This retrospective cohort study using the MIMIC-IV database found that for every 10 mmHg drop in early peak blood pressure (SBP, DBP, and MAP) in ICU liver failure patients, the risk of developing WRF increased by 8%, 11%, and 11%, respectively. This correlation was independent of the patient's baseline clinical characteristics, including baseline blood pressure. In addition, a 10 mmHg drop in early peak blood pressure (SBP, DBP, MAP) was associated with a 14%, 20%, and 44% increased risk of 60-day hospital mortality, respectively. Although the presence of WRF did not significantly affect the relationship between early blood pressure drop and the risk of 60-day hospitalized death, patients with WRF demonstrated a higher hazard ratio for early blood pressure drop, leading to 60-day in-hospital death. These findings underscore the importance of blood pressure monitoring and management in patients with liver failure. Clinicians should remain vigilant in identifying patients at risk of experiencing a substantial early drop in blood pressure, as this may indicate a higher likelihood of developing WRF and subsequent adverse outcomes. Strategies to prevent or mitigate this drop in blood pressure, such as optimizing fluid status and adjusting medication regimens, may improve patient outcomes.
In addition to examining the link between an early peak blood pressure drop and the risk and prognosis of WRF in ICU patients with liver failure, we identified independent predictors of an early peak drop in SBP, DBP, and MAP. These factors include older age, increased respiratory rate, elevated heart rate, elevated INR, elevated blood potassium levels, and concomitant respiratory failure. However, the strongest predictors of the peak drop in SBP, DBP, and MAP were their respective baseline levels. Our findings are consistent with those of previous studies concerning predictors of early SBP drop in patients with AHF, in which a higher baseline SBP emerged as the strongest predictor [11, 13, 14]. However, it is important to note that this finding may be attributed to "regression toward the mean" rather than specific pathophysiologic mechanisms, which makes predicting early blood pressure drop based on patient characteristics challenging.
The observed association between a larger early SBP drop and WRF in the early ICU stay in patients with liver failure may be explained by its impact on the circulatory system. Liver failure is characterized by dilation of visceral arterial vessels, leading to a drop in systemic vascular resistance [15, 16]. This can increase the synthesis of vasodilators, resulting in more pronounced vasodilation that cannot be compensated for by an increase in cardiac output [17]. A reduction in effective blood volume within the systemic circulation may lead to decreased intravascular blood volume, potentially resulting in decreased renal blood flow. Ultimately, these hemodynamic changes within the kidneys and alterations in renal autoregulation may contribute to WRF [18]. Moreover, during liver failure, the activation of systemic vasoconstrictor systems—including the renin-angiotensin-aldosterone system, sympathetic nervous system, and vasopressin— can induce renal vasoconstriction. This occurs even in the presence of an elevated cardiac output, further contributing to WRF [19].
Our subgroup analysis revealed a consistent association between the early drop in blood pressure (SBP, DBP, and MAP) and the risk of WRF across all subgroups (age, sex, BMI, race, baseline blood pressure, and comorbidities), indicating the stability of this relationship within each subgroup. Previous studies have indicated a significant positive correlation between baseline SBP and WRF risk. However, when considering these factors in a multivariate regression model, an early SBP drop, rather than baseline SBP levels, was independently linked to a higher risk of WRF [20]. In our study, the connection between an early peak drop in blood pressure and a heightened risk of WRF persisted within the subgroups with higher baseline blood pressure and hypertension. This suggests that in clinical practice, a significant early drop in blood pressure should be avoided, even in patients with higher baseline blood pressure or concomitant hypertension in ICU patients with liver failure.
Portal hypertension is a key feature of disease progression in cirrhosis [21]. A previous study by Garg et al. revealed that baseline hepatic venous pressure gradient (HVPG) is a predictor of mortality in patients with acute-on-chronic liver failure (ACLF) and that early elevation of portal pressure may increase the risk of variceal bleeding [22]. Elevated portal pressure leads to systemic hemodynamic changes, such as increased cardiac output (CO), decreased peripheral vascular resistance, and a reduction in MAP. Our study showed that an early drop in blood pressure in ICU patients with liver failure was an independent predictor of 60-day hospitalization. A 10 mmHg drop in early SBP, DBP, or MAP was associated with a 14%, 20%, and 44% increase in the risk of 60-day hospital death, respectively. Our findings suggest that an early blood pressure drop may serve as a more accessible and cost-effective predictor of prognosis than more complex measurements such as HVPG. Early peak blood pressure drop measurements are readily available in clinical practice and can provide valuable information for risk stratification and prognostic assessment [23]. Additionally, several studies have indicated that poorer baseline renal function and acute kidney injury (AKI) are independently associated with a poorer prognosis [24, 25]. Our study demonstrated that patients with a pronounced early drop in blood pressure and the development of WRF had the highest 60-day risk of in-hospital death, similar to previous studies, despite statistically insignificant differences in P for interaction. These findings present novel ideas for diagnostic and prognostic assessment. However, further validation and studies are warranted to confirm their clinical applications.
Our study has several strengths. First, this is the first study to explore the relationship between early blood pressure drop, WRF, and prognosis in ICU patients with liver failure. Furthermore, we investigated the associations between early DBP and MAP drop, WRF, and prognosis for the first time. Second, the study utilized data from the MIMIC IV database, offering the advantages of a large sample size and numerous blood pressure measurements taken at short intervals. Third, a subgroup analysis was conducted to examine the relationship between early blood drop and renal function deterioration in the different subgroups. The results consistently demonstrate this association across various subgroups, thus enhancing the generalizability and applicability of the findings. Finally, the study was adjusted for potential confounding factors, including baseline blood pressure, to assess the independent correlation between early blood pressure drop and outcomes, thereby minimizing the impact of other factors and providing a more accurate estimation of the relationship.
Nonetheless, our study had some limitations. The included patients with liver failure were diagnosed using ICD-10 codes, which may have introduced bias in the available information about the liver failure cohort. Additionally, as this was a retrospective cohort study, a causal relationship between the early peak blood pressure drop and the occurrence and mortality rate of WRF could not be proven. Nevertheless, this large-scale cohort study utilizing a comprehensive database and multiple statistical methods demonstrated a correlation between early peak blood pressure drop and WRF, offering valuable clinical reference points. Finally, owing to the complex interactions between diseases, some confounding factors may still exist that could potentially mask or magnify the relationship between the study factors and the WRF.