Elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis: A hypothesis generating post hoc analysis

Background: Microcirculatory driving pressure is defined as the difference between post-arteriolar and venular pressure. In previous research, an absence of correlation between mean arterial blood pressure (MAP) and microcirculatory perfusion has been observed. However, the microcirculation may be considered as a low pressure compartment with capillary pressure closer to venous than to arterial pressure. From this perspective, it is conceivable that central venous pressure (CVP) plays a more important role in determination of capillary perfusion. We aimed to explore associations between CVP and microcirculatory perfusion.Methods: We performed a post-hoc analysis of a prospective study in septic patients who were resuscitated according a strict non-CVP guided treatment protocol. Simultaneous measurements of hemodynamics and sublingual Sidestream Dark Field imaging were obtained 0 and 30 minutes after fulfillment of resuscitation goals. Data were examined for differences in microcirculatory variables for CVP ≤ or > 12 mmHg and its evolution over time, as well as for predictors of a microvascular flow index (MFI) 12 mmHg) group as compared to patients in the 'low' CVP (≤12 mmHg) group (1.4 ± 0.9 vs. 1.9 ± 0.9, P = 0.006; and 88 ± 21% vs. 95 ± 8%, P = 0.006 respectively). Perfusion pressure (MAP-CVP) and cardiac output did not differ significantly between both CVP groups. From time point 0 to 30 minutes, a significant increase in MFI (from 1.6 ± 0.6 to 1.8 ± 0.9, P = 0.027) but not in PPV, was observed, while CVP and perfusion pressure significantly decreased in the same period. In a multivariate model CVP > 12 mmHg was the only significant predictor for a capillary MFI < 2.6 (Odds ratio 2.5 (95% confidence interval 1.1-5.8), P = 0.026).Conclusion: We observed a significant association between a higher CVP and impairment of microcirculatory blood flow. Further research is needed to elaborate on our hypothesis generating findings that an elevated CVP may act as an outflow obstruction of organ perfusion

Ultrafiltration rate is an important determinant of microcirculatory alterations during chronic renal replacement therapy

Background: Hemodialysis (HD) with ultrafiltration (UF) in chronic renal replacement therapy is associated with hemodynamic instability, morbidity and mortality. Sublingual Sidestream Dark Field (SDF) imaging during HD revealed reductions in microcirculatory blood flow (MFI). This study aims to determine underlying mechanisms. Methods: The study was performed in the Medical Centre Leeuwarden and the Lithuanian University of Health Sciences. Patients underwent 4-h HD session with linear UF. Nine patients were subject to combinations of HD and UF: 4 h of HD followed by 1 h isolated UF and 4 h HD with blood-volume-monitoring based UF. Primary endpoint: difference in MFI before and after intervention. During all sessions monitoring included blood pressure, heartrate and SDF-imaging. Trial registration number: NCT01396980. Results: Baseline characteristics were not different between the two centres as within the HD/UF modalities. MFI was not different before and after HD with UF. Total UF did not differ between modalities. Median MFI decreased significantly during isolated UF [2.8 (2.5-2.9) to 2.5 (2.2-2.8), p = 0.03]. Baseline MFI of each UF session was correlated with MFI after the intervention (r s = 0.52, p = 0.006). Conclusion: During HD with UF or isolated HD we observed no changes in MFI. This indicates that non-flow mediated mechanisms are of unimportance. During isolated UF we observed a reduction in MFI in conjunction with a negative intravascular fluid balance. The correlation between MFI before and after intervention suggests that volume status at baseline is a factor in microvascular alterations. In conclusion we observed a significant decrease of sublingual MFI, related to UF rate during chronic renal replacement therapy

Focus on focus: Lack of coherence between systemic and microvascular indices of oedema formation

Background: Fluid therapy remains a cornerstone of therapy in shock states. However, fluid overloading ultimately results in oedema formation which is related to excess morbidity and mortality. Handheld microscopes are now frequently used to study the sublingual microcirculation. As a corollary, these devices measure focal distance, or surface to capillary distance. Physiologically, this could represent a microvascular index of oedema formation and could have the potential to guide fluid therapy. This potential tool should be investigated, especially given the frequently reported lack of coherence between systemic and microvascular parameters in the critically ill. Therefore, we set out to assess the correlation between microvascular focal distance and systemic indices of oedema formation, specifically fluid balance and weight gain. Methods: Following ex vivo testing of focal distance measurement reliability, we conducted a prospective observational cohort study in patients admitted to the intensive care unit of our university teaching hospital. We determined surface to capillary distance using sidestream dark field (SDF) and incident dark field (IDF) imaging by assessing the focal distance point or object distance range at which a sharp recording could be made. Measurements were performed in post-cardiac surgery patients and in patients following emergency admission at two time points separated by at least several hours. Data on fluid balance, weight and weight gain were collected simultaneously. Results: Sixty patients were included. The focal setting, focus point for SDF and the object distance range for IDF did not differ significantly between time points. Focus was not correlated with difference in fluid balance or weight gain. Conclusions: There is a lack of coherence between surface to capillary distance as determined by SDF or IDF imaging and fluid balance or weight gain. Thus, focal distance as a microvascular index of oedema formation cannot currently be used as a proxy for systemic indices of oedema formation. However, given the lack of coherence, further research should determine whether focal distance may provide better guidance for fluid therapy than traditional markers of overzealous fluid administration