Review of Respiratory Medicine - Volumen 25, N�mero 1 - March 2025

Original Articles

Forced Vital Capacity, Tidal Volume and Diaphragmatic Function in Adults Submitted to Liver Transplantation. Prospective Case Series

Capacidad vital forzada, volumen tidal y función diafragmática en adultos sometidos a trasplante hepático. Estudio prospectivo de una serie de casos

ABSTRACT

Background: Liver transplantation is an upper-abdominal surgery that was previously linked to postoperative diaphragmatic dysfunction.

Objectives: our objective was to describe the evolution of forced vital capacity, tidal volume and diaphragmatic function in adults submitted to liver transplantation.

Materials and methods: Prospective case series including adults submitted to liver transplantation in a university hospital in Argentina between March and December of 2023. Tidal volume, forced vital capacity and diaphragmatic function (excursion and thickening fraction) were the main variables. Variables were measured once before the transplantation (pre-LT) and two times after the transplantation (immediate and late post-LT). Descriptive statistics were used to describe the variables according to their distribution, while paired samples were compared using the Friedman and ANOVA tests, respectively.

Results: Sample of 7 subjects, 6 males with a mean age of 62.4 years (SD 4.2), BMI of 31.6 kg/m² (SD 3.2), APACHE II of 12.2 points (SD 5.8) and median MELD-Na of 20 points (IQR 19-22). Forced vital capacity showed a significant statistical reduction of 42.44% (p=0.01) respectively in the immediate post-LT stage. Diaphragmatic excursion showed a statistically significant reduction after surgery of 30.01% in the immediate post-LT compared to baseline (p=0.03). Tidal volume and thickening fraction of the diaphragm did not show any significant changes compared to previous values.

Conclusions: Subjects submitted to liver transplantation show a significant reduction of forced vital capacity and diaphragmatic excursion in the immediate postoperative period.

Key words: Liver transplantation, Lung capacities, Diaphragm, Diaphragm paralysis, Ultraso­nography, ICU

RESUMEN

Introducción: El trasplante hepático es una cirugía abdominal superior previamente vinculada a una disfunción diafragmática posoperatoria.

Objetivos: El objetivo fue describir la evolución de la capacidad vital forzada, el volumen tidal y la función diafragmática en adultos sometidos a trasplante hepático.

Materiales y métodos: Estudio prospectivo de serie de casos en la cual se incluyeron sujetos sometidos a trasplante hepático en un hospital universitario de Argentina desde marzo a diciembre de 2023. La capacidad vital forzada, el volumen tidal y la función diafragmática (excursión y fracción de acortamiento) fueron las variables principales. Se realizó una medición antes del trasplante (pre-TH) y 2 posteriores (post-TH inme­diata y tardía). Se utilizó la estadística descriptiva para describir variables según su distribución y se compararon las muestras emparejadas con las pruebas de Friedman y ANOVA, respectivamente.

Resultados: Muestra de siete sujetos, seis masculinos con una edad media de 62,4 años (DE 4,2), IMC de 31,6 kg/m² (DE 3,2), APACHE II de 12,2 puntos (DE 5,8) y me­diana de MELD-Na de 20 puntos (RIQ 19-22). La capacidad vital forzada presentó una reducción estadísticamente significativa del 42,44 % (p = 0,01) respectivamente en el post-TH inmediato. La excursión diafragmática mostró una reducción estadísticamente significativa de 30,01 % (p = 0,03) en el post-TH inmediato respecto del basal. El vo­lumen tidal y la fracción de acortamiento no demostraron ningún cambio significativo con relación a valores previos.

Conclusiones: Los sujetos sometidos a trasplante hepático presentan una reducción significativa en la capacidad vital forzada y excursión diafragmática en el posoperatorio inmediato.

Palabras clave: Trasplante hepático, Capacidades pulmonares, Diafragma, Parálisis diafrag­mática, Ultrasonografía, UCI

Received: 05/01/2024

Accepted: 01/18/2025

INTRODUCTION

Liver transplantation (LT) is the only universally accepted therapeutic option for the treatment of end-stage liver disease, acute fulminant hepatic failure, and hepatocellular carcinoma, among other conditions.¹ LT is a type of major abdominal surgery that involves a wide surgical field and prolonged times.²

This type of surgery and its approach have been included as a possible causal mechanism of right phrenic nerve injury due to clamping of the suprahepatic inferior vena cava, resulting in dia­phragmatic dysfunction, decreased lung function, hypoxemia, and alterations in the thoracic cavity.^3-6

In patients who underwent LT, the reported postoperative incidence of unilateral diaphrag­matic paresis and paralysis is 79% and 38%, re­spectively.⁵ The severity of acquired diaphragmatic dysfunction, combined with increased restrictive loads due to the physiopathological consequences of end-stage liver disease (pleural effusion, ascites, and muscle weakness), further predispose patients to decreased lung function.^7,8

In this context, it has been reported that 11% of patients require mechanical ventilation (MV) after liver transplantation (LT), and 36.1% of them undergo re-intubation.⁹ Additionally, the occur­rence of immediate postoperative pulmonary com­plications and the high rate of acute respiratory failure after MV withdrawal increase in-hospital mortality.^7;10-12

Ultrasonography is a non-invasive and vali­dated diagnostic tool for bedside assessment of diaphragmatic function in both normal and pathological conditions.¹³ The ultrasound evalu­ation of the diaphragm has been validated in patients with end-stage liver cirrhosis and LT, using the thickening fraction of the diaphragm (TFdi) and diaphragmatic excursion (DE) as preoperative predictors of prolonged MV dura­tion following LT.^14,15

Currently, there are no published studies us­ing these parameter as primary variables for this specific population, nor has their progression been monitored after LT. In order to understand the impact of LT on these variables, our main objective is to describe the evolution of forced vital capacity, tidal volume, and diaphragmatic function in adults submitted to LT.

MATERIALS AND METHODS

Study objectives

The primary objective was to describe the evolution of for­ced vital capacity, tidal volume, and diaphragmatic function in adult patients submitted to LT. The secondary objectives were to assess the need for supplemental oxygen, the dura­tion of MV, and length of stay in the Intensive Care Unit.

Study design

Prospective case series including adult patients submitted to LT. The study was conducted at the Hospital Universita­rio Austral (Pilar, Argentina). The recruitment, data collec­tion, and follow-up period took place between March 2023 and December 2023. The study was designed in accordance with the STROBE guidelines for observational studies.¹⁶

The study included patients aged ≥ 18 years who had been previously evaluated by the institution’s hepatology department and admitted to the LT candidate list and sig­ned informed consent. Exclusion criteria: 1) Subjects with previous diagnosis of right diaphragmatic dysfunction, 2) Subjects who had been tracheostomized, 3) Subjects with chronic supplemental oxygen requirement, and 4) Subjects with grade IV hepatic encephalopathy according to the West Haven criteria.¹⁷

Patients who were not transplanted, or required a tracheostomy, or died during the follow-up period were excluded from the study.

The study protocol was reviewed and approved by the institution’s Research and Ethics Committee (CIE No. P 22-049). Additionally, the study received approval from the Joint Health Research Commission (CCIS, for its acronym in Spanish) of the Province of Buenos Aires (NO-2023- 28455006-GDEA-DPEG FFM SALGO).

Variables

• Clinical and demographic data: sex, age, BMI, risk fac­tors, and comorbidities.

• Hepatic and surgical parameters: etiology of liver dis­ease, MELD-Na score (points), surgical time (hours).

• ICU and hospital stay: APACHE II score (points), du­ration of MV (hours), need for supplemental oxygen* (days), ICU and hospital length of stay (days).

• Respiratory measurements: tidal volume and forced vital capacity.

• Diaphragmatic function: diaphragmatic excursion and diaphragmatic thickening fraction.

Measurement protocol

Each variable was measured by a group of kinesiologists trained and certified in pulmonary and diaphragmatic ultrasonography by the relevant local society, “ASARUC Sono Academy^©.” Each subject was attended to by two ki­nesiologists responsible for obtaining informed consent and explaining the study procedures, interviewing each subject, and collecting clinical and demographic data. Subsequently, another kinesiologist performed the ultrasonographic mea­surement (DE and TFdi).

Additionally, pulmonary volumes and forced vital capa­city were measured using ventilometry (TV and FVC). It has been demonstrated that the measurement of pulmonary volumes and forced vital capacity using a ventilometer has a high correlation with measurement through incentive spirometry (r = 0.7, p < 0.001).¹⁸

The variables were collected at three time points (one measurement before LT and two measurements afterward). Post-LT measurements were conducted at two moments: immediate post-LT (48 hours after extubation in the ICU) and late post-LT (during outpatient follow-up after hospital discharge). Subjects were included in the study consecu­tively and non-randomly. The late post-LT measurement was performed after hospital discharge, when the subject returned for outpatient follow-up. To minimize bias, the average number of days between the pre-LT measurement and the late post-LT measurement was reported (with respect to the surgical intervention).

All measurements of FVC, TV, and diaphragmatic function were taken with the subject in supine position at a 30-45° inclination. Each measurement was taken three ti­mes in a non-consecutive manner and then averaged, except for FVC, where the highest value obtained was recorded.

• Forced vital capacity and tidal volume: a hand-held ana­log ventilometer was used (Ferraris Medical Limited^©). The ventilometer is illustrated along with its accessories in Figure 1. It was positioned at the subject’s mouth, and the subject was instructed to breathe calmly. The TV was averaged over three measurements and expressed in milliliters (mL). The FVC was measured by instruct­ing the subject to inhale to their maximum capacity and then exhale forcefully for at least 6 seconds through the mouth, without coughing. The best value from the three measurements was recorded and expressed in liters (L).

• Diaphragmatic function: a portable ultrasound machine was used for academic purposes during the study (Fu­jifilm^© SonoSite M-Turbo), provided by Tecnoimagen S.A. Figure 2 shows various ultrasound images obtained in both B-mode and M-mode for the different variables. For the DE measurement, a convex 5-1 MHz transducer was used in M-mode, positioned along the anterior axil­lary line between the 8th and 10th ribs. The DE was expressed in centimeters (cm). In order to evaluate the TFdi, a linear 5-10 MHz transducer was used in M-mode. This variable was expressed as a percentage (%), and it was calculated using the following equation:¹⁹

The ultrasound measurement of diaphragmatic function has been classified as a non-invasive tool with high repro­ducibility and accuracy, with a reported intraclass correla­tion coefficient (ICC) between 0.87-0.99 for intraobserver agreement and 0.56-0.98 for interobserver agreement.²⁰

Statistical analysis

Categorical variables were described using absolute and relative frequency (%). Continuous numerical data were expressed as mean and standard deviation or as median and interquartile range, depending on the normality distribu­tion. The normality of the variables was assessed using the Shapiro-Wilk test. Friedman and one-way ANOVA tests were used for comparing paired non-parametric and parametric samples, respectively. Each set of values was compared to the pre-LT value. These comparisons were made to evaluate differences between mean or median values across different stages. The significance level was set at a p-value ≤ 0.05. Any subject with more than 10% missing data was excluded from the protocol. Data analysis was performed using IBM SPSS Statistics for Windows, version 27.0 (Armonk, NY: IBM Corp), while graphs were created using GraphPad Prism version 9.0.0 for Windows (GraphPad Software, Boston, Massachusetts, USA).

RESULTS

The subjects were included and listed in the study according to the previously mentioned eligibility criteria during the recruitment and follow-up pe­riod, as illustrated in the flow diagram of Figure 3.

The clinical and demographic data of the sample are detailed in Table 1, including risk factors and comor­bidities. Baseline parameters of the sample were co­llected during the first assessment in the pre-LT stage.

Forced vital capacity, tidal volume and diaphragmatic function

The average time difference in days between the pre-LT measurement and the surgical intervention was 82 days (SD 68.95), while for the late post-LT measurement, the difference had a median of 33 days (IQR 30-66).

Forced vital capacity and tidal volume

The immediate post-LT TV had a median of 613.3 mL (IQR 340-1017) compared to the pre- LT value of 816.7 mL (IQR 690-1287), resulting in a non-significant decrease of 24.91% (p=0.21). Subsequently, the TV continued to decline in the late post-LT stage, though not significantly, as il­lustrated in Figure 4.

The mean FVC was 1.75 L (SD 0.43) imme­diately after LT, compared to its pre-LT value of 3.04 L (SD 0.67), resulting in a statistically significant decrease of 42.44% (mean difference: 1.28 L, CI: 0.35- 2.22, p= 0.01). In the late post- LT stage, the FVC showed a respective increase but did not reach its baseline pre-LT value, as illustrated in Figure 5.

Diaphragmatic function

The DE exhibited a baseline value of 2.17 cm (IQR 1.7-2.3), which decreased to 1.30 cm (IQR 1.1-1.7) in the immediate post-LT stage. This difference of 30.01% was statistically significant (p=0.03). In contrast, in the late post-LT stage, this variable did not show a significant difference compared to its baseline value, as illustrated in Figure 6.

The TFdi showed a baseline pre-LT value of 33.23% (SD 7.42), which then slightly decreased to 30.38% (SD 20.12) in the immediate post-LT stage, as illustrated in Figure 7. The difference is not significant. At a later stage, the TFdi showed an increase, reaching an average of 45.21% (SD 26.85), even surpassing its pre-LT value.

Column chart with error bars representing average and standard deviation. LT: liver trans­plantation. NS: not significant. One-way ANOVA test for related parametric samples.

Surgical procedure and ICU/hospital stay

The subjects underwent an average surgery time of 5.50 hours (SD 1.98). Upon ICU admission, the APACHE II score showed an average value of 12.29 points (SD 5.82), with a mechanical ventilation duration of 8.30 hours (SD 6.74). The need for supplemental oxygen had a mean duration of 1.14 days (SD 0.69). The median ICU stay was 4 days (IQR 3–7), while the median hospital stay was 8 days (IQR 7–18).

DISCUSSION

Our results reflect a significant reduction in forced vital capacity and diaphragmatic excursion in the immediate postoperative period following a liver transplant (LT).

The decrease in forced vital capacity and tidal volume could be linked to pulmonary and tho­racic alterations occurring in the context of upper abdominal surgery, including increased thora­coabdominal elastance, alveolar occupancy or atelectasis, pain, and sedation.^9;21-23 Moreover, the persistent decline in the TV in the late post-LT stage, unlike the behavior observed in FVC could be explained by internal environmental changes that modulate the high ventilatory drive seen in LT candidates, reflected by high values in P0.1, TV, and respiratory alkalosis.^24-26

The reduction in the DE might be associated with the suprahepatic inferior vena cava clamping mechanism, which affects the course of the right phrenic nerve during the LT, as well as the cephalic displacement of the diaphragm due to perihepatic inflammation, which restricts the excursion.^5;24 In contrast, the TFdi showed a late increase compared to its baseline value. This phenomenon, which dif­fers from the other variables, could be attributed to the short surgical time (5.5 hours) and the duration of post-LT MV (8.3 hours) compared to reports from other studies (10-hour of surgery and >24 hours of MV).²⁴

The reduction in forced vital capacity and tidal volume observed in our study (42.44% for FVC and 24.91% for TV) are similar to those previously reported in patients undergoing upper abdominal surgeries and LT.^21;27 The decrease in DE (40.01%) falls below normal values for healthy individuals (1.5–2.3 cm) and aligns with previous reports by Kim et al.^21;28-30

Main study limitations: 1) single-center study with a small sample size; 2) non-randomized sample; 3) lack of standardization in pre- and post-LT measurement timing due to the nature of the transplantation process and clinical evolution following surgery.

Future studies should be randomized, with larger sample sizes and extended follow-up peri­ods. Ultrasound measurements of the diaphragm could be compared with the left hemidiaphragm. Internal environment parameters could provide information regarding the metabolic status and ventilatory drive.

These findings contribute to medical evidence, once again demonstrating that the postoperative period of abdominal surgeries such as LT leads to an acute deterioration in respiratory function. This direct and indirect impairment of respiratory capacity, a significant disadvantage in the early postoperative stage, could trigger incipient respi­ratory failure in a context of increased demands.

To conclude, subjects submitted to LT in our study show a significant reduction of forced vital capacity and diaphragmatic excursion in the im­mediate postoperative period.

Notes

* The need for supplemental oxygen was defined as the use of any device delivering oxygen at a concentration above 0.21 for at least 16 hours per day.

Conflict of interest

This group of authors and researchers have no conflicts of interest to declare regarding this study.

Acknowledgement

We would like to express our gratitude to all our colleagues in the department who contributed to this study with their help. Finally, we extend our thanks to Tecnoimagen S.A. for providing an ultrasound machine for academic purposes in conducting this study.

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