Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature

AbSTRAcT Most of the clinical data on the safety profile of desmopressin (DDAvP), which is an effective treatment for both polyuric conditions and bleeding disorders, originate from studies on the tailoring of drug treatment, whereas few reports exist describing severe side effects secondary to drug-drug interaction. We herein describe a case of severe hyponatremia complicated by seizure and coma due to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) in a patient on DDAvP replacement therapy for central diabetes insipidus (DI). A 50-yr-old caucasian man, with congenital central DI, developed an episode of generalized tonic-clonic seizure, resulting in coma immediately after being admitted to the Emergency Unit for weakness and emesis. based on his medical history and clinical findings, water intoxication secondary to ketoprofen intake (200 mg/day for the last 3 days) concomitant with DDAvP replacement therapy (Minirin ® 60 mcg 4 tablets a day) was hypothesized as being the cause of the severe euvolemic hypotonic hyponatremia (natremia 113 mEq/l, plasma osmolality 238 mOsm/Kg). After standard emergency procedures, appropriate gradual restoration of serum sodium levels to the normal range was achieved in 72 hours. Hydratation was maintained according to water excretion and desmopressin therapy was re-introduced. We discuss this case report in the context of the published literature. The present report first highlights the potentially lifethreatening side effects associated with over-the-counter NSAIDs during DDAvP replacement therapy for central DI. Risks and benefits of co-treatment should be carefully considered and therapeutic alternatives to NSAIDs should be recommended to patients with central DI in order to improve DDAvP safety

Implications of ICU triage decisions on patient mortality: a cost-effectiveness analysis

INTRODUCTION: Intensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors. METHODS: This multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved. RESULTS: Admission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for 40% predicted mortality, respectively. Average cost per life saved for all patients was $103,771 (€82,358) and cost per life-year saved was$7,065 (€5,607). These figures decreased substantially for patients with predicted mortality higher than 40%, $60,046 (€47,656) and$4,088 (€3,244), respectively. Results were very similar when considering three-month mortality. Sensitivity analyses performed to assess the robustness of the results provided findings similar to the main analyses. CONCLUSIONS: Not only does ICU appear to produce an improvement in survival, but the cost per life saved falls for patients with greater severity of illness. This suggests that intensive care is similarly cost effective to other therapies that are generally regarded as essential

SAPS 3—From evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description

OBJECTIVE: Risk adjustment systems now in use were developed more than a decade ago and lack prognostic performance. Objective of the SAPS 3 study was to collect data about risk factors and outcomes in a heterogeneous cohort of intensive care unit (ICU) patients, in order to develop a new, improved model for risk adjustment. DESIGN: Prospective multicentre, multinational cohort study. PATIENTS AND SETTING: A total of 19,577 patients consecutively admitted to 307 ICUs from 14 October to 15 December 2002. MEASUREMENTS AND RESULTS: Data were collected at ICU admission, on days 1, 2 and 3, and the last day of the ICU stay. Data included sociodemographics, chronic conditions, diagnostic information, physiological derangement at ICU admission, number and severity of organ dysfunctions, length of ICU and hospital stay, and vital status at ICU and hospital discharge. Data reliability was tested with use of kappa statistics and intraclass-correlation coefficients, which were >0.85 for the majority of variables. Completeness of the data was also satisfactory, with 1 [0–3] SAPS II parameter missing per patient. Prognostic performance of the SAPS II was poor, with significant differences between observed and expected mortality rates for the overall cohort and four (of seven) defined regions, and poor calibration for most tested subgroups. CONCLUSIONS: The SAPS 3 study was able to provide a high-quality multinational database, reflecting heterogeneity of current ICU case-mix and typology. The poor performance of SAPS II in this cohort underscores the need for development of a new risk adjustment system for critically ill patients. ELECTRONIC SUPPLEMENTARY MATERIAL: Electronic supplementary material is included in the online fulltext version of this article and accessible for authorised users: http://dx.doi.org/10.1007/s00134-005-2762-

Hospital mortality of adults admitted to Intensive Care Units in hospitals with and without Intermediate Care Units: a multicentre European cohort study.

INTRODUCTION: The aim of the study was to assess whether adults admitted to hospitals with both Intensive Care Units (ICU) and Intermediate Care Units (IMCU) have lower in-hospital mortality than those admitted to ICUs without an IMCU. METHODS: An observational multinational cohort study performed on patients admitted to participating ICUs during a four-week period. IMCU was defined as any physically and administratively independent unit open 24 hours a day, seven days a week providing a level of care lower than an ICU but higher than a ward. Characteristics of hospitals, ICUs and patients admitted to study ICUs were recorded. The main outcome was all-cause in-hospital mortality until hospital discharge (censored at 90 days). RESULTS: One hundred and sixty-seven ICUs from 17 European countries enrolled 5,834 patients. Overall, 1,113 (19.1%) patients died in the ICU and 1,397 died in hospital, with a total of 1,397 (23.9%) deaths. The illness severity was higher for patients in ICUs with an IMCU (median Simplified Acute Physiology Score (SAPS) II: 37) than for patients in ICUs without an IMCU (median SAPS II: 29, P <0.001). After adjustment for patient characteristics at admission such as illness severity, and ICU and hospital characteristics, the odds ratio of mortality was 0.63 (95% CI 0.45 to 0.88, P = 0.007) in favour of the presence of IMCU. The protective effect of the IMCU was absent in patients who were admitted for basic observation, for example, after surgery (odds ratio 1.15, 95% CI 0.65 to 2.03, P = 0.630) but was strong in patients admitted to an ICU for other reasons (odds ratio 0.54, 95% CI 0.37 to 0.80, P = 0.002). CONCLUSIONS: The presence of an IMCU in the hospital is associated with significantly reduced adjusted hospital mortality for adults admitted to the ICU. This effect is relevant for the patients requiring full intensive treatment. TRIAL REGISTRATION: Clinicaltrials.gov NCT01422070. Registered 19 August 2011