Faculty Bibliography

Irrespective of initiating factors, the peripheral circulation shows two general phases during the development and treatment of shock. Most published reports support earlier knowledge that the peripheral circulation is among the first to deteriorate and the last to be restored. With the advent of new and old techniques that allow us to continuously monitor peripheral perfusion, we may further shift our focus from pressure-based to flow-based resuscitation. The persisting challenge is the validation (effect on outcome parameters) of peripheral perfusion monitoring tools that can be simple and readily available worldwide.

OBJECTIVES: To study regional perfusion during experimental endotoxemic and obstructive shock and compare the effect of initial cardiac output-targeted fluid resuscitation with optimal cardiac output-targeted resuscitation on different peripheral tissues. DESIGN: Controlled experimental study. SETTING: University-affiliated research laboratory. SUBJECTS: Fourteen fasted anesthetized mechanically ventilated domestic pigs. INTERVENTIONS: Domestic pigs were randomly assigned to the endotoxemic (n = 7) or obstructive shock (n = 7) model. Central and regional perfusion parameters were obtained at baseline, during greater than or equal to 50% reduction of cardiac output (T1), after initial resuscitation to baseline (T2), and after optimization of cardiac output (T3). MEASUREMENTS AND MAIN RESULTS: Regional perfusion was assessed in the sublingual, intestinal, and muscle vascular beds at the different time points and included visualization of the microcirculation, measurement of tissue oxygenation, and indirect assessments of peripheral skin perfusion. Hypodynamic shock (T1) simultaneously decreased all regional perfusion variables in both models. In the obstructive model, these variables returned to baseline levels at T2 and remained in this range after T3, similar to cardiac output. In the endotoxemic model, however, the different regional perfusion variables were only normalized at T3 associated with the hyperdynamic state at this point. The magnitude of changes over time between the different vascular beds was similar in both models, but the endotoxemic model displayed greater heterogeneity between tissues. CONCLUSIONS: This study demonstrates that the relationship between the systemic and regional perfusion is dependent on the underlying cause of circulatory shock. Further research will have to demonstrate whether different microvascular perfusion variables can be used as additional resuscitation endpoints.

Background. Setting the optimal level of positive end-expiratory pressure (PEEP) in critically ill patients remains a matter of debate. "Best" PEEP is regarded as minimal lung collapse and overdistention to prevent lung injury. In this study, global and regional variables were evaluated in a porcine model to identify which variables should be used to visualize "best" PEEP. Methods. Eight pigs (28-31 kg) were studied during an incremental and decremental PEEP trial before and after the induction of acute lung injury (All) with oleic acid. Arterial oxygenation, compliance, lung volume, dead space, esophageal pressure and electrical impedance tomography (EIT) were recorded at the end of each PEEP step. Results. After All, "best" PEEP was comparable at 15 cmH(2)O between regional compliance of the dorsal lung region by EIT and the global indicators: dynamic compliance, arterial oxygenation, alveolar dead space and venous admixture. After All, the intratidal gas distribution was able to detect regional overdistention at 15 cmH(2)O PEEP. "Best" PEEP based on transpulmonary pressure was lower and no optimal level could be found based on lung volume measurements alone. In addition, the recruitment phase significantly improved end-expiratory lung volume, PaO2, venous admixture and regional and global compliance, both in All and the "healthy" lung. Conclusion. Most of the evaluated parameters indicate comparable 'best' PEEP levels. However, a combination of these parameters, and especially EIT-derived intratidal gas distribution, might provide additional information. The application of lung recruitment was beneficial in both All and the "healthy" lung.

Recently, the ventilatory variation in pre-ejection period (DeltaPEP) was found to be useful in the prediction of fluid-responsiveness of patients in shock. In the present study we investigated the behavior of the ventilation-induced variations in the systolic timing intervals in response to a graded hemorrhage protocol. The timing intervals studied included the ventilatory variation in ventricular electromechanical delay (DeltaEMD), isovolumic contraction period (determined from the arterial pressure waveform, DeltaAIC), pulse travel time (DeltaPTT), and DeltaPEP. DeltaAIC and DeltaPEP were evaluated in the aorta and carotid artery (annotated by subscripts Ao and CA) and were compared with the responses of pulse pressure variation (DeltaPPAo) and stroke volume variation (DeltaSV). The graded hemorrhage protocol, followed by resuscitation using norepinephrine and autologous blood transfusion, was performed in eight anesthetized Yorkshire X Landrace swine. DeltaAICAo, DeltaAICCA, DeltaPEPAo, DeltaPEPCA, DeltaPPAo, DeltaPPCA, and DeltaSV showed significant increases during the graded hemorrhage and significant decreases during the subsequent resuscitation. DeltaAICAo, DeltaAICCA, DeltaPEPAo, and DeltaPEPCA all correlated well with DeltaPPAo and DeltaSV (all r >/= 0.8, all P < 0.001). DeltaEMD and DeltaPTT did not significantly change throughout the protocol. In contrast with DeltaPEPAo, which was significantly higher than DeltaPEPCA (P < 0.01), DeltaAICAo was not different from DeltaAICCA. In conclusion, ventilation-induced preload variation principally affects the arterially determined isovolumic contraction period (AIC). Moreover, DeltaAIC can be determined solely from the arterial pressure waveform, whereas DeltaPEP also requires ECG measurement. Importantly, DeltaAIC determined from either the carotid or aortic pressure waveform are interchangeable, suggesting that, in contrast with DeltaPEP, DeltaAIC may be site independent.

Definitions of shock and resuscitation endpoints traditionally focus on blood pressures and cardiac output. This carries a high risk of overemphasizing systemic hemodynamics at the cost of tissue perfusion. In line with novel shock definitions and evidence of the lack of a correlation between macro- and microcirculation in shock, we recommend that macrocirculatory resuscitation endpoints, particularly arterial and central venous pressure as well as cardiac output, be reconsidered. In this viewpoint article, we propose a three-step approach of resuscitation endpoints in shock of all origins. This approach targets only a minimum individual and context-sensitive mean arterial blood pressure (for example, 45 to 50 mm Hg) to preserve heart and brain perfusion. Further resuscitation is exclusively guided by endpoints of tissue perfusion irrespectively of the presence of arterial hypotension ('permissive hypotension'). Finally, optimization of individual tissue (for example, renal) perfusion is targeted. Prospective clinical studies are necessary to confirm the postulated benefits of targeting these resuscitation endpoints.