This is one of the few studies to address APP in critically ill cirrhotic patients. 6,9,19
The typical patient in our cohort was a 57-year-old male with alcoholic liver disease, and ascites, admitted in intensive care due to infection and presenting AhP.
One of the main findings in this study was a high prevalence of AhP, in approximately half of the population at ICU admission, and in over two thirds of patients during their ICU stay. Comparing with general populations of intensive care patients, our cohort of critically ill liver cirrhosis patients presented lower APP. 20,21
Two previous studies in critically ill cirrhotic patients reported a high prevalence of AhP, and described how an increase in APP, through the use of therapeutic large-volume paracentesis, was associated with improved hepatosplanchnic blood flow.6,9 In the first study, Al-Dorzi et al. analyzed 61 septic shock patients, reporting a prevalence of AhP of 70% at ICU admission. Interestingly, an APP of 55 mmHg was identified as the best cut-off value to discriminate survivors from non-survivors, and AhP (IAP < 60 mmHg) was not significantly associated with any of the studied outcomes in multivariate analysis. This study concluded that IAH was associated with increased ICU morbidity and mortality, although no independent risk factors for IAH were found.9 In the second study, Mayr et al. reported a prevalence of AhP between 25–50% of cases (inferred from a median APP value of 63 [57, 70] mmHg, n = 22), and was able to quantify hepatosplanchnic blood flow impairment due to IAH and, importantly, observe an increase in APP (accompanied by a decrease of IAP and CVP, without change in circulating volume) after therapeutic large-volume paracentesis. These results were corroborated by ultrasound hepatic artery resistance index and hepatic vein maximum flow velocity assessments, as well as through the indocyanine green plasma disappearance rate, which is positively correlated to APP, inversely correlated to IAP, and considered a dynamic surrogate marker of hepatic perfusion and hepatocellular function.8 Our study confirms a high prevalence of AhP among critically ill cirrhotic patients. Furthermore, our results confirm that AhP occurs prominently during the first week of ICU stay and encourage future studies of AhP, IAH and ACS to focus on this time frame.9,22
Overall, at ICU admission, we observed IAP values above the critical IAH threshold (≥ 12 mmHg), and both MAP (> 65 mmHg) and APP (> 60mmHg) within normal thresholds. Both causative factors, MAP and IAP, showed a significant impact on APP, independently from each other. This is important since IAH could have been the only clinically relevant factor in this cohort of cirrhotic patients, where a high baseline IAP would be expected due to ascites, and low MAP due to critical illness could be promptly avoided with vasopressor support at ICU admission. Very interestingly, paracentesis was found to be an independent protective factor associated with a lower likelihood of AhP at ICU admission, suggesting a possible therapeutic benefit. Additionally, baseline paracentesis was more frequently performed in patients with AhP and IAH, revealing an increased clinical awareness for these critical pressures and, furthermore, it was independently associated with the presence of IAH, indicating that ascites was the cause for increased IAP. Such observation strengthens the rationale for immediate action on these critical pressures with an individualized, targeted approach, including therapeutic paracentesis and vasopressors. Nonetheless, the overall frequency of paracentesis at admission was surprisingly low when compared to the number of patients with IAH and/or ascites, even taking into account possible missing data on paracentesis performed immediately prior to ICU admission, and even more so, given that paracentesis is indicated in practically all decompensated cirrhotic patients with ascites, and that it has been suggested as a key inpatient quality measure.23
When we looked further into AhP during the first week of ICU stay, ACLF score for multiple organ failure appeared as an expected independent risk factor, considering critically ill cirrhotic patients with typical spontaneous bacterial peritonitis, ruptured esophageal varices or hepato-renal syndrome. Noteworthily, patients with AhP had higher cardiovascular and renal failure rates.
Importantly, neither AhP nor IAH were independently associated with mortality in our cohort, perhaps due to the small sample size and the multifactorial nature of critical illness. Acidemia and West-Haven hepatic encephalopathy score were the only independent risk factors for 28-day mortality, with a highlight on the vital importance of acute neurologic disfunction in critically ill cirrhotic patients. Curiously, ammonia, a known marker of hepatic encephalopathy, did not differ between survivors and non-survivors, pointing us towards alternative non-liver related causes of neurologic dysfunction, such as sepsis or shock, and leading us to question the clinical meaning of ammonia levels and its role in therapeutic decision in the critically ill cirrhotic. Unambiguously, 90-day mortality was associated with SAPS II score and total bilirubin at ICU admission, representing the dual nature of both “acute” critical illness and “chronic” liver disease in this population of critically ill liver cirrhosis patients.
Finally, the presence/development of AhP was associated with longer ICU LOS, thus indicating greater comorbidity and higher healthcare costs in this sub-group of patients.
In the light of our findings, we argue in favor of immediate clinical management of AhP at ICU admission, to prevent deleterious effects of persistent critical pressures, as suggested in the literature.11,12,17,24,25 Abdominal hypoperfusion must be considered for emergent treatment and prevention in cirrhotic patients in intensive care.
Limitations
Limitations in this study include slow recruitment, further aggravated during the COVID-19 pandemic, resulting in a relatively small sample size, and a high proportion of patients with missing baseline APP data due to work load and adherence to study protocol issues. Additionally, the absence of longitudinal data on organ dysfunction and the impact of therapies aimed at optimizing APP, including the period preceding ICU admission, precluded further results and outcome analysis. Interactions between AhP and mechanical ventilation, renal and other organ failures should be specific addressed in the future.
Strengths of this study include the fact that it is the largest prospective study addressing APP in consecutive critically ill cirrhotic patients, minimizing a possible selection bias, provides new data on therapeutic abdominal paracentesis in this setting, and opens the field for further research.26