control group (Group C) or to Group H. CPB-prime in Group C was Ringer's solution. In group H, 4 ml/kg of Ringer's solution was replaced by the hypertonic saline/hydroxyethyl starch solution. After 60 min stabilization, CPB was initiated and continued for 120 min. All animals were allowed drifting of normal temperature (39.0 degrees C) to about 35.0 degrees C. Fluid was added to the CPB circuit as needed to maintain a 300-ml level in the venous reservoir. Blood chemistry, hemodynamic parameters, fluid balance, plasma volume, fluid extravasation rate (FER), tissue water content and acid-base parameters were measured/calculated. Total fluid need during 120 min CPB was reduced by 60% when hypertonic saline/hydroxyethyl starch solution was added to the CPB prime (p < 0.01). The reduction was related to a lowered FER. The effect was most pronounced during the first 30 min on CPB, with 0.6 (0.43) (Group H) compared with 1.5 (0.40) ml/kg/min (Group C) (p < 0.01). Hemodynamics and laboratory parameters were similar in both groups. Serum concentrations of sodium and chloride increased to maximum levels of 148 (1.5) and 112 (1.6) mmol/l in Group H. To conclude: addition of 7.2% hypertonic saline and 6% poly (O-2-hydroxyethyl) starch solution to crystalloid CPB prime reduces fluid needs and FER during tepid CPB.

Fluid overload during cardiopulmonary bypass is effectively reduced by a continuous infusion of hypertonic saline/dextran (HSD)

Objective. Cardiopulmonary bypass (CPB) is associated with fluid overload. We examined how a continuous infusion of hypertonic saline/dextran (HSD) influenced fluid shifts during CPB. Materials and methods. Fourteen animals were randomized to a control-group (CT-group) or a hypertonic saline/dextran-group (HSD-group). Ringer's solution was used as CPB-prime and as maintenance fluid at a rate of 5 ml/kg/h. In the HSD group, 1 ml/kg/h of the maintenance fluid was substituted with HSD. After 60 min of normothermic CPB, hypothermic CPB was initiated and continued for 90 min. Fluid was added to the CPB-circuit as needed to maintain a constant level in the venous reservoir. Fluid balance, plasma volume, total tissue water (TTW), intracranial pressure (ICP) and fluid extravasation rates (FER) were measured/calculated. Results. In the HSD-group the fluid need was reduced with 60% during CPB compared with the CT-group. FER was 0.38(0.06) ml/kg/min in the HSD-group and 0.74 (0.16) ml/kg/min in the CT-group. TTW was significantly lower in the heart and some of the visceral organs in the HSD-group. In this group ICP remained stable during CPB, whereas an increase was observed in the CT-group (p <0.01). Conclusions. A continuous infusion of HSD reduced the fluid extravasation rate and total fluid gain during CPB. TTW was reduced in the heart and some visceral organs. During CPB ICP remained normal in the HSD-group, whereas an increase was present in the CT-group. No adverse effects were observed.

Elevated flow rate during cardiopulmonary bypass is associated with fluid accumulation

High flow rates during cardiopulmonary bypass are assumed to increase fluid accumulation. This study aimed to determine whether two different flow rates during cardiopulmonary bypass alter the intraoperative fluid balance and extravasation rate. Sixteen pigs underwent 60 minutes of normothermic bypass, followed by 90 minutes of hypothermic bypass. A high-flow group (HF group, n = 8) had a cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) and a low-flow group (LF group, n = 8) had a rate of 80 mL x kg(-1) x min(-1). Blood chemistry, hemodynamic parameters, plasma and interstitial colloid osmotic pressure, net fluid balance, plasma volume, fluid extravasation rate, and total tissue water content were measured or calculated. Results are presented as mean (standard deviation). The average net fluid balance during cardiopulmonary bypass was 1.02 (0.25) and 0.73 (0.23) mL x kg(-1) x min(-1) in the HF group and LF group, respectively (P < .05). The average fluid extravasation rate was 0.98 (0.22) and 0.77 (0.22) mL x kg(-1) x min(-1) in the HF group and the LF group (P = .07). Total water content was higher in the kidneys (P < .05) and tended to be higher in the lungs (P = .05), liver (P = .07), and brain (P = .07) of the HF group than in those of the LF group. The between-group differences in net fluid balance and fluid extravasation rate were present during the first 30 minutes of normothermic cardiopulmonary bypass. Thereafter, the values stabilized and remained similar in the two groups. Plasma volume and systemic vascular resistance differed between the groups. Cardiopulmonary bypass flow rate of 110 mL x kg(-1) x min(-1) was associated with higher positive net fluid balance and fluid extravasation rate than 80 mL x kg(-1) x min(-1). The effect was mainly observed in the initial phase of cardiopulmonary bypass.

Intraoperative fluid balance during cardiopulmonary bypass: effects of different mean arterial pressures

This study investigated whether two levels of mean arterial pressure (MAP) during cardiopulmonary bypass did influence per-operative fluid shifts. Sixteen pigs underwent 60 minutes of normothermic cardiopulmonary bypass (CPB) followed by 90 minutes of hypothermic CPB. Eight animals had a MAP of 60-80mmHg by norepinephrine (HP group). Another 8 animals had a MAP of 40-45 mmHg by phentolamine (LP group). Blood chemistry, plasma/interstitial colloid osmotic pressures, plasma volume, fluid balance, fluid extravasation rate and tissue water content were measured or calculated. The plasma volume was significantly lower in the HP group compared with the LP group after 60 minutes of CPB. Net fluid balance was 0.18 (0.05) ml x kg(-1) x min(-1) in the HP group and 0.21 ml x kg(-1) x min(-1) in the LP group (P > 0.05) while fluid extravasation rate was 1.18 (0.5) and 1.13 (0.4) ml x kg(-1) x min(-1) in the HP group and the LP group during CPB (P > 0.05). Net fluid balance and fluid extravasation rate were similar in the animals with elevated and with lowered MAP during CPB.

Reduced fluid gain during cardiopulmonary bypass in piglets using a continuous infusion of a hyperosmolar/hyperoncotic solution

The aim of this study was to evaluate how a continuous infusion of a hyperosmolar/hyperoncotic solution influences fluid shifts and intracranial pressure during cardiopulmonary bypass in piglets. Fourteen animals, randomized to the control (CT) group or the hypertonic saline/hydroxyethyl starch (HyperHaes) (HSH) group, received acetated Ringer's solution as prime and supplemental fluid. The HSH group received, in addition, HyperHaes 1 ml/kg/h. After 1 h of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (28 degrees C) was initiated and continued for 90 min. Fluid balance, plasma volume, tissue water content, acid-base parameters and intracranial pressure were recorded, and protein masses and fluid extravasation rates were calculated. At the start of normothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.06) to 1.57 (0.71) and 0.19 (0.09) to 0.82 (0.14) in the CT and HSH groups, respectively, with no between-group differences (P = 0.081) During hypothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.14) to 0.51 (0.10) (P < 0.01) and 0.15 (0.08) to 0.33 (0.08) (P < 0.05), respectively, with significantly lower extravasation rates in the HSH group (P < 0.01). In the HSH group, the total fluid gain during cardiopulmonary bypass decreased by about 50% (P < 0.05) and the tissue water content was significantly lower in the left and right heart as well as in the lungs. The intracranial pressure remained stable in the HSH group, but increased in the CT group. A continuous infusion of HSH (HyperHaes) during cardiopulmonary bypass reduced the fluid extravasation rate and the total fluid gain during bypass. No electrolyte or acid-base disturbances were present. The intracranial pressure remained stable in the HSH group.

Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage

Cardiopulmonary bypass (CPB) is associated with increased fluid filtration occasionally leading to post-operative organ dysfunction. One of the factors determining fluid filtration is the capillary hydrostatic pressure which depends on arterial pressure, venous pressure and pre- to post-capillary resistance ratio. The purpose of this study was to assess whether lowering of the mean arterial pressure and/or the central venous pressure could reduce fluid extravasation during normothermic and hypothermic CPB. Seven piglets were given nitroprusside to a mean arterial pressure of 35-40 mmHg during 60 min of normothermic and 90 min of hypothermic CPB (LP group). They were compared with a control group (C group, n = 7) without blood pressure interventions. Blood chemistry, net fluid balance, plasma volume, colloid osmotic pressure in plasma and interstitial fluid, intravascular protein masses, fluid extravasation rate and total tissue water content were measured or calculated. Mean arterial pressure was significantly lower in the LP group than in the C group during CPB. Plasma volume tended to increase in the LP group (P > 0.05), but remained essentially unchanged in the C group. Net fluid balance in the LP group was more positive than in the C group 30 min after CPB start [1.02 (0.15) vs. 0.56 (0.13) ml/kg/min (Mean (SEM) P < 0.05)]. Fluid extravasation rate tended to be higher in the LP group and total tissue water content of the gastrointestinal tract, left myocardium and skin was significantly elevated compared with the C group. During CPB, lowering of the mean arterial pressure using nitroprusside did not reduce fluid extravasation. On the contrary, the data may implicate an increase in edema formation during low pressure CPB.

Cold-induced fluid extravasation during cardiopulmonary bypass in piglets can be counteracted by use of iso-oncotic prime

Hypothermic cardiopulmonary bypass is associated with increased fluid extravasation. This study aimed to compare whether iso-oncotic priming solutions, in contrast to crystalloids, could reduce the cold-induced fluid extravasation during cardiopulmonary bypass in piglets. Three groups were studied: the control group (CT group; n = 10), the albumin group (Alb group; n = 7), and the hydroxyethyl starch group (HES group; n = 7). Prime (1000 mL) and supplemental fluid were acetated Ringer solution, 4% albumin, and 6% hydroxyethyl starch, respectively. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (cooling to 28 degrees C within 15 minutes) was initiated and continued to 90 minutes. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit levels, and tissue water content were recorded, and protein masses and fluid extravasation rates were calculated. Colloid osmotic pressure in plasma decreased immediately after the start of cardiopulmonary bypass in the CT group but remained stable in the Alb and HES groups. Colloid osmotic pressure in interstitial fluid tended to decrease in the CT group and remained unchanged in the Alb group, whereas a slight increase was observed in the HES group. Immediately after the start of cooling, fluid extravasation rates increased from 0.15 +/- 0.10 to 0.64 +/- 0.12 mL . kg -1 . min -1 in the CT group, whereas no such increase was observed in the Alb and HES groups. The changes in fluid extravasation rates were reflected by corresponding changes in tissue water content. The use of albumin or hydroxyethyl starch as prime to preserve the colloid osmotic pressure during cardiopulmonary bypass causes a reduction in the cold-induced fluid extravasation compared with that seen with crystalloids. Albumin seems more effective than hydroxyethyl starch to limit cold-induced fluid shifts during cardiopulmonary bypass.

Fluid shift is moderate and short‐lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets

Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time-course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB. Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.

Time course variations of haemodynamics, plasma volume and microvascular fluid exchange following surface cooling: an experimental approach to accidental hypothermia

Objective: To describe how surface cooling influences fluid distribution, vascular capacity and haemodynamic variables. Methods: Seven anaesthetised pigs, following normothermic stabilization for 60 min, were cooled to 27.8 ± 1.6 °C. Fluid balance, haemodynamics, colloid osmotic pressures (plasma/interstitial fluid), haematocrit [s-albumin/protein] were recorded and plasma volume measured together with tissue perfusion during normothermia, cooling and stable hypothermia (coloured microspheres). Fluid shifts and changes in albumin and protein masses were calculated. At the end tissue water content was assessed. Results: Haemodynamic variables changed with the start of cooling in parallel with a decreasing cardiac output. During hypothermia the haematocrit increased from 0.31 ± 0.01 to 0.35 ± 0.01 ( P < 0.01). Plasma volume decreased from 1139.0 ± 65.4 ml at start of cooling to 882.0 ± 67.5 ml 3 h later ( P < 0.05). In parallel the plasma albumin and protein masses decreased from 37.8 ± 2.5 g and 54.6 ± 4.0 g to 28.0 ± 2.7 g ( P < 0.05) and 41.2 ± 4.1 g ( P > 0.05), respectively. The main changes occurred 120–180 min after start of each experiment. In this period the fluid extravasation rate was elevated ( P < 0.05) without influencing the colloid osmotic pressure of plasma/interstitial fluid. The increased fluid filtration was reflected by an increase in tissue water content. Conclusion: Our results are in favour of a shift of plasma from circulation to the interstitial space during surface cooling. This conclusion is based on the parallel losses of fluid and proteins from circulation with unchanged colloid osmotic pressures (plasma/interstitial fluid). Inflammation may be involved.

Can the use of methylprednisolone, vitamin C, or α-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 α-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 α-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. Conclusion Pretreatment with methylprednisolone, vitamin C, or α-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.

Fluid extravasation during cardiopulmonary bypass in piglets--effects of hypothermia and different cooling protocols.

Hypothermic cardiopulmonary bypass (CPB) is associated with capillary fluid leak and edema generation which may be secondary to hemodilution, inflammation and hypothermia. We evaluated how hypothermia and different cooling strategies influenced the fluid extravasation rate during CPB. Fourteen piglets were given 60 min normothermic CPB, followed by randomization to two groups: 1: rapid cooling (RC-group) ( approximately 15 min to 28 degrees C); 2: slow cooling (SC-group) ( approximately 60 min to 28 degrees C). Ringer's solution was used as CPB prime and for fluid supplementation. Fluid input/losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum-proteins and total tissue water (TTW) were measured and fluid extravasation rates calculated. Start of normothermic CPB resulted in a 25% hemodilution. During the first 5-10 min the fluid level of the reservoir fell markedly due to an intravascular volume loss necessitating fluid supplementation. Thereafter a steady state was reached with a constant fluid need of 0.14 +/- 0.04 ml kg-1 min-1. After start of cooling the fluid needs increased in the following 30 min to 0.91 +/- 0.11 ml kg-1 min-1 in the RC group (P < 0.001) and 0.63 +/- 0.10 ml kg-1 min-1 in the SC-group (P < 0.001) with no statistical between-group differences. Fluid extravasation rates after start of hypothermic CPB increased from 0.20 +/- 0.08 ml kg-1 min-1 to 0.71 +/- 0.13 (P < 0.01) and 0.62 +/- 0.13 ml kg-1 min-1 (P < 0.05) in the RC- and SC-groups, respectively, without any changes in degree of hemodilution. TTW increased in most tissues, whereas the intravascular albumin and protein masses remained constant with no between group differences. Hypothermia increased fluid extravasation during CPB independent of cooling strategy. Intravascular albumin and protein masses remained constant. Since inflammatory fluid leakage usually results in protein rich exudates, our data with no net protein leakage may indicate that mechanisms other than inflammation could contribute to fluid extravasation during hypothermic CPB.

Studies on fluid extravasation related to induced hypothermia during cardiopulmonary bypass in piglets.

Hypothermia, commonly used for organ protection during cardiopulmonary bypass (CPB), has been associated with changes in plasma volume, hemoconcentration and microvascular fluid shifts. Fluid pathophysiology secondary to hypothermia and the mechanisms behind these changes are still largely unknown. In a recent study we found increased fluid needs during hypothermic compared to normothermic CPB. The aim of the present study was to characterize the distribution of the fluid given to maintain normovolemia. In addition, we wanted to investigate the quantity and quality of the fluid extravasated during hypothermic compared to normothermic CPB. Two groups of anesthetized piglets were studied during 2 h of hypothermic (28 degrees C) (n=7) or normothermic (38 degrees C) (n=7) CPB. Net fluid balance (input-output) was recorded. Changes in colloid osmotic pressures of plasma (COPp) and interstitial fluid (COPi), plasma volume (PV), hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), s-osmolality, s-albumin and s-total protein was followed throughout the experiments. Fluid extravasation rate was calculated. In addition, total tissue water content was measured and compared with a control group (n=6) (no CPB). During hypothermic compared with normothermic CPB, the average net positive fluid balance from 10-120 min of extracorporeal circulation was 1.35+/-0.06 ml x kg(-1) x min(-1) and 0.33+/-0.03 ml x kg(-1) x min(-1) respectively (P<0.0001). We found a marked increase in fluid extravasation during hypothermic CPB. The extravasation rate during hypothermia was 1.8+/-0.2 ml x kg(-1) x min(-1), (1st hour) and 1.1+/-0.2 ml x kg(-1) x min(-1) (2nd hour) compared with 0.8+/-0.2 ml x kg(-1) x min(-1), and 0.1+/-(0.1) ml x kg(-1) x min(-1) during normothermia, respectively (P<0.01). The total intravascular protein and albumin masses remained constant in both groups. Following hypothermic CPB, the water content increased significantly in all tissues and organs. During hypothermic CPB an increased extravasation of fluid from the intravascular to the interstitial space was found. As no leakage of proteins could be demonstrated, based on stable values for albumin and protein masses throughout the experiments, the extravasated fluid contained mainly water and small solutes.