Background and objective Arterial base excess and lactate levels are key parameters in the assessment of critically ill patients. The use of venous blood gas analysis may be of clinical interest when no arterial blood is available initially. Methods Twenty-four pigs underwent progressive normovolaemic haemodilution and subsequent progressive haemorrhage until the death of the animal. Base excess and lactate levels were determined from arterial and central venous blood after each step. In addition, base excess was calculated by the Van Slyke equation modified by Zander (BEz). Continuous variables were summarized as mean ± SD and represent all measurements (n = 195). Results Base excess according to National Committee for Clinical Laboratory Standards for arterial blood was 2.27 ± 4.12 versus 2.48 ± 4.33 mmol l−1 for central venous blood (P = 0.099) with a strong correlation (r2 = 0.960, P < 0.001). Standard deviation of the differences between these parameters (SD-DIFBE) did not increase (P = 0.355) during haemorrhage as compared with haemodilution. Arterial lactate was 2.66 ± 3.23 versus 2.71 ± 2.80 mmol l−1 in central venous blood (P = 0.330) with a strong correlation (r2 = 0.983, P < 0.001). SD-DIFLAC increased (P < 0.001) during haemorrhage. BEz for central venous blood was 2.22 ± 4.62 mmol l−1 (P = 0.006 versus arterial base excess according to National Committee for Clinical Laboratory Standards) with strong correlation (r2 = 0.942, P < 0.001). SD-DIFBEz/base excess increased (P < 0.024) during haemorrhage. Conclusion Central venous blood gas analysis is a good predictor for base excess and lactate in arterial blood in steady-state conditions. However, the variation between arterial and central venous lactate increases during haemorrhage. The modification of the Van Slyke equation by Zander did not improve the agreement between central venous and arterial base excess.

Background: Arterial base excess (BE) and lactate levels are key parameters in the assessment of critically ill patients. The use of venous blood gas analysis may be of clinical interest when no arterial blood is available initially. Methods: 24 pigs underwent progressive normovolemic haemodilution and subsequent progressive haemorrhage until the death of the animal. BE and lactate levels were determined from arterial and central venous blood after each step. In addition, BE was calculated by the Van Slyke equation modified by Zander (BEz). Continuous variables were summarized as mean ± SD and represent all measurements (n=195). Results: BE by National Committee for Clinical Laboratory Standards (NCCLS) for arterial blood was 2.27 ± 4.12 mmol/l versus 2.48 ± 4.33 mmol/l for central venous blood (p=0.099) with a strong correlation (r=0.960, p<0.001). Standard deviation of the differences between these parameters (SD-DIFBE) did not increase (p=0.355) during haemorrhage as compared with haemodilution. Arterial lactate was 2.66 ± 3.23 mmol/l versus 2.71 ± 2.80 mmol/l in central venous blood (p=0.330) with a strong correlation (r=0.983, p<0.001). SD-DIFLAC increased (p<0.001) during haemorrhage. BEz for central venous blood was 2.22 ± 4.62 mmol/l (p=0.006 vs BE arterial NCCLS) with strong correlation (r=0.942, p<0.001). SDDIFBEz/BE increased (p<0.024) during haemorrhage. Conclusions: Central venous blood gas analysis is a good predictor for BE and lactate in arterial blood in steady state conditions. However, the variation between arterial and central venous lactate increases during haemorrhage. The modification of the Van Slyke equation by Zander did not improve the agreement between central venous and arterial BE.

Background Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to their volume expansion effect and their pharmacokinetic characteristics. The goal of the current study was to determine the pharmacokinetics of CMS and CM-HES and to investigate their influence on blood coagulation in comparison with the standard low-molecular, low-substituted HES (130/0.42) used in Europe. Methods The study was conducted as a randomized, blinded, parallel three-group study in 30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a single dose, and serial blood sampling was performed over 20 h to measure plasma concentration and molecular weight and to assess blood coagulation. Concentration-effect relations were assessed by pharmacokinetic-pharmacodynamic analysis. Results CMS and CM-HES showed significantly higher plasma concentrations and molecular weights over 20 h (P for both<0.001) with smaller volumes of distribution and longer elimination rates during the terminal phase (P for both<0.01) when compared with HES. CMS and CM-HES impaired whole blood coagulation more than HES as assessed by Thrombelastograph analysis (Haemoscope Corporation, Niles, IL). However, similar effects of all three starch preparations on blood coagulation were found when related to the plasma concentrations in mass units. Conclusions Carboxymethylation of starch results in an increased intravascular persistence and a slower fragmentation compared with HES. The greater impairment of blood coagulation by CMS and CM-HES seems to be caused by the higher plasma concentrations.

Background High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES. Methods A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. Results The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). Conclusion Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.

BACKGROUND:Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. METHODS:Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. RESULTS:Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. CONCLUSION:High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.