Psychological Dimensions of Palliative Care Consultation: Approaches to Seriously Ill Patients at the End of Life.

Mental health clinicians often hear seriously ill patients ask the unanswerable: Why did this happen? What is the meaning of my suffering? In the inpatient setting, general medical ward, or oncology unit, patients are confronted with their mortality in new, urgent ways. Palliative medicine, or the specialized, comprehensive care of patients facing a life-limiting illness, occupies a unique and liminal space. Although often practiced by clinicians with non-mental health training backgrounds, there exists ample psychological content to be explored in the palliative care encounter. In this article, we present the case of a husband and international businessperson who experienced terminal complications from an advanced stage lung cancer. His illness was not responsive to multiple cancer-directed treatments, and he developed respiratory failure requiring high levels of supplemental oxygen support, from which he was unable to wean. Palliative care consultation was sought with the multiple objectives of ameliorating his severe death anxiety and persistent dyspnea as well as assisting in the clarification of his end-of-life wishes. Our goal with this case presentation and related discussion is to introduce the psychological aspects of palliative medicine to psychiatrists and psychotherapists.

Toxicity assessment of gelsenicine and the search for effective antidotes.

BACKGROUND: Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth (G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. OBJECTIVE: This study aimed to analyse the toxicity characteristics of gelsenicine. METHODS: Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. RESULTS: In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood-brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. CONCLUSIONS: Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine-related poisoning and its toxicity mechanisms.

A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure.

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors' biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.

Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial.

BACKGROUND: Mechanical ventilation (MV) is a life-saving technology that restores or assists breathing. Like any treatment, MV has side effects. In some patients it can cause diaphragmatic atrophy, injury, and dysfunction (ventilator-induced diaphragmatic dysfunction, VIDD). Accumulating evidence suggests that VIDD makes weaning from MV difficult, which involves increased morbidity and mortality. METHODS AND ANALYSIS: This paper describes the protocol of a randomized, controlled, open-label, multicenter trial that is designed to investigate the safety and effectiveness of a novel therapy, temporary transvenous diaphragm pacing (TTVDP), to improve weaning from MV in up to 88 mechanically ventilated adult patients who have failed at least two spontaneous breathing trials over at least 7 days. Patients will be randomized (1:1) to TTVDP (treatment) or standard of care (control) groups. The primary efficacy endpoint is time to successful extubation with no reintubation within 48 h. Secondary endpoints include maximal inspiratory pressure and ultrasound-measured changes in diaphragm thickness and diaphragm thickening fraction over time. In addition, observational data will be collected and analyzed, including 30-day mortality and time to discharge from the intensive care unit and from the hospital. The hypothesis to be tested postulates that more TTVDP patients than control patients will be successfully weaned from MV within the 30 days following randomization. DISCUSSION: This study is the first large-scale clinical trial of a novel technology (TTVDP) aimed at accelerating difficult weaning from MV. The technology tested provides the first therapy directed specifically at VIDD, an important cause of delayed weaning from MV. Its results will help delineate the place of this therapeutic approach in clinical practice and help design future studies aimed at defining the indications and benefits of TTVDP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03096639 . Registered on 30 March 2017.

Interhospital ECMO Transport: Regional Focus.

Utilization of extracorporeal membrane oxygenation (ECMO) has increased dramatically over the last decade. Despite this trend, many medical centers have limited, if any, access to this technology or the resources necessary to manage these complex patients. In an effort to improve the current infrastructure of regional ECMO care, ECMO centers of excellence have an obligation to partner with facilities within their communities and regions to increase access to this potentially life-saving technology. While the need for this infrastructure is widely acknowledged in the ECMO community, few reports describe the actual mechanisms by which a successful interfacility transport program can operate. As such, the purpose of this document is to describe the elements of and methods for providing safe and efficient mobile ECMO services from the perspective of an experienced, high-volume tertiary ECMO center of excellence in the Southeastern United States.

Long-term experience with diaphragm pacing for traumatic spinal cord injury: Early implantation should be considered.

BACKGROUND: Cervical spinal cord injury can result in catastrophic respiratory failure requiring mechanical ventilation with high morbidity, mortality, and cost. Diaphragm pacing was developed to replace/decrease mechanical ventilation. We report the largest long-term results in traumatic cervical spinal cord injury. METHODS: In this retrospective review of prospective institutional review board protocols, all patients underwent laparoscopic diaphragm mapping and implantation of electrodes for diaphragm strengthening and ventilator weaning. RESULTS: From 2000 to 2017, 92 patients out of 486 diaphragm pacing implants met the criteria. The age at time of injury ranged from birth to 74 years (average: 27 years). Time on mechanical ventilation was an average of 47.5 months (range, 6 days to 25 years, median = 1.58 years). Eighty-eight percent of patients achieved the minimum of 4 hours of pacing. Fifty-six patients (60.8%) used diaphragm pacing 24 hours a day. Five patients had full recovery of breathing with subsequent diaphragm pacing removal. Median survival was 22.2 years (95% confidence interval: 14.0-not reached) with only 31 deaths. Subgroup analysis revealed that earlier diaphragm pacing implantation leads to greater 24-hour use of diaphragm pacing and no need for any mechanical ventilation. CONCLUSION: Diaphragm pacing can successfully decrease the need for mechanical ventilation in traumatic cervical spinal cord injury. Earlier implantation should be considered.

How New Support Devices Change Critical Care Delivery.

Mechanical support devices are used to support failing cardiac, respiratory, or both systems. Since Gibbon developed the cardiopulmonary bypass in 1953, collaborative efforts by medical centers, bioengineers, industry, and the National Institutes of Health have led to development of mechanical devices to support heart, lung, or both. These devices are used as a temporary or long-term measures for acute collapse of circulatory system and/or respiratory failure. Patients are managed on these support devices as a bridge to recovery, bridge to long term devices, or bridge to transplant. The progress in development of these devices has improved mortality and quality of life in select groups of patients. Care of these patients requires a multidisciplinary team approach, which includes cardiac surgeons, critical care physicians, cardiologists, pulmonologists, nursing staff, and perfusionists. Using a team approach improves outcomes in these patients.

The Impact of Acute Organ Dysfunction on Long-Term Survival in Sepsis.

OBJECTIVES: To estimate the impact of each of six types of acute organ dysfunction (hepatic, renal, coagulation, neurologic, cardiac, and respiratory) on long-term mortality after surviving sepsis hospitalization. DESIGN: Multicenter, retrospective study. SETTINGS: Twenty-one hospitals within an integrated healthcare delivery system in Northern California. PATIENTS: Thirty thousand one hundred sixty-three sepsis patients admitted through the emergency department between 2010 and 2013, with mortality follow-up through April 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute organ dysfunction was quantified using modified Sequential Organ Failure Assessment scores. The main outcome was long-term mortality among sepsis patients who survived hospitalization. The estimates of the impact of each type of acute organ dysfunction on long-term mortality were based on adjusted Cox proportional hazards models. Sensitivity analyses were conducted based on propensity score-matching and adjusted logistic regression. Hospital mortality was 9.4% and mortality was 31.7% at 1 year. Median follow-up time among sepsis survivors was 797 days (interquartile range: 384-1,219 d). Acute neurologic (odds ratio, 1.86; p < 0.001), respiratory (odds ratio, 1.43; p < 0.001), and cardiac (odds ratio, 1.31; p < 0.001) dysfunction were most strongly associated with short-term hospital mortality, compared with sepsis patients without these organ dysfunctions. Evaluating only patients surviving their sepsis hospitalization, acute neurologic dysfunction was also most strongly associated with long-term mortality (odds ratio, 1.52; p < 0.001) corresponding to a marginal increase in predicted 1-year mortality of 6.0% for the presence of any neurologic dysfunction (p < 0.001). Liver dysfunction was also associated with long-term mortality in all models, whereas the association for other organ dysfunction subtypes was inconsistent between models. CONCLUSIONS: Acute sepsis-related neurologic dysfunction was the organ dysfunction most strongly associated with short- and long-term mortality and represents a key mediator of long-term adverse outcomes following sepsis.

Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.

BACKGROUND: Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality. METHODS AND FINDINGS: We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily), moderate (900 to 1,799 mg daily), or high (≥1,800 mg daily). A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID) use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256) and 6.8% of controls (313 of 4,619) were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p < 0.001; adjusted OR [aOR] 1.49, 95% CI 1.18 to 1.88, p < 0.001) compared to opioid prescription alone. In the dose-response analysis, moderate-dose (OR 2.05, 95% CI 1.46 to 2.87, p < 0.001; aOR 1.56, 95% CI 1.06 to 2.28, p = 0.024) and high-dose (OR 2.20, 95% CI 1.58 to 3.08, p < 0.001; aOR 1.58, 95% CI 1.09 to 2.27, p = 0.015) gabapentin use was associated with a nearly 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use. As expected, we found no significant association between co-prescription of opioids and NSAIDs and opioid-related death (OR 1.11, 95% CI 0.98 to 1.27, p = 0.113; aOR 1.14, 95% CI 0.98 to 1.32, p = 0.083). In an exploratory analysis of patients at risk of combined opioid and gabapentin use, we found that 46.0% (45,173 of 98,288) of gabapentin users in calendar year 2013 received at least 1 concomitant prescription for an opioid. This study was limited to individuals eligible for public drug coverage in Ontario, we were only able to identify prescriptions reimbursed by the government and dispensed from retail pharmacies, and information on indication for gabapentin use was not available. Furthermore, as with all observational studies, confounding due to unmeasured variables is a potential source of bias. CONCLUSIONS: In this study we found that among patients receiving prescription opioids, concomitant treatment with gabapentin was associated with a substantial increase in the risk of opioid-related death. Clinicians should consider carefully whether to continue prescribing this combination of products and, when the combination is deemed necessary, should closely monitor their patients and adjust opioid dose accordingly. Future research should investigate whether a similar interaction exists between pregabalin and opioids.

Survival and medical utilization of children and adolescents with prolonged ventilator-dependent and associated factors.

Over the course of a year, more than 20,000 patients in Taiwan require prolonged mechanical ventilation (PMV). Data from the National Health Insurance Research Database for patients between 2005 and 2011 were used to conduct a retrospective analysis on ventilator dependence. The study subjects were PMV patients aged <17 years in Taiwan. A multiple regression model employing general estimating equations was applied to investigate the factors affecting the use of medical resources by children and adolescent PMV patients. A Cox proportional hazard model was incorporated to explore the factors affecting the survival of these patients. Data were collected for a total of 1,019 children and adolescent PMV patients in Taiwan. The results revealed that the average number of outpatient visits per subject was 32.1 times per year, whereas emergency treatments averaged 1.56 times per year per subject and hospitalizations averaged 160.8 days per year per subject. Regarding average annual medical costs, hospitalizations accounted for the largest portion at NT$821,703 per year per subject, followed by outpatient care at NT$123,136 per year per subject and emergency care at NT$3,806 per year per subject. The demographic results indicated that the patients were predominately male (61.24%), with those under 1 year of age accounting for the highest percentage (36.38%). According to the Kaplan-Meier curve, the 1-year and 5-year mortality rates of the patients were approximately 32% and 47%, respectively. The following factors affecting the survival rate were considered: age, the Charlson Comorbidity Index (CCI), diagnosis type necessitating ventilator use, and whether an invasive ventilator was used. This study investigated the use of medical resources and the survival rates of children and adolescent PMV patients. The findings of this study can serve as a reference for the National Health Insurance Administration in promoting its future integrated pilot projects on ventilator dependency.

Importance of diaphragm thickness in amyotrophic lateral sclerosis patients with diaphragm pacing system implantation.

INTRODUCTION: Severe respiratory failure develops as a result of the involvement of the respiratory muscles in patients with amyotrophic lateral sclerosis (ALS). Implantation of diaphragm pacing system (DPS) has been carried out on ALS patients since 2005 to avoid these situations, but the importance of diaphragm thickness has not yet been established clearly. MATERIAL AND METHOD: We retrospectively evaluated 34 ALS patients who had previously implanted DPS to detect the importance of diaphragm thickness. We investigated the effect of diaphragm thickness, which was measured by preoperative thorax computerized tomography on preoperative respiratory function tests (RFT), arterial blood gas (ABG) analysis, postoperative 3- and 6-month oxygen saturations and mortality. RESULTS: The right diaphragm thickness was calculated as 4.60 (2.95-6.00) mm, while the left diaphragm thickness was 4.10 (2.77-6.00) mm. Six patients died during the follow-up period. We did not detect a significant relationship between ABG parameters, RFT and diaphragm thickness. However, according to our observations, the diaphragm thickness was significantly related to mortality. The right diaphragm was significantly thinner in cases that required preoperative respiratory support and had percutaneous endoscopic gastrostomy. When the cut-off values for the diaphragm thickness were accepted as 3.50 mm, significantly higher mortality among patients below this was observed. CONCLUSION: Diaphragm thickness is an important criterion in cases for which DPS implantation is planned. We consider that avoidance of DPS implantation is more suitable for cases with a diaphragm thickness below 3.50 mm because of mortality.

Risk factors for mortality in Down syndrome.

BACKGROUND: Down syndrome is a genetic condition that contributes to a significantly shorter life expectancy compared with the general population. We investigated the most common comorbidities in a population of acute hospital patients with Down syndrome and further explored what the most common risk factors for mortality are within this population. METHOD: From our database of one million patients admitted to National Health Service (NHS) Trusts in northern England, we identified 558 people who had Down syndrome. We compared this group with an age- and gender-matched control group of 5580 people. RESULTS: The most prevalent comorbid diseases within the Down's population were hypothyroidism (22.9%) and epilepsy (20.3%). However, the conditions that had the highest relative risks (RRs) in the Down's population were septal defects and dementia. Respiratory failure, dementia and pneumonia were the most significantly related comorbidities to mortality in the Down syndrome population. In the control population, respiratory failure, dementia and renal failure were the most significant disease contributors. When these contributors were analysed using multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy were the identified risk factors for in-hospital mortality in the Down syndrome population. Respiratory failure was the sole risk factor for mortality in the Down syndrome population [RR = 9.791 (1.6-59.9) P ≤ 0.05], when compared with the risk factors for mortality in the control population. CONCLUSIONS: There is significant medical morbidity in Down syndrome. This morbidity contributes to the lower life expectancy. Respiratory failure is a risk factor for mortality in Down syndrome. We need to thoroughly investigate people with Down syndrome to ensure any treatable illnesses are well managed.

Association of weekend admission with hospital length of stay, time to chemotherapy, and risk for respiratory failure in pediatric patients with newly diagnosed leukemia at freestanding US children's hospitals.

IMPORTANCE: In adult patients with leukemia, weekend admission is associated with increased inpatient mortality. It is unknown whether weekend diagnostic admissions in pediatric patients with leukemia demonstrate similar adverse outcomes. OBJECTIVE: To estimate adverse clinical outcomes associated with weekend admission in the first hospitalization of pediatric patients with newly diagnosed leukemia. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study from 1999 to 2011 featured index hospital admissions identified from the Pediatric Health Information System database. Participants were children with newly diagnosed acute lymphoid leukemia or acute myeloid leukemia. EXPOSURES: Weekend (Saturday and Sunday) or weekday index admission. MAIN OUTCOMES AND MEASURES: Inpatient mortality, length of inpatient stay, time to chemotherapy, and organ-system failure in index admission. RESULTS: A total of 10 720 patients with acute lymphoid leukemia and 1323 patients with acute myeloid leukemia were identified; 2009 patients (16.7%) were admitted on the weekend. While the total daily number of patients receiving intensive care unit-level care was constant regardless of the day of admission, these patients represented a larger percentage of total admissions on weekends. In adjusted analyses, patients admitted on the weekend did not have an increased rate of mortality during the first admission (odds ratio, 1.0; 95% CI, 0.8-1.6). Patients whose initial admission for leukemia occurred during a weekend had a significantly increased length of stay (1.4-day increase; 95% CI, 0.7-2.1), time to initiation of chemotherapy (0.36-day increase; 95% CI, 0.3-0.5), and risk for respiratory failure (odds ratio, 1.5; 95% CI, 1.2-1.7) after adjusting for demographics, severity of illness, and hospital-level factors. CONCLUSIONS AND RELEVANCE: While pediatric patients with newly diagnosed leukemia admitted on weekends do not have higher mortality rates, they have a prolonged length of stay, increased time to chemotherapy, and higher risk for respiratory failure. Patients who are severely ill at presentation represent a higher proportion of weekend index admissions. Optimizing weekend resources by increasing staffing and access to diagnostic and therapeutic resources may help to reduce hospital length of stay across all weekend admissions and may also ensure the availability of comprehensive care for those weekend admissions with higher acuity.

Long-term evaluation of phrenic nerve pacing for respiratory failure due to high cervical spinal cord injury.

OBJECTIVES: Phrenic nerve pacing is a method of respiratory support that can replace mechanical ventilation in high-level cervical spinal cord injury patients with diaphragmatic paralysis. Our objective was to evaluate survival and long-term quality of life in patients with external respiratory support by PNP vs volumetric respirator in patients with severe respiratory insufficiency due to a high-level spinal cord injury. DESIGN: This is a retrospective review study of a prospectively collected database for evaluate the survival and a questionnaire for quality of life has been collected face-to-face or by telephone at present. PATIENTS: Cervical SCI patients with permanent respiratory support (PNP or MV). METHODS: Long-term evaluation of a cohort of PNP-supported patients. We performed a comparison between these patients and volumetric respirator-supported patients. For survival analysis, we used the Kaplan-Meier method and Cox proportional hazards model. The health-related quality of life was assessed with SF-36 questionnaire, a general HRQL evaluation. RESULTS: One hundred twenty six patients on permanent respiratory support were evaluated during the study period. Of these, 38 were on PNP and 88 were mechanically ventilated. Paced patients were younger and had a longer survival, but in a multivariate analysis adjusted for age using a multiple logistic correlation we found that length of survival was greater for PNP patients. In terms of HRQL, the PNP-supported patients showed better results in terms of social functioning. CONCLUSIONS: PNP is a stable and effective method of long-term respiratory support in this type of patients (SCI patients dependent on external respiratory support). In these patients it improves the length of survival and some social issues by quality of life when compared with patients under MV.

Spinal muscular atrophy type 1: are proactive respiratory interventions associated with longer survival?

CONTEXT: Spinal muscular atrophy type 1, an autosomal recessive motor neuron disease, is a leading genetic cause of death in infancy and early childhood. OBJECTIVE: To determine whether the early initiation of noninvasive respiratory interventions is associated with longer survival. DESIGN: Single-institution retrospective cohort study identified children with spinal muscular atrophy type 1 from January 1, 2002 to May 1, 2009 who were followed for 2.3 mean yrs. SETTING: Tertiary care children's hospital and outpatient clinics in a vertically integrated healthcare system. PATIENTS OR OTHER PARTICIPANTS: Forty-nine children with spinal muscular atrophy type 1 were grouped according to the level of respiratory support their caregivers chose within the first 3 months after diagnosis: proactive respiratory care (n = 26) and supportive care (n = 23). INTERVENTIONS: Proactive respiratory care included bilevel noninvasive ventilation during sleep and twice a day cough assist while supportive respiratory care included suctioning, with or without supplemental oxygen. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier survival curves were assessed based on intention to treat. Children treated with early proactive respiratory support had statistically longer survival compared to supportive care (log rank 0.047); however, the adjusted hazard ratio for survival was not statistically different (2.44 [95% confidence interval 0.84-7.1]). Children in the proactive group were more likely to be hospitalized for respiratory insufficiency (83% vs. 46%) and had shortened time after diagnosis until first hospital admission for respiratory insufficiency (median 118 vs. 979 days). CONCLUSION: Longer survival time with spinal muscular atrophy type 1 is associated with early, noninvasive respiratory care interventions after diagnosis.

Nutritional depletion in relation to mortality in patients with chronic respiratory insufficiency treated with long-term oxygen therapy.

OBJECTIVE: An association between malnutrition, weight loss and mortality has been demonstrated in patients with chronic obstructive pulmonary disease (COPD), but the prognostic influence of low body-mass index (BMI) and plasma concentrations of albumin and cholesterol is less clear in patients with chronic respiratory insufficiency treated with domiciliary long-term oxygen therapy (LTOT). We therefore analysed the prognostic value of BMI, plasma albumin and cholesterol concentrations in patients receiving LTOT. PATIENTS AND METHODS: From 1996 to 2001, LTOT was initiated in 255 patients. Analysis of the impact of nutritional status on survival was confined to a study group of 108 patients in whom the main outcomes, i.e. BMI, plasma cholesterol and albumin, were measured. Standard laboratory methods were used in the biochemical analyses. Pulmonary function was assessed with bodyplethysmography. RESULTS: 63 patients (58.3%) survived for two years post-initiation of LTOT and 45 patients (41.7%) did not. There were no differences between these two groups in pulmonary function tests and arterial blood gases at the start of LTOT. Overall, 10.2% of the study population were underweight, defined as BMI <20 kg/m2. Compared with patients who survived two years of LTOT, those who did not survive were older (69.3+/-0.9 versus 64.7+/-1.2 years, p<0.01), had significantly lower BMI (24.5+/-0.7 versus 26.5+/-0.7 kg/m2, p < 0.05), lower plasma cholesterol (4.61+/-0.19 versus 5.22+/-0.13 mmol/l, p<0.01) and lower plasma albumin concentrations (41.4+/-0.4 versus 42.8+/-0.4 g/l, p <0.05). Logistic regression analysis revealed that, in addition to age (p < 0.01), both BMI (p < 0.05) and cholesterol (p < 0.05) significantly affected the 2-year survival. CONCLUSION: This study suggests that nutritional status is closely linked with prognosis in patients with chronic respiratory insufficiency treated with domiciliary LTOT: low BMI, low plasma cholesterol and low albumin are related to worse 2-year survival in such patients.

Bipap improves survival and rate of pulmonary function decline in patients with ALS.

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease that frequently causes death within five years of diagnosis. The majority of deaths are due to pulmonary complications resulting from respiratory muscle weakness and bulbar involvement. A promising respiratory intervention is the recently introduced bi-level intermittent positive pressure (Bipap), which is a noninvasive ventilator modality shown to reduce the work of breathing and improve not only gas exchange, but also exercise tolerance and sleep quality. The aim of this study was to assess the utility of Bipap in prolonging survival in ALS. We retrospectively analyzed the results of Bipap use in 122 patients followed at Hahnemann University. All patients in this study were offered Bipap when their forced vital capacity (FVC) dropped below 50% of predicted value. Group 1 (n=38) accepted Bipap and used it more than 4 h/day. Group 2 (n=32) did not tolerate Bipap well and used it less than 4 h/day. Group 3 (n=52) refused to try Bipap. There was a statistically significant improvement in survival from initiation of Bipap in Group 1 (14.2 months) compared to Group 2 (7.0 months, P=0.002) or 3 (4.6 months, P<0.001) respectively. Furthermore, when the slope of vital capacity decline was examined, the group that used Bipap more than 4 h/day had slower decline in vital capacity (-3.5% change/month) compared to Group 2 (-5.9% change/month, P=0.02) and Group 3 (-8.3% change/month, P<0.001). We conclude that Bipap can significantly prolong survival and slow the decline of FVC in ALS. Our results suggest that all patients with ALS be offered Bipap when their FVC drops below 50%, at the onset of dyspnea, or when a rapid drop in %FVC is noted.

Increased urinary loss of uric acid in adults with acute respiratory failure requiring mechanical ventilation.

INTRODUCTION: The purpose of this study was to test a hypothesis of increased urinary excretion of uric acid as an indicator of adenosine triphosphate (ATP) degradation in adult patients with acute respiratory failure, and to look for a correlation to the clinical outcome. STUDY DESIGN: Prospectively 31 patients with acute respiratory failure were studied. The patients were divided into two groups according to the clinical outcome: the need for solely supplemental oxygen (group 1), death or mechanical ventilation (group 2). METHODS: Uric acid was determined by spectrophotometry. RESULTS: Mean uric acid excretion was 39 mumol/kg (range, 7 to 92 mumol/kg) body weight/per 24 h in group 1 (16 patients) compared with 65 mumol/kg/24 h (range, 8 to 253 mumol/kg/24 h) in group 2 (13 patients were mechanically ventilated, and two patients died). The difference was highly significant (p less than 0.0001). CONCLUSION: Increased amount of urinary uric acid was related to the severity of acute respiratory failure in adults.