Intractable Feeding Intolerance in Children With Severe Neurological Impairment: A Retrospective Case Review of Nine Children Known to a Pediatric Palliative Care Service
Child; Palliative Care; child; article; female; human; male; preschool child; palliative therapy; hospice; clinical article; intensive care; school child; documentation; Only Child; ethics; patient referral; adolescent; infant; stomach tube; deterioration; retrospective study; drug combination; conversation; nomenclature; neurologic disease; feeding difficulty; parenteral nutrition; case study; enteric feeding; neurodisability; digestive system function disorder
BACKGROUND: Intractable feeding intolerance in children with severe neurological impairment (SNI) is poorly defined and understood. <br/>OBJECTIVE(S): (1) To describe 9 children with SNI, where intractable feeding intolerance was thought to be a contributor to their deterioration or death. (2) To consider terminology to describe the severe end of the spectrum of feeding difficulties in children with SNI. <br/>RESULT(S): Mean age at death was 10.3 years (range: 5 - 15.6), and median time from palliative care referral to death was 3.1 months. Location of death was home (n = 3), hospice (n = 1), and hospital (n = 5) with 1 death in intensive care. Gastrointestinal "failure" or "dysfunction" were documented for 7 children, (median time between documentation and death was 3.9 months (range: .1 to 13.1)). All children were fed via a gastrostomy tube during their life (median age of insertion 2.5 years (range: 1.2 to 6.8 years)), and 7 via the jejunal route (median age of insertion 9.2 years (range 2.4 to 14.7 years)). Children lived a median of 9 percent of their lives after jejunal tube feeding was commenced. No child had home-based parenteral nutrition. Multiple symptom management medications were required. <br/>CONCLUSION(S): 'Intractable feeding intolerance' describes a clinical crossroads in a child's life where there is an opportunity to consider the appropriateness of further interventions. Further work should explore predictors of intractable feeding intolerance and the delicate balance between cause or contributor to death. The importance of clinician-family prognostic conversations and goal-concordant care both during life and in the terminal phase is highlighted.
Katz NT; Cooper MS; Kularatne A; Prebble A; McGrath KH; McCallum Z; Antolovich G; Sutherland I; Sacks BH
American Journal of Hospice and Palliative Care
2023
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<a href="https://journals.sagepub.com/doi/10.1177/10499091231169497">10.1177/10499091231169497</a>
Crossing the line? Ethics of parenteral nutrition in paediatric neurodisability complicated by intestinal failure
Ethics; Intestinal failure; Neurodisability; Parenteral nutrition; Pediatrics
Children with severe neurological impairment (such as cerebral palsy or congenital anomalies) are living longer, although medically complex, lives. Feeding intolerance is an increasing problem that is emerging as a new end-of-life issue. Long-term parenteral nutrition (LTPN) is technically feasible in these children. However, clinicians are concerned about whether it is appropriate in these circumstances or whether it constitutes a treatment 'too far'. This narrative review of the literature identifies, categorises and explores the ethical foundations and reasons for clinician hesitancy about the use of LTPN in this population. The categories of reasons are: lack of clear diagnostic criteria for feeding failure; risks of LTPN to the child; burden of LTPN to the family/caregivers; burden of LTPN to the child; difficulty in cessation of LTPN; and the concept that feeding failure may be a preterminal sign. These reasons are all ultimately about risks and burden outweighing the benefits. We argue that the risks of LTPN have decreased over time, the burden for individual children and their parents may be less than imagined, and the benefit is a realistic prospect. Case-by-case consideration, giving due weight to child and parental perspectives, can show that LTPN is ethically justified for some children with severe neurological impairment. Copyright © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
McCallum Z; Delany C; Gillam L
Archives of Disease in Childhood
2022
<a href="http://doi.org/10.1136/archdischild-2021-323500" target="_blank" rel="noreferrer noopener">10.1136/archdischild-2021-323500</a>
Priorities for Nutrition Research in Pediatric Critical Care
child; Child; Child Nutrition Disorders/prevention & control/*therapy; Child Nutritional Physiological Phenomena; Children; Consensus; Critical Care/*methods; Critical Illness; Delphi Technique; enteral nutrition; Humans; Intensive Care; Intensive care units (paediatric); Internationality; Nutritional Support/*methods; parenteral nutrition; Pediatric; research
BACKGROUND: Widespread variation exists in pediatric critical care nutrition practices, largely because of the scarcity of evidence to guide best practice recommendations. OBJECTIVE: The objective of this paper was to develop a list of topics to be prioritized for nutrition research in pediatric critical care in the next 10 years. METHODS: A modified 3-round Delphi process was undertaken by a newly established multidisciplinary group comprising 11 international researchers in the field of pediatric critical care nutrition. Items were ranked on a 5-point Likert scale. RESULTS: Forty-five research topics (with a mean priority score >3(0-5) were identified within the following 10 domains: the pathophysiology and impact of malnutrition in critical illness; nutrition assessment: nutrition risk assessment and biomarkers; accurate assessment of energy requirements in all phases of critical illness; the role of protein intake; the role of pharmaco-nutrition; effective and safe delivery of enteral nutrition; enteral feeding intolerance: assessment and management; the role of parenteral nutrition; the impact of nutrition status and nutrition therapies on long-term patient outcomes; and nutrition therapies for specific populations. Ten top research topics (that received a mean score >4(0-5) were identified as the highest priority for research. CONCLUSIONS: This paper has identified important consensus-derived priorities for clinical research in pediatric critical care nutrition. Future studies should determine topics that are a priority for patients and parents. Research funding should target these priority areas and promote an international collaborative approach to research in this field, with a focus on improving relevant patient outcomes.
Tume L N; Valla F V; Floh A A; Goday P; Jotterand Chaparro C; Larsen B; Lee J H; Moreno Y M F; Pathan N; Verbruggen S; Mehta N M
Journal of Parenteral and Enteral Nutrition
2019
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<a href="http://doi.org/10.1002/jpen.1498" target="_blank" rel="noreferrer noopener">10.1002/jpen.1498</a>
Characteristics and Outcomes of Critical Illness in Children With Feeding and Respiratory Technology Dependence
Adolescent; Artificial/adverse effects/*statistics & numerical data; Biomedical Technology; Case-Control Studies; Child; Critical Care/*methods; Critical Illness/therapy; Health Care/*statistics & numerical data; Humans; Infant; Intensive Care Units; Newborn; Outcome Assessment; Parenteral Nutrition; Pediatric/statistics & numerical data; Preschool; Prospective Studies; Respiration; Severity of Illness Index; Total/adverse effects/*statistics & numerical data
OBJECTIVES: Children with dependence on respiratory or feeding technologies are frequently admitted to the PICU, but little is known about their characteristics or outcomes. We hypothesized that they are at increased risk of critical illness-related morbidity and mortality compared with children without technology dependence. DESIGN: Secondary analysis of prospective, probability-sampled cohort study of children from birth to 18 years old. Demographic and clinical characteristics were assessed. Outcomes included death, survival with new morbidity, intact survival, and survival with functional status improvement. SETTING: General and cardiovascular PICUs at seven participating children's hospitals as part of the Trichotomous Outcome Prediction in Critical Care study. SUBJECTS: Children from birth to 18 years of age as part of the Trichotomous Outcome Prediction in Critical Care study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children with technology dependence composed 19.7% (1,989/10,078) of PICU admissions. Compared with those without these forms of technology dependence, these children were younger, received more ICU-specific therapeutics, and were more frequently readmitted to the ICU. Death occurred in 3.7% of technology-dependent patients (n = 74), and new morbidities developed in 4.5% (n = 89). Technology-dependent children who developed new morbidities had higher Pediatric Risk of Mortality scores and received more ICU therapies than those who did not. A total of 3.0% of technology-dependent survivors (n = 57) showed improved functional status at hospital discharge. CONCLUSIONS: Children with feeding and respiratory technology dependence composed approximately 20% of PICU admissions. Their new morbidity rates are similar to those without technology dependence, which contradicts our hypothesis that children with technology dependence would demonstrate worse outcomes. These comparable outcomes, however, were achieved with additional resources, including the use of more ICU therapies and longer lengths of stay. Improvement in functional status was seen in some technology-dependent survivors of critical illness.
Heneghan J A; Reeder R W; Dean J M; Meert K L; Berg R A; Carcillo J; Newth C J L; Dalton H; Tamburro R; Pollack M M
Pediatric Critical Care Medicine
2019
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<a href="http://doi.org/10.1097/pcc.0000000000001868" target="_blank" rel="noreferrer noopener">10.1097/pcc.0000000000001868</a>
Feed-induced Dystonias in Children with Severe Central Nervous System Disorders
infant; adolescent; cerebral palsy; percutaneous endoscopic gastrostomy; retrospective study; priority journal; practice guideline; case study; school child; preschool child; intestine obstruction; human; article; child; female; male; clinical article; Rett syndrome; gastroesophageal reflux; infantile spasm; intestinal dysmotility; baclofen/dt [Drug Therapy]; dystonia/dt [Drug Therapy]; motor dysfunction; onset age; central nervous system disease; dystonia/dt [Drug Therapy]; feed induced dystonia; 1134-47-0 (baclofen); acquired brain injury; baclofen/tl [Intrathecal Drug Administration]; feed induced dystonia/dt [Drug Therapy]; gastroscopy; hydrocephalus; hyperglycinemia; intestine motility; microcephaly; peristalsis; reflux esophagitis; Sanfilippo syndrome; total parenteral nutrition; constipation; feeding difficulties; tone and motor problems; MPSIII; West syndrome; pharmacologic intervention; parenteral nutrition; dystonia; GERD; intestinal dysmotility
Dystonias can arise from any painful stimuli in neurologically disabled children. Classically, feed-induced dystonias from mediastinal pain due to severe gastroesophageal reflux disease are described as Sandifer spasm. We report a case series of 12 severely neurologically impaired children with enteral feed-induced dystonias. Intestinal dysmotility was demonstrated in several. Improvements are seen with jejunal feeds or gut rest with total parenteral nutrition. Use of parenteral nutrition in children with severe neurodisability requires thorough discussion with patient groups and commissioners to give clinicians guidelines to standardize care.
Mordekar S R; Velayudhan M; Campbell D I
Journal of Pediatric Gastroenterology and Nutrition
2017
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<a href="http://doi.org/10.1097/MPG.0000000000001543" target="_blank" rel="noreferrer noopener">10.1097/MPG.0000000000001543</a>
Patients with malignant hematological disorders treated on a palliative care unit: prognostic impact of clinical factors
adolescent; Female; Humans; Male; retrospective studies; Survival Rate; Adult; Analgesics; Prospective Studies; Aged; Middle Aged; Risk Factors; Time Factors; Serum Albumin; Parenteral Nutrition; Palliative Care; Opioid; Databases; Factual; Disease-Free Survival; Blood Transfusion; Hematologic Neoplasms; Hemoglobins; Idiopathic; Platelet Count; Purpura; Thrombocytopenic
A reliable estimation of prognosis in patients receiving palliative care is desirable in order to facilitate clinical decision finding. For patients with advanced hematological malignancies, only few data are available to estimate prognosis of the individual's remaining life span. Here, we sought to investigate potential clinical prognostic parameters in patients with hematological malignancies admitted to a palliative care unit. Using a prospectively collected database, we analyzed clinical and laboratory parameters regarding their prognostic impact in 290 patients with malignant hematological diseases. The parameters included patient-related factors such as Eastern Cooperative Oncology Group (ECOG) performance status, need for transfusions, parenteral nutrition or analgetics, and laboratory values (hemoglobin, platelet count, lactic dehydrogenase (LDH), albumin, total protein, calcium, and C-reactive protein (CRP)) as well as referral symptoms (including anemia, infection, fever, fatigue, and dyspnea). In univariate analyses, LDH (>248 U/l), albumin corrected calcium (>2.55 mmol/l), CRP (>50 mg/l), albumin (<30 g/l), platelet count (<90 × 10(9)/l), total protein (≤60 g/l), hemoglobin (<10 g/dl), opioid treatment, performance status (ECOG >2), and need for parenteral nutrition or blood transfusion significantly correlated with impaired survival. Multivariate analysis showed that low performance status, low platelet count, opioid based pain therapy, high LDH, and low albumin were associated with poor prognosis. Using these five parameters, patients were divided into three "risk groups": low risk (presence of zero to one factor), intermediate risk (two to three factors), and high risk. Median survival for the poor risk patients was 10 days, and the intermediate and low risk patients survived a median of 63 and 440 days, respectively (p < 0.0001). Several clinical and laboratory parameters were associated with a poor prognosis of patients with hematological malignancies treated on a palliative care unit. These parameters might help clinicians to estimate prognosis of remaining life span and individualize treatment and/or end-of-life care options for patients.
2014-02
Kripp M; Willer A; Schmidt C; Pilz LR; Gencer D; Buchheidt D; Hochhaus A; Hofmann W-K; Hofheinz R-D
Annals Of Hematology
2014
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Journal Article
<a href="http://doi.org/10.1007/s00277-013-1861-7" target="_blank" rel="noreferrer">10.1007/s00277-013-1861-7</a>
Palliative sedation therapy in the last weeks of life: a literature review and recommendations for standards
Humans; Risk Assessment; Fluid Therapy; Informed Consent; International Cooperation; Parenteral Nutrition; Practice Guidelines; Neoplasms; Palliative Care/standards; Pain/drug therapy; Attitude to Death/ethnology; Terminal Care/standards; Hypnotics and Sedatives/administration & dosage/classification/therapeutic use
PURPOSE: Palliative sedation therapy (PST) is a controversial issue. There is a need for internationally accepted definitions and standards. METHODS: A systematic review of the literature was performed by an international panel of 29 palliative care experts. Draft papers were written on various topics concerning PST. This paper is a summary of the individual papers, written after two meetings and extensive e-mail discussions. RESULTS: PST is defined as the use of specific sedative medications to relieve intolerable suffering from refractory symptoms by a reduction in patient consciousness, using appropriate drugs carefully titrated to the cessation of symptoms. The initial dose of sedatives should usually be small enough to maintain the patients' ability to communicate periodically. The team looking after the patient should have enough expertise and experience to judge the symptom as refractory. Advice from palliative care specialists is strongly recommended before initiating PST. In the case of continuous and deep PST, the disease should be irreversible and advanced, with death expected within hours to days. Midazolam should be considered first-line choice. The decision whether or not to withhold or withdraw hydration should be discussed separately. Hydration should be offered only if it is considered likely that the benefit will outweigh the harm. PST is distinct from euthanasia because (1) it has the intent to provide symptom relief, (2) it is a proportionate intervention, and (3) the death of the patient is not a criterion for success. PST and its outcome should be carefully monitored and documented. CONCLUSION: When other treatments fail to relieve suffering in the imminently dying patient, PST is a valid palliative care option.
2007
de Graeff A; Dean M
Journal Of Palliative Medicine
2007
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Journal Article
<a href="http://doi.org/10.1089/jpm.2006.0139" target="_blank" rel="noreferrer">10.1089/jpm.2006.0139</a>
Parenteral nutrition in advanced cancer: indications and clinical practice guidelines
Female; Humans; Male; Palliative Care; Aged; Middle Aged; Patient Selection; Parenteral Nutrition; Practice Guidelines; IM; Cachexia/et [Etiology]; Cachexia/th [Therapy]; Gastric Outlet Obstruction/co [Complications]; Intestinal Fistula/co [Complications]; Neoplasms/co [Complications]; Neoplasms/th [Therapy]
Cachexia is a disturbing and disfiguring aspect of many advanced cancers. Parenteral nutrition (PN) is a controversial and expensive treatment for cancer cachexia. Guidelines for the use of PN for these patients have been suggested. These two case reports will highlight some of the issues around the etiology of cancer cachexia, the clinical dilemmas and the use of clinical practice guidelines. [References: 23]
2005
Mirhosseini N; Fainsinger RL; Baracos V
Journal Of Palliative Medicine
2005
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Journal Article
<a href="http://doi.org/10.1089/jpm.2005.8.914" target="_blank" rel="noreferrer">10.1089/jpm.2005.8.914</a>
Does gastrostomy tube feeding in children with cerebral palsy increase the risk of respiratory morbidity?
Child; Female; Humans; Male; Longitudinal Studies; Parenteral Nutrition; adolescent; Preschool; Non-U.S. Gov't; Research Support; infant; Gastrostomy/adverse effects; Cerebral Palsy/therapy; Risk Assessment/methods; home; Lung Diseases/etiology
BACKGROUND: Children with severe neurological impairment may have significant oral motor dysfunction and are at increased risk of nutritional deficiencies, poor growth, and aspiration pneumonia. Gastrostomy tube feeding is increasingly being used for nutritional support in these children. AIM: To examine the occurrence of respiratory morbidity before and after gastrostomy feeding tube insertion in children with severe neurological disabilities. METHODS: This study was nested in a longitudinal, prospective, uncontrolled, multicentre cohort study designed to investigate the outcomes of gastrostomy tube feeding in 57 children with severe neurological disabilities. Parents completed a questionnaire prior to (visit 1) and 6 and 12 months (visits 2 and 3) following the gastrostomy, detailing number of chest infections requiring antibiotics and/or hospital admission. RESULTS: Mean number of chest infections requiring antibiotics was 1.8 on visit 1 and 0.9 on visit 3. Hospital admissions for chest infections fell significantly from 0.5 to 0.09. CONCLUSION: This study provides no evidence for an increase in respiratory morbidity following insertion of a feeding gastrostomy in children with cerebral palsy.
2006
Sullivan P; Morrice JS; Vernon-Roberts A; Grant H; Eltumi M; Thomas AG
Archives Of Disease In Childhood
2006
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Journal Article
<a href="http://doi.org/10.1136/adc.2005.084442" target="_blank" rel="noreferrer">10.1136/adc.2005.084442</a>
Diagnosis and management of MNGIE syndrome in children: case report and review of the literature
Child; Female; Humans; Parenteral Nutrition; adolescent; Tomography; X-Ray Computed; Duodenum/radiography; Gastrointestinal Diseases/physiopathology/radiography/therapy; Mitochondrial Encephalomyopathies/physiopathology/radiography/therapy; Stomach/radiography; Total; Ubiquinone/therapeutic use; Vitamins/therapeutic use
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare disorder that presents in childhood; however, marked delay in diagnosis is common. We report a case and review the literature describing the typical features that should alert pediatricians to the diagnosis. We also describe a novel management strategy for providing symptomatic relief.
2002
Teitelbaum JE; Berde CB; Nurko S; Buonomo C; Perez-Atayde AR; Fox VL
Journal Of Pediatric Gastroenterology And Nutrition
2002
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Journal Article
<a href="http://doi.org/10.1097/00005176-200209000-00029" target="_blank" rel="noreferrer">10.1097/00005176-200209000-00029</a>
Irreversible intestinal failure
Child; Humans; Parenteral Nutrition; Adaptation; infant; Physiological; Gastrointestinal Motility; Intestinal Absorption; Digestive Physiology; Hirschsprung Disease/complications; Intestinal Pseudo-Obstruction/complications/surgery; Intestines/transplantation; Liver Diseases/prevention & control; Malabsorption Syndromes/etiology/therapy; Short Bowel Syndrome/complications/surgery
Intestinal failure (IF) can be defined as the reduction of functional gut mass below the minimal amount necessary for digestion and absorption adequate to satisfy the nutrient and fluid requirements for maintenance in adults or growth in children. In developed countries, IF mainly includes individuals with the congenital or early onset of conditions requiring protracted or indefinite parenteral nutrition (PN). Short bowel syndrome was the first commonly recognized cause of protracted IF. The normal physiologic process of intestinal adaptation after extensive resection usually allows for recovery of sufficient intestinal function within weeks to months. During this time, patients can be sustained on parenteral nutrition. Only a few children have permanent intestinal insufficiency and life-long dependency on PN. Non-transplant surgery including small bowel tapering and lengthening may allow weaning from PN in some cases. Hormonal therapy with recombinant human growth hormone has produced poor results while therapy with glucagon-like peptide-2 holds promise. Congenital diseases of enterocyte development such as microvillus inclusion disease or intestinal epithelial dysplasia cause permanent IF for which no curative medical treatment is currently available. Severe and extensive motility disorders such as total or subtotal intestinal aganglionosis (long segment Hirschsprung disease) or chronic intestinal pseudo-obstruction syndrome may also cause permanent IF. PN and home-PN remain are the mainstays of therapy regardless of the cause of IF. Some patients develop complications while receiving long-term PN for IF especially catheter related complications (thrombosis, sepsis) and liver disease. These patients may be candidates for intestinal transplantation. This review discusses the causes of irreversible IF and emphasizes the specific medico-surgical strategies for prevention and treatment of these conditions at several stages of IF.
2004
Goulet O; Ruemmele F; Lacaille F; Colomb V
Journal Of Pediatric Gastroenterology And Nutrition
2004
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Journal Article
<a href="http://doi.org/10.1097/00005176-200403000-00006" target="_blank" rel="noreferrer">10.1097/00005176-200403000-00006</a>
Must patients always be given food and water?
Humans; United States; Withholding Treatment; Social Values; Euthanasia; Risk Assessment; Moral Obligations; Ethics; Parenteral Nutrition; Medical; Death and Euthanasia; Analytical Approach; RDF Project; Passive; Life Support Care/legislation & jurisprudence; Malpractice/legislation & jurisprudence; Philosophical Approach
KIE: The widespread consensus that withholding certain life-sustaining treatments, especially those entailing substantial suffering, is sometimes in a patient's best interest conflicts with our basic instincts when the treatments are food and water. Lynn and Childress examine the medical aspects of various nutritional options and the moral obligations pertinent to decision making. They conclude that, in certain limited cases, malnutrition and dehydration need not be corrected and that nutrition and hydration are not distinguishable morally from other life-sustaining treatments that may on occasion be withheld or withdrawn.
1983
Lynn J; Childress JF
The Hastings Center Report
1983
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Journal Article
<a href="http://doi.org/10.2307/3560572" target="_blank" rel="noreferrer">10.2307/3560572</a>
Comfort care for terminally ill patients. The appropriate use of nutrition and hydration
Female; Humans; Male; Withholding Treatment; Prospective Studies; Aged; Middle Aged; New York; Risk Assessment; Fluid Therapy; Parenteral Nutrition; quality of life; 80 and over; Empirical Approach; Death and Euthanasia; Hunger; Nursing Homes/standards; Nutrition; NY); Palliative Care/psychology; Psychological; St. John's Home (Rochester; Stress; Terminal Care/methods/psychology/standards; Thirst; Xerostomia/therapy
OBJECTIVE--To determine the frequency of symptoms of hunger and thirst in a group of terminally ill patients and determine whether these symptoms could be palliated without forced feeding, forced hydration, or parenteral alimentation. DESIGN--Prospective evaluation of consecutively admitted terminally ill patients treated in a comfort care unit. SETTING--Ten-bed comfort care unit in a 471-bed long-term care facility. PARTICIPANTS--Mentally aware, competent patients with terminal illnesses monitored from time of admission to time of death while residing in the comfort care unit. MAIN OUTCOME MEASURES--Symptoms of hunger, thirst, and dry mouth were recorded, and the amounts and types of food and fluids necessary to relieve these symptoms were documented. The subjective level of comfort was assessed longitudinally in all patients. RESULTS--Of the 32 patients monitored during the 12 months of study, 20 patients (63%) never experienced any hunger, while 11 patients (34%) had symptoms only initially. Similarly, 20 patients (62%) experienced either no thirst or thirst only initially during their terminal illness. In all patients, symptoms of hunger, thirst, and dry mouth could be alleviated, usually with small amounts of food, fluids, and/or by the application of ice chips and lubrication to the lips. Comfort care included use of narcotics for relief of pain or shortness of breath in 94% of patients. CONCLUSIONS--In this series, patients terminally ill with cancer generally did not experience hunger and those who did needed only small amounts of food for alleviation. Complaints of thirst and dry mouth were relieved with mouth care and sips of liquids far less than that needed to prevent dehydration. Food and fluid administration beyond the specific requests of patients may play a minimal role in providing comfort to terminally ill patients.
1994
McCann RM; Hall WJ; Groth-Juncker A
Jama
1994
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Journal Article
<a href="http://doi.org/10.1001/jama.1994.03520160047041" target="_blank" rel="noreferrer">10.1001/jama.1994.03520160047041</a>
Terminal dehydration, a compassionate treatment
Female; Male; Palliative Care; Adult; Aged; Fluid Therapy; Enteral Nutrition; Parenteral Nutrition; 80 and over; Psychological; Human; Case Report; Withholding Treatment; Terminal Care/standards; Risk Assessment; Stress
1992
Printz LA
Archives Of Internal Medicine
1992
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Journal Article