Time of Dissociation Between Microcirculation, Macrocirculation, and Lactate Levels in a Rabbit Model of Early Endotoxemic Shock

Time of Dissociation Between Microcirculation, Macrocirculation, and Lactate Levels in a Rabbit Model of Early Endotoxemic Shock

Septic shock remains a significant cause of morbidity and mortality in critically ill patients. Despite advancements in understanding and treatment, the relationship between macrocirculation and microcirculation in septic shock remains controversial. The loss of coherence between microcirculation and macrocirculation has been observed in late-stage septic shock, but the timing of this dissociation in early-stage endotoxemic shock has not been clearly studied. This study aimed to determine the earliest possible time of detecting the loss of coherence between microcirculation and macrocirculation in early-stage endotoxemic shock using a rabbit model.

The study involved 24 female New Zealand white rabbits, which were randomized into two groups: an endotoxemic shock group (n = 14) and a control group (n = 10). The endotoxemic shock group received an intravenous infusion of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg over 10 minutes), while the control group received the same volume of saline. Microcirculatory perfusion parameters were assessed in the sublingual mucosa using sidestream dark-field video microscopy. Systemic hemodynamics and blood lactate levels were measured at baseline and over a 120-minute period.

Results showed that 90 minutes after completing the LPS infusion, all animals in the endotoxemic shock group developed a hypodynamic septic condition characterized by low cardiac output and increased systemic vascular resistance. By 120 minutes, the mean arterial pressure (MAP) decreased by 25%, confirming ongoing endotoxemic shock. However, significant decreases in sublingual microcirculatory parameters of small vessels, including microvascular flow index (MFI), perfused vessel density (PVD), and proportion of small perfused vessels (PPV), were observed as early as 30 minutes after completing the LPS infusion. Threshold decreases of 30% in these parameters were found 60 minutes post-infusion. Lactate levels significantly increased to more than 2 mmol/L at 90 minutes and more than 4 mmol/L at 120 minutes in the endotoxemic shock group.

These findings indicate that changes in microcirculatory perfusion precede changes in macrocirculation and lactate levels in early-stage endotoxemic shock. The study highlights the distinct nature of microcirculation, macrocirculation, and oxygen metabolism in the early stages of endotoxic shock.

The relationship between macrocirculation and microcirculation in septic shock has been a subject of extensive research. While normalization of macrocirculatory parameters has been a focus of therapeutic strategies, recent multicenter trials have shown that such normalization does not necessarily improve survival. Global hemodynamic parameters like cardiac output, blood pressure, and venous saturation are poor indicators of tissue perfusion. This study aimed to explore whether the dissociation between macrocirculation and microcirculation occurs earlier in the course of septic shock, before the onset of macrocirculatory hemodynamic disorder and fluid resuscitation.

The endotoxemic shock model was chosen for its reproducibility and defined window of opportunity for intervention. LPS, a component of the outer membrane of Gram-negative bacteria, induces a systemic inflammatory response that mimics septic shock. The study monitored sublingual microcirculation using sidestream dark-field imaging (SDF), a technique that allows for non-invasive assessment of microvascular blood flow.

The study design involved surgical preparation of the rabbits, including the placement of arterial and venous catheters for continuous monitoring of hemodynamic parameters. Microcirculatory measurements were taken at baseline and at 30, 60, 90, and 120 minutes post-LPS infusion. Blood samples were collected for arterial blood gas and lactate level measurements at the same time points.

The results demonstrated a clear temporal dissociation between microcirculatory and macrocirculatory changes. Microcirculatory parameters began to deteriorate as early as 30 minutes post-LPS infusion, while significant macrocirculatory changes were not observed until 90 minutes. Lactate levels, a marker of tissue hypoxia, increased significantly later, at 90 and 120 minutes. This temporal sequence suggests that microcirculatory dysfunction occurs early in the course of endotoxemic shock and precedes macrocirculatory collapse and metabolic derangement.

The study also examined the relationship between microcirculatory parameters and lactate levels. No significant correlations were found between any microcirculatory perfusion variables and lactate levels, suggesting that lactate levels may not be a reliable early indicator of microcirculatory dysfunction. This finding underscores the importance of direct assessment of microcirculation in the early stages of septic shock.

The implications of these findings are significant for clinical practice. Early detection of microcirculatory dysfunction could guide more targeted and effective interventions, potentially improving outcomes in septic shock patients. The study suggests that monitoring microcirculation, in addition to macrocirculatory parameters, could provide a more comprehensive assessment of tissue perfusion and guide resuscitation efforts.

However, the study has several limitations. The endotoxemic shock model, while reproducible, does not fully replicate the complexity of human septic shock. The short duration of the study (120 minutes) may not capture later changes in microcirculation and macrocirculation. Additionally, the study focused on sublingual microcirculation, which may not reflect perfusion in other critical regions, such as the splanchnic area.

In conclusion, this study provides valuable insights into the temporal dissociation between microcirculation, macrocirculation, and lactate levels in early-stage endotoxemic shock. The findings highlight the importance of early microcirculatory assessment and suggest that microcirculatory dysfunction precedes macrocirculatory collapse and metabolic derangement. These results could inform future research and clinical practice, potentially leading to more effective strategies for the early detection and management of septic shock.

doi.org/10.1097/CM9.0000000000000887

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