Key words : Acute kidney injury, Intensive care unit, Liver transplantation, Pediatric patient, Posttransplant complications

Introduction

Liver transplant is the most effective treatment for end-stage liver diseases in adult and pediatric patients.¹

After pediatric liver transplant, extubation is recommended as a safe procedure at the end of the surgery in the operating room (OR) unless there is an absolute necessity to maintain mechanical ventilation during posttransplant recovery, and extubation is now safely performed before exit from the operating theater in many centers.^2-4

The most important factor in the widespread use of this practice is that the prolonged times for mechanical ventilation are associated with higher morbidity, longer lengths of stay in the intensive care unit (ICU) or in the hospital, higher hospital financial costs, and higher rates of mortality.^4,5

It is known that prolonged mechanical ventilation is a risk factor for the development of acute kidney injury (AKI) among adult liver transplant recipients.^6,7 We aimed to examine whether there is a relationship between early extubation and AKI, since AKI is observed at a remarkable rate of 34% to 67% after pediatric liver transplant and significantly increases morbidity and mortality.^8,9

We investigated whether early immediate tracheal extubation would reduce the incidence of acute kidney injury in pediatric liver transplant recipients. The primary outcome in our study was to determine the incidence of AKI in pediatric liver transplant recipients with early immediate tracheal extubation, and the secondary outcome was to determine whether the length of stay in the ICU or hospital and the rate of mortality were different in pediatric liver transplant recipients with early immediate tracheal extubation versus patients whose mechanical ventilation persisted into the posttransplant recovery phase.

Materials and Methods

After Ethics Committee approval, data from pediatric liver transplant recipients (<18 years) admitted to our ICU from January 2012 to December 2020 were analyzed retrospectively.

Patients over the age of 18 years, patients with chronic renal failure, and patients with missing data were excluded from the study. Collected data included demographic characteristics (age, sex, body weight, and body mass index), systemic diseases, drugs, perioperative laboratory values and hemodynamic parameters, perioperative urine output, incidence of intraoperative massive hemorrhage (massive hemorrhage was defined according to Hellstern and Haubelt,¹⁰ as blood loss exceeding 150 mL/min), extubation time, length of stay in the ICU or hospital, and hospital mortality.

Early extubation was defined as extubation in the OR. Patients were divided into 2 groups according to the extubation time: those who were extubated in the OR and those who were extubated in the ICU.

We defined AKI according to the Kidney Disease Improving Global Outcomes guidelines based on serum creatinine and urine output.¹¹ We evaluated the incidence and stages of early postoperative AKI among the included pediatric liver transplant recipients.

The same anesthetic technique was used in all patients. Anesthesia was induced with a combination of propofol (1.5-2.5 mg/kg) and fentanyl (3-5 µg/kg). Rocuronium was given to facilitate endotracheal intubation (0.5-1.2 mg/kg) and maintain paralysis during surgery (0.01-0.012 mg/kg/min). Anesthesia maintenance was achieved with a sevoflurane-air-oxygen mixture and an infusion of remifentanil (0.1-0.2 µg/kg/min). Patients were routinely monitored with electrocardiography, pulse oximetry, capnography, nasopharyngeal temperature, invasive arterial blood pressure (radial pressure), and central venous pressure via the subclavian or internal jugular vein and cardiac output (PiCCO multipara-metric advanced hemodynamic monitor; Pulsion Medical Systems). After surgery, all patients were admitted to the ICU.

The same surgery, anesthesia, and intensivist teams were assigned during the perioperative period of all liver transplants.

This study was approved by the Baskent University Institutional Review Board (project No. KA 21/310).

Statistical analyses
For statistical analysis, SPSS software was used (version 20.0; IBM Corporation). The chi-square test was used to compare categorical variables. In terms of continuous variables, the Mann-Whitney U test was applied to investigate differences in groups. In summary statistics, the mean (with minimum to maximum) was used for continuous variables, and frequency distribution (with percentage) were used for categorical variables. Graphs were generated from percentages and frequencies to summarize the results. P < .05 was considered statistically significant.

Results

During the study period, 226 liver transplants were performed in our hospital, 140 of which were for pediatric patients. After excluding patients with chronic kidney disease/compensated kidney disease diagnosis and missing medical data, we analyzed 132 pediatric liver transplant recipients (Figure 1). The mean age of transplant recipients was 58.2 ± 60.1 months (4-204 months), and 72 (54.5%) were male patients. One hundred and twenty (90.9%) patients received transplants from living donors. According to the degree of donor/recipient kinship, there were 104 first-degree donors, 4 second-degree donors, 10 third-degree donors, and 2 fourth-degree donors. The demographic characteristics and graft type of patients included in the study are shown in Table 1. The most frequent diagnosis was biliary atresia (n = 40; 30.3%), and all diagnoses are listed in Table 2. Comorbidities and preoperative medical treat-ments are listed in Table 3. Table 4 lists the preoperative laboratory results.

Early immediate tracheal extubation in the OR was performed in 86 pediatric liver transplant recipients (65.2%). Postoperative AKI was seen in 4 (18.2%) pediatric patients, of whom 15 (11.4%) had stage 1 AKI, 8 (6.1%) had stage 2, and 1 (0.8%) had stage 3 (Table 5). Patients with or without early tracheal extubation in the OR were similar in terms of demographic characteristics, etiologies, comorbidities, and preoperative and postoperative laboratory results (Tables 1-4). There was no statistically significant difference between the 2 groups regarding deve-lopment of AKI (18.6% vs 17.4%; P > .05) (Table 5).

Length of stay in ICU and hospital was significantly shorter in pediatric liver transplant recipients who were extubated in the OR (3.5 ± 3.5 vs 9.1 ± 12.5 days, P < .001; 23.1 ± 15.9 vs 35.4 ± 19.4 days, respectively) (Table 6). There was no statistically significant difference in the 28-day mortality between the 2 groups (P = .4), but hospital mortality was significantly lower in patients who were extubated in the OR versus those who did not receive early extubation (23.1 ± 15.9 vs 35.4 ± 19.4 days, respectively; P < .001) (Table 6).

Discussion

Early immediate tracheal extubation in the OR was performed in 65.2% of patients in our cohort. The incidence of early postoperative AKI was 18.2%, and there was no association between early immediate tracheal extubation and development of AKI among pediatric liver transplant recipients. Length of ICU stay and length of hospital stay were significantly shorter in patients who were extubated in the OR. There was no difference in 28-day mortality in both groups, but hospital mortality was significantly lower in patients who were extubated in the OR.

Extubation in the OR after liver transplant is a common clinical approach in the pediatric patient group as well as in the adult patient population.^12,13

In addition to clinics that routinely extubate pediatric liver transplant recipients in the ICU, there are clinics that report extubation in the OR with an incidence of 57% to 73%, especially in recent years.13,14 As we know it is a safe procedure, we have been applying the principle of extubation in the OR at the end of the surgery in our center for many years in our pediatric patients who meet the weaning criteria, in an effort prevent complications due to prolonged mechanical ventilation.^2,3 Our incidence of extubation in the OR is 65.2%, which is similar to the rates reported by clinics with high rates of early extubation.

In addition to the limited reports on early postoperative AKI in pediatric liver transplant recipients, the incidence has been reported with a wide range, from 17.6% to 67%.8,9,15 In our cohort, the incidence of AKI was found to be 18.2%, which is in line with recent published results, but our results are closer to the lower end of this wide range. Ferah and colleagues reported the incidence of AKI, which they evaluated with Acute Kidney Injury Network criteria (17.6%) and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria (37.8%).¹⁴ In our study, we determined the incidence of AKI to be 18.2% according to the Kidney Disease Improving Global Outcomes criteria. We think that this significant difference between the incidences in the studies is due to differences in the patient population and the methodologies, as well as differences in the criteria used for the definition of AKI.

Presence of biliary atresia, increased time of anhepatic phase, lower postoperative jaundice clearance, tacrolimus toxicity, use of diuretics, and ICU course with longer durations of mechanical ventilation are all postoperative AKI risk factors reported in pediatric liver transplant recipients.^1,16

The effects of positive-pressure mechanical ventilation (PPMV) on extrathoracic organs and hemodynamics have been investigated for many years. Positive-pressure mechanical ventilation reduces cardiac output by many mechanisms, which reduces renal perfusion and causes deterioration in kidney function. It is known that the increase in intrathoracic pressure during PPMV causes a decrease in renal plasma flow, glomerular filtration rate, and urine output. Another implication of the decrease in cardiac output caused by PPMV is the increase right ventricular afterload due to compression on mediastinal structures and pul-monary vessels, which causes a decrease in renal perfusion. Therefore, regardless of these mechanisms, the negative effect of PPMV on the kidney is known.17 For all these reasons, we hypothesized that the incidence of AKI would be lower in patients who were extubated in OR. Although there was no statistical difference between the 2 groups, the incidence of AKI was found to be lower in patients who were extubated in the OR. In studies that found a relationship between AKI and prolonged mechanical ventilation in pediatric liver transplant recipients, prolonged mechanical ventilation times were reported to be longer than 40 hours (5.5 days). In our study, the mean extubation time was as short as 76 hours even in the group that was extubated in the ICU, which showed that 67% were extubated within <24 hours and which is below the duration of mechanical ventilation in other studies. Thus, AKI development was not significantly lower in the group extubated in ICU, and we attribute this to very low extubation times versus previous studies.

Many published studies have reported that immediate extubation reduces ICU-hospital length of stay and reduces hospital financial costs.^2-5,13 Similar to those studies, we found that patients who were extubated in the OR had shorter durations of ICU and hospital stays. We think that these data are another indication that OR extubation can be performed safely under suitable conditions.

It is known that as the duration of mechanical ventilation increases, complications and mortality increase in these patients.^2,18 In our study, we found that hospital mortality was lower in pediatric liver transplant recipients who were extubated in the OR, similar to the previously published information.

Our study has some limitations, such as the retrospective context and the limited number of patients. In addition, there is no other study that has investigated the relationship between OR extubation and AKI, and there are few studies of the effects of early extubation in pediatric liver transplant recipients. In our study, we used a parameter that increases more slowly in patients with low muscle mass, such as creatinine, and we did not use early biomarkers. Therefore, we did not observe the relationship that we expected.

Conclusions

Early extubation was performed in nearly two-thirds of our cohort, but our results show that there was no association between early extubation and development of AKI in pediatric liver transplant recipients.

References:

References


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