Thyroid Storm in the ICU: A Retrospective Multicenter Study.

OBJECTIVES: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. DESIGN: Retrospective, multicenter, national study over an 18-year period (2000-2017). SETTING: Thirty-one French ICUs. PATIENTS: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. CONCLUSIONS: Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.

Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure.

BACKGROUND: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. METHODS: Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. RESULTS: The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30-1.72]; RCT: p value 0.004, median OR 1.51 [1.36-1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. CONCLUSION: Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.

Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial.

Importance: High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). Objective: To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy. Design, Setting, and Participants: The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao2 <60 mm Hg or Spo2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. Interventions: Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). Main Outcomes and Measures: The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao2:Fio2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. Results: Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao2:Fio2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, -0.5% [95% CI, -7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, -5.1% [95% CI, -12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao2:Fio2 (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, -1.8/min [95% CI, -3.2 to -0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, -1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, -0.6% [95% CI, -4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, -2 days [95% CI, -7.3 to +3.3]), or patient comfort and dyspnea scores. Conclusions and Relevance: Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. Trial Registration: clinicaltrials.gov Identifier: NCT02739451.

Coronary Spasm after an Injection of Vincristine.

Cardiotoxicity, including heart failure, thromboembolic events, and myocardial ischemia, is a concern for cardiologists and oncologists. The most frequently involved drugs are anthracyclines. We report an episode of coronary spasm due to vincristine, a vinca alkaloid, in a 49-year-old man treated for a diffuse undifferentiated carcinoma. The patient suffered recurrent episodes of typical chest pain with ST-elevation in the inferior area. Coronary spasm was confirmed by an angiogram, which showed normal coronary arteries. No recurrence occurred with the medical management. Coronary spasm induced by vincristine is a newly described facet of chemotherapy-related cardiotoxicity.

Differential Perceptions of Noninvasive Ventilation in Intensive Care among Medical Caregivers, Patients, and Their Relatives: A Multicenter Prospective Study-The PARVENIR Study.

BACKGROUND: Noninvasive ventilation (NIV) requires a close "partnership" between a conscious patient and the patient's caregivers. Specific perceptions of NIV stakeholders and their impact have been poorly described to date. The objectives of this study were to compare the perceptions of NIV by intensive care unit (ICU) physicians, nurses, patients, and their relatives and to explore factors associated with caregivers' willingness to administer NIV and patients' and relatives' anxiety in relation to NIV. METHODS: This is a prospective, multicenter questionnaire-based study. RESULTS: Three hundred and eleven ICU physicians, 752 nurses, 396 patients, and 145 relatives from 32 ICUs answered the questionnaire. Nurses generally reported more negative feelings and more frequent regrets about providing NIV (median score, 3; interquartile range, [1 to 5] vs. 1 [1 to 5]; P < 0.0001) compared to ICU physicians. Sixty-four percent of ICU physicians and only 32% of nurses reported a high level of willingness to administer NIV, which was independently associated with NIV case-volume and workload. A high NIV session-related level of anxiety was observed in 37% of patients and 45% of relatives. "Dyspnea during NIV," "long NIV session," and "the need to have someone at the bedside" were identified as independent risk factors of high anxiety in patients. CONCLUSIONS: Lack of willingness of caregivers to administer NIV and a high level of anxiety of patients and relatives in relation to NIV are frequent in the ICU. Most factors associated with low willingness to administer NIV by nurses or anxiety in patients and relatives may be amenable to change. Interventional studies are now warranted to evaluate how to reduce these risk factors and therefore contribute to better management of a potentially traumatic experience. (Anesthesiology 2016; 124:1347-59).

Ethical Dilemmas Faced by Military Health Personnel During High-Intensity Conflict: The Crucial Issue of Triage.

Russia's invasion of Ukraine has triggered the biggest conflict in Europe since the Second World War. It has forced countries to prepare for engagement on a massive scale, namely, a high-intensity war between nation states. A potential massive influx of wounded personnel risks saturating logistical supply chains and requires changes to not only medical care but also a paradigm shift. In this context, the principle of distributive justice is key. The aim is to save as many lives as possible through triage, which consists in "doing the greatest good for the greatest number." This idea is fundamental, as an emergency that has passed is no longer an emergency. However, international texts and treaties not only underline that the sole criterion for triage is clinical severity, but they also fail to take into account the patient's status (civilian, friend, and foe). In a high-intensity warfare situation, these texts, and the medical-surgical triage criteria they provide are insufficient, as caregivers may be required to make decisions based on the status of the patient. The need to make such choices could cause psychological suffering among military caregivers, as individuals are recurrently faced with difficult ethical dilemmas. One way to prevent this happening is to provide predeployment training in wartime medical ethics. The latter would include both instruction in international humanitarian law and practical simulations of clinical situations where the person is faced with an ethical dilemma.

The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation.

INTRODUCTION: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC). METHODS: This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC. RESULTS: This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003). CONCLUSIONS: Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.

Survival in neutropenic patients with severe sepsis or septic shock.

OBJECTIVE: To determine whether the survival gains achieved in critically ill cancer patients in recent years exist in the subset with neutropenia and severe sepsis or septic shock. DESIGN: Retrospective 11-yr study (1998-2008). SETTING: Medical intensive care unit in a teaching hospital. PATIENTS: Four hundred twenty-eight intensive care unit patients with cancer, neutropenia, and severe sepsis or septic shock. The primary outcome was hospital mortality. RESULTS: The main underlying diseases were acute leukemia (35.7%), lymphoma (31.7%), and solid tumors (16.5%). Two hundred thirty-seven (55.5%) patients had microbiologically documented infections, 141 (32.9%) clinically documented infections, and 50 (11.9%) fever of unknown origin. Acute noninfectious conditions were diagnosed in 175 of 428 (41%) patients, including 26 of 50 (52%) patients with fever of unknown origin, 66 of 141 (47%) patients with clinically documented infections, and 83 of 237 (35%) patients with microbiologically documented infections. Early indwelling catheter removal was performed routinely in the 107 (25%) patients without clinical evidence of a septic focus at intensive care unit admission. Early beta-lactam plus aminoglycoside therapy was used in 391 (91.3%) patients. Hospital mortality was 49.8%. Hospital mortality decreased from 58.7% (108 of 184) in 1998-2003 to 43% in 2004-2008 (105 of 244, p = .006). Multivariate analysis identified nine independent predictors of hospital mortality, of which six were associated with higher mortality (older age; need for vasopressors; neurologic, respiratory, or hepatic dysfunction; and acute noninfectious condition) and three with lower mortality (intensive care unit admission after 2003, combination antibiotic therapy including an aminoglycoside, and early indwelling catheter removal). CONCLUSION: In neutropenic patients with severe sepsis or septic shock, survival improved over time. Aminoglycoside use and early catheter removal in patients with undocumented sepsis may improve survival. Acute noninfectious conditions are associated with increased mortality, underlining the need for thorough and repeated clinical assessments.

Important questions asked by family members of intensive care unit patients.

OBJECTIVES: Relatives often lack important information about intensive care unit patients. High-quality information is crucial to help relatives overcome the often considerable situational stress and to acquire the ability to participate in the decision-making process, most notably regarding the appropriate level of care. We aimed to develop a list of questions important for relatives of patients in the intensive care unit. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter study. Questions asked by relatives of intensive care unit patients were collected from five different sources (literature, panel of 28 intensive care unit nurses and physicians, 1-wk survey of nurses and 1-wk survey of physicians in 14 intensive care units, and in-depth interviews with 14 families). After a qualitative analysis (framework approach and thematic analysis), questions were rated by 22 relatives and 14 intensive care unit physicians, and the ratings were analyzed using principal component analysis and hierarchical clustering. RESULTS: The five sources produced 2,135 questions. Removal of duplicates and redundancies left 443 questions, which were distributed among nine predefined domains using a framework approach ("diagnosis," "treatment," "prognosis," "comfort," "interaction," "communication," "family," "end of life," and "postintensive care unit management"). Thematic analysis in each domain led to the identification of 46 themes, which were reworded as 46 different questions. Ratings by relatives and physicians showed that 21 of these questions were particularly important for relatives of intensive care unit patients. CONCLUSION: This study increases knowledge about the informational needs of relatives of intensive care unit patients. This list of questions may prove valuable for both relatives and intensive care unit physicians as a tool for improving communication in the intensive care unit.

[Meeting the needs of families of patients in intensive care units]. / Communiquer avec les families des patients en réanimation.

As patients in intensive care units (ICUs) are not always able to decide for themselves, their family must receive thorough information on the diagnosis, prognosis and available treatments (unless the patient has expressed his/her opposition). It is crucial to provide this information before requesting the family's involvement. Together, the family and ICU physicians can ensure that the patient receives the most appropriate care. Next-of-kin may either be called on to make decisions (as surrogates) or simply to offer their considered opinion. Good communication and information are a source of comfort and empowerment for the family, especially in end-of-life settings. Finally, we examine areas warrantingfurther research on the family-physician relationship in ICUs.

Outcomes of Patients Treated with Prehospital Noninvasive Ventilation: Observational Retrospective Multicenter Study in the Northern French Alps.

Noninvasive ventilation (NIV) improves the outcome of acute cardiogenic pulmonary edema (AcPE) and acute exacerbation of chronic obstructive pulmonary disease (aeCOPD) but is not recommended in pneumonia. The aim of this study was to assess the appropriateness of the use of NIV in a prehospital setting, where etiological diagnostics rely mainly on clinical examination. This observational multicenter retrospective study included all the patients treated with NIV by three mobile medical emergency teams in 2015. Prehospital diagnoses and hospital diagnoses were extracted from the medical charts. The appropriateness of NIV was determined by matching the hospital diagnosis to the current guidelines. Among the 14,067 patients screened, 172 (1.2%) were treated with NIV. The more frequent prehospital diagnoses were AcPE (n = 102, 59%), acute respiratory failure of undetermined cause (n = 46, 28%) and aeCOPD (n = 17, 10%). An accurate prehospital diagnosis was more frequent for AcPE (83/88, 94%) than for aeCOPD (14/32, 44%; p < 0.01). Only two of the 25 (8%) pneumonia cases were diagnosed during prehospital management. Prehospital NIV was inappropriate for 32 (21%) patients. Patients with inappropriate NIV had a higher rate of in-hospital intubation than patients with appropriate NIV (38% vs. 8%; p < 0.001). This high frequency of inappropriate NIV could be reduced by an improvement in the prehospital detection of aeCOPD and pneumonia.

Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure.

BACKGROUND: Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. RESULTS: In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1-3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69-7.01) vs. 6.10 (4.48-8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557-0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82-0.96], p = 0.04). CONCLUSION: A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies.

Surrogate decision makers for incompetent ICU patients: a European perspective.

PURPOSE OF REVIEW: Frequently, ICU patients lack the capacity to share discussions and make decisions about their health. Designation of a surrogate and advance directives have been proposed to empower patients and give more place to their autonomy. Even though legitimacy of surrogates is now recognized by physicians, patients' management must take into account new legislations emphasizing patients' autonomy all over Europe. RECENT FINDINGS: Over the last decade, most western European countries have recognized the validity of advance directives and the process of substitute decision making when a patient is incapacitated. Although the laws of these countries reflect the same approach, there are several differences in the mode of designation of surrogates and in their decisional authority. SUMMARY: The present review compares the legal framework of surrogacy in Belgium, Denmark, England, France, Germany, the Netherlands, Spain, and Switzerland. France is the country that confers the weakest power to surrogates in decision making. Patients' competence and the ability of surrogate decision makers to cope with ICU's burden are discussed as the main limitations of the substitute decision-making process. Measures to improve substitute decision making and to limit harmful repercussions are suggested.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

BACKGROUND: Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. METHODS/DESIGN: This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. DISCUSSION: The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

Treatment intensity, age and outcome in medical ICU patients: results of a French administrative database.

BACKGROUND: Intensive care unit (ICU) patients are aging, and older age has been associated with higher mortality in ICU. As previous studies have reported that older age was also associated with less intensive treatment, we investigated the relationship between age, treatment intensity and mortality in medical ICU patients. METHODS: Data were extracted from the administrative database of 18 medical ICUs. Patients with a unique medical ICU stay and a Simplified Acute Physiology Score II (without age-related points) >15 were included. Treatment intensity was described with a novel indicator, which is a four-group classification based upon the most frequent ICU procedures. The relationship between age, treatment intensity and hospital mortality was analyzed with the estimation of standardized mortality ratio in the four groups of treatment intensity. RESULTS: A total of 23,578 patients, including 3203 patients aged ≥80 years, were analyzed. Hospital mortality increased from 13 % for the younger patients (age < 40 years) to 38 % for the older patients (age ≥ 80 years), while Simplified Acute Physiology Score II (without age-related points) increased only from 36 (age < 40 years) to 43 (age ≥ 80). Hospital mortality increased with age in the four groups of treatment intensity. Standardized mortality ratio increased with age among the patients with less intensive treatment but was not associated with age among the patients with the highest treatment intensity. CONCLUSION: Our results support the fact that the increase in mortality with age among ICU patients is not related to an increase in severity. Using a new tool to estimate ICU treatment intensity, our study suggests that mortality of ICU patients increases with age whatever the treatment intensity is. Further investigations are required to determinate whether this increase in mortality among older ICU patients is related to undertreatment or to a lower efficiency of organ support treatment.

[Wounded in action: the platinum ten minutes and the golden hour]. / Blessés au combat, dix minutes en platine, une heure en or.

In the battlefield, the majority of casualties die within ten minutes of the trauma. Most injuries result from an explosion and haemorrhage plays a central role. To improve survival rates, the French Army Health Service has developed a chain of survival from the battlefield to France based on prehospital combat casualty care, forward medical support during the first hour and damage control surgery.

Causes and risk factors of death in patients with thrombotic microangiopathies.

PURPOSE: Although plasma therapy of thrombotic micro-angiopathies (TMAs) has dramatically improved survival, the outcome remains fatal in up to 15 % of patients. We investigated the causes and risk factors of death in patients with TMA. METHODS: Retrospective matched case-control national-registry study of 57 patients who died within 180 days of TMA diagnosis and 48 survivors matched on age, gender, and baseline platelet count and creatinine level. The study period was 1995-2007. Factors associated with mortality were identified using a conditional logistic regression model. RESULTS: Median time from TMA symptom onset to death was 7 (5-14) days. The leading causes of death were nosocomial infections, myocardial infarction, stroke, and pulmonary embolism. Cases and controls did not differ significantly regarding haemolysis parameters, ADAMTS13 activity, or neurological or gastrointestinal involvement. TMA was more frequently related to HIV or cancer in patients who died. Compared to survivors, non-survivors more often had cardiac involvement at diagnosis (38 vs. 6 %, p = 0.03) and less often received plasma exchange therapy (60 vs. 92 %, p = 0.004). Only two factors were independently associated with mortality by multivariate analysis: cardiac involvement at diagnosis (odds ratio, 5.96; 95 % confidence interval, 1.06-33.4) and plasma exchange therapy (odds ratio, 0.25; 95 % confidence interval, 0.06-0.99). CONCLUSION: Our data emphasise the adverse prognostic significance of cardiac abnormalities and support routine plasma exchange in patients with TMA. Given the high risk of cardiac and neurological complications, adequate monitoring should be proposed to these patients in appropriate hospital settings.