Identifying opportunities to increase organ donation after brain death. An observational study in Sweden 2009-2014.

BACKGROUND: There is a wide gap between the number of organ donors and patients on waiting lists for transplantation. The purpose of this Swedish nationwide study of the critical pathway for organ donation after brain death (DBD) was to identify missed opportunities for organ donation. METHODS: We performed a prospective, observational study of all ICU deaths in Sweden from Jan 1, 2009 to Dec 31, 2014. The protocol structure followed the critical pathway for organ donation, which was developed and tested during 2008. We analysed differences in donation incidences between healthcare providers (counties) and patient characteristics using descriptive statistics and logistic regression. RESULTS: The number of DBD per million population (pmp) was 14.9, varying almost 10-fold from 4.3 to 40.6 DBD pmp between counties. Regional variation in DBD decreased when we assigned the donor to the place of residence (from 6.9 to 27.7 DBD pmp). Women were more likely to become donors compared to men [crude odds ratio (OR) 1.60, 95% confidence interval (CI) 1.38-1.85, P < 0.001]. The increased likelihood remained after adjusting for age, comorbidity, and main diagnostic categories (OR 1.49, 95% CI 1.25-1.77, P < 0.001). An end-of-life decision was found in 50.9% of possible organ donors. CONCLUSIONS: Regional differences in DBD were considerable, and women were more likely to become donors than men. There is a need for increased awareness of the potential for organ donation as an integral part of end-of-life clinical care. In-depth analysis of these differences may reveal opportunities for action that could lead to increased DBD.

National survey of potential heart beating solid organ donors in Sweden.

Sweden has about 135 heart beating solid organ donors per year among 9.2 million inhabitants. Earlier estimations have suggested that 250-300 of potential heart beating donors might be available in the country annually. The present study is the first nationwide survey to establish the number of potential heart-beating donors, based on all patient deaths in Swedish intensive care units (ICUs). In the present study, a potential heart-beating solid organ donor was strictly defined as "a patient in an ICU on mechanical ventilation with the diagnosis of brain death." All 85 eligible ICUs reported all patient deaths over a 3 month period of October through December 2007. The instrument consisted of 10 questions. The majority of data were entered electronically by the ICU staff into the "Swedish Intensive Care Registry." The total number of reported patient deaths was 875 with 7.4% of patients who died meeting the criteria for a potential heart-beating solid organ donor. Actually 51% of them became donors. Reasons for not becoming a donor were refusals in 31%, medical reasons in 14%, impossibility to obtain consent in 1.5%, and no suitable recipient in 3%. Furthermore, 1.5% of patients did not become donors because of preferential forensic examinations. The main conclusion of the study was that the actual number of potential heart-beating solid organ donors in Sweden seems to be less than earlier estimates. Another interesting observation is the existence of a group of artificially ventilated, brain injury patients in whom the death was diagnosed by cardiac arrest. We think that this group of patient deaths deserves further investigation in future projects.

Characteristics and long-term outcome of acute exacerbations in chronic obstructive pulmonary disease: an analysis of cases in the Swedish Intensive Care Registry during 2002-2006.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a major and growing health problem. The purpose of this work was to examine characteristics, resource use and long-term survival in patients with an acute exacerbation of COPD that were admitted to Swedish intensive care units (ICU). METHODS: Patient characteristics at admission, length of stay (LOS), resource use and outcome were collected for admissions due to COPD during 2002-2006 in the database of the Swedish Intensive Care Registry. Vital status was secured for 99.6% of the patients. Kaplan-Meier survival estimates were computed for index admissions only. RESULTS: We identified 1009 patients with 1199 admissions due to COPD (1.3% of all intensive care admissions). The mean (SD) age was 70.2 (9.1) years and the proportion of women were 61.5%. Mean (SD) Acute Physiology and Chronic Health Evaluation II probability of hospital death was 0.31 (0.19). Median LOS was 28 (interquartile range 52) h. The number of readmissions was 190 during the 5-year study. Older patients had fewer readmissions (OR 0.96, 95% CI: 0.95-0.98/year increase in age). ICU mortality was 7.3% (87 of 1199 admissions) and 30-day mortality was 26.0% (262 of 1009 index admissions). Median survival was 14.5 months and 31% of patients survived 3 years after the index admission. CONCLUSIONS: Short (30 days) and long-term survival is poor in acute COPD. Readmissions are frequent reflecting the severity of this chronic illness. Patients are less likely to be readmitted with increasing age which may be due to withholding of further intensive care.

Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5.

Recent reviews suggest that chronic kidney disease (CKD) can affect the pharmacokinetics of nonrenally eliminated drugs, but the impact of CKD on individual elimination pathways has not been systematically evaluated. In this study we developed a comprehensive dataset of the effect of CKD on the pharmacokinetics of CYP2D6- and CYP3A4/5-metabolized drugs. Drugs for evaluation were selected based on clinical drug-drug interaction (CYP3A4/5 and CYP2D6) and pharmacogenetic (CYP2D6) studies. Information from dedicated CKD studies was available for 13 and 18 of the CYP2D6 and CYP3A4/5 model drugs, respectively. Analysis of these data suggested that CYP2D6-mediated clearance is generally decreased in parallel with the severity of CKD. There was no apparent relationship between the severity of CKD and CYP3A4/5-mediated clearance. The observed elimination-route dependency in CKD effects between CYP2D6 and CYP3A4/5 may inform the need to conduct clinical CKD studies with nonrenally eliminated drugs for optimal use of drugs in patients with CKD.

A longitudinal study of language acquisition in autistic and Down syndrome children.

Findings from a longitudinal study of language acquisition in a group of autistic children are presented. Six autistic subjects and six children with Down syndrome, matched on age and MLU at the start of the study, were followed over a period of between 12 and 26 months. Language samples were collected in the children's homes while they interacted with their mothers. Samples of 100 spontaneous child utterances from the transcripts were analyzed using the following measures: MLU, Index of Productive Syntax, lexical diversity, and form class distribution. The results indicate that the majority of these autistic children followed the same general developmental path as the Down syndrome children in this study, and normal children reported in the literature, in the acquisition of grammatical and lexical aspects of language, and confirm previous findings suggesting that autism does not involve a fundamental impairment in formal aspects of language.

Lack of drug dosing guidelines for critically ill patients receiving continuous renal replacement therapy.

Acute kidney injury requiring continuous renal replacement therapy is common, costly, and associated with mortality rates of up to 60%. Accurate pharmacokinetic data are essential to developing rational individualized dosing strategies and providing optimal care to these patients, yet few such data exist, probably due in part to an absence of regulatory guidance on the issue. The Kidney Health Initiative is working with stakeholders to propose strategies to address this in a standardized manner.

Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup.

BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). METHODS: After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. RESULTS: Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). CONCLUSION: APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.

Emerging evidence of the impact of kidney disease on drug metabolism and transport.

Several lines of emerging evidence indicate that kidney disease differentially affects uptake and efflux transporters and metabolic enzymes in the liver and gastrointestinal (GI) tract, and uremic toxins have been implicated as the cause. In patients with kidney disease, even drugs that are eliminated by nonrenal transport and metabolism could lead to important unintended consequences if they are administered without dose adjustment for reduced renal function. This is particularly so in the case of drugs with narrow therapeutic windows and may translate into clinically significant variations in exposure and response.

Withdrawal of medical treatment in the ICU. A cohort study of 318 cases during 1994-2000.

BACKGROUND: Many deaths in intensive care occur after life support has been withdrawn or withheld. In Sweden there are no guidelines for the withholding or withdrawal of life-sustaining treatments, and information on the frequency of such decisions is scarce. Open and conscious accounts of crucial standpoints in theses decisions are important. The aim of this study was to determine the incidence of decisions to withdraw medical therapy in a Swedish, general intensive care unit (ICU), the underlying reasons and outcomes. METHODS: In this historical cohort study in a 10 bed ICU, we studied the records of the 3904 patients admitted during the period 1994-2000. RESULTS: Medical therapy was withdrawn in 318 (8.1%) patients. During the study period, 466 patients died in the ICU, of which 191 (41.0%) had had a withdrawal decision. Of the 318 patients with a withdrawal decision followed up, 191 (60.1%) died in the ICU, 104 (32.7%) later on a general ward, and 23 (7.2%) were discharged alive from the hospital. The main reasons for withdrawing therapy were failure to respond to treatment in 119 (37%), poor prognosis of the acute disease in 119 (37%), poor prognosis of coexisting chronic disease in 62 (20%) and the patient's own request in 18 (6%) of the cases. The median time from ICU-admission to a withdrawal decision was 2.8 days. The median time from a withdrawal decision to death was 0.6 days (191 patients) in the ICU, 2.4 days (104 patients) in the general ward and 1.4 months (19 patients) for those dying after hospital discharge. In five cases a renewed evaluation was performed. CONCLUSION: Medical therapy was withdrawn in the ICU in 8.1% of patients and the chief reasons were failure to respond to therapy or poor prognosis of the acute disease. Four patients were still alive five years later. The time interval from admission to a withdrawal decision was short.