Authors: Professor Simon Lal and Dr Benjamin Crooks, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, UK

Key words: Intestinal failure; home parenteral nutrition; catheter-related bloodstream infection; intestinal-failure-associated liver disease; multi-disciplinary team

Learning points

• Meticulous central venous catheter care is essential in patients receiving home parenteral nutrition (HPN) to minimise catheter associated complications
• Intestinal failure-associated liver disease (IFALD) is a multifactorial condition; steps should be taken to address nutritional and non-nutritional factors to minimise the risk of IFALD in HPN-dependent patients
• A multi-disciplinary team approach is key to optimising outcomes for patients with chronic intestinal failure

Introduction

Intestinal failure (IF) is defined as reduced gut function resulting in an inability to absorb the necessary macronutrients, micronutrients, and/or water required to maintain health or facilitate growth, such that intravenous supplementation is required.¹ Whereas type 1 and 2 IF are acute conditions lasting weeks to months, type 3 IF, also termed chronic IF (CIF), is a chronic condition in metabolically stable patients who require long-term home parenteral nutrition (HPN) for months to years.^1,2

Classification of CIF

The causes of CIF can be categorised in a number of ways, including the timing of presentation (congenital versus acquired), the pathophysiological mechanism (short bowel syndrome, intestinal fistula, intestinal dysmotility, mechanical obstruction, or extensive small bowel mucosal disease), or the underlying disease process (benign versus malignant conditions) .¹

Over the past 30‒40 years, the aetiology of CIF has shifted in the UK, with occurrence secondary to Crohn’s disease decreasing and that due to surgical complications rising.^3‒5 This change may reflect, at least in part, significant advancements in medical and surgical interventions for inflammatory bowel disease coupled with an increase in surgical complications occurring in older patients with more comorbidities. Furthermore, there has been an increase in CIF resultant from mechanical intestinal obstruction, which is frequently associated with malignant disease, and this is reflected in the increase in provision of HPN as part of palliative care.³

Complications of HPN

Whilst essential to maintaining life in those with CIF, HPN is associated with significant complications, including central venous catheter (CVC) complications (infection, thrombosis), IF-associated liver disease (IFALD), metabolic bone disease, renal disease, and psychological impact. The most life-threatening complications are discussed in the following sections.

CVC Associated Complications

Patients with CIF require a CVC for the safe administration of HPN, and CVC-related complications are a major source of morbidity and occasionally mortality.⁶ Exceptional CVC care should be a priority for all teams managing IF.

Catheter-Related Bloodstream Infections (CRBSI)

The European Society of Clinical Nutrition and Metabolism suggests that the incidence of CRBSI in HPN patients can be used as a care-quality indicator.⁷ The adoption of CRBSI prevention strategies is crucial in providing optimal care to HPN-dependent patients (Table 1).

The most important intervention is the provision of a dedicated CVC-care protocol, which should be adopted by patients and carers accessing the catheter. The British Intestinal Failure Alliance (BIFA) has provided guidance outlining key principles of catheter care to minimise the risk of CRBSI.⁸

Table 1: Risk factors for complications in patients on HPN and associated preventative strategies

Abbreviations: CRBSI, catheter related bloodstream infection; CVC, central venous catheter; HPN, home parenteral nutrition; PN, parenteral nutrition; IFALD, intestinal failure associated liver disease; SIBO, small intestinal bacterial overgrowth.

CRBSI should be suspected in patients presenting with fever and/or rigors shortly after commencing PN infusion.^6,9 However, these do not present in all patients, and other signs can include general malaise, raised bilirubin and/or inflammatory marker levels, and hypoalbuminaemia.^9,10 CRBSI diagnosis relies on testing of paired central and peripheral blood cultures using qualitative (differential time to positivity shown by organism growth from CVC hub >2 hours before growth from peripheral sample), and/or quantitative (pour plate assessment of microbial colony count form CVC hub ≥threefold that from peripheral sample) assessments.^6,11 In order to minimise the need for recurrent CVC changes risking loss of venous access, CVC salvage with appropriate systemic antimicrobials and antibiotic CVC locks should be attempted for most bacterial infections.¹² CVC removal is recommended if there is haemodynamic compromise or in the case of metastatic or fungal infections.^6,10,13 The CVC should not generally be used for parenteral support during salvage.¹⁰ CVC salvage should be confirmed by resolution of signs of infection as well as negative blood cultures collected 48 hours after completion of treatment.⁶

CVC Thrombosis

CVC thrombosis is a serious complication. It can result in progressive loss of venous access and, subsequently, the need to consider referral for small-bowel transplant. CVC thrombosis is most commonly associated with a poorly positioned CVC tip. However, recurrent CRBSIs can also contribute to thrombosis risk, as can mechanical damage caused by re-siting of CVCs which have not been successfully salvaged. Another contributory factor to CVC thrombosis is underlying susceptibility for thrombosis.¹⁴

Signs and symptoms of CVC thrombosis include swelling in the head, face and arms, a positional headache, distended jugular veins and venous collaterals over the chest wall. Treatment depends on chronicity and clinical presentation; in the acute setting, urgent imaging is required and targeted thrombolysis should be considered with input from the vascular radiology team. In the chronic setting, long-term anticoagulation may be required and venoplasty or venous stenting should be considered on an individualised basis following discussion with specialist vascular teams.¹⁴

IFALD

IFALD refers to liver injury related to IF and PN without another evident cause. It is a multifactorial condition with a range of risk factors associated with the individual patient (eg, recurrent CRBSI, shorter length of small bowel, colon not in continuity, small intestinal bacterial overgrowth, lack of oral/enteral nutrition) and their HPN requirements (eg, macronutrient excesses, continuous PN infusion).¹⁵

Deranged liver function tests are common in HPN patients, as are histological liver abnormalities; however, diagnostic criteria to allow classification and prognostication in IFALD are lacking.¹⁶ Furthermore, non-invasive tools for diagnosing and monitoring IFALD, such as transient elastography, lack evidence in CIF, and recent studies suggest the results may be unreliable.^15,17 ESPEN has recently recommended that IFALD should be diagnosed by the presence of abnormal liver function tests and/or evidence of radiological and/or histological liver abnormalities, in patients with IF in the absence of other primary parenchymal liver pathology, other hepatotoxic factors and biliary obstruction.¹⁸ The decision regarding whether to perform a liver biopsy ‒ the gold standard for diagnosis ‒ should be made on a case-by-case basis.

As the cause of IFALD is multifactorial, its management should be individualised and often requires multiple simultaneous approaches. In general terms, management can be divided into nutritional and non-nutritional strategies (Table 1).^15,19 Ultimately, patients with progressive liver fibrosis should be considered for early referral for isolated intestinal transplantation, which might lead to reversal of fibrosis.¹⁸ Clinicians are encouraged to consider performing a liver biopsy in patients at high risk of IFALD to allow for timely referral to the transplant team before progression to advanced fibrosis or cirrhosis, which could require a combined liver and intestinal transplant and has a worse prognosis.²⁰

HPN Monitoring

The care of patients with types 2 and 3 IF receiving HPN is best delivered by an expert multidisciplinary team (MDT) that includes physicians, surgeons, specialist nurses, dieticians, psychologists, and pharmacists. In England, integrated IF centres are being designated to care for the surgical and medical needs of patients with severe IF, and these will be linked to HPN centres within each region, in order to concentrate clinical expertise and achieve optimal outcomes.²¹ The centres will provide close monitoring of patients and regular review by an MDT. Such assessments should include a detailed history and examination to review aspects of fluid balance and nutritional status as well as other signs and symptoms related to underlying disease. A thorough dietetic review, including anthropometry, is essential. Required blood monitoring is outlined in Table 2.²² Clinical review must also consider assessment of IF-related complications, including metabolic bone disease assessed and monitored by means of a dual-energy X-ray absorptiometry scan. A study has demonstrated preferential outcomes, in terms of mortality, CRBSI rates and CVC thrombosis, for HPN patients managed in larger volume centres, indicating that centralised multidisciplinary care in specialised centres is beneficial for optimal outcomes.²³

Table 2: Recommended haematological and biochemical monitoring in clinically stable HPN patients

Abbreviations: U&E, urea and electrolytes. LFT, liver function tests.

Indications for Intestinal Transplant

Early isolated intestinal transplant should be considered in appropriate patients, as it can significantly improve outcomes compared with the use of multi-visceral grafts.²⁰ Referral should be considered in the following settings: risk of life-threatening complications of HPN (eg, progressive IFALD, recurrent severe CRBSI, impending loss of vascular access); parenteral support is inadequate (eg, extreme fluid losses, ultra-short bowel, significantly impaired quality of life); and need for other organ transplants that require intestines for anatomical or functional reasons. ²⁴ More information is available from the NHS Blood and Transplant Service.²⁵

Summary

CIF requires the provision of long term HPN which may be associated with significant complications. A holistic, MDT approach is required in order to optimise patient outcomes and minimise the risk of complications.

Abbreviations

IF, intestinal failure; CIF, chronic intestinal failure; HPN, home parenteral nutrition; CVC, central venous catheter; IFALD, intestinal failure associated liver disease; CRBSI, catheter related bloodstream infection; BIFA, British Intestinal Failure Alliance; SIBO, small intestinal bacterial overgrowth; ESPEN, The European Society of Nutrition and Metabolism; MDT, multidisciplinary team.

Author Biographies

Professor Simon Lal is a professor of gastroenterology at the University of Manchester and has been Clinical Lead of the Intestinal Failure Unit at Salford Royal, one of England’s two national reference centres, since 2012.

Dr Ben Crooks is a gastroenterology trainee in Manchester. He was awarded his MD from the University of Manchester in 2020 for his research in diet and inflammatory bowel disease. He has recently completed an advanced training fellowship in clinical nutrition in the Intestinal Failure Unit at Salford Royal and is now in his final year of specialty training.