Monitoring intra‐abdominal pressure after liver transplantation in children

IAH after LTX can impair perfusion and threaten graft viability. This study aimed to assess the feasibility of longitudinal IAP measurements as an IAH screening method in children after LTX. A cohort of 23 children with a mean age (range) 3.1 (3 months–14 years) who underwent LTX between May 2017 and February 2018 were evaluated retrospectively. Longitudinal IAP measurements were compared to bedside Doppler US monitoring data. In total, 425 IAP measurements and 257 US examinations were performed. The mean ± SD (range) time expenditure for IAP measurement was 1.9 ± 0.4 (0.5‐3.2) minutes. The mean post‐operative IAP was 7.9 ± 3.6 (1‐25) mm Hg. IAH (IAP ≥ 10 mm Hg) was noted in 102 (24%) of 257 measurements. Agitation had a significant impact on IAP (estimate: 9.3 mm Hg, CI: 6.72‐11.97, P < .01). In patients with TAC, IAP was increased (6.7 ± 2.1 vs 8.7 ± 3.1 mm Hg, P = .02) while peak portal venous velocities decreased (38 ± 27 vs 26 ± 22 cm/s, P = .03) after patch reduction. An abdominal compartment syndrome with severely impaired vascular flow was noted in one patient. Episodes of elevated IAP were noted in a large proportion of patients, underscoring the need for IAP monitoring in pediatric liver transplant recipients. The safety and low time expenditure associated with IAP measurement could be included easily into standard nursing procedures for these patients.


Abstract
IAH after LTX can impair perfusion and threaten graft viability. This study aimed to assess the feasibility of longitudinal IAP measurements as an IAH screening method in children after LTX. A cohort of 23 children with a mean age (range) 3.1 (3 months-14 years) who underwent LTX between May 2017 and February 2018 were evaluated retrospectively. Longitudinal IAP measurements were compared to bedside Doppler US monitoring data. In total, 425 IAP measurements and 257 US examinations were performed. The mean ± SD (range) time expenditure for IAP measurement was 1.9 ± 0.4 (0.5-3.2) minutes. The mean post-operative IAP was 7.9 ± 3.6 (1-25) mm Hg. IAH (IAP ≥ 10 mm Hg) was noted in 102 (24%) of 257 measurements.
In patients with TAC, IAP was increased (6.7 ± 2.1 vs 8.7 ± 3.1 mm Hg, P = .02) while peak portal venous velocities decreased (38 ± 27 vs 26 ± 22 cm/s, P = .03) after patch reduction. An abdominal compartment syndrome with severely impaired vascular flow was noted in one patient. Episodes of elevated IAP were noted in a large proportion of patients, underscoring the need for IAP monitoring in pediatric liver transplant recipients. The safety and low time expenditure associated with IAP measurement could be included easily into standard nursing procedures for these patients.

| INTRODUC TI ON
Pediatric LTX is an established procedure for children with endstage liver disease or congenital metabolic disorders. Because the majority of pediatric patients requiring LTX are younger than 1 year old and there are few pediatric donor organs available, partial adult organs are often used. 1 A size mismatch between a small abdominal cavity and a relatively large split organ in small children can lead to traction and insufficient compliance of the abdominal wall, 2-5 a circumstance that has the potential to produce high IAP. Impaired arterial and portal blood flow due to an elevated IAP can lead to graft dysfunction. [6][7][8][9][10][11] Therefore, a TAC with a patch is often used to enlarge the abdominal cavity in small children receiving a liver transplant. [3][4][5] Vascular flow assessment with Doppler US is the goldstandard method for monitoring graft perfusion though it does not detect IAP directly. 12,13 In 2013, the WSACS published consensus guidelines to standardize definitions and management of IAH. 14 In children, IAH is defined as an IAP ≥ 10 mm Hg (grade I, 10-12 mm Hg; grade II, 13-15; grade III, 16-19 mm Hg; grade IV ≥ 20 mm Hg). 14 IAH affects 15%-45% of PICU patients. 15,16 Excessively high IAP that interferes with vascular inflow and venous return and thereby endangers the viability of abdominal organs constitutes a condition known as abdominal compartment syndrome, which is diagnosed in 0.7%-4.7% of children treated in PICUs and associated with very high mortality (40%-80%). [17][18][19][20] The clinical relevance of IAH and abdominal compartment syndrome in intensive care patients and their impacts on morbidity and mortality have come into focus in recent years. [14][15][16][17][18][19][20][21] This study aimed to analyze longitudinal IAP measurements in children who underwent LTX. IAP values were compared to other standards of monitoring graft viability, including US, laboratory, and clinical parameters.

| Subjects
This retrospective single-center study was legitimated by the local medical statue (details for blinding omitted) and written-informed consent was waived. All examinations were conducted according to the Declaration of Helsinki. All 23 pediatric patients who underwent LTX between the 26th of May in 2017 and the 5th of February in 2018 at our center were included in this study. Their demographics, clinical characteristics (including indications for LTX and donor liver characteristics), intra-operative variables (including primary vs temporary closure), and post-operative care variables are summarized in Table 1. Primary abdominal closure was performed when possible; TAC with a silicon patch (reinforced Silicon Sheeting, Invotec International) tailored to the needs was applied when donor grafts were too large for the recipient patient's abdominal cavity.

| IAP measurement
According to WSACS's recommendations, 14 we measured IAP intra-vesically. We used a hydrostatic manometer, the UnoMeter™ under sterile conditions to prime the system once after installation in order to remove the air from the tubing system. The IAP measurements were performed in a completely supine position at end expiration. The zero reference of the IAP monitoring system was zeroed at the mid-axillary point. The Unometer AbdoPressure tubing system was then lifted above the patient's level, and the hose clip was opened to allow a passive backflow of the patient's urine into the bladder. When the water column settled into a steady state, IAP was read and documented in mm Hg. IAP measurements were performed in the PICU at least every 8 hours until the patient was discharged from PICU. To evaluate the influence of patch reduction on IAP, the last IAP value obtained during the 4 hours preceding and the first IAP value obtained during the 4 hours after patch reduction were analyzed.
The IAP monitoring device was removed in cases of severe Foley catheter leakage or oliguria for more than 6 hours. In all patients, urine cultures were obtained at least every 7 days. The patient's level of arousal/agitation was classified as calm, moderately agitated, and severely agitated. In a random sample of 10 patients, the time required for IAP measurements was taken. For each IAP value, we calculated the APP with the formula: APP = MAP − IAP.

| Doppler US examination
Doppler US investigations were carried out by experienced radiologists using a commercial Scanner (GE Logiq 9 US system, GE Medical

| Statistical analysis
For qualitative data, counts and percentages were calculated. For quantitative data, means and SDs were calculated. We used a paired t test to compare data before vs after patch reduction. We used a multiple linear mixed model to investigate the potential impact of time after transplantation, diuresis, volume balance, creatinine, and agitation on IAP. To analyze the influence of IAP on US parameters, we calculated a linear mixed model. All analyses were performed in SPSS 23 for Mac (IBM SPSS Statistics, IBM Corporation), GraphPad Prism V6.0c (GraphPad Software), and R version 3.5.2 (R Core Team, Vienna, Austria). A P value <0.05 was considered statistically significant.

| IAP
The mean number of IAP pressure measurements performed per patient during the post-operative period ± SD (range) for the 23 patients in the study was 18.5 ± 12.7 (5-54), constituting a total of 425 IAP measurements (Figure 1). Nurses spent a mean ± SD (range) of 1.9 ± 0.4 (0.5-3.2) minutes measuring and 0.3 ± 0.1 (0.2-0.6) minutes documenting IAP values. In 16 (3.6%) of 441 attempts, the measurements were unsuccessful, most often due to IAP monitoring device malfunction. We noted no complications of IAP measurements, and all urine cultures were negative.
Post-operatively, the mean IAP ± SD (range) following LTX for all 23 patients was 7.9 ± 3.6 (1-25) mm Hg. The mean APP ± SD (range) in all patients was 68 ± 14 (33-125) mm Hg. Increased IAP fulfilling the criterion of abdominal hypertension (≥10 mm Hg) 12  First post-operative IAP values after LTX did not differ significantly between cases with primary abdominal closure and TAC ( Table 2).
The first post-operative APP values were also similar in both groups.
As shown in Figure 2, a slight increase in mean IAP values occurred after the patch reduction procedure in patients with a TAC (before 6.7 ± 2.1 mm Hg vs after 8.7 ± 3.1 mm Hg, P = .02). The mean APP values remained similar after patch reduction compared to the values before patch reduction (before 70 ± 13 mm Hg vs after 68 ± 13 mm Hg, P = .32).
Multiple mixed linear model analysis showed a significant effect of the level of agitation on the IAP (estimate: 9.3 mm Hg, CI: 6.72-11.97, P < .01), whereas diuresis, fluid balance, and creatinine did not affect and impending liver dysfunction, in this patient. A protruding, firm, and painful abdomen was observed clinically. Immediate decompression with patch insertion was performed, resulting in a reduction of the IAP to 6.5 mm Hg and a normalization of the hepatic artery RI value to 0.8 ( Figure 3).

| US
The mean number of Doppler US examinations performed per patient ± SD (range) during the post-operative period was 11.2 ± 6.5 , resulting in a total of 257 measurements in 23 patients.  Although we observed a relatively high prevalence of IAH episodes in our cohort, a higher prevalence was reported in adult patients after LTX. 25 In contrast to that adult series, we did not detect a significant effect of IAH on diuresis, fluid balance, or kidney function, perhaps due to the substantially higher percentage of patients with IAH in the adult study. A direct effect of elevated IAP on graft viability cannot be excluded, given that microvascular perfusion was not tested in this study. 11 In response to patch reduction, patients with TAC in our study had significantly reduced portal venous inflow in association with a slight increase in IAP (Table 3). Our observations of significantly increased hepatic artery flow velocities during IAH episodes, compared to periods with normal IAP, suggest that high IAP may impact graft perfusion, even in a heterogeneous population of children.

| D ISCUSS I ON
We identified the level of agitation as a significant risk factor for high IAP. Severely agitated children had significantly higher IAP values than both calm and moderately agitated children, a finding that can be explained by the effects of crying and pressing. A multiple mixed model analysis showed that severe agitation increased the IAP by 9.3 mm Hg, which is a very relevant effect given that the threshold for IAH is 10 mm Hg. High IAP due to traction after abdominal closure itself may cause further pain and distress. Our results suggest that severe agitation (eg, due to pain) in children recovering from LTX may lead to critically high IAP values and thus may threaten graft viability. Therefore, we recommend close monitoring of these patients for signs of pain with effective pain treatment in accordance with WSASC's guidelines. 14 To exclude the effects of agitation on IAP measurements, the WSASC recommends that IAP be measured when children are calm. 26 In the context of LTX in children, however, this may not be possible at times. We suggest conducting IAP mea-

ACK N OWLED G M ENT
The authors thank the entire PICU team for supporting the study and the anesthesia team for their intra-operative support.

CO N FLI C T O F I NTE R E S T
There is no conflict of interest.