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: The decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors. METHODS: We designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment. RESULTS: Some variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h. CONCLUSIONS: Perfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend thereafter. This fact should be taken into account to determine the most appropriate criteria to stop resuscitation opportunely and avoid the risk of over-resuscitation.

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.

AIM: To determine whether external leg compression (ELC) around the legs could prevent and restore central hypovolemia induced by head-up tilt (HUT) maneuver. MATERIALS & METHODS: The dynamic effect of ELC was determined using 50 cm H2O inflation pressure. HUT was performed without ELC (control model), with ELC inflated before HUT (prevention model) and after HUT (restore model). RESULTS: The decrease in stroke volume (SV) during the prevention model versus control model was 17 +/- 3% versus 27 +/- 3%. The restore model increased SV by 24 +/- 2%. Similarly, peripheral perfusion measured by perfusion index (PI) and tissue oxygen saturation (STO2) was smaller in the prevention model than in the control model (PI: 65 +/- 3% vs 79 +/- 2%; STO2: 4 +/- 1% vs 9 +/- 1%). In the restore model, PI increased by 117 +/- 24% and STO2 increased by 3 +/- 1%. CONCLUSION: In this study, inflatable ELC around the legs was able to prevent and restore SV and peripheral perfusion in a model of acute central hypovolemia.

High thoracic spine or cervical injury may cause long-term orthostatic hypotension (OH). To stabilize hemodynamics and prevent presyncope symptoms in these patients, noninvasive management is preferable. We describe a case of a 61-year-old man who experienced presyncope symptoms as a result of severe OH due to spinal cord injury, after 60 degrees head-up tilt position. The patient was referred to the intensive care unit where he was successfully managed with an inflatable external leg compression (ELC). Accordingly, inflatable ELC succeeded not only in improving presyncope symptoms, but also in preventing orthostatic hypotension for several hours. ELC may be an alternative way to stabilize hemodynamics and prevent presyncope symptoms in patients with OH following spinal cord injury.

Increased blood lactate levels (hyperlactataemia) are common in critically ill patients. Although frequently used to diagnose inadequate tissue oxygenation, other processes not related to tissue oxygenation may increase lactate levels. Especially in critically ill patients, increased glycolysis may be an important cause of hyperlactataemia. Nevertheless, the presence of increased lactate levels has important implications for the morbidity and mortality of the hyperlactataemic patients. Although the term lactic acidosis is frequently used, a significant relationship between lactate and pH only exists at higher lactate levels. The term lactate associated acidosis is therefore more appropriate. Two recent studies have underscored the importance of monitoring lactate levels and adjust treatment to the change in lactate levels in early resuscitation. As lactate levels can be measured rapidly at the bedside from various sources, structured lactate measurements should be incorporated in resuscitation protocols.