Risk factors of prolonged mechanical ventilation after liver transplantation: a retrospective cohort study

doi:10.21203/rs.3.rs-3757368/v1

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Risk factors of prolonged mechanical ventilation after liver transplantation: a retrospective cohort study

https://doi.org/10.21203/rs.3.rs-3757368/v1

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Background

The risk factors of prolonged mechanical ventilation (PMV) in patients after liver transplantation remain unclear. The aim was to evaluate the risk factors of PMV to guide clinical nursing programs for early extubation and reduction of PMV complications by a retrospective cohort study.

Methods

505 patients were recruited to conduct a retrospective cohort study by a logistic regression model to determine risk factors for PMV patients after liver transplantation.

Results

129 (25.5%) of 505 patients required PMV. The PMV-associated factors were significantly different between the PMV group and the non-PMV group, which included MELD score, ASA score and TP level. According to logistic regression analysis, MELD score ≥ 18 points, ASA score > 3, TP < 60 g/L, et al., are higher risk for PMV.

Conclusion

The incidence of PMV after liver transplantation is 25.5%. A MELD score ≥ 18 points, ASA rating > 3, TP < 60 g/L, et al, are independent risk factors for PMV.

Liver transplantation

Prolonged mechanical ventilation

Risk factors

Liver diseases

MELD score

Nursing

Liver transplantation is an effective method for the treatment of various end-stage liver diseases [1]. Mechanical ventilation is an important method used for the postoperative treatment of patients who receive liver transplants. After the operation, the patient's consciousness is gradually re-established while breathing and haemodynamics are stable, and it meets the offline screening standards. After passing the spontaneous breathing test, mechanical ventilation can be stopped. Most patients receive mechanical ventilation for no more than 24 hours, but some patients will require prolonged mechanical ventilation (PMV) [2]. At present, there is no uniform standard for the definition of PMV [3]. For patients transferred to the intensive care unit (ICU) after surgery, PMV is generally defined as requiring mechanical ventilation for more than 24 hours, and many studies on PMV after liver transplantation also generally use this standard [4–8]. As there is no consensus on the time threshold for PMV, the incidence rate of postoperative PMV reported by different studies is 2.9–26.9%, which is quite different [9–12].

Studies have shown that the incidence of PMV after liver transplantation is 25.3–42.7%[8, 13, 14]. PMV increases both the pressure in the thoracic cavity of patients and the resistance to the reflux of the inferior vena cava, leading to further increases in the incidences of both pleural and abdominal effusions in patients[15, 16]; it also has adverse effects on the blood flow of patients after liver transplantation, hindering the return of blood to the liver, affecting the recovery of liver function, aggravating the suffering of the patient, reducing the ability of daily living, prolonging the stay in the ICU, and increasing the economic burden of the patient[17–19]. PMV after liver transplantation can cause increased levels of systemic inflammatory mediators, increased lung injury, release of inflammatory mediators and increased infections (such as ventilator-associated pneumonia), increasing patient mortality [20]. Some scholars have reported that the mortality rate of mechanically ventilated patients in the ICU is 31% (95% CI: 29%-32%) [21]. In patients with PMV after liver transplantation, the length of stay in the ICU is longer. The mortality rate (28.9%-29.2%) of the PMV group within 1 year after the operation was significantly higher than that of the non-PMV group (7.7%-11.3%) [14, 22].

With the advancement of surgical techniques, damage control, stress reduction and the concept of accelerating the recovery of patients have gradually attracted attention in liver transplantation. Early discontinuation of mechanical ventilation is an important measure to speed up the recovery of patients after liver transplantation. Early removal of tracheal intubation can improve the patient's venous return, increase cardiac output and hepatic blood flow, and improve the venous return of the donor liver, which is conducive to the recovery of liver function after transplantation [15, 16].

A large number of studies have confirmed that the early removal of tracheal intubation after liver transplantation is safe and feasible, but there are still some patients with PMV due to various factors in clinical practice [23–25]. For this reason, domestic and foreign scholars have conducted some studies on PMV and its risk factors after liver transplantation, but it is still unclear. Existing studies have shown that risk factors for PMV after liver transplantation may include hepatic encephalopathy, high end-stage liver disease (Model for End-Stage Liver Disease [MELD]) score and low urine output, but the results of the studies are inconsistent due to differences in the surgical technology and perioperative management level of each transplant centre, as well as the small sample sizes of some studies [8, 13, 14, 22, 26, 29].

Therefore, this study used a retrospective analysis of large samples to clarify the risk factors for PMV after liver transplantation to scientifically guide clinical medical staff to correctly identify the risk factors for PMV, develop corresponding medical and nursing plans, implement predictive interventions to encourage the early discontinuation of mechanical ventilation and reduce PMV in patients, which has the potential to accelerate patient recovery and improve patient prognosis.

Cohort information

This study is a retrospective cohort study conducted in REDACTED

Data collection and variables

The data were collected from January 2018 to December 2020, including patients over 18 years old who were mechanically ventilated after liver transplantation and stayed in the ICU for at least 24 hours. Patients undergoing liver transplantation combined with other organs were excluded.The inclusion and exclusion criteria of patients are shown in Fig. 1.

Variables included general data and clinical data. (1) General data: age, gender, height, weight, and body mass index (BMI); (2) Clinical data: heart function, routine blood tests, blood lipids, liver function, MELD score, ASA score, history of surgery, family history of liver disease, history of respiratory disease, history of coronary heart disease, history of diabetes, history of smoking, history of drinking, operation time, time of anhepatic phase, warm ischaemic time of the donor liver, cold ischaemic time of the donor liver, urine output, fluid transfusion volume, bleeding volume, blood transfusion volume, blood pressure, mechanical ventilation time, and ICU time.

The higher the MELD score is, the worse the prognosis of the patient, with low risk (≤ 14 points), intermediate risk (15–18 points); and high risk (> 18 points) classes. The ASA rating is divided into five levels: ASA level 1 patients are physically healthy, well-developed and nourished, with all organs functioning normally; ASA level 2 patients have mild systemic diseases, except for medical diseases, and have complete functional compensation; ASA level 3 patients have more serious systemic diseases, with physical activity being limited, but can still cope with daily activities; ASA level 4 patients have severe systemic diseases, lose the ability to perform daily activities, and often face threats to life; and ASA level 5 patients are dying patients whose lives cannot be maintained for 24 hours regardless of surgery.

Data analysis

SPSS 22.0 software was used to perform a univariate analysis of the collected the data that are possible risk factors. Measurement data: When the data were normally distributed, they were expressed as the mean ± standard deviation (SD), that is, x ± SD, and the independent sample T test was used for comparisons between groups. When the data were skewed, they were expressed as the median ± interquartile range (IQR), that is, M ± IQR. The nonparametric Mann-Whitney U test was used for comparisons between groups, and the difference was considered to be statistically significant if P < 0.05. Enumeration data: The chi-square test was used for comparisons between groups. We introduced meaningful variables in single factor analysis into the logistic regression equation, used the maximum likelihood estimation method to find the regression coefficient, and then obtained the odds ratio (OR) from the regression coefficient. P < 0.05 was considered statistically significant, and it was determined according to the risk factors for PMV after liver transplantation in ICU patients.

Cohort information

A total of 524 patient data points were collected in this study, of which 18 patients lacked cardiac colour Doppler ultrasound test results and 1 lacked routine blood test results, with part of the data being missing, so they were eliminated. Finally, we included 505 patient data points. The average age of the patients was 50.67 ± 10.14 years, of which 393 patients were males (77.8%) and 112 patients were females (22.2%); there were 129 (25.5%) patients with PMV and 376 (74.5%) patients without PMV (Table 1).

Table 1. General information of patients

SD, standard deviation; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared.

Univariate analysis

This study conducted a univariate analysis of the risk factors for PMV after liver transplantation. The results showed that the PMV group and non-PMV group had significant differences in the MELD score, ASA score, surgical history, white blood cell (WBC) count, red blood cell (RBC) count, total protein (TP), total bilirubin (TBil), urine output, bleeding volume, plasma input, RBC input, autologous blood input, crystal input, and reintubation (P <0.05) (Table 2).

Table 2. Comparison of the clinical characteristics

Note:* is the χ² value; # is the t value; & is the Z value. P<0.05 means the difference is statistically significant.

Multi-factor analysis

In this study, the MELD score, ASA score, surgical history, WBC count, RBC count, TP, TBil, urine output, bleeding volume, plasma input, RBC input, autologous blood input, crystal input, and reintubation were used as the independent variables, the occurrence of PMV after liver transplantation was used as the dependent variable, and binary logistic regression analysis was performed. （The independent variable assignment table is shown in Table 3）.The study found that a MELD score ≥18 points (OR: 2.45, 95% CI: 1.27-4.72), ASA rating >3 (OR: 1.91, 95% CI: 1.15-3.19), TP <60 g/L (OR: 2.92, 95% CI: 1.85-4.62), excessive bleeding (OR: 1.00, 95% CI: 1.00-1.00), excessive plasma input (OR: 1.00, 95% CI: 1.00-1.00), excessive autologous blood input (OR: 1.00, 95% CI: 1.00-1.00) and reintubation (OR: 15.81, 95% CI: 5.67-44.13) are independent risk factors for PMV (Table 4).

Table 3. Variable assignment table for influencing factor analysis

Table 4. Logistic regression analysis of PMV risk factors

*P < 0.05 indicates that the difference is statistically significant.

This study also tested the sensitivity and fit of the logistic model, and the results showed that the sensitivity and fit of the logistic model were both good (Table 5).

Table 5. Fit test of logistic regression model

In recent years, domestic and foreign scholars have conducted some studies on PMV after liver transplantation, and research reports by domestic scholars have shown that the incidence of PMV after liver transplantation is 42.7–44%[8, 13]. Through this study, it was found that 25.5% of patients had PMV after liver transplantation, and the incidence of PMV declined annually. In recent years, with the continuous improvement of surgical technology and the continuous advancement of the concept of accelerated rehabilitation, it is possible to discontinue mechanical ventilation early[29]. To minimize the patient's perioperative stress response and promote the early recovery of organ function, clinical medical staff realized the importance of early extubation. At the same time, expert consensus recommends assessing whether mechanically ventilated patients have the conditions for weaning and the necessity for indwelling tracheal intubation[28]. If possible, tracheal intubation should be discontinued as soon as possible to shorten the time of mechanical ventilation as much as possible. Therefore, the incidence of PMV after liver transplantation showed a downward trend year by year.

Many current studies have found that a high MELD score is a risk factor for PMV after liver transplantation [14, 26, 29]. The MELD score is a commonly used score to evaluate the severity of end-stage liver disease and has a valuable correlation with the prognosis of patients after liver transplantation. This study found that a MELD score ≥ 18 points (OR: 2.45, 95% CI: 1.27–4.72) is a risk factor for PMV after liver transplantation. The higher the score is, the more severe the liver disease may be. At the same time, other organs are involved, and functional disorders such as hepatic encephalopathy and hypoxaemia occur, which affect the recovery of patients. Therefore, it becomes a risk factor for PMV.

It is consistent with previous studies, an ASA rating > 3 (OR: 1.91, 95% CI: 1.15–3.19) was an independent risk factor for PMV in patients after liver transplantation [29]. The higher the ASA level is, the greater the risk during anaesthesia. As a result, patients may experience haemodynamic instability and inhibition of breathing and circulation, resulting in PMV. Nurses need to promptly evaluate and monitor high ASA rated patients with breathing and blood pressure.

This study found that excessive bleeding (OR: 1.00, 95% CI: 1.00–1.00) is a risk factor for PMV after liver transplantation, which is consistent with the results of previous studies [30]. The study showed that patients with a bleeding volume of more than 5000 mL had a significantly longer mechanical ventilation time after surgery and a high perioperative mortality rate. Liver transplantation is complicated and prone to haemorrhage. The body will have insufficient blood volume. Low blood volume is usually accompanied by hypotension and leads to insufficient internal organ perfusion, which affects respiratory function and causes PMV in patients after surgery. Excessive plasma input (OR: 1.00, 95% CI: 1.00–1.00) and excessive autologous blood input (OR: 1.00, 95% CI: 1.00–1.00) are independent risks factors for PMV after liver transplantation. A large volume of blood transfusions during the operation will increase the heart’s load and aggravate the occurrence of pulmonary hypertension [31]. PMV may also occur due to excessive blood volume in a short period of time, volume overload, pulmonary oedema, or lung injury. Therefore, it is necessary to strengthen the monitoring of the haemodynamic status during the operation and dynamically monitor blood loss and central venous pressure changes during the operation.

In addition, research showed that reintubation (OR: 15.81, 95% CI: 5.67–44.13) is a risk factor for PMV after liver transplantation. The reason may be that the respiratory tract is damaged due to repeated intubation, which increases the chance of bacteria entering the respiratory tract, easily causes infection and weakens the patient's respiratory function, thereby increasing the incidence of PMV [32].

Identifying risk factors for PMV is very important for the clinical nursing of mechanically ventilated patients. Identifying risk factors for PMV as early as possible helps clinical nurses to timely develop and implement corresponding nursing plans for specific risk factors, so as to promote early extubation of patients.

Definfying risk factors for PMV can help nurses do preoperative assessment and postoperative care. Nurses should assess the performance of increased intracranial pressure, such as headache and vomiting, and be alert to the occurrence of cerebral edema and hepatic encephalopathy. Actively handle preoperative comorbidities, complications, correct organ failure, and also evaluate the patient's nutritional status, appropriately strengthen nutrition, improve body resistance, reduce the occurrence of postoperative infection, reduce mechanical ventilation dependence, and reduce the occurrence of postoperative PMV. Guide the patient on respiratory function exercise to facilitate early postoperative extubation. In addition, do a good job of liver and kidney function and coagulation function examination, focus on the changes of serum bilirubin and creatinine, according to the examination results of the timely supplement of coagulation substances, to prevent coagulation dysfunction.After surgery, we should focus on the renal function of patients, try to avoid the use of nephrotoxic drugs, maintain the relatively stable renal blood flow, and prevent acute renal failure. To improve the cognitive level of patients and family members on PMV after liver transplantation, nurses should conduct timely conduct health education, guide patients to carry out respiratory function exercise, and realize early extubation. In addition, health education and discharge follow-up should be done to guide patients' rehabilitation and improve their quality of life.

Limitations

This study has some limitations. First, it is a single-centre study, and the study population has certain limitations. In the future, further studies with multiple centres and large samples are needed. Second, this study was retrospective, and the results were affected by various factors. More prospective studies are needed. A comprehensive understanding of the risks of PMV and its risk factors will help with early postoperative extubation, promote patient recovery, and improve patient prognosis.

This study showed that a MELD score ≥ 18 points, ASA rating > 3, TP < 60 g/L, excessive bleeding, excessive plasma input, excessive autologous blood input, and reintubation are independent risk factors for PMV after liver transplantation. Early identification of risk factors will help to stop mechanical ventilation as soon as possible, reducing the occurrence of PMV and improving patient prognosis. The results of this study may allow more nursing researchers to further explore the risk prediction model of PMV after liver transplantation, predict the high-risk patients of PMV through the risk prediction model, and provide guidance for clinical nurses to develop the nursing plans for PMV patients.

Relevance Statement

This article is relevant to nursing research, the results may allow more nursing researchers to further explore the risk prediction model of PMV after liver transplantation, predict the high-risk patients of PMV through the risk prediction model, and provide guidance for clinical nurses to develop the nursing plans for PMV patients.

Ethics approval and consent to participate

This research meets the requirements of medical ethics and has received the ethical approval Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (IIT 2021667) and complied with the Declaration of Helsinki. This research strictly follows the principle of confidentiality and will only be used for academic research and will not be disclosed. This research has been agreed the Application to Waiver Informed Consent by Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no conflict of interest.

Funding

This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.LGF22G010004.

Authors' contributions

Huafen Wang and Fangyan Lu: the conception and design of the study, or

acquisition of data, or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content, final approval of the version to be submitted.

Ningna Yu: the conception and design of the study,or acquisition of data, or analysis and interpretation of data,drafting the article or revising it critically for important intellectual content,final approval of the version to be submitted.

Shichao Shen and Wei Su: the conception and design of the study, acquisition of data, analysis and interpretation of data.

Acknowledgments

We gratefully appreciate the multiple team of REDACTED for support in data collection during the execution of the research. Moreover, we sincerely appreciate the highly qualified native English speaking editors at American Journal Experts (AJE) for providing reputable English language editing service (Verification code: BA5E-3DFF-F18A-DE1B-2880) for our manuscript.

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Table 1 to 5 are available in the Supplementary Files section.

No competing interests reported.

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You are reading this latest preprint version

Risk factors of prolonged mechanical ventilation after liver transplantation: a retrospective cohort study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Methods and Materials

Cohort information

Data collection and variables

Data analysis

Results

Discussion

Limitations

Conclusion

Relevance Statement

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1