Introduction

Hepatic encephalopathy (HE) is the critical stage of liver failure, especially in acute cases. Patients with grade 3 or 4 HE is often intubated and underwent mechanical ventilation to prevent life-threatening complications (1,2). However, there is no concrete evidence that routine intubation has benefit for patients with advanced delirium associated with HE (3,4). In contrast, this procedure has its own various risks, such as nosocomial pneumonia, hypotension, increased mortality, and prolonged hospital stays (5,6). Thus, mechanical ventilation in patients with grade 3-4 HE has been associated with increased in-hospital mortality due to compromised immunity, altered drug metabolism, and circulatory dysfunction (7,8). The aim of this study was to determine the effects of preferring non-invasive ventilation (NIV) instead of intubation in patients with grade 3 HE in the aspect of clinical outcome.

Methods

In this study, the records of patients followed in the University of Health Sciences Turkey, Başakşehir Çam and Sakura City Hospital between January 2022 and March 2023 were retrospectively reviewed. Patients with grade 3 HE related to acute or chronic hepatic failure to respiratory impairment due to cardiovascular insufficiency were included in the study. All these patients underwent NIV and continued to receive extracorporeal liver support therapy (9). “Acute Physiology and Chronic Health Evaluation (APACHE II)”, “West Haven Classification” and “Glasgow Coma Scale” were used to stage the clinical conditions. The ethical rules of this study were determined in accordance with the Declaration of Helsinki. All necessary precautions were taken to ensure the confidentiality and protection of data.

This study was approved by the Ethics Committee of University of Health Sciences Turkey, Başakşehir Çam and Sakura City Hospital (approval number: 336, date: 26.07.2023).

Statistical Analysis

Statistical analyzes were performed using SPSS 20 (IBM Corp., Armonk, NY). The normal distribution of study data was evaluated using the Kolmogorov-Smirnov analysis. Demographic characteristics, intensive care unit (ICU) length of stay, APACHE and PRISM scores, and NIV parameters of the patients were presented as median (range), while laboratory values at admission to the ICU were presented as mean (standard deviation).

Results

A total of 41 patients with grade 3 HE were included. Of these patients, 24 were female and 17 were male. Thirteen of the patients were children with a mean age of 8 (range: 0-16 years), while the mean age of the 28 adult patients was 57 (range: 49-70) years. NIV was applied to the 28 adult patients for a mean of 8 days (range: 3-13 days) and to the 13 pediatric patients for a mean of 9 days (range: 4-14 days) until recovery, liver transplantation, or progression to grade 4 HE occurred. The application was performed for 20 hours per day. Nine patients (22%) progressed to grade 4 HE due to a rapid increase in hepatic failure and required protracheal intubation. These nine patients who were not suitable for liver transplantation or could not find a suitable donor died. Recovery was achieved in the other 24 patients who received NIV, and no additional complications such as nosocomial pneumonia, respiratory disorders, hypotension, or cognitive impairment were observed. Eight other patients who received NIV underwent liver transplantation and achieved recovery. The demographic, etiological and intensive care scoring values of the patients are presented in Table 1, the NIV values in Table 2 and the laboratory values in Table 3.

Discussion

HE, which worsens to grade 3-4 is typically managed with intubation and mandatory mechanical ventilation according to literature and algorithms (10). However, studies have shown that routine intubation for airway protection in patients with grade 3-4 HE may potentially be related to increased risk of complications and in-hospital mortality (11-13). In this study, survival rates of 78% and 22% were determined in 41 patients.

In this study, the expected complications of intubation, such as nosocomial infections, cardiovascular and cognitive disorders, and increased mortality were not seen in our patients undergoing NIV who had different demographic, etiological, mortality scoring, and laboratory results. The most remarkable and often cited complication of intubation, aspiration pneumonia, was observed to be prevented.

The data in the literature about the outcomes of NIV in patients with HE are very limited. Our study showed that NIV in HE patients could significantly reduce complications and mortality compared with the reported outcomes for intubated patients. The results of a recent study written by Saffo and Garcia-Tsao (14) support our results although our study excludes grade 4 HE. According to this comprehensive study, 40% of HE patients who were intubated within the first 48 h died in the hospital, while 19% of those who were not intubated died overall. The mortality rate for intubated patients reached 70% after the first 2 days. In the same study, hospital stay was found to be statistically significantly longer for intubated patients compared with those who were not intubated.

The mechanism of complications that occur in intubated patients with HE has a defined physiological basis, which is circulatory, neurological, and immune dysfunction seen in intubated patients (15). Endotracheal intubation can worsen cardiovascular, cognitive, and immune function due to its increased risk of shock, delirium, infection, and other complications in patients with liver failure (16,17).

Study Limitations

The exclusion of patients with grade 4 HE is the main limitation of this case series. Therefore, we compared our results with the outcomes of intubated HE patients reported in the literature (14,18). We also did not have any patients in our center with HE who were not underwent with non-invasive or invasive respiratory support. This is an understandable situation because our ICU is a part of a liver transplantation center and not an ICU for general supportive aims.

Conclusion

This study supports the use of NIV instead of intubation for grade 3 HE patients with acute and chronic liver failure. The lower risk of complications and mortality of NIV highlights the need for careful consideration when deciding whether to intubate grade 3 HE patients. However, the lack of a control group undermines our courage to declare the need for more detailed retrospective or prospective studies to improve the optimal management of these patients before making definitive clinical recommendations.

Acknowledgments: I would like to thank the Apheresis specialist technicians, Intensive Care Nurses, and Assistant Doctors for their participation

Ethics Committee Approval: This study was approved by the Ethics Committee of University of Health Sciences Turkey, Başakşehir Çam and Sakura City Hospital (approval number: 336, date: 26.07.2023).

Informed Consent: Retrospective study.

Peer-review: Externally and internally peer-reviewed.

Authorship Contributions: Surgical and Medical Practices - İ.O., M.Ç.; Concept - İ.O., M.Ç.; Design - İ.O.; Data Collection or Processing - İ M.Ç., E.K.; Analysis or Interpretation - İ.O., M.Ç., E.K.; Literature Search - M.Ç., E.K.; Writing - İ.O., E.K.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.