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- Dubniks, Maris
(författare)
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ASPECTS OF FLUID THERAPY: An experimental study of the effects of systemic inflammation, microvascular permeability, blood pressure and plasma volume
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adequate circulating blood volume is a prerequisite for circulatory stability. Fluid therapy aims at correcting hypovolaemia, and is an important part of the haemodynamic management of perioperative and critically ill patients. The efficacy of plasma volume substitution largely depends on the pharmacological properties of the colloid solutions used. However, according to the 2-pore theory for transvascular exchange of fluid and macromolecules, it can also be influenced by such physiological factors as systemic inflammation, microvascular permeability, blood pressure, and prevailing plasma volume. This doctoral thesis based on 5 experimental studies performed on the rat and on the guinea pig, is aimed at evaluating the plasma volume expanding capacity of currently used colloid solutions and the changes in plasma volume in experimental models representing clinically relevant constellations of the above mentioned physiological factors. It also evaluated and compared the ability of activated protein C and prostacyclin to counteract an increased protein leakage in septic inflammation. Plasma volume expanding capacity of currently used colloid solutions was evaluated in standardized models of hypovolaemia. Plasma volume was measured with a 125I-albumin dilution technique. The studies showed that both during normal and increased microvascular permeability 6% dextran-70 and 5% albumin were more effective plasma expanders than 6% HES 130/0.4 and 4% gelatin. HES and gelatin were equally effective and produced similar increase in plasma volume as did normal saline given in 4-times larger volume. Both dextran and albumin showed an absorbing effect which was still present 3 h after infusion, but abolished when permeability was increased. During increased permeability all studied colloid solutions and normal saline were less effective regarding the plasma volume expanding capacity. The effects of the prevailing plasma volume and the increase in blood pressure accomplished by noradrenalin infusion were also studied regarding the subsequent changes in plasma volume during normal and increased permeability. The results showed that the increase in blood pressure and plasma volume, separately or in combination, was associated with larger plasma volume loss which was consequently larger during increased than during normal permeability. On the other hand, the refill of plasma volume, normally seen in hypovolaemia after haemorrhage, was counteracted by noradrenalin infusion. The physiological mechanisms explaining these findings most likely are associated with the changes in hydrostatic capillary pressure which is dependent on autoregulatory capacity, post-/precapillary resistance ratio, and systemic arterial and venous pressures. In the endotoxin induced inflammation, both activated protein C and prostacyclin reduced protein leakage in the gut and improved arterial oxygenation, and prostacyclin reduced protein leakage in the lung.
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| 2. |
- Dubniks, Maris, et al.
(författare)
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Change in plasma volume from a state of hyper-, normo- or hypovolemia with or without noradrenalin infusion in the rat.
- 2008
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 76, s. 75-79
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Tidskriftsartikel (refereegranskat)abstract
- Fluid substitution is important in critically ill patients to maintain normovolemia, but there is always a risk that the treatment is too aggressive resulting in fluid overload, or is insufficient with maintenance of hypovolemia. The present study on the rat aims at evaluating the change in plasma volume after 2.5 h from a state of hyper- and hypovolemia. The analysis was made without and with noradrenalin infusion, based on the fact that noradrenalin infusion is a common drug to maintain an adequate arterial pressure, and noradrenalin may induce transcapillary filtration. Plasma volume was determined at baseline and at the end of the experiments with a (125)I-albumin tracer technique. Arterial and central venous pressure, and urine output were recorded. We showed that induction of hypervolemia with a 5% albumin solution (15 ml/kg) resulted in successive loss of plasma volume, which was aggravated with noradrenalin infusion. Hypovolemia induced by hemorrhage (15 ml/kg) resulted in transcapillary absorption, an absorption almost abolished during noradrenalin infusion. There was no plasma volume loss in the sham group. Urine output was higher under hypervolemia than under normovolemia, which in turn was higher than under hypovolemia. We conclude that hypervolemia induces plasma volume loss, which is aggravated by noradrenalin infusion. The compensatory absorption effect after hemorrhage is counteracted by noradrenalin. The results can be explained by differences in hydrostatic capillary pressure via alterations in arterial and venous pressure, according to the 2-pore theory of transcapillary fluid exchange.
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| 3. |
- Dubniks, Maris, et al.
(författare)
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Comparison of the plasma volume-expanding effects of 6% dextran 70, 5% albumin, and 6% HES 130/0.4 after hemorrhage in the guinea pig.
- 2009
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Ingår i: The Journal of trauma. - 1529-8809. ; 67:6, s. 1200-1204
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We still lack comparing data of the plasma volume (PV)-expanding effect of the most commonly used colloids including dextran 70. This study compares the PV-expanding effects of 6% dextran 70, 5% albumin, and 6% hydroxyethylstarch (HES) 130/0.4 after a standardized hemorrhage. METHODS: The prospective and randomized study on 33 anesthetized adult male guinea pigs involved three groups (n = 11 each); the dextran group, the albumin group, and the HES group. The left carotis artery was cannulated for blood pressure measurements and blood samples, and the right jugular vein was cannulated for infusions. After hemorrhage of 20 mL/kg for 8 minutes, the animals were transfused with 20 mL/kg of the colloid for 10 minutes. PV was determined with a I-albumin tracer dilution technique at baseline and 3 hours after the colloid infusion. The PV just after hemorrhage was calculated as the baseline value minus bled PV. Blood gases were measured at baseline, after hemorrhage, just after the colloid infusion and at the end of the experiment. RESULTS: The increase in PV 3 hours after the colloid infusion, including the 20 mL infused, was 36.3 mL/kg +/- 2.3 mL/kg in the dextran group, 26.4 mL/kg +/- 4.7 mL/kg in the albumin group, and 17.6 mL/kg +/- 3.5 mL/kg in the HES group. At the end of the experiment, hematocrit was lower in the dextran group than in the albumin and the HES groups. Urine production was higher in the HES group than in the dextran and the albumin groups. CONCLUSION: After hemorrhage, the PV-expanding capacity of 6% dextran 70 was better than that of 5% albumin, which was in turn better than that of HES 130/0.4 given in equal volumes.
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| 5. |
- Dubniks, Maris, et al.
(författare)
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Plasma volume expansion of 5% albumin, 4% gelatin, 6% HES 130/0.4, and normal saline under increased microvascular permeability in the rat.
- 2007
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 33:2, s. 293-299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the colloids 5% albumin, 4% gelatin, and 6% HES 130/0.4 with one another and with normal saline regarding their plasma expanding effects at increased permeability and to compare the results with those from a previous study at normal permeability. Design and setting: Prospective controlled randomized laboratory study in a university research laboratory. Subjects: 48 adult male Sprague-Dawley rats. Interventions: Permeability was increased by an injection of 0.5 ml dextran 70 using the fact that dextran causes anaphylactic reaction in the rat. Plasma volume was determined (I-125 albumin tracer technique) after anesthesia, 1 h after dextran injection (before infusion for 10-15 min of 20 ml/kg bw of each of the colloids or 80 ml/kg saline), and 3 h later. Blood pressure, hematocrit, blood gases, and electrolytes were measured. CVP was measured in four rats. Measurements and results: Plasma volume was 41.1 +/- 1.9 ml/kg at baseline (n = 9), and 29.1 +/- 4.1 ml/kg (n = 35) 1 h after the dextran injection. Three hours after infusion of the plasma expander plasma volume had increased by 17.1 +/- 3.4 ml/kg in the albumin group, 7.9 +/- 3.6 ml/kg in the gelatin group, 7.4 +/- 4.4 ml/kg in the HES group, and 12.2 +/- 3.1 ml/kg in the saline group. It was unchanged in a control group given no solution (n = 7 for all groups). Conclusion: Albumin was a more effective plasma volume expander than gelatin or HES or saline (saline in 4 times larger volume). Gelatin and HES were equally effective. All solutions showed a smaller plasma expanding effect than observed in a previous study with normal permeability.
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| 6. |
- Dubniks, Maris, et al.
(författare)
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The effects of activated protein C and prostacyclin on arterial oxygenation and protein leakage in the lung and the gut under endotoxaemia in the rat.
- 2008
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 52, s. 381-387
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Tidskriftsartikel (refereegranskat)abstract
- Background: Based on the anti-adhesive/anti-aggregatory and permeability-reducing properties of activated protein C (APC) and prostacyclin (PGI(2)), we analysed and compared these substances regarding their efficacy in counteracting transcapillary leakage of albumin in the lung and the gut, and in improving arterial oxygenation under a condition of inflammation. Methods: The randomized and blinded study was performed on 31 adult male Sprague-Dawley rats. Inflammation was induced by continuous infusion of Escherichia coli endotoxin (lipopolysaccharide, LPS). Six hours after the start of the LPS infusion (240,000 U/kg/h), a simultaneous infusion of saline (control group) or 8 mug/kg/min of human recombinant APC or 2 ng/kg/min of PGI(2) was started and continued for 24 h (n=8 per group). The study also included a sham group. Transcapillary leakage of albumin was measured from the ratio between tissue radioactivity [counts per minute (cpm)/g tissue] and actual amount of radioactivity given (cpm/g body weight of (125)I-albumin). Oxygenation was assessed from arterial and central venous blood samples. Results: LPS induced albumin leakage in the gut and the lung, and impaired blood oxygenation. In the lung, the leakage was lower in the PGI(2) group than in the APC and the control groups (P<0.05). In the gut, it was lower in the APC and the PGI(2) groups than in the control group (P<0.05). Oxygenation was better in the APC and PGI(2) groups than in the control group. Conclusion: Our data suggest that both APC and low-dose PGI(2) are beneficial in LPS-induced inflammation in the rat, by reducing albumin leakage and improving blood oxygenation.
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