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Cost and Quality of Life After Intestinal Transplantation

2006; Elsevier BV; Volume: 130; Issue: 2 Linguagem: Inglês

10.1053/j.gastro.2005.09.066

1528-0012

Debra L. Sudan,

Enhanced Recovery After Surgery

Intestinal transplantation has become a standard treatment for intestinal failure in patients with life-threatening complications of TPN. Although the long-term survival of patients with continued parenteral nutrition is higher than after intestinal transplantation, the 1 and 2 year survival is comparable. Here we examine other aspects of the treatment options available for patients with intestinal failure including the cost of the therapy and the quality of life. The cost of parenteral nutrition compared to intestinal transplantation reveals that transplantation is cost-effective in patients that maintain graft function within 1 to 3 years after surgery. The quality of life after transplantation is probably equal to or better than quality of life on TPN and children report quality of life similar to normal school children. Although currently reserved for those with life-threatening complications, intestinal transplantation may soon be an option for any patient permanently dependent on parenteral nutrition. Intestinal transplantation has become a standard treatment for intestinal failure in patients with life-threatening complications of TPN. Although the long-term survival of patients with continued parenteral nutrition is higher than after intestinal transplantation, the 1 and 2 year survival is comparable. Here we examine other aspects of the treatment options available for patients with intestinal failure including the cost of the therapy and the quality of life. The cost of parenteral nutrition compared to intestinal transplantation reveals that transplantation is cost-effective in patients that maintain graft function within 1 to 3 years after surgery. The quality of life after transplantation is probably equal to or better than quality of life on TPN and children report quality of life similar to normal school children. Although currently reserved for those with life-threatening complications, intestinal transplantation may soon be an option for any patient permanently dependent on parenteral nutrition. Intestinal transplantation has become a standard therapy for patients with life-threatening complications of parenteral nutrition (PN). 1Kaufman S.S. Atkinson J.B. Bianchi A. et al.Indications for pediatric intestinal transplantation a position paper of the American Society of Transplantation.Pediatr Transplant. 2001; 5: 80-87Crossref PubMed Scopus (293) Google Scholar Results appear to be improving over time, leading some to advocate for intestinal transplantation for quality-of-life indications, similar to kidney transplantation. Two studies have shown short-term (1-year) patient survival after isolated intestinal transplantation to be 92% and 88%, respectively, which is similar to survival on PN. 2Sudan D.L. Kaufman S.S. Shaw Jr., B.W. et al.Isolated intestinal transplantation for intestinal failure.Am J Gastroenterol. 2000; 95: 1506-1515Crossref PubMed Google Scholar, 3Fishbein T.M. Kaufman S.S. Florman S.S. et al.Isolated intestinal transplantation proof of clinical efficacy.Transplantation. 2003; 76: 636-640Crossref PubMed Scopus (121) Google Scholar Long-term survival after intestinal transplantation, however, is currently not as good as survival on PN. The International Intestinal Transplant Registry reports that 5-year patient survival is only 50% after intestinal transplantation, compared with 60%–80% 5-year survival on PN. 4Grant D. Intestinal transplantation 1997 report of the international registry.Transplantation. 1999; 67: 1061-1064Crossref PubMed Scopus (304) Google Scholar, 5Messing B. Lemann M. Landais P. et al.Prognosis of patients with nonmalignant chronic intestinal failure receiving long-term home parenteral nutrition.Gastroenterology. 1995; 108: 1005-1010Abstract Full Text PDF PubMed Scopus (211) Google Scholar, 6Howard L. Ament M. Fleming C.R. et al.Current use and clinical outcome of home parenteral and enteral nutrition therapies in the United States.Gastroenterology. 1995; 109: 355-365Abstract Full Text PDF PubMed Scopus (453) Google Scholar, 7Vantini I. Benini L. Bonfante F. et al.Survival rate and prognostic factors in patients with intestinal failure.Dig Liver Dis. 2004; 36: 46-55Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar Current recommendations, therefore, reserve intestinal transplantation for those with life-threatening complications of PN. It is likely that patient survival (both short- and long-term) will continue to improve as has been seen in other solid organ allografts. As outcomes improve after intestinal transplantation, we must begin to examine and compare other factors beyond patient survival, including cost and quality of life relative to continuation of PN. PN is expensive, ranging from $75,000 to $150,000 per year, excluding the costs of home nursing support, equipment, and materials and may be 20% higher in the first year than subsequent years. 8Reddy P. Malone M. Cost and outcome analysis of home parenteral and enteral nutrition.JPEN J Parenter Enteral Nutr. 1998; 22: 302-310Crossref PubMed Scopus (92) Google Scholar, 9Schalamon J. Mayr J.M. Hollwarth M.E. Mortality and economics in short bowel syndrome.Best Pract Res Clin Gastroenterol. 2003; 17: 931-942Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar In addition, patients require rehospitalization 0.5 to 1.0 times/year at a cost ranging from $0 to $140,000/year for hospitalization and treatment of PN-related complications. 8Reddy P. Malone M. Cost and outcome analysis of home parenteral and enteral nutrition.JPEN J Parenter Enteral Nutr. 1998; 22: 302-310Crossref PubMed Scopus (92) Google Scholar Considerable cost savings are seen in patients with short bowel syndrome who are able to wean from TPN, but weaning is unlikely if patients are TPN dependent for more than 2 years. 7Vantini I. Benini L. Bonfante F. et al.Survival rate and prognostic factors in patients with intestinal failure.Dig Liver Dis. 2004; 36: 46-55Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar, 8Reddy P. Malone M. Cost and outcome analysis of home parenteral and enteral nutrition.JPEN J Parenter Enteral Nutr. 1998; 22: 302-310Crossref PubMed Scopus (92) Google Scholar Ironically, despite the considerably lower cost of enteral nutrition, the patients who are able to wean from TPN may have difficulty obtaining insurance coverage for the tube-feeding supplements they require to avoid PN. The only other therapeutic alternative to parenteral or enteral nutrition therapy in patients with intestinal failure is intestinal transplantation. The cost of intestinal transplantation is highest in the first year after transplantation, primarily as a result of the high costs surrounding surgery and in-hospital costs during perioperative recovery. A discussion of cost must emphasize the difference between charges and actual costs. Hospital charges are based on multiple formulas and vary by hospital. Actual costs on the other hand are difficult to determine and are estimated by each center based on services required, days of hospitalization, and cost of overhead, such as salaries for nursing and other personnel. The 2001 report from the International Intestinal Transplant Registry reveals that the mean length of the initial hospitalization after intestinal transplantation is in the range of 60–84 days (http://www.intestinaltransplant.org/). Because the cost of the initial hospitalization differs depending on the length of stay, those recipients with the shortest duration of initial hospitalization (ie, isolated intestinal transplant recipients) have a lower cost. At the University of Nebraska, the average length of hospitalization for those included in Table 1 is approximately 15%–20% shorter than the International Intestinal Transplant Registry published results. The estimated cost for the initial hospitalization after intestinal transplantation is summarized in Table 1 and ranges from $130,000 to $250,000 depending on the type of allograft. 10Abu-Elmagd K.M. Reyes J. Fung J.J. et al.Evolution of clinical intestinal transplantation improved outcome and cost effectiveness.Transplant Proc. 1999; 31: 582-584Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Although it is not clear whether the methods for estimating the costs were the same from these 2 institutions, and inflation has altered the value of the dollar over this time frame, it would appear that there has not been a dramatic change in the cost of intestinal transplantation over the past 5 years.Table 1Summary of the Average Cost of the Initial Hospitalization for Intestinal TransplantationType of allograftPublished cost of intestinal transplant procedures at the University of Pittsburgh 10Abu-Elmagd K.M. Reyes J. Fung J.J. et al.Evolution of clinical intestinal transplantation improved outcome and cost effectiveness.Transplant Proc. 1999; 31: 582-584Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar 1994–1998Cost of intestinal transplantation at the University of Nebraska Medical Center (2002–2003)Isolated intestine$132,285$135,000Liver/small bowel$214,716$207,000Multivisceral$219,098N/A Open table in a new tab Other contributions to the overall cost of intestinal transplantation are much more difficult to evaluate because of the lack of published data but should include the costs of hospital readmission after transplantation and the cost of immunosuppressive or other medications. Anderson and Horslen examined the incidence and duration of rehospitalization after intestinal transplantation and found that, although hospital readmission is still common in the second year after intestinal transplantation (on average 4 episodes per patient; average duration 8 days), both the incidence and the duration of rehospitalizations decrease over subsequent years (on average 2 episodes per patient; average duration 6 days in the third and fourth years after transplantation). 11Andersen D.A. Horslen S. An analysis of the long-term complications of intestinal transplant patients.Progr Transplant. 2004; 14: 277-282PubMed Google Scholar Table 2 summarizes the reasons for readmission to the hospital after intestinal transplantation. A crude estimate of the costs of rehospitalization for intestinal transplant recipients (based on a published per diem rate for hospitalization in pediatric patients with asthma, ie, $816/day of hospitalization) 12Stanford R. McLaughlin T. Okamoto L.J. The cost of asthma in the emergency department and hospital.Am J Respir Crit Care Med. 1999; 160: 211-215Crossref PubMed Scopus (111) Google Scholar suggests that yearly rehospitalization costs may average approximately $9792–23,500/year. In addition, immunosuppressive medications are required lifelong to prevent allograft rejection in virtually all recipients of solid organ grafts. Although no published estimates of the costs of these medications after intestinal transplantation are identified, it is likely that the cost is similar to what others have estimated ($12,000 per year) after renal transplantation. 13Woodward R.S. Schnitzler M.A. Lowell J.A. et al.Effect of extended coverage of immunosuppressive medications by Medicare on the survival of cadaveric renal transplants.Am J Transplant. 2001; 1: 69-73Crossref PubMed Scopus (53) Google Scholar It would seem therefore that, despite the persistent need for rehospitalization and the requirement for long-term administration of fairly expensive medications, intestinal transplantation is cost-effective therapy for the treatment of intestinal failure in those patients who maintain graft function.Table 2A Summary of the Incidence (Average Number of Admissions per Patient at Risk) and Reasons for Hospital Readmission After Intestinal Transplantation Relative to Length of Time After TransplantationYear after transplantationSecond (n = 76)Third (n = 56)Fourth (n = 43)≥Fifth (n = 32)Reasons for readmission Infection1.60.70.70.9 Gastrointestinal Complications0.70.60.70.9 Dehydration0.50.20.20.3 Rejection0.30.20.20.2 Pulmonary Complications0.10.2<0.1<0.1 Renal<0.1<0.1<0.10 Surgery0.1<0.10.10.1 Hematology/oncology<0.1<0.100 Other<0.1<0.10.10.1Average length of hospital stay, days866—Frequency of hospitalization per patient3.622—NOTE. Information summarized from manuscript published by Andersen and Horslen. 11Andersen D.A. Horslen S. An analysis of the long-term complications of intestinal transplant patients.Progr Transplant. 2004; 14: 277-282PubMed Google Scholarn, number of patients at risk. Open table in a new tab NOTE. Information summarized from manuscript published by Andersen and Horslen. 11Andersen D.A. Horslen S. An analysis of the long-term complications of intestinal transplant patients.Progr Transplant. 2004; 14: 277-282PubMed Google Scholar n, number of patients at risk. A thorough discussion of the difficulties in performing studies of quality of life is beyond the scope of this manuscript, but, clearly, the results may vary depending on how the study is conducted, the instrument used, and by the person who responds. 14Theunissen N.C. Vogels T.G. Koopman H.M. et al.The proxy problem child report versus parent report in health-related quality of life research.Qual Life Res. 1998; 7: 387-397Crossref PubMed Scopus (542) Google Scholar, 15Moinpour C.M. Lyons B. Schmidt S.P. et al.Substituting proxy ratings for patient ratings in cancer clinical trials an analysis based on a Southwest Oncology Group trial in patients with brain metastases.Qual Life Res. 2000; 9: 219-231Crossref PubMed Scopus (44) Google Scholar, 16Rogers J. Ridley S. Crispin P. et al.Reliability of the next of kins’ estimates of critically ill patients’ quality of life.Anaesthesia. 1997; 52: 1137-1143Crossref PubMed Scopus (72) Google Scholar In addition, there is very little information on which we can currently make assessments or comparisons because few studies of the quality of life of patients on PN or after intestinal transplantation have been performed. The quality of life of patients receiving PN was the subject of a review by Dr Howard at the Intestinal Failure Workshop sponsored by the National Institutes of Health in February 2004 and appears on page S52 in this issue. An understanding of quality of life on TPN, however, is important to the potential intestinal transplant recipient and therefore will be briefly addressed. First, it is important to recognize that the overall health of these 2 populations are distinct because the majority of patients on TPN do not suffer from life-threatening complications, and only those who do are considered for intestinal transplantation. Second, as with intestinal transplant recipients, there are a limited number of preliminary studies describing the quality of life of patients on PN. These studies suggest that there is some decrease in quality of life for patients on TPN in several domains when compared with population norms. 17Pironi L. Paganelli F. Mosconi P. et al.The SF-36 instrument for the follow-up of health-related quality-of-life assessment of patients undergoing home parenteral nutrition for benign disease.Transplant Proc. 2004; 36: 255-258Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 18Jeppesen P.B. Langholz E. Mortensen P.B. Quality of life in patients receiving home parenteral nutrition.Gut. 1999; 44: 844-852Crossref PubMed Scopus (173) Google Scholar, 19Richards D. Irving M. Assessing the quality of life of patients with intestinal failure on home parenteral nutrition.Gut. 1997; 40: 218-222PubMed Google Scholar The earliest quality-of-life study of intestinal transplant recipients is from the International Intestinal Transplant Registry in which proxy assessments from either a physician or nurse caring for the intestinal transplant recipients is reported (http://www.intestinaltransplant.org/). In 1997, the registry reported that 85% of intestinal transplant recipients, who were more than 6 months after transplantation, had a Karnofsky score of 90%–100%. The interpretation of this Karnofsky score would be that the majority of intestinal transplant recipients have an excellent quality of life, described as normal, no evidence of disease, or able to carry on normal activities with minimal or minor symptoms. The limitation of this assessment is the brief nature of the instrument, ie, there is no information that distinguishes which aspect of quality of life is impaired in those with lower scores, and the assessments are not made by the recipients themselves but by proxy caregivers. A more descriptive study from the University of Nebraska found that most patients consumed all of their calories by mouth or through tube feedings and that TPN was only rarely required and usually only for a temporary period during a later illness. 20Sudan D.L. Iverson A. Weseman R.A. et al.Assessment of function, growth and development, and long-term quality of life after small bowel transplantation.Transplant Proc. 2000; 32: 1211-1212Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar In addition, intestinal transplant recipients were able to maintain good growth velocity and had few rehospitalizations or complications beyond the first year after transplantation. 20Sudan D.L. Iverson A. Weseman R.A. et al.Assessment of function, growth and development, and long-term quality of life after small bowel transplantation.Transplant Proc. 2000; 32: 1211-1212Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Most intestinal transplant recipients at the time of the study had returned to work or school, although some had required physical and/or occupational therapy to return to their level of previous function. 20Sudan D.L. Iverson A. Weseman R.A. et al.Assessment of function, growth and development, and long-term quality of life after small bowel transplantation.Transplant Proc. 2000; 32: 1211-1212Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar The limitation of this study, like the Karnofsky score, was the proxy nature of the assessment, (ie, parents in 90% of respondents). In addition, the study design was ad hoc, ie, lacked an evaluation of the validity and reliability of the instrument. Two studies with apparently some overlap from the University of Pittsburgh compared adult intestinal transplant recipients to patients on PN and found that quality of life after intestinal transplantation is equal to or better than quality of life on TPN and appears to improve for transplant recipients in at least some aspects over time. 21Rovera G.M. DiMartini A. Schoen R.E. et al.Quality of life of patients after intestinal transplantation.Transplantation. 1998; 66: 1141-1145Crossref PubMed Scopus (78) Google Scholar, 22DiMartini A. Rovera G.M. Graham T.O. et al.Quality of life after small intestinal transplantation and among home parenteral nutrition patients.JPEN J Parenter Enteral Nutr. 1998; 22: 357-362Crossref PubMed Scopus (102) Google Scholar The reliability of the DiMartini et al study is limited because all assessments of quality of life were made after transplantation relying on recollection of the quality of life before transplantation. 22DiMartini A. Rovera G.M. Graham T.O. et al.Quality of life after small intestinal transplantation and among home parenteral nutrition patients.JPEN J Parenter Enteral Nutr. 1998; 22: 357-362Crossref PubMed Scopus (102) Google Scholar The study by Rovera et al included patients who subsequently developed liver failure in the home PN group and therefore may not be reflective of most adult patients on home PN. 21Rovera G.M. DiMartini A. Schoen R.E. et al.Quality of life of patients after intestinal transplantation.Transplantation. 1998; 66: 1141-1145Crossref PubMed Scopus (78) Google Scholar Both studies used an instrument developed for liver transplant recipients, and it is not clear whether this instrument is appropriate for the evaluation of intestinal transplant recipients or patients on home PN. Despite these limitations, the results are useful as preliminary findings and suggest that quality of life in most intestinal transplant recipients is at least no worse than on TPN and may be better. More recently, a study using a well-validated test (the Child Health Questionnaire) 23Landgraf J.M. Abetz L. John E. Ware J. Child health questionnaire (CHQ) a user’s manual. Healthact, Boston, MA1999Google Scholar found that pediatric patients rate their quality of life similar to normal school children. 24Sudan D. Horslen S. Botha J. et al.Quality of life after pediatric intestinal transplantation the perception of pediatric recipients and their parents.Am J Transplant. 2004; 4: 407-413Crossref PubMed Scopus (81) Google Scholar These patients at the time of the study were preadolescent, with a mean age of approximately 11 years. These surprisingly good results may be a reflection of the young age of most of these patients at the time of transplantation. Most of the patients have little or no recollection of pretransplantation complications or perioperative pain and seem to have adapted well to whatever differences exist between themselves and their peers. 24Sudan D. Horslen S. Botha J. et al.Quality of life after pediatric intestinal transplantation the perception of pediatric recipients and their parents.Am J Transplant. 2004; 4: 407-413Crossref PubMed Scopus (81) Google Scholar On the other hand, teenagers have a high rate of noncompliance after kidney and liver transplantation. It remains to be seen whether intestinal transplant recipients will find the psychologic and social aspects of quality of life during the teenage years as favorable as they do in the preteen years. In contrast, the same study by Sudan et al from the University of Nebraska revealed that parental proxy assessments were worse than the pediatric self-assessments in multiple domains and that the parents rated their child’s quality of life worse than normal children in several domains. 24Sudan D. Horslen S. Botha J. et al.Quality of life after pediatric intestinal transplantation the perception of pediatric recipients and their parents.Am J Transplant. 2004; 4: 407-413Crossref PubMed Scopus (81) Google Scholar Similar results from another center were presented at the International Small Bowel Transplant Symposium in Miami, Florida, in September 2003 by Kosmach et al but have not yet been published. Interestingly, the parental proxy assessments of pediatric liver transplant recipients at the University of Cincinnati also revealed a similar decreased quality of life compared with normal children. 25Bucuvalas J. Britto M. Krug S. et al.Health-related quality of life in pediatric liver transplant recipients a single-center study.Liver Transpl. 2003; 9: 62-71Crossref PubMed Scopus (117) Google Scholar Studies of parental proxy assessments generally have shown lower scores than their child’s self-assessment. 14Theunissen N.C. Vogels T.G. Koopman H.M. et al.The proxy problem child report versus parent report in health-related quality of life research.Qual Life Res. 1998; 7: 387-397Crossref PubMed Scopus (542) Google Scholar, 15Moinpour C.M. Lyons B. Schmidt S.P. et al.Substituting proxy ratings for patient ratings in cancer clinical trials an analysis based on a Southwest Oncology Group trial in patients with brain metastases.Qual Life Res. 2000; 9: 219-231Crossref PubMed Scopus (44) Google Scholar In the oncology literature, this discordance has been attributed to parental anxiety. 14Theunissen N.C. Vogels T.G. Koopman H.M. et al.The proxy problem child report versus parent report in health-related quality of life research.Qual Life Res. 1998; 7: 387-397Crossref PubMed Scopus (542) Google Scholar Parental anxiety is certainly elevated early after transplantation as one would expect but may also remain elevated long-term because of the high risk of death associated with graft loss. 26Tarbell S.E. Kosmach B. Parental psychosocial outcomes in pediatric liver and/or intestinal transplantation pretransplantation and the early postoperative period.Liver Transpl Surg. 1998; 4: 378-387Crossref PubMed Scopus (41) Google Scholar Because of the limited number of studies, strong conclusions cannot yet be drawn regarding the quality of life after intestinal transplantation; however, these early results are encouraging and suggest that quality of life is reasonably good after intestinal transplantation and perhaps similar to that of normal individuals. Repeat studies in a larger sample of intestinal transplant recipients are required to confirm these preliminary findings. In summary, survival after intestinal transplantation is approaching, but has not yet matched, survival of continuing PN in the absence of life-threatening complications. Intestinal transplantation is therefore reserved for patients with PN-associated liver disease, loss of vascular access, and recurrent life-threatening, catheter-related sepsis. The cost of the initial hospitalization after intestinal transplantation is high (similar to the cost of PN for 1 year), and the incidence of rehospitalization appears 2- to 3-fold more common after transplantation than for patients on PN. Beyond the first year, however, the yearly cost of hospitalization and immunosuppressive medication is less after transplantation than the cost of continued PN. That means that, if a patient maintains a functional graft, intestinal transplantation becomes cost-effective within 1 to 3 years after the procedure. Although the shortcomings of the available quality-of-life studies of intestinal transplant recipients may have introduced significant bias, which cannot be assessed, the findings in each study revealed that most intestinal transplant recipients have a good or normal quality of life after transplantation and that their quality of life may be better than when they were on PN. If well-designed studies can confirm these preliminary findings of quality of life, and survival continues to improve with experience as it has for other solid organ allografts, intestinal transplantation may soon be offered to any patient with permanent intestinal failure at lower cost than continued PN.