Intestinal failure [IF], characterised by the inability to maintain adequate nutrition or fluid-electrolyte balance without parenteral support, often results in chronic visceral pain due to structural and functional gut abnormalities [8, 9]. Inflammatory changes, bacterial overgrowth and dysmotility contribute to nociceptive and neuropathic pain mechanisms [10, 11]. The reliance on parenteral nutrition introduces additional risks, including intravenous catheter infections, and intestinal failure associated liver disease, which exacerbate discomfort [9]. Opioids remain a cornerstone of analgesia management in IF but are fraught with challenges. Prolonged use is linked to opioid-induced hyperalgesia, dependency, and its potential to exacerbate gut dysmotility [10, 12, 13]. Oral opioid analgesics are often ineffective due to intestinal absorption challenges, necessitating intravenous, sublingual or transdermal routes [8, 10]. Addition of adjuvants such as gabapentin can address neuropathic components whilst minimising dependency, but circles back to lack of gut absorption through the oral route [14, 15]. Notably for our patient, gabapentin or pregabalin were not trialled due to concerns of gastrointestinal malabsorption; however parenteral clonidine was proven to be an effective analgesia adjunct.

Transdermal options such as buprenorphine and fentanyl patches are widely used for chronic visceral pain in IF. Buprenorphine’s partial μ-opioid agonism and κ-antagonism reduce constipation risk compared to full opioid agonists [16]. Transdermal drugs such as fentanyl and buprenorphine patches provide steady analgesia but require intact dermal perfusion, which may be compromised in malnourished and cachectic patients [17]. Sublingual buprenorphine and fentanyl avoid intestinal absorption issues in IF patients, and avoid inconsistent absorption from jejunostomies or ileostomies, providing rapid relief during acute pain flares [16, 17]. However, limitations include worsening of ileus and motility disorders (especially in patients with short gut syndrome), bacterial overgrowth, opioid dependency and regulatory restrictions in Australia on opioid naïve patients, particularly with fentanyl [10, 16, 17]. Furthermore, 30% of patients develop erythema and pruritus at the application sites for transdermal formulations, which complicates long term use [16, 17]. Recent advancements in pain relief for IF patients include teduglutide, a glucagon-like peptide-2 [GLP-2] analogue that enhances intestinal adaptation by increasing villus height and crypt depth, and reduces abdominal pain by mitigating mucosal inflammation [18]; eluxadoline, a peripherally acting μ-opioid agonist/δ-antagonist that reduces visceral hypersensitivity in diarrhea-predominant conditions [15]; and low dose transdermal clonidine which reduces colonic hypermotility and visceral pain via α2-adrenergic modulation [19]. However, high costs, accessibility barriers and risk of biliary complications prevent from mainstream use.

Intervention strategies such as coeliac plexus neurolysis and splanchnic nerve blocks have been considered for specific patient populations. Coeliac plexus neurolysis targets sympathetic nerves innervating the upper abdominal viscera. In IF patients with chronic pancreatitis or radiation enteritis as the predominant feature of their abdominal pain, coeliac plexus blocks reduced pain scores by 50–70% for three to six months [20]. Similarly, by targeting splanchnic nerves near the T11 – T12 vertebrae, this block is preferred for patients with retroperitoneal fibrosis or extensive abdominal adhesions [21]. Although not extensively studied, long term epidural or intrathecal blocks and other implanted neuraxial devices are generally considered unsuitable for managing pain related to IF. This is due to the higher risk of autonomic instability, potential motor blockade which could exacerbate muscle atrophy in malnourished patients and, and higher rates of catheter-related infections due to their immunocompromised status [22]. Non-pharmacological interventions, such as cognitive-behavioural therapy and acupuncture are underutilised despite evidence supporting their role in reducing opioid reliance [23, 24].

Given our patient’s complex needs, multidisciplinary coordination amongst specialties, including gastroenterology, surgery, APS, CPS and palliative care was required. Multiple studies demonstrate that multidisciplinary teams significantly improve pain control and quality of life in cancer patients. A prospective study conducted in China of 92 cancer inpatients found that individualised interventions by an interprofessional team consisting of surgeons, interventional radiologists, palliative care physicians, pain physicians, psychologists, nutritionists and nurses led to a reduced pain burden and pain scores, for patients receiving concurrent chemotherapy [25]. Notably, an Australian mixed-methods observational study demonstrated that patients participating in a chronic pain program with structured phone follow-up experienced a 44% reduction in annual hospitalisations, highlighting the critical role of continuity of care [26].

Collaboration between palliative care and pain medicine specialists is most effective when embedded within joint clinical frameworks. A survey of palliative care physicians found that institutions with dedicated collaboration systems and regular case conferences reported 2.5 times higher referral rates to pain medicine specialists, and co-managed 37% of cancer pain cases compared to 6% in less collaborative environments [27]. Despite physicians acknowledging the importance of their respective role in patients’ care, key barriers to referrals in non-collaborative systems include role ambiguity, lack of funding for interdisciplinary time (which in turn disincentivises collaboration) and insufficient time for intricate discussions [28,29,30]. Successful collaborative palliative care service models include a combination of hospital-based consult teams and community-based palliative care. Inpatient palliative care teams reduce intensive care unit admissions by 25% through early symptom management and discharge planning, whereas community palliative care programs reduce hospitalisation rates by almost 40% [31, 32]. A more collaborative interdisciplinary care coordination with the in-patient and community service models might have helped avoid our patient’s unsuccessful discharge to the community and the limited time spent there before her final admission, which ultimately led to her demise. Notably she was not linked to any rare disease communities such as “Rare Voices”, which, through their capacity building and authentic engagement, recognise shared healthcare experiences of rare diseases and offer practical examples to address patient and family needs [33].

Non-cancer conditions such as chronic obstructive pulmonary disease [COPD], end-stage congestive cardiac failure and dementia account for 60% of people with palliative care needs, but only 14% of specialist palliative care referrals [34, 35]. Prognostic uncertainty, compounded by variable disease trajectories, causes delays in referrals, as clinicians hesitate to label patients as “palliative” [35, 36]. This is exemplified in this case, where the patient and her family were in-denial of her life-limiting disease, given the rarity of gastrointestinal hypoganglionosis, and its limited data on long-term outcomes [5]. Tools like the surprise question ("Would I be surprised if this patient died in the next year?") and the Supportive and Palliative Care Indicators Tool [SPICT] improve identification but lack sensitivity in early-stage illness [32, 36]. Early palliative care integration, concurrent with disease-modifying treatments, enhances quality of life. For example, COPD patients receiving earlier palliative care report 30% fewer hospitalisations and improved dyspnoea management, via prioritising the relief of burdensome symptoms such as dyspnoea, fatigue and pain over prognosis [36, 37]. Strategies involving early goals of care discussions and facilitating early advance care planning reduces intensive care unit admissions by 50% in geriatric populations with advanced heart failure [38]. The “Bowtie model”, as described by Hawley in 2014, presents an integrative framework that combines palliative care with chronic disease management from the point of diagnosis in patients with serious illnesses [39]. This approach aims to facilitate earlier acceptance of palliative care, irrespective of the prognosis or severity of the diagnosis. Embracing uncertainty and adopting early integration of palliative care principles at the onset of diagnosis may have yielded a different and more comfortable outcome for the patient and her family.

There are a few limitations in this case report. Methadone was not trialled as an option due to the patient’s non-compliance with chronic pain outpatient services and medication non-adherence. Recognised for its transmucosal and oral absorption characteristics as well as its NMDA receptor antagonism, methadone may be useful for patients with intestinal failure and for reducing opioid tolerance in those that require long term opioid therapy with an uncertain life expectancy [40,41,42]. Additionally, the intravenous ketamine dosing did not follow standard protocols described in the literature; however, this compromise was intentionally done to prioritise patient safety [43].