Factors associated with strong opioid use for noncancer pain in patients with chronic intestinal failure.

BACKGROUND: Chronic analgesic use is described in home parenteral nutrition (HPN)-dependent patients, but there are limited data on factors associated with opioid use for noncancerous pain. METHODS: Patients attending a national UK intestinal failure reference center were divided in two groups according to strong opioid (SO) usage; risk factors for SO usage were analyzed using logistic regression. RESULTS: A total of 168 HPN-dependent patients were included. During the study period, 73 patients (43.5%) had documented SO usage (SO group), whereas the remainder did not (No-SO group). The prevalence of Crohn's disease among the No-SO group was twofold higher than among the SO group (43.2% vs 24.7%; P = 0.013), whereas those with surgical complications were twice as prevalent among the SO group (19.2% vs 8.4%, respectively; P = 0.04). The rate of working-age unemployment was significantly higher in the SO group (90.6%) than the No-SO group (55.6%; P = 0.001). Multivariate regression showed unemployment as an independent risk factor for SO usage (OR, 6.005; 95% CI, 1.435-25.134), whereas Crohn's disease (OR, 0.284; 95% CI, 0.09-0.898) and <4 intravenous support (IVS) nights per week (OR, 0.113; 95% CI, 0.012-1.009) were protective factors. The life-long incidence of catheter-related bloodstream infection (CRBSI) was comparable between groups (34.2% SO vs 27.4% No-SO; P = 0.336). CONCLUSION: SO use is frequent among HPN-dependent patients and associated with high rates of unemployment and ≥4 IVS nights per week, but not with increased rate of CRBSI. The reduced usage among patients with Crohn's disease warrants further evaluation but might be due to the chronicity as compared with other IF etiologies.

Standardised survival and excess Life Years Lost in patients with type 3 intestinal failure.

BACKGROUND & AIMS: Long term outcomes have been reported in home parenteral nutrition (HPN)-dependent patients with type 3 intestinal failure (IF), but there are limited survival data standardised to the general population that would help provide a meaningful prognosis for patients and clinicians. The primary aim of this study was therefore to investigate the survival of HPN-dependent patients and to evaluate the specific impact of type 3 IF on their life expectancy standardised to that of the general population. METHODS: This was a cohort study of adult patients initiated on HPN between 1978 and 2018 at a national UK IF reference centre and followed up until death or censoring date of 31st December 2020. The standardised mortality ratio (SMR) was calculated as observed deaths divided by expected deaths using UK Office for National Statistics database. Excess Life Years Lost (LYL) were calculated separately for each sex as the differences in average life expectancy between patients with type 3 IF and the general population. Survival data were evaluated using cox regression models adjusting for confounding. RESULTS: In total, 1046 patients were identified, with a total observation time of 7344.1 patient-years. Patients with malignancy (n = 206) were excluded from the survival analysis. Of the remaining 840 patients, 398 were alive by the end of follow-up. The probability of survival was 91.8% at 1 year, 69.3% at 5 years, 54.3% at 10 years, 29.8% at 20 years and 16.7% at 30 years. Patients who did not achieve nutritional autonomy had an increased likelihood of death compared to patients who ceased HPN. In total, 40 (9.0%) deaths were HPN or IF-related, while underlying disease leading to IF accounted for 98 (22.2%) deaths. There were 270 (61.1%) deaths not related to IF, with the majority of these patients dying from infections unrelated to HPN. Overall mortality rates were higher among patients with a diagnosis of type 3 IF compared with the general UK population with a SMR of 7.48 (95% CI 6.80 to 8.21) and an excess mortality rate of 54.0 per 1000 person-years. All mechanisms of IF were associated with excess mortality, with SMR ranging from 6.82 (95% CI 5.98 to 7.72) for short bowel syndrome to 15.51 (95% CI 11.73 to 20.03) for dysmotility. On average, the excess LYL was 17.45 years for males and 17.39 years for females compared with the general population of the same age. CONCLUSION: This the largest single-centre series reporting survival outcomes in patients with type 3 IF over more than a four-decade period and the first to report LYL in this patient cohort. Type 3 IF was associated with more than seven-fold higher mortality rates than for the general UK population and shorter life expectancies of more than 17 years. Survival, however, was better in those able to achieve nutritional autonomy. Since the majority of deaths were due to non-HPN or non-IF causes, there is clearly a need now to further explore these causes of death in order to improve our understanding of excessive mortality in type 3 IF and develop ways to prevent it.

Home Parenteral Nutrition in Patients with Advanced Cancer: Quality Outcomes from a Centralized Model of Care Delivery.

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010-2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area. A total of 126 patients were included, with a median distance between the patient's home and the IF center of 17.5 km (IQR 10.9-39.1; maximum 317.4 km). A total of 28 (22%) patients experienced at least one HPN-related complication, the most common being a central venous catheter (CVC) occlusion and electrolyte abnormalities. The catheter-related bloodstream infection (CRBSI) rate was 0.49/1000 catheter days. The CVC type, administration of concomitant chemotherapy via a distinct CVC lumen separate from PN, venting gastrostomy and distance between the patient's home and the IF center were not associated with CRBSI or mechanical CVC complications. A total of 82 (65.1%) patients were readmitted while on HPN, but only 7 (8.5%) of these readmissions were HPN-related. A total of 44 (34.9%) patients died at home, 41 (32.5%) at a hospice and 41 (32.5%) in a hospital. In conclusion, this study demonstrates that a centralized approach to IF care can provide HPN to patients over a large geographical area while maintaining low HPN-related complications that are comparable to patients requiring HPN for benign conditions and low hospital readmission rates.

Long-Term Outcomes in Patients with Intestinal Failure Due to Short Bowel Syndrome and Intestinal Fistula.

Short bowel syndrome (SBS) and enterocutaneous or enteroatmospheric fistulas are common indications for home parenteral nutrition (HPN). However, there are few data describing factors influencing surgical decision-making or outcomes particularly following fistula development. We aimed to compare outcomes between patients with SBS and fistulas and explore surgical decision-making. HPN-dependent adults from 2001−2018 at a national reference centre were included in this study. HPN cessation was analysed using death as competing risk. In total, 465 patients (SBS (62%), fistula (38%)) were included, with median HPN dependency of 2.6 years. In total, 203 patients underwent reconstructive surgery; while frailty was the commonest reason for not undergoing surgery (49.2%), 22.7% declined surgery. Overall, 170 ceased HPN, with a probability of 13.8%, 34.1% and 38.3% at 1, 5 and 10 years, respectively. Patients undergoing surgery had higher nutritional autonomy rates (109.8 incidences/1000 patient years) compared to those not undergoing surgery (18.1 incidences/1000 patient years; p < 0.001). A total of 295 patients (63.4%) were predicted to cease HPN based on gastrointestinal anatomy but only 162/295 (54.9%) achieved this; those unable to do so were older with a higher comorbidity index. There were no differences in long-term nutritional and survival outcomes or surgical decisions between patients with SBS and fistulas, or between enterocutaneous and enteroatmospheric fistulas. This study represents one of the largest datasets describing the ability of HPN-dependent patients with SBS or fistulas to achieve nutritional autonomy. While reconstructive surgery facilitates HPN cessation, approximately one-fifth of patients declined surgery despite HPN dependency. These data will better inform patient expectation and help plan alternative therapies.

Factors affecting antidepressant use by patients requiring home parenteral nutrition.

BACKGROUND: Home parenteral nutrition (HPN) is a life-saving therapy for patients with chronic intestinal failure but can be associated with a degree of psychological distress. The factors associated with the need for antidepressants (ADs) in this cohort have not yet been described. METHODS: The study involved prospective data collection from patients attending an HPN clinic at a national intestinal failure referral center. Patients requiring HPN as a result of active malignancy were excluded. Patients were divided in 2 groups according to AD usage; demographic, anthropometric, socioeconomic characteristics, and intravenous supplementation (IVS) regimens were compared between groups. RESULTS: A total of 184 patients were recruited between July 2018 and April 2019, with an overall prevalence of AD use of 41.7% (70/168 patients). Daily mean IVS volume was significantly higher among patients taking AD ("AD" group; 2125.48 ± 991.8 ml/day, "no-AD" group; 1828.54 ± 847.0 ml/day, P = .039), with the proportion of patients needing high-volume IVS (≥3000 ml/day) being 3 times higher in the AD group (20.0%(14/70 patients) vs 6.1% (6/98 patients), P = .006). The average energy IVS infusion per day was similar between the groups. CONCLUSION: This is the first study to demonstrate that AD use correlates with higher IVS volume rather than energy requirements in HPN patients, suggesting that high IVS volume requirements may be better associated with the patient's disease burden. Early and tailored mental health intervention may be beneficial in those with high IVS volume requirements.

Causes and Prognosis of Intestinal Failure in Crohn's Disease: An 18-year Experience From a National Centre.

BACKGROUND AND AIMS: Intestinal failure [IF] is a feared complication of Crohn's disease [CD]. Although cumulative loss of small bowel due to bowel resections is thought to be the dominant cause, the causes and outcomes have not been reported. METHODS: Consecutive adult patients referred to a national intestinal failure unit over 2000-2018 with a diagnosis of CD, and subsequently treated with parenteral nutrition during at least 12 months, were included in this longitudinal cohort study. Data were extracted from a prospective institutional clinical database and patient records. RESULTS: A total of 121 patients were included. Of these, 62 [51%] of patients developed IF as a consequence of abdominal sepsis complicating abdominal surgery; small bowel resection, primary disease activity, and proximal stoma were less common causes [31%, 12%, and 6%, respectively]. Further, 32 had perianastomotic sepsis, and 15 of those had documented risk factors for anastomotic dehiscence. On Kaplan-Meier analysis, 40% of all patients regained nutritional autonomy within 10 years and none did subsequently; 14% of patients developed intestinal failure-associated liver disease. On Kaplan-Meier analysis, projected mean age of death was 74 years.2. CONCLUSIONS: IF is a severe complication of CD, with 60% of patients permanently dependent on parenteral nutrition. The most frequent event leading directly to IF was a septic complication following abdominal surgery, in many cases following intestinal anastomosis in the presence of significant risk factors for anastomotic dehiscence. A reduced need for abdominal surgery, an increased awareness of perioperative risk factors, and structured pre-operative optimisation may reduce the incidence of IF in CD.

Discharging Women with Advanced Ovarian Cancer on Home Parenteral Nutrition: Making and Implementing the Decision.

Increasingly, patients with advanced ovarian cancer in bowel obstruction are receiving home parenteral nutrition (HPN). Little is known about making and implementing the decision. This study explored the decision-making process for HPN and investigated the barriers and facilitators to implementation. This was a qualitative study underpinned by phenomenology involving 93 longitudinal in-depth interviews with 20 patients, their relatives and healthcare professionals, over 15 months. Participants were interviewed a maximum of four times. Interview transcripts were analysed thematically as per the techniques of Van Manen. We found variance between oncologists and patients regarding ownership of the HPN decision. The oncologists believed they were engaging in a shared decision-making process. However, patients felt that the decision was oncologist-driven. Nevertheless, they were content to have the treatment, when viewing the choice as either HPN or death. In implementing the decision, the principal mutable barrier to a timely discharge was communication difficulties across professional disciplines and organisations. Facilitators included developing a single point-of-contact between organisations, improving communication and implementing standardised processes. Oncologists and patients differ in their perceptions of how treatment decisions are made. Although patients are satisfied with the process, it might be beneficial for healthcare professionals to check patients' understanding of treatment.

Palliative home parenteral nutrition in patients with ovarian cancer and malignant bowel obstruction: experiences of women and family caregivers.

BACKGROUND: Malnutrition is a problem in advanced cancer, particularly ovarian cancer where malignant bowel obstruction (MBO) is a frequent complication. Parenteral nutrition is the only way these patients can received adequate nutrition and is a principal indication for palliative home parenteral nutrition (HPN). Giving HPN is contentious as it may increase the burden on patients. This study investigates patients' and family caregivers' experiences of HPN, alongside nutritional status and survival in patients with ovarian cancer and MBO. METHODS: This mixed methods study collected data on participant characteristics, clinical details and body composition using computed tomography (CT) combined with longitudinal in-depth interviews underpinned by phenomenological principles. The cohort comprised 38 women with ovarian cancer and inoperable MBO admitted (10/2016 to 12/ 2017) to a tertiary referral hospital. Longitudinal interviews (n = 57) were carried out with 20 women considered for HPN and 13 of their family caregivers. RESULTS: Of the 38 women, 32 received parenteral nutrition (PN) in hospital and 17 were discharged on HPN. Nutritional status was poor with 31 of 33 women who had a CT scan having low muscle mass, although 10 were obese. Median overall survival from admission with MBO for all 38 women was 70 days (range 8-506) and for those 17 on HPN was 156 days (range 46-506). Women experienced HPN as one facet of their illness, but viewed it as a "lifeline" that allowed them to live outside hospital. Nevertheless, HPN treatment came with losses including erosion of normality through an impact on activities of daily living and dealing with the bureaucracy surrounding the process. Family caregivers coped but were often left in an emotionally vulnerable state. CONCLUSIONS: Women and family caregivers reported that the inconvenience and disruption caused by HPN was worth the extended time they had at home.

Home parenteral nutrition for people with inoperable malignant bowel obstruction.

BACKGROUND: People with advanced ovarian or gastrointestinal cancer may develop malignant bowel obstruction (MBO). They are able to tolerate limited, if any, oral or enteral (via a tube directly into the gut) nutrition. Parenteral nutrition (PN) is the provision of macronutrients, micronutrients, electrolytes and fluid infused as an intravenous solution and provides a method for these people to receive nutrients. There are clinical and ethical arguments for and against the administration of PN to people receiving palliative care. OBJECTIVES: To assess the effectiveness of home parenteral nutrition (HPN) in improving survival and quality of life in people with inoperable MBO. SEARCH METHODS: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE (Ovid), Embase (Ovid), BNI, CINAHL, Web of Science and NHS Economic Evaluation and Health Technology Assessment up to January 2018, ClinicalTrials.gov (http://clinicaltrials.gov/) and in the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/). In addition, we handsearched included studies and used the 'Similar articles' feature on PubMed for included articles. SELECTION CRITERIA: We included any studies with more than five participants investigating HPN in people over 16 years of age with inoperable MBO. DATA COLLECTION AND ANALYSIS: We extracted the data and assessed risk of bias for each study. We entered data into Review Manager 5 and used GRADEpro to assess the quality of the evidence. MAIN RESULTS: We included 13 studies with a total of 721 participants in the review. The studies were observational, 12 studies had only one relevant treatment arm and no control and for the one study with a control arm, very few details were given. The risk of bias was high and the certainty of evidence was graded as very low for all outcomes. Due to heterogeneity of data, meta-analysis was not performed and therefore the data were synthesised via a narrative summary.The evidence for benefit derived from PN was very low for survival and quality of life. All the studies measured overall survival and 636 (88%) of participants were deceased at the end of the study. However there were varying definitions of overall survival that yielded median survival intervals between 15 to 155 days (range three to 1278 days). Three studies used validated measures of quality of life. The results from assessment of quality of life were equivocal; one study reported improvements up until three months and two studies reported approximately similar numbers of participants with improvements and deterioration. Different quality of life scales were used in each of the studies and quality of life was measured at different time points. Due to the very low certainty of the evidence, we are very uncertain about the adverse events related to PN use. Adverse events were measured by nine studies and data for individual participants could be extracted from eight studies. This revealed that 32 of 260 (12%) patients developed a central venous catheter infection or were hospitalised because of complications related to PN. AUTHORS' CONCLUSIONS: We are very uncertain whether HPN improves survival or quality of life in people with MBO as the certainty of evidence was very low for both outcomes. As the evidence base is limited and at high risk of bias, further higher-quality prospective studies are required.

Survival and nutritional dependence on home parenteral nutrition: Three decades of experience from a single referral centre.

BACKGROUND: Home parenteral nutrition (HPN) is the mainstay of treatment for patients with Type 3 intestinal failure (IF), however long term data on mortality and nutritional outcomes are limited. OBJECTIVES: To assess the long-term survival and requirements for ongoing HPN in patients receiving treatment at a UK national referral centre for intestinal failure. METHODS: Patients with IF who received HPN for more than 3 months at this Intestinal Failure Unit between 1978 and 2011 had their clinical records reviewed. SPSS 20 was utilised to perform Cox regression analysis and generate Kaplan Meier curves, with the aim of identifying factors associated with death and the continued need for HPN. RESULTS: Case notes from 545 patients were reviewed. Overall survival (OS) in patients without malignancy at commencement of IF was 93%, 71%, 59% and 28% at 1, 5, 10 and 20 years after starting treatment. Crohn's disease, mesenteric ischaemia and chronic intestinal pseudo-obstruction were associated with a better OS than scleroderma and radiation enteritis on multivariate analysis. Older age at onset of IF was associated with poor OS, while shorter small bowel length or central line sepsis was not. 15% (25/170) of deaths were due to complications of HPN (central line sepsis = 10, IF-associated liver disease = 15). Continued HPN dependence in survivors was 83%, 63%, 59% and 53% at 1, 5, 10 and 15 years, respectively. Among the 153 patients without malignancy who achieved nutritional independence from HPN, 77 (50.3%) did so after surgical reconstruction of the alimentary tract (HPN duration mean 19 months, range 3-126 months). 76 patients (49.7%) weaned from HPN without undergoing surgical reconstruction. CONCLUSION: This is the largest reported data set on long-term survival and dependence on HPN and will inform the indications, benefits and risks of treatment in disease specific groups. A significant proportion of patients achieved nutritional autonomy without surgical intervention.

Central Venous Catheter Salvage in Home Parenteral Nutrition Catheter-Related Bloodstream Infections: Long-Term Safety and Efficacy Data.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are a serious complication in the provision of home parenteral nutrition (HPN). Antibiotic salvage of central venous catheters (CVCs) in CRBSI is recommended; however, this is based on limited reports. We assessed the efficacy of antibiotic salvage of CRBSIs in HPN patients. MATERIALS AND METHODS: All confirmed CRBSIs occurring in patients receiving HPN in a national intestinal failure unit (IFU), between 1993 and 2011, were analyzed. A standardized protocol involving antibiotic and urokinase CVC locks and systemic antibiotics was used. RESULTS: In total, 588 patients were identified with a total of 2134 HPN years, and 297 CRBSIs occurred in 137 patients (65 single and 72 multiple CRBSIs). The overall rate of CRBSI in all patients was 0.38 per 1000 catheter days. Most (87.9%) infections were attributable to a single microorganism. In total, 72.5% (180/248) of CRBSIs were salvaged when attempted (coagulase-negative staphylococcus, 79.8% [103/129], Staphylococcus aureus, 56.7% [17/30]; polymicrobial infections, 67.7% [21/30]; and miscellaneous, 66.1% [39/59]). CVC salvage was not attempted in 49 episodes because of life-threatening sepsis (n = 18), fungal infection (n = 7), catheter problems (n = 20), and CVC tunnel infection (n = 4). Overall, the CVC was removed in 33.7% (100/297) of cases. There were 5 deaths in patients admitted to the IFU for management of the CRBSI (2 severe sepsis at presentation, 3 metastatic infection). CONCLUSIONS: This is the largest reported series of catheter salvage in CRBSIs and demonstrates successful catheter salvage in most cases when using a standardized protocol.

Outcome of reconstructive surgery for intestinal fistula in the open abdomen.

OBJECTIVE: To determine factors which influence the outcome of surgical techniques to close enterocutaneous fistulas within the open abdomen. SUMMARY BACKGROUND DATA: Enterocutaneous fistulation within an open abdominal wound is associated with considerable morbidity and mortality. The factors that influence the outcome of reconstructive surgery are unclear. METHODS: Sixty-one patients undergoing 63 operations to close enterocutaneous fistulas associated with open abdominal wounds were referred to a national center for further management. Once sepsis had been eradicated, nutritional status restored and local conditions in the abdomen judged to be suitable, fistulas were resected and the abdominal wall reconstructed by suture repair with and without component separation, or by suture repair in combination with absorbable or nonabsorbable prosthetic mesh. Patients were followed up for 16 to 84 months postoperatively. RESULTS: There were 3 postoperative deaths (4.8%). Major complications, including postoperative respiratory and surgical site infection occurred in 52 of 63 (82.5%) procedures. Refistulation occurred in 7 cases (11.1%) but was more common when the abdominal wall was reconstructed with prosthetic mesh (7 of 29, 24.1%) than with sutures (0 of 34, 0%). Porcine collagen mesh was associated with a particularly high rate of refistulation (5 of 12, 41.7%). CONCLUSIONS: Simultaneous reconstruction of the intestinal tract and abdominal wall remains associated with a high complication rate, justifying the management of such patients in specialized units. Simultaneous reconstruction of the abdominal wall with prosthetic mesh is associated with a particularly high incidence of recurrent postoperative fistulation and should be avoided if possible.