HYPA study: protocol for investigating intra-abdominal hypertension and abdominal compartment syndrome in patients undergoing open and robotic pancreatic procedures

Abstract

Background

Intra-abdominal hypertension and abdominal compartment syndrome are frequently presented in critically ill patients admitted to intensive care units. Patients undergoing pancreatic procedures are susceptible to gastroparesis, postoperative ileus, intra-abdominal collection or extensive fluid resuscitation, all of which are risk factors for elevation of intra-abdominal pressure. This study aims to assess the incidence of intra-abdominal hypertension and abdominal compartment syndrome following pancreatic procedures; explore potential correlations between intra-abdominal hypertension and the development of postoperative complications such as anastomotic dehiscence, pancreatic fistulas, ileus or delayed gastric emptying and compare the occurrence of intra-abdominal hypertension in patients undergoing robotic versus open pancreatic procedures.

Methods

The HYPA study is a prospective observational study conducted at a high-volume pancreatic centre. Patients admitted to the intensive care unit between 1 January 2025 and 31 December 2027, following pancreatic procedures, will be enrolled. Intra-abdominal pressure will be measured using a standardised protocol during the postoperative intensive care unit stay. The collected data will include perioperative factors such as fluid management, surgical complications and postoperative outcomes, including delayed gastric emptying, pancreatic fistula and infections. Statistical models will analyse correlations between intra-abdominal hypertension, abdominal compartment syndrome and postoperative morbidity.

Discussion

This study aims to provide evidence supporting routine intra-abdominal pressure monitoring in this surgical population, enabling earlier diagnosis and intervention. By evaluating the potential benefits of robotic pancreatic surgery in reducing intra-abdominal hypertension-related complications, the findings could guide future clinical protocols, enhance postoperative outcomes and contribute to the growing evidence supporting minimally invasive pancreatic surgery.

Trial registration

Number: NCT06672601 ClinicalTrials.Gov. Date 01.11.2024.

Background

Intra-abdominal hypertension (IAH) is defined as sustained or repeated intra-abdominal pressure (IAP) above 12 mmHg and is classified into Grades I-IV (Table 1). Abdominal compartment syndrome (ACS) is characterised by an intra-abdominal pressure exceeding 20 mm/Hg, along with dysfunction of one or more organ systems [1]. IAH and ACS frequently occur in critically ill patients admitted to the intensive care unit (ICU) and are independent predictors of increased morbidity and mortality. IAH and ACS are frequently observed in patients with acute pancreatitis, major burns, septic shock or abdominal trauma, and after aortic aneurysm repair or liver transplantation [2–5]. According to some studies, the incidence of IAH ranges from 25% to 49%, while the prevalence of ACS is reported to be 3%−6% in all ICU admissions [2, 6, 7]. IAH is classified into primary, secondary and tertiary forms, depending on the underlying pathology and pathogenesis [7].

The pathophysiological effects of IAH and ACS result in splanchnic, pancreatic, and intestinal hypoperfusion, along with renal impairment and respiratory dysfunction. [4, 8–12]. Pancreatic procedures are associated with a high morbidity rate up to 41% [13, 14] and impose a significant physiological insult to the patient’s homeostasis. Patients undergoing pancreatic procedures are at high risk of postoperative complications, including delayed gastric emptying, postoperative pancreatic fistula (POPF), surgical site infection, ileus, postoperative haemorrhage or post-pancreatectomy acute pancreatitis [15–17]. Perioperatively, these patients frequently undergo extensive volume resuscitation due to systemic inflammatory response syndrome, which heightens the risk of progressive visceral oedema and impaired tissue perfusion - both critical factors in anastomotic healing [18–20]. Massive fluid resuscitation and fluid overload are independent risk factors for IAH and ACS, both of which increase morbidity and mortality in ICU patients [21, 22].

POPF is one of the most severe postoperative complications and remains a major cause of morbidity and mortality in pancreatic surgery. The incidence of POPF after pancreatoduodenectomy (Whipple procedure, PD) ranges between 11.2% and 21.3%, while in distal pancreatectomy, it is 20.4% [23, 24]. POPF can lead to intra-abdominal collection, intra-abdominal infections, post pancreatectomy haemorrhage, sepsis, prolonged delayed gastric emptying, extended length of hospital stay, reduce quality of life, increased re-operations rates and higher hospital costs [23–25]. All of the aforementioned conditions play a critical role in the onset of IAH and ACS and are recognized as significant risk factors, contributing to increased morbidity and mortality. When combined with other risk factors such as obesity, postoperative pain and sepsis, patients undergoing pancreatic procedures are at higher risk for the development of IAH and ACS.

The primary objective of this study is to assess the risk and prevalence of intra-abdominal hypertension and abdominal compartment syndrome in patients undergoing elective open or robotic pancreatic procedures. The secondary objective aims to explore potential correlations between IAH and the occurrence of postoperative complications such as anastomotic dehiscence, delayed gastric emptying, postoperative ileus and postoperative pancreatic fistulas development, and to understand how these complications contribute to increased morbidity and mortality. The tertiary objective is to compare open and robotic pancreatic procedures in terms of incidence of intra-abdominal hypertension and ACS.

Methods

The HYPA study is a prospective observational study conducted at a high-volume pancreatic centre. Between 1 January 2025 and 31 December 2027, all patients admitted to the ICU after elective open or robotic pancreatic procedures for tumorous expansion or chronic pancreatitis including pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, Beger procedure, and enucleations will be enrolled in this study.

Inclusion criteria

• – Patients ≥ 18-years-old

• – Indication for an elective pancreatic procedure

• – Written informed consent

Exclusion criteria

• – Patients <18 years old.

• – Contraindication for urinary catheter placement.

  – Refusal to participate in the study.

Measurement

IAP will be measured following a standardised protocol in accordance with the recommendations of the World Society of Abdominal Compartment Syndrome (WSACS) [1]. Measurement will commence immediately upon admission to the ICU and will be conducted every six hours for seven consecutive days or until the patient is discharged from the ICU[1]. IAP will be assessed using a urinary bladder catheter connected to a pressure transducer, with the introduction of 20 ml of sterile saline while the patient is in the supine position [26]. To minimize patient burden and infection risk, urinary catheters will be removed as soon as they are no longer clinically required, particularly in patients undergoing fast-track or enhanced recovery pathways.

Data collection

Data on all known risk factors for intra-abdominal hypertension and abdominal compartment syndrome associated with pancreatic procedures will be collected. The primary risk factors include age, body mass index, gastroparesis, ileus, intra-abdominal collection, abdominal infections (peritonitis, abscess, pancreatitis), massive fluid resuscitation, positive fluid balance, sepsis, septic shock, transfusion of the blood components and the use of positive end-expiratory pressure [1–3, 26, 27]. Additional data that will be monitored include diabetes, prior surgical history, ascites, cirrhosis, duration of operation, perioperative blood loss, duration of mechanical ventilation, length of ICU stay, serum lactate, drain output, amylase positivity in drains, diuresis, acid-base balance, hypothermia, coagulopathy and the incidence of other postoperative complications such as postoperative pancreatic fistula, biliary leak, anastomotic dehiscence, delayed gastric emptying, surgical site infection and morbidity and 90-day mortality.

Statistical analysis

The association between intra-abdominal hypertension and postoperative outcomes will be evaluated using generalised linear models. For numerical laboratory measurement a linear model for the log of the value will be used. For binary outcomes, we will use logistic regression with Firth’s bias correction. The correction improves inferences when the outcome is rare as well as under (near) complete separation. For ordinal outcomes we will use cumulative ordinal regression; for duration outcomes negative binomial regression. Each association will be evaluated in an unadjusted model, using only the intra-abdominal hypertension as the predictor and in an adjusted model also using body mass index, ileus, massive volume resuscitation and intra-abdominal collections as additional predictors.Within each family of questions (adjusted and unadjusted associations) multiple comparisons will be handled using the Benjamini-Hochberg method to control the false discovery rate at 5% (i.e., p-values are inflated to ensure that among results with adjusted p < 0.05 at most 5% are false positives).

Missing data will be addressed by performing both complete-case analysis and a worst-case analysis as a sensitivity check. For the worst-case analysis, we will impute all missing data points with the value that maximally contradicts the observed effect from the complete-case analysis (chosen from within the range of the values we actually observe). I.e. If a complete case analysis indicates an increase in prevalence/severity of a complication for subjects with IAH, all missing values for IAH subjects will be replaced by the lowest observed value and all missing values for non-IAH subjects will be replaced by the highest observed value.

Sample size

Based on past experiences in our center, we expect to encounter 55 – 60 eligible subjects per year with an anticipated 90% enrollment rate for a total of 150 subjects. This sample size is sufficient to estimate the incidence of IAH in our target population within 8 percentage points (worst case radius of the 95% Clopper-Pearson interval). At the same time, the sample size is enough to detect a good proportion of strong associations with major complications. Previous studies have provided estimates of IAH incidence in similar populations ranging from 13% to 53% [2, 3, 9, 30, 31], with average incidence of 30%. Assuming our study observes this average incidence, we obtain at least 80% power to detect associations with binary outcomes where the incidence without IAH is at least 20% and odds ratio is at least 3. When the odds ratio is 2, the power is at least 47%. Power is further substantially increased for ordinal and continuous outcomes.

Treatment

Patients who develop IAH will be managed in accordance with current guidelines and the identified underlying cause, with reassessments conducted every four hours. Treatment will be adjusted gradually based on IAP measurements and the patient’s clinical status. Interventions may include decompression using a nasogastric or rectal tube, administration of promotility agents such as neostigmine, achievement of zero or negative fluid balance, percutaneous catheter drainage of fluid collections under computed tomography guidance, and if required, intubation and abdominal wall relaxation [28].For patients with ACS, an interdisciplinary consultation will be conducted, and intervention will be based on a standardised protocol, clinical findings and WSACS recommendations[1]. For patients meeting the criteria, abdominal decompression and open abdomen techniques with vacuum assisted closure will be performed [29]. Intra-abdominal pressure will continue to be monitored after each intervention except open abdomen techniques in order to document the dynamic response of IAP to therapeutic measures such as percutaneous drainage, gastrointestinal decompression, or fluid balance optimization.

Discussion

Patients undergoing elective pancreatic procedures meet all the criteria for IAH and ACS development. However, only a few studies describe limited data on small groups focusing on IAP and IAH in patients following elective abdominal surgery [2, 3, 9, 30, 31]. For example, Smit and al. reported on a group of 25 patients who underwent pancreatic resection, of which 4 (16%) developed IAH [2]. Vidal observed IAH in 30 (53%) surgical patients [30]. Sugrue described elevated IAP in 12 out of 89 patients (13,48%) [9], while Blaser identified IAH in 55 patients (35.9%) following elective surgery [3]. Murphy reported an incidence of IAH in 14 patients (34%) [31]. Although these studies included a relatively small sample size, the occurrence of IAH may still hold clinical significance. Taken together, these studies suggest that the incidence of IAH in surgical patients lies between 13% and 53%, with an average of 30%. We therefore expect that the incidence of IAH in our patient population will be in this range. The concept of damage control surgery in abdominal trauma has led to the adoption of temporary abdominal closure techniques in high-risk patients to prevent IAH and ACS. However, for patients undergoing elective pancreatic procedures, there is currently no established protocol or consensus advocating for the routine measurement of IAP or the use of open abdomen techniques, despite the potentially comparable risk of IAH and ACS. To date, no systematic, prospective observational study has specifically examined IAP monitoring in patients following elective pancreatic procedures, nor has the correlation with the onset of IAH been adequately investigated. Pancreatic resections are complex abdominal procedures associated with a significant risk of postoperative complications and a high morbidity rate [13, 14]. Common postoperative conditions, including extensive volume resuscitation, third-space fluid shifts, tissue oedema, gastroparesis, ileus and intra-abdominal fluid collection, are all recognized risk factors for IAH and ACS. Despite the high prevalence of these risk factors, IAP measurement is often neglected in this patient population. As a result, the development of IAH may be underdiagnosed, potentially missing opportunities for early intervention. The shift towards minimally invasive procedures, such as robotic surgery with particular emphasis on enhanced recovery after surgery (ERAS) protocols is evident. Currently, few studies are investigating the benefits of robotic pancreatic procedures compared to open surgeries, particularly the PD [32–34]. Studies comparing open versus minimally invasive distal pancreatectomy describe the superiority of the robotic approach. However, none of these studies have specifically investigated intra-abdominal pressure monitoring or the incidence of IAH/ACS in this context.

The aim of this study is to complement ongoing randomised clinical trials comparing open versus robotic pancreatic procedures, specifically focusing on PD [32–34]. The objective of the study is to investigate the potential additional benefits of minimally invasive techniques and to contribute new data on postoperative intensive care, with a particular focus on the development of IAH and ACS. Patients undergoing robotic pancreatic resections due to more delicate tissue manipulation, reduced blood loss and the need of crystalloid administration may have a lower risk of intra-abdominal hypertension. If this hypothesis is true, and patients undergoing robotic pancreatic resections do not develop IAH, it could offer additional support for favouring minimally invasive techniques over open surgeries. Nonetheless, the efficacy of robotic PD remains a topic of ongoing debate as the current evidence continues to be inconclusive. IAH and ACS in patients after major elective abdominal surgery may be underdiagnosed. Early risk stratification of patients at risk of IAH development and preventative IAP measurement could lead to earlier diagnosis and reduction of postoperative morbidity and mortality. In a small selected group of high-risk patients, with complicated intraoperative course, massive blood loss, extensive fluid administration, or hemodynamic instability requiring vasoactive support, prophylactic use of the open abdomen with a planned second look could be considered to prevent the development of IAH and ACS in the ICU.

The study has some limitations. It is a single-centre, observational study, which precludes randomization. To minimise potential bias, the department of biostatistics was consulted to help adjust the study design. Despite its limitations, we are confident that the study will yield valuable data on the occurrence and genesis of IAP, IAH and ACS in patients undergoing elective pancreatic procedures. This study builds upon the recommendations for research on IAH and ACS made by an international conference of experts, continuing the investigation of key topics highlighted in previous research efforts [35]. If our findings confirm that intra-abdominal hypertension is both frequent and clinically relevant in this population, the results could translate into clinical recommendations for routine intra-abdominal pressure monitoring in high-risk patients admitted to the ICU. Such monitoring may allow earlier detection of complications or fluid overload and enable timely intervention. In the next step, we aim to establish multicentre collaborations and initiate a prospective randomized trial to evaluate whether routine IAP monitoring improves outcomes across different surgical populations with a focus on hepato-biliary, major colorectal and idiopathic bowel disease surgeries.

Abbreviations

IAP

Intra-abdominal pressure

IAH

Intra abdominal hypertension

ACS

Acute compartment syndrome

PD

Pancreatoduodenectomy

ICU

Intensive care unit

POPF

Postoperative pancreatic fistula

DGE

Delayed gastric emptying

SSI

Surgical site infection

Authors’ contributions

Štěpán-Ota Schütz is a surgical resident and a postgraduate student at Charles University in Prague in the field of experimental surgery. He designed the project. He will coordinate all of the team members. He registered the study and prepared the study protocol. He will collect the data. He will participate in the preparation of data publication. Pavel Záruba helped with project design. He acts as a senior consultant. He will perform the surgeries. He will participate in the preparation of data publication. Aleš Rára helped with the project design. He acts as a senior consultant with a specialisation in intensive care medicine. Michal Soták helped with the project design. He revised and edited the manuscript critically. He acts as a senior consultant with specialisation in intensive care medicine. Šarlota Havlíková helped with manuscript preparation and proofreading and she will participate in the data collection. Martin Modrák contributed to the statistical analysis and will participate in the interpretation of statistical data. Tomáš Tyll will act as a consultant for the technical and administrative part of the project and will participate in the preparation of data publication. Radek Pohnán will help with data collection and interpretation. He will act as a consultant for partial tasks of the project. He will participate in the preparation of data publication.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

 This study was approved by the ethics committee, and informed consent to participate was obtained from participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.